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Showing drug card for Levothyroxine (DB00451)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:43
Primary Accession Number DB00451
Secondary Accession Number
  • APRD00235
  • EXPT02993
Name Levothyroxine
Drug Type
  • Approved
  • Small Molecule
Description The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. [PubChem]
Synonyms
  1. (-)-Thyroxine
  2. 3,3',5,5'-Tetraiodo-L-thyronine
  3. L-Thryoxin
  4. L-Thyroxine
  5. Laevothyroxinum
  6. Levo-t
  7. Levothyroxin
  8. Levothyroxine Sodium
  9. O-(4-Hydroxy-3,5-diidophenyl)-3,5-diiodo-L-tyrosine
  10. T4 levothyroxine
  11. THX
  12. Tetraiodothyronine
  13. Thyroxine iodine
Brand Names
  1. Eltroxin
  2. Euthyrox
  3. Laevoxin
  4. Letter
  5. Levaxin
  6. Levolet
  7. Levothroid
  8. Levothyrox
  9. Levoxine
  10. Levoxyl
  11. Novothyrox
  12. Oroxine
  13. Synthroid
  14. Synthroid Sodium
  15. Thyratabs
  16. Thyrax
  17. Thyreoideum
  18. Thyro-tabs
  19. Thyroxevan
  20. Thyroxin
  21. Thyroxinal
  22. Unithroid
Brand Mixtures
  1. Liotrix (Levothyroxine + Liothyronine)
  2. Thyrolar (Levothyroxine + Liothyronine)
Chemical IUPAC Name (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Chemical Formula C15H11I4NO4
Chemical Structure Structure
CAS Registry Number 51-48-9
InChI Identifier InChI=1/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1/f/h22H
InChI Key XUIIKFGFIJCVMT-LXHGQMKLDQ
KEGG Drug Not Available
KEGG Compound C01829 Link Image
PubChem Compound 5819 Link Image
PubChem Substance 7854286 Link Image
ChEBI ID 18332 Link Image
PharmGKB ID PA450221 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02245948 Link Image
RxList Link http://www.rxlist.com/cgi/generic/levothy.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/syn1421.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Levothyroxine Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Chalmers et al., J. Chem. Soc. 1949, 3424
Average Molecular Weight 776.8700
Monoisotopic Molecular Weight 776.6867
State Solid
Melting Point 235.5 oC
Experimental Water Solubility 0.105 mg/mL Source: PhysProp
Predicted Water Solubility 8.98e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4 Source: PhysProp
Predicted LogP 1.15 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.94 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
Canonical SMILES NC(CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
Drug Category
  • Anticoagulants
  • Antithyroid Agents
ATC Codes
AHFS Codes
  • 68:36.04
Indication For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.
Pharmacology Levothyroxine (T4) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold.
Mechanism of Action Levothyroxine acts like the endogenous thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxin-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then takes place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved.
Absorption Bioavailability varies from 48% to 80%. Human studies have confirmed the importance of an intact jejunum and ileum for levothyroxine absorption and have shown some absorption from the duodenum.
Toxicity LD50=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.
Protein Binding > 99%
Biotransformation Hepatic (primarily via cytochrome P450 isozyme 3A4).
Half Life 6 to 7 days
Dosage Forms
Form Route
Powder, for solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Thyroid hormones increase the anticoagulant effect
Anisindione Thyroid hormones increase the anticoagulant effect
Calcium Calcium decreases absorption of levothyroxine
Cholestyramine The resin decreases the absorption of thyroid hormones
Colestipol The resin decreases the absorption of thyroid hormones
Dicumarol Thyroid hormones increase the anticoagulant effect
Digoxin The thyroid hormone decreases the effect of digoxin
Iron Iron decreases absorption of levothyroxine
Raloxifene Raloxifene decreases absorption of levothyroxine
Sucralfate Sucralfate decreases the effect of levothyroxine
Warfarin Thyroid hormones increase the anticoagulant effect
Food Interactions
  • Consistent administration in relation to meals is recommended.
  • No iron within 4 hours of taking this medication.
  • Take 30-60 minutes before breakfast.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
  4. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. Mu-crystallin homolog
  2. Thyroid hormone receptor beta-1
  3. Transthyretin
  4. Serum albumin
  5. Thyroxine-binding globulin
  6. Thyroid hormone receptor alpha
  7. Transthyretin
  8. Transthyretin
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 116
Target 1 Name Mu-crystallin homolog
Target 1 Synonyms
  1. NADP-regulated thyroid-hormone-binding protein
Target 1 Gene Name CRYM
Target 1 Protein Sequence >Mu-crystallin homolog 
MSRVPAFLSAAEVEEHLRSSSLLIPPLETALANFSSGPEGGVMQPVRTVVPVTKHRGYLG
VMPAYSAAEDALTTKLVTFYEDRGITSVVPSHQATVLLFEPSNGTLLAVMDGNVITAKRT
AAVSAIATKFLKPPSSEVLCILGAGVQAYSHYEIFTEQFSFKEVRIWNRTKENAEKFADT
VQGEVRVCSSVQEAVAGADVIITVTLATEPILFGEWVKPGAHINAVGASRPDWRELDDEL
MKEAVLYVDSQEAALKESGDVLLSGAEIFAELGEVIKGVKPAHCEKTTVFKSLGMAVEDT
VAAKLIYDSWSSGK
Target 1 Number of Residues 319
Target 1 Molecular Weight 33776
Target 1 Theoretical pI 4.80
Target 1 GO Classification Not Available
Target 1 General Function Amino acid transport and metabolism
Target 1 Specific Function Binds thyroid hormone. Presumably involved in the regulation of the free intracellular concentration of triiodothyronine and access to its nuclear receptors
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 1066343 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q14894 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CRYM_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cytoplasm
Target 1 Gene Sequence >945 bp 
ATGAGCCGGGTACCAGCGTTCCTGAGCGCGGCCGAGGTGGAGGAACACCTCCGCAGCTCC
AGCCTCCTCATCCCGCCTCTAGAGACGGCCCTGGCCAACTTCTCCAGCGGTCCCGAAGGA
GGGGTCATGCAGCCCGTGCGCACCGTGGTGCCGGTGACCAAGCACAGGGGCTACCTGGGG
GTCATGCCCGCCTACAGTGCTGCAGAGGATGCACTGACCACCAAGTTGGTCACCTTCTAC
GAGGACCGCGGCATCACCTCGGTCGTCCCTTCCCACCAGGCTACTGTGCTACTCTTTGAG
CCCAGCAATGGCACCCTGCTGGCGGTCATGGATGGAAATGTCATAACTGCAAAGAGAACA
GCTGCAGTTTCTGCCATTGCCACCAAGTTTCTGAAACCTCCCAGCAGTGAAGTGCTGTGC
ATCCTTGGGGCTGGGGTCCAGGCCTACAGCCATTATGAGATCTTCACAGAGCAGTTCTCC
TTTAAGGAGGTGAGGATATGGAACCGCACCAAAGAAAATGCAGAGAAGTTTGCAGACACA
GTGCAAGGAGAGGTACGGGTCTGTTCTTCGGTCCAGGAGGCTGTGGCAGGTGCAGATGTG
ATCATCACAGTCACCCTGGCAACAGAGCCCATTTTGTTTGGTGAATGGGTGAAGCCAGGG
GCTCACATCAATGCTGTTGGAGCCAGCAGACCTGACTGGAGAGAACTGGATGATGAGCTC
ATGAAAGAAGCTGTGCTGTACGTGGATTCCCAGGAGGCTGCCCTGAAGGAGTCTGGAGAT
GTCCTGCTGTCAGGGGCCGAGATCTTTGCTGAGCTGGGAGAAGTGATTAAGGGAGTGAAA
CCAGCCCACTGTGAGAAGACCACGGTGTTCAAGTCTTTGGGAATGGCAGTGGAAGACACA
GTTGCAGCCAAACTCATCTATGATTCCTGGTCATCTGGTAAATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID CRYM Link Image
Target 1 GenAtlas ID CRYM Link Image
Target 1 HGNC ID HGNC:2418 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16p13.11-p12.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [PubMed Link Image]
  2. Kim RY, Gasser R, Wistow GJ: mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9292-6. [PubMed Link Image]
  3. Segovia L, Horwitz J, Gasser R, Wistow G: Two roles for mu-crystallin: a lens structural protein in diurnal marsupials and a possible enzyme in mammalian retinas. Mol Vis. 1997 Sep 9;3:9. [PubMed Link Image]
  4. Vie MP, Evrard C, Osty J, Breton-Gilet A, Blanchet P, Pomerance M, Rouget P, Francon J, Blondeau JP: Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein. Mol Endocrinol. 1997 Oct;11(11):1728-36. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 346
Target 2 Name Thyroid hormone receptor beta-1
Target 2 Synonyms Not Available
Target 2 Gene Name THRB
Target 2 Protein Sequence >Thyroid hormone receptor beta-1 
MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQ
TTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKCKGYIPSYLDKDELCVVCGDKATGYHYR
CITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL
DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWK
QKRKFLPEDIGQAPIVNAPEGGKVDLEAFSHFTKIITPAITRVVDFAKKLPMFCELPCED
QIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGGLGVVSDAIFDLGMSL
SSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPK
LLMKVTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFED
Target 2 Number of Residues 468
Target 2 Molecular Weight 52788
Target 2 Theoretical pI 7.11
Target 2 GO Classification
Function
thyroid hormone receptor activity
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 2 General Function Involved in transcription factor activity
Target 2 Specific Function High affinity receptor for triiodothyronine
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 31207 Link Image
Target 2 UniProtKB/Swiss-Prot ID P10828 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name THB1_HUMAN Link Image
Target 2 PDB ID 1Y0X Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Nucleus
Target 2 Gene Sequence >1371 bp 
ATGACAGAAAATGGCCTTACAGCTTGGGACAAACCGAAGCACTGTCCAGACCGAGAACAC
GACTGGAAGCTAGTAGGAATGTCTGAAGCCTGCCTACATAGGAAGAGCCATTCAGAGAGG
CGCAGCACGTTGAAAAATGAACAGTCGTCGCCACATCTCATCCAGACCACTTGGACTAGC
TCAATATTCCATCTGGACCATGATGATGTGAACGACCAGAGTGTCTCAAGTGCCCAGACC
TTCCAAACGGAGGAGAAGAAATGTAAAGGGTACATCCCCAGTTACTTAGACAAGGACGAG
CTCTGTGTAGTGTGTGGTGACAAAGCCACCGGGTATCACTACCGCTGTATCACGTGTGAA
GGCTGCAAGGGTTTCTTTAGAAGAACCATTCAGAAAAATCTCCATCCATCCTATTCCTGT
AAATATGAAGGAAAATGTGTCATAGACAAAGTCACGCGAAATCAGTGCCAGGAATGTCGC
TTTAAGAAATGCATCTATGTTGGCATGGCAACAGATTTGGTGCTGGATGACAGCAAGAGG
CTGGCCAAGAGGAAGCTGATAGAGGAGAACCGGGAGAAAAGACGGCGGGAAGAGCTGCAG
AAGTCCATCGGGCACAAGCCAGAGCCCACAGACGAGGAATGGGAGCTCATCAAAACTGTC
ACCGAAGCCCATGTGGCGACCAACGCCCAAGGCAGCCACTGGAAGCAAAAACCGAAATTT
CTGCCAGAAGACATTGGACAAGCACCAATAGTCAATGCCCCAGAAGGTGGAAAGGTTGAC
TTGGAAGCCTTCAGCCATTTTACAAAAATCATCACACCAGCAATTACCAGAGTGGTGGAT
TTTGCCAAAAAGTTGCCTATGTTTTGTGAGCTGCCATGTGAAGACCAGATCATCCTCCTC
AAAGGCTGCTGCATGGAGATCATGTCCCTTCGCGCTGCTGTGCGCTATGACCCGGAAAGT
GAGACTTTAACCTTGAATGGGGAAATGGCAGTGATACGGGGCCAGCTGAAAAATGGGGGT
CTTGGGGTGGTGTCAGACGCCATCTTTGACCTAGGCATGTCTCTGTCTTCTTTCAACCTG
GATGACACTGAAGTAGCCCTCCTTCAGGCCGTCCTGCTGATGTCTTCAGATCGCCCGGGG
CTTGCCTGTGTTGAGAGAATAGAAAAGTACCAAGATAGTTTCCTGCTGGCCTTTGAACAC
TATATCAATTACCGAAAACACCACGTGACACACTTTTGGCCAAAACTCCTGATGAAGGTG
ACAGATCTGCGGATGATAGGAGCCTGCCATGCCAGCCGCTTCCTGCACATGAAGGTGGAA
TGCCCCACAGAACTCCTCCCCCCTTTGTTCCTGGAAGTGTTCGAGGATTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID THRB Link Image
Target 2 GenAtlas ID THRB Link Image
Target 2 HGNC ID HGNC:11799 Link Image
Target 2 Chromosome Location 3
Target 2 Locus 3p24.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. [PubMed Link Image]
  2. Cugini CD Jr, Leidy JW Jr, Chertow BS, Berard J, Bradley WE, Menke JB, Hao EH, Usala SJ: An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid hormone receptor in a kindred with generalized resistance to thyroid hormones results in a receptor with significant 3,5,3'-triiodothyronine binding activity. J Clin Endocrinol Metab. 1992 May;74(5):1164-70. [PubMed Link Image]
  3. Behr M, Loos U: A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA beta thyroid hormone receptor gene in a family with generalized thyroid hormone resistance. Mol Endocrinol. 1992 Jul;6(7):1119-26. [PubMed Link Image]
  4. Adams M, Nagaya T, Tone Y, Jameson JL, Chatterjee VK: Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome. Clin Endocrinol (Oxf). 1992 Mar;36(3):281-9. [PubMed Link Image]
  5. Sasaki S, Nakamura H, Tagami T, Miyoshi Y, Tanaka K, Imura H: A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone. Mol Cell Endocrinol. 1992 Apr;84(3):159-66. [PubMed Link Image]
  6. Shuto Y, Wakabayashi I, Amuro N, Minami S, Okazaki T: A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone. J Clin Endocrinol Metab. 1992 Jul;75(1):213-7. [PubMed Link Image]
  7. Usala SJ, Menke JB, Watson TL, Wondisford FE, Weintraub BD, Berard J, Bradley WE, Ono S, Mueller OT, Bercu BB: A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor. Mol Endocrinol. 1991 Mar;5(3):327-35. [PubMed Link Image]
  8. Parrilla R, Mixson AJ, McPherson JA, McClaskey JH, Weintraub BD: Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two "hot spot" regions of the ligand binding domain. J Clin Invest. 1991 Dec;88(6):2123-30. [PubMed Link Image]
  9. Usala SJ, Menke JB, Watson TL, Berard WE, Bradley C, Bale AE, Lash RW, Weintraub BD: A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance. J Clin Endocrinol Metab. 1991 Jan;72(1):32-8. [PubMed Link Image]
  10. Sakurai A, Nakai A, DeGroot LJ: Structural analysis of human thyroid hormone receptor beta gene. Mol Cell Endocrinol. 1990 Jun 18;71(2):83-91. [PubMed Link Image]
  11. 2153155 Usala SJ, Tennyson GE, Bale AE, Lash RW, Gesundheit N, Wondisford FE, Accili D, Hauser P, Weintraub BD: A base mutation of the C-erbA beta thyroid hormone receptor in a kindred with generalized thyroid hormone resistance. Molecular heterogeneity in two other kindreds. J Clin Invest. 1990 Jan;85(1):93-100.
  12. 2510172 Sakurai A, Takeda K, Ain K, Ceccarelli P, Nakai A, Seino S, Bell GI, Refetoff S, DeGroot LJ: Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8977-81.
  13. 2879243 Weinberger C, Thompson CC, Ong ES, Lebo R, Gruol DJ, Evans RM: The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18-31;324(6098):641-6.
  14. 3034496 Weinberger C, Giguere V, Hollenberg S, Rosenfeld MG, Evans RM: Human steroid receptors and erbA proto-oncogene products: members of a new superfamily of enhancer binding proteins. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 2:759-72.
  15. 7746322 Rastinejad F, Perlmann T, Evans RM, Sigler PB: Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature. 1995 May 18;375(6528):203-11.
  16. 7833659 Refetoff S, Weiss RE, Wing JR, Sarne D, Chyna B, Hayashi Y: Resistance to thyroid hormone in subjects from two unrelated families is associated with a point mutation in the thyroid hormone receptor beta gene resulting in the replacement of the normal proline 453 with serine. Thyroid. 1994 Fall;4(3):249-54.
  17. 8175986 Weiss RE, Chyna B, Duell PB, Hayashi Y, Sunthornthepvarakul T, Refetoff S: A new point mutation (C446R) in the thyroid hormone receptor-beta gene of a family with resistance to thyroid hormone. J Clin Endocrinol Metab. 1994 May;78(5):1253-6.
  18. 8381821 Geffner ME, Su F, Ross NS, Hershman JM, Van Dop C, Menke JB, Hao E, Stanzak RK, Eaton T, Samuels HH, et al.: An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype. J Clin Invest. 1993 Feb;91(2):538-46.
  19. 8514853 Weiss RE, Weinberg M, Refetoff S: Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families. J Clin Invest. 1993 Jun;91(6):2408-15.
  20. 8664910 Pohlenz J, Schonberger W, Wemme H, Winterpacht A, Wirth S, Zabel B: New point mutation (R243W) in the hormone binding domain of the c-erbA beta 1 gene in a family with generalized resistance to thyroid hormone. Hum Mutat. 1996;7(1):79-81.
  21. 8889584 Seto D, Weintraub BD: Rapid molecular diagnosis of mutations associated with generalized thyroid hormone resistance by PCR-coupled automated direct sequencing of genomic DNA: detection of two novel mutations. Hum Mutat. 1996;8(3):247-57.
Target 2 Drug References Not Available
Drug Target 3 [top]
Target 3 ID 373
Target 3 Name Transthyretin
Target 3 Synonyms
  1. ATTR
  2. Prealbumin
  3. TBPA
  4. TTR
  5. Transthyretin precursor
Target 3 Gene Name TTR
Target 3 Protein Sequence >Transthyretin precursor 
MASHRLLLLCLAGLVFVSEAGPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDT
WEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDS
GPRRYTIAALLSPYSYSTTAVVTNPKE
Target 3 Number of Residues 149
Target 3 Molecular Weight 15887
Target 3 Theoretical pI 5.58
Target 3 GO Classification
Function
binding
steroid binding
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 3 General Function Involved in steroid binding
Target 3 Specific Function Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-20
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 189582 Link Image
Target 3 UniProtKB/Swiss-Prot ID P02766 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TTHY_HUMAN Link Image
Target 3 PDB ID 1KED Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Secreted protein
Target 3 Gene Sequence >444 bp 
ATGGCTTCTCATCGTCTGCTCCTCCTCTGCCTTGCTGGACTGGTATTTGTGTCTGAGGCT
GGCCCTACGGGCACCGGTGAATCCAAGTGTCCTCTGATGGTCAAAGTTCTAGATGCTGTC
CGAGGCAGTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCTGCTGATGACACC
TGGGAGCCATTTGCCTCTGGGAAAACCAGTGAGTCTGGAGAGCTGCATGGGCTCACAACT
GAGGAGGAATTTGTAGAAGGGATATACAAAGTGGAAATAGACACCAAATCTTACTGGAAG
GCACTTGGCATCTCCCCATTCCATGAGCATGCAGAGGTGGTATTCACAGCCAACGACTCC
GGCCCCCGCCGCTACACCATTGCCGCCCTGCTGAGCCCCTACTCCTATTCCACCACGGCT
GTCGTCACCAATCCCAAGGAATGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID TTR Link Image
Target 3 GenAtlas ID TTR Link Image
Target 3 HGNC ID HGNC:12405 Link Image
Target 3 Chromosome Location 18
Target 3 Locus 18q12.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Naylor HM, Newcomer ME: The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP. Biochemistry. 1999 Mar 2;38(9):2647-53. [PubMed Link Image]
  2. Klabunde T, Petrassi HM, Oza VB, Raman P, Kelly JW, Sacchettini JC: Rational design of potent human transthyretin amyloid disease inhibitors. Nat Struct Biol. 2000 Apr;7(4):312-21. [PubMed Link Image]
  3. Nakamura M, Hamidi Asl K, Benson MD: A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy. Amyloid. 2000 Mar;7(1):46-50. [PubMed Link Image]
  4. de Carvalho M, Moreira P, Evangelista T, Ducla-Soares JL, Bento M, Fernandes R, Saraiva MJ: New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy. Muscle Nerve. 2000 Jul;23(7):1016-21. [PubMed Link Image]
  5. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  6. Blevins G, Macaulay R, Harder S, Fladeland D, Yamashita T, Yazaki M, Hamidi Asl K, Benson MD, Donat JR: Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. Neurology. 2003 May 27;60(10):1625-30. [PubMed Link Image]
  7. Almeida MR, Ferlini A, Forabosco A, Gawinowicz M, Costa PP, Salvi F, Plasmati R, Tassinari CA, Altland K, Saraiva MJ: Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis. Hum Mutat. 1992;1(3):211-5. [PubMed Link Image]
  8. Jacobson DR, McFarlin DE, Kane I, Buxbaum JN: Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement. Hum Genet. 1992 May;89(3):353-6. [PubMed Link Image]
  9. Uemichi T, Murrell JR, Zeldenrust S, Benson MD: A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy. J Med Genet. 1992 Dec;29(12):888-91. [PubMed Link Image]
  10. Izumoto S, Younger D, Hays AP, Martone RL, Smith RT, Herbert J: Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70. Neurology. 1992 Nov;42(11):2094-102. [PubMed Link Image]
  11. 1517749 Kametani F, Ikeda S, Yanagisawa N, Ishi T, Hanyu N: Characterization of a transthyretin-related amyloid fibril protein from cerebral amyloid angiopathy in type I familial amyloid polyneuropathy. J Neurol Sci. 1992 Apr;108(2):178-83.
  12. 1520326 Murakami T, Atsumi T, Maeda S, Tanase S, Ishikawa K, Mita S, Kumamoto T, Araki S, Ando M: A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy. Biochem Biophys Res Commun. 1992 Aug 31;187(1):397-403.
  13. 1520336 Nishi H, Kimura A, Harada H, Hayashi Y, Nakamura M, Sasazuki T: Novel variant transthyretin gene (Ser50 to Ile) in familial cardiac amyloidosis. Biochem Biophys Res Commun. 1992 Aug 31;187(1):460-6.
  14. 1544214 Jones LA, Skare JC, Cohen AS, Harding JA, Milunsky A, Skinner M: Familial amyloidotic polyneuropathy: a new transthyretin position 30 mutation (alanine for valine) in a family of German descent. Clin Genet. 1992 Feb;41(2):70-3.
  15. 1570831 Saraiva MJ, Almeida Mdo R, Sherman W, Gawinowicz M, Costa P, Costa PP, Goodman DS: A new transthyretin mutation associated with amyloid cardiomyopathy. Am J Hum Genet. 1992 May;50(5):1027-30.
  16. 1656975 Saeki Y, Ueno S, Yorifuji S, Sugiyama Y, Ide Y, Matsuzawa Y: New mutant gene (transthyretin Arg 58) in cases with hereditary polyneuropathy detected by non-isotope method of single-strand conformation polymorphism analysis. Biochem Biophys Res Commun. 1991 Oct 15;180(1):380-5.
  17. 1666289 Gu JR, Jiang HQ, He LP, Li DZ, Zhou XM, Dai WL, Qian LF, Chen YQ, Schweinfest C, Papas T: Transthyretin (prealbumin) gene in human primary hepatic cancer. Sci China B. 1991 Nov;34(11):1312-8.
  18. 1734866 Murakami T, Maeda S, Yi S, Ikegawa S, Kawashima E, Onodera S, Shimada K, Araki S: A novel transthyretin mutation associated with familial amyloidotic polyneuropathy. Biochem Biophys Res Commun. 1992 Jan 31;182(2):520-6.
  19. 1877623 Harrison HH, Gordon ED, Nichols WC, Benson MD: Biochemical and clinical characterization of prealbuminCHICAGO: an apparently benign variant of serum prealbumin (transthyretin) discovered with high-resolution two-dimensional electrophoresis. Am J Med Genet. 1991 Jun 15;39(4):442-52.
  20. 1932142 Harding J, Skare J, Skinner M: A second transthyretin mutation at position 33 (Leu/Phe) associated with familial amyloidotic polyneuropathy. Biochim Biophys Acta. 1991 Oct 21;1097(3):183-6.
  21. 1979335 Moses AC, Rosen HN, Moller DE, Tsuzaki S, Haddow JE, Lawlor J, Liepnieks JJ, Nichols WC, Benson MD: A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. J Clin Invest. 1990 Dec;86(6):2025-33.
  22. 1997217 Skare JC, Milunsky JM, Milunsky A, Skare IB, Cohen AS, Skinner M: A new transthyretin variant from a patient with familial amyloidotic polyneuropathy has asparagine substituted for histidine at position 90. Clin Genet. 1991 Jan;39(1):6-12.
  23. 2015890 Christmanson L, Betsholtz C, Gustavsson A, Johansson B, Sletten K, Westermark P: The transthyretin cDNA sequence is normal in transthyretin-derived senile systemic amyloidosis. FEBS Lett. 1991 Apr 9;281(1-2):177-80.
  24. 201845 Blake CC, Oatley SJ: Protein-DNA and protein-hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor? Nature. 1977 Jul 14;268(5616):115-20.
  25. 2046936 Ii S, Minnerath S, Ii K, Dyck PJ, Sommer SS: Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations. Neurology. 1991 Jun;41(6):893-8.
  26. 2161654 Ueno S, Uemichi T, Yorifuji S, Tarui S: A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases. Biochem Biophys Res Commun. 1990 May 31;169(1):143-7.
  27. 2363717 Ueno S, Uemichi T, Takahashi N, Soga F, Yorifuji S, Tarui S: Two novel variants of transthyretin identified in Japanese cases with familial amyloidotic polyneuropathy: transthyretin (Glu42 to Gly) and transthyretin (Ser50 to Arg). Biochem Biophys Res Commun. 1990 Jun 29;169(3):1117-21.
  28. 2891727 Wallace MR, Dwulet FE, Williams EC, Conneally PM, Benson MD: Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis. J Clin Invest. 1988 Jan;81(1):189-93.
  29. 2990465 Wallace MR, Naylor SL, Kluve-Beckerman B, Long GL, McDonald L, Shows TB, Benson MD: Localization of the human prealbumin gene to chromosome 18. Biochem Biophys Res Commun. 1985 Jun 28;129(3):753-8.
  30. 2995367 Tsuzuki T, Mita S, Maeda S, Araki S, Shimada K: Structure of the human prealbumin gene. J Biol Chem. 1985 Oct 5;260(22):12224-7.
  31. 3022108 Maeda S, Mita S, Araki S, Shimada K: Structure and expression of the mutant prealbumin gene associated with familial amyloidotic polyneuropathy. Mol Biol Med. 1986 Aug;3(4):329-38.
  32. 3135807 Cornwell GG 3rd, Sletten K, Johansson B, Westermark P: Evidence that the amyloid fibril protein in senile systemic amyloidosis is derived from normal prealbumin. Biochem Biophys Res Commun. 1988 Jul 29;154(2):648-53.
  33. 3675594 Strahler JR, Rosenblum BB, Hanash SM: Identification and characterization of a human transthyretin variant. Biochem Biophys Res Commun. 1987 Oct 14;148(1):471-7.
  34. 3722385 Wallace MR, Dwulet FE, Conneally PM, Benson MD: Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis. J Clin Invest. 1986 Jul;78(1):6-12.
  35. 3818577 Mita S, Maeda S, Shimada K, Araki S: Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy. J Biochem (Tokyo). 1986 Nov;100(5):1215-22.
  36. 4044580 Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS: Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem. 1985 Sep 25;260(21):11793-8.
  37. 4054629 Sasaki H, Yoshioka N, Takagi Y, Sakaki Y: Structure of the chromosomal gene for human serum prealbumin. Gene. 1985;37(1-3):191-7.
  38. 4216640 Blake CC, Geisow MJ, Swan ID, Rerat C, Rerat B: Strjcture of human plasma prealbumin at 2-5 A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding. J Mol Biol. 1974 Sep 5;88(1):1-12.
  39. 4607556 Kanda Y, Goodman DS, Canfield RE, Morgan FJ: The amino acid sequence of human plasma prealbumin. J Biol Chem. 1974 Nov 10;249(21):6796-805.
  40. 6093805 Mita S, Maeda S, Shimada K, Araki S: Cloning and sequence analysis of cDNA for human prealbumin. Biochem Biophys Res Commun. 1984 Oct 30;124(2):558-64.
  41. 6300852 Pras M, Prelli F, Franklin EC, Frangione B: Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin. Proc Natl Acad Sci U S A. 1983 Jan;80(2):539-42.
  42. 6487335 Nakazato M, Kangawa K, Minamino N, Tawara S, Matsuo H, Araki S: Revised analysis of amino acid replacement in a prealbumin variant (SKO-III) associated with familial amyloidotic polyneuropathy of Jewish origin. Biochem Biophys Res Commun. 1984 Sep 28;123(3):921-8.
  43. 6583672 Dwulet FE, Benson MD: Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. Proc Natl Acad Sci U S A. 1984 Feb;81(3):694-8.
  44. 6651852 Tawara S, Nakazato M, Kangawa K, Matsuo H, Araki S: Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type). Biochem Biophys Res Commun. 1983 Nov 15;116(3):880-8.
  45. 671542 Blake CC, Geisow MJ, Oatley SJ, Rerat B, Rerat C: Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A. J Mol Biol. 1978 May 25;121(3):339-56.
  46. 7474944 Gustavsson A, Jahr H, Tobiassen R, Jacobson DR, Sletten K, Westermark P: Amyloid fibril composition and transthyretin gene structure in senile systemic amyloidosis. Lab Invest. 1995 Nov;73(5):703-8.
  47. 7599630 Saraiva MJ: Transthyretin mutations in health and disease. Hum Mutat. 1995;5(3):191-6.
  48. 7754382 Monaco HL, Rizzi M, Coda A: Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein. Science. 1995 May 19;268(5213):1039-41.
  49. 7850982 Booth DR, Tan SY, Hawkins PN, Pepys MB, Frustaci A: A novel variant of transthyretin, 59Thr-->Lys, associated with autosomal dominant cardiac amyloidosis in an Italian family. Circulation. 1995 Feb 15;91(4):962-7.
  50. 7910950 Yamamoto K, Hsu SP, Yoshida K, Ikeda S, Nakazato M, Shiomi K, Cheng SY, Furihata K, Ueno I, Yanagisawa N: Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro). Muscle Nerve. 1994 Jun;17(6):637-41.
  51. 7914929 Uemichi T, Gertz MA, Benson MD: Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107). J Med Genet. 1994 May;31(5):416-7.
  52. 7923855 Skare J, Jones LA, Myles N, Kane K, Milunsky A, Cohen A, Skinner M: Two transthyretin mutations (glu42gly, his90asn) in an Italian family with amyloidosis. Clin Genet. 1994 Jun;45(6):281-4.
  53. 8019560 Jacobson DR, Buxbaum JN: A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient "SKO" with familial amyloidotic polyneuropathy. Hum Mutat. 1994;3(3):254-60.
  54. 8038017 Hesse A, Altland K, Linke RP, Almeida MR, Saraiva MJ, Steinmetz A, Maisch B: Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant. Br Heart J. 1993 Aug;70(2):111-5.
  55. 8081397 Jacobson DR, Gertz MA, Buxbaum JN: Transthyretin VAL107, a new variant associated with familial cardiac and neuropathic amyloidosis. Hum Mutat. 1994;3(4):399-401.
  56. 8089102 Berni R, Malpeli G, Folli C, Murrell JR, Liepnieks JJ, Benson MD: The Ile-84-->Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein. J Biol Chem. 1994 Sep 23;269(38):23395-8.
  57. 8095302 Benson MD 2nd, Turpin JC, Lucotte G, Zeldenrust S, LeChevalier B, Benson MD: A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family. J Med Genet. 1993 Feb;30(2):120-2.
  58. 8133316 Yasuda T, Sobue G, Doyu M, Nakazato M, Shiomi K, Yanagi T, Mitsuma T: Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly). J Neurol Sci. 1994 Jan;121(1):97-102.
  59. 8257997 Almeida Mdo R, Lopez-Andreu F, Munar-Ques M, Costa PP, Saraiva MJ: Transthyretin ALA 71: a new transthyretin variant in a Spanish family with familial amyloidotic polyneuropathy. Hum Mutat. 1993;2(5):420-1.
  60. 8309582 Murakami T, Tachibana S, Endo Y, Kawai R, Hara M, Tanase S, Ando M: Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant. Neurology. 1994 Feb;44(2):315-8.
  61. 8352764 Shiomi K, Nakazato M, Matsukura S, Ohnishi A, Hatanaka H, Tsuji S, Murai Y, Kojima M, Kangawa K, Matsuo H: A basic transthyretin variant (Glu61-->Lys) causes familial amyloidotic polyneuropathy: protein and DNA sequencing and PCR-induced mutation restriction analysis. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1090-6.
  62. 8382610 Terry CJ, Damas AM, Oliveira P, Saraiva MJ, Alves IL, Costa PP, Matias PM, Sakaki Y, Blake CC: Structure of Met30 variant of transthyretin and its amyloidogenic implications. EMBO J. 1993 Feb;12(2):735-41.
  63. 8428915 Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L: The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. J Biol Chem. 1993 Feb 5;268(4):2416-24.
  64. 8579098 Vidal R, Garzuly F, Budka H, Lalowski M, Linke RP, Brittig F, Frangione B, Wisniewski T: Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G) Am J Pathol. 1996 Feb;148(2):361-6.
  65. 8990019 Jacobson DR, Pan T, Kyle RA, Buxbaum JN: Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis. Hum Mutat. 1997;9(1):83-5.
  66. 9789022 Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchettini JC, Kelly JW: Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12956-60.
  67. 9818054 Schormann N, Murrell JR, Benson MD: Tertiary structures of amyloidogenic and non-amyloidogenic transthyretin variants: new model for amyloid fibril formation. Amyloid. 1998 Sep;5(3):175-87.
Target 3 Drug References
  1. Masuda Y, Yoshimura T, Kajiwara J, Ryan JJ: [Trend of PCB/PCDF concentrations in the blood of Yusho patients for 38 years after the incidence] Fukuoka Igaku Zasshi. 2007 May;98(5):182-95. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 587
Target 4 Name Serum albumin
Target 4 Synonyms
  1. Serum albumin precursor
Target 4 Gene Name ALB
Target 4 Protein Sequence >Serum albumin precursor 
MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPF
EDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEP
ERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF
FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAV
ARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK
ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYAR
RHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFE
QLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVV
LNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTL
SEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLV
AASQAALGL
Target 4 Number of Residues 619
Target 4 Molecular Weight 69367
Target 4 Theoretical pI 6.21
Target 4 GO Classification
Function
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
extracellular region
extracellular space
Target 4 General Function Involved in antioxidant activity
Target 4 Specific Function Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-18
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 28590 Link Image
Target 4 UniProtKB/Swiss-Prot ID P02768 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name ALBU_HUMAN Link Image
Target 4 PDB ID 1HA2 Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Secreted protein
Target 4 Gene Sequence >1830 bp 
ATGAAGTGGGTAACCTTTATTTCCCTTCTTTTTCTCTTTAGCTCGGCTTATTCCAGGGGT
GTGTTTCGTCGAGATGCACACAAGAGTGAGGTTGCTCATCGGTTTAAAGATTTGGGAGAA
GAAAATTTCAAAGCCTTGGTGTTGATTGCCTTTGCTCAGTATCTTCAGCAGTGTCCATTT
GAAGATCATGTAAAATTAGTGAATGAAGTAACTGAATTTGCAAAAACATGTGTTGCTGAT
GAGTCAGCTGAAAATTGTGACAAATCACTTCATACCCTTTTTGGAGACAAATTATGCACA
GTTGCAACTCTTCGTGAAACCTATGGTGAAATGGCTGACTGCTGTGCAAAACAAGAACCT
GGGAGAAATGAATGCTTCTTGCAACACAAAGATGACAACCCAAACCTCCCCCGATTGGTG
AGACCAGAGGTTGATGTGATGTGCACTGCTTTTCATGACAATGAAGAGACATTTTTGAAA
AAATACTTATATGAAATTGCCAGAAGACATCCTTACTTTTATGCCCCGGAACTCCTTTTC
TTTGCTAAAAGGTATAAAGCTGCTTTTACAGAATGTTGCCAAGCTGCTGATAAAGCTGCC
TGCCTGTTGCCAAAGCTCGATGAACTTCGGGATGAAGGGAAGGCTTCGTCTGCCAAACAG
AGACTCAAGTGTGCCAGTCTCCAAAAATTTGGAGAAAGAGCTTTCAAAGCATGGGCAGTA
GCTCGCCTGAGCCAGAGATTTCCCAAAGCTGAGTTTGCAGAAGTTTCCAAGTTAGTGACA
GATCTTACCAAAGTCCACACGGAATGCTGCCATGGAGATCTGCTTGAATGTGCTGATGAC
AGGGCGGACCTTGCCAAGTATATCTGTGAAAATCAAGATTCGATCTCCAGTAAACTGAAG
GAATGCTGTGAAAAACCTCTGTTGGAAAAATCCCACTGCATTGCCGAAGTGGAAAATGAT
GAGATGCCTGCTGACTTGCCTTCATTAGCTGCTGATTTTGTTGAAAGTAAGGATGTTTGC
AAAAACTATGCTGAGGCAAAGGATGTCTTCTTGGGCATGTTTTTGTATGAATATGCAAGA
AGGCATCCTGATTACTCTGTCGTGCTGCTGCTGAGACTTGCCAAGACATATGAAACCACT
CTAGAGAAGTGCTGTGCCGCTGCAGATCCTCATGAATGCTATGCCAAAGTGTTCGATGAA
TTTAAACCTCTTGTGGAAGAGCCTCAGAATTTAATCAAACAAAATTGTGAGCTTTTTGAG
CAGCTTGGAGAGTACAAATTCCAGAATGCGCTGTTAGTTCGTTACACCAAGAAAGTACCC
GAAGTGTCAACTCCAACTCTTGTAGAGGTCTCAAGAAACCTAGGAAAAGTGGGCAGCAAA
TGTTGTAAACATCCTGAAGCAAAAAGAATGCCCTGTGCAGAAGACTATCTATCCGTGGTC
CTGAACCAGTTATGTGTGTTGCATGAGAAAACGCCAGTAAGTGACAGAGTCACCAAATGC
TGCACAGAATCCTTGGTGAACAGGCGACCATGCTTTTCAGCTCTGGAAGTCGATGAAACA
TACGTTCCCAAAGAGTTTAATGCTGAAACATTCACCTTCCATGCAGATATATGCACACTT
TCTGAGAAGGAGAGACAAATCAAGAAACAAACTGCACTTGTTGAGCTCGTGAAACACAAG
CCCAAGGCAACAAAAGAGCAACTGAAAGCTGTTATGGATGATTTCGCTGCTTTTGTAGAG
AAGTGCTGCAAGGCTGACGATAAGGAGACCTGCTTTGCCGAGGAGGGTAAAAAACTTGTT
GCTGCAAGTCAAGCTGCCTTAGGCTTATAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID ALB Link Image
Target 4 GenAtlas ID ALB Link Image
Target 4 HGNC ID HGNC:399 Link Image
Target 4 Chromosome Location 4
Target 4 Locus 4q11-q13
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K: Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng. 1999 Jun;12(6):439-46. [PubMed Link Image]
  2. Bhattacharya AA, Curry S, Franks NP: Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures. J Biol Chem. 2000 Dec 8;275(49):38731-8. [PubMed Link Image]
  3. Minchiotti L, Campagnoli M, Rossi A, Cosulich ME, Monti M, Pucci P, Kragh-Hansen U, Granel B, Disdier P, Weiller PJ, Galliano M: A nucleotide insertion and frameshift cause albumin Kenitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges. Eur J Biochem. 2001 Jan;268(2):344-52. [PubMed Link Image]
  4. Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, Xing G, Dong C, Zhai Y, Wan J, Ouyang S, Li L, Zhang S, Zhou K, Zhang Y, Wu C, He F: Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 2001 Aug;11(8):1392-403. [PubMed Link Image]
  5. Spahr CS, Davis MT, McGinley MD, Robinson JH, Bures EJ, Beierle J, Mort J, Courchesne PL, Chen K, Wahl RC, Yu W, Luethy R, Patterson SD: Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics. 2001 Jan;1(1):93-107. [PubMed Link Image]
  6. Petitpas I, Grune T, Bhattacharya AA, Curry S: Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol. 2001 Dec 14;314(5):955-60. [PubMed Link Image]
  7. Meloun B, Moravek L, Kostka V: Complete amino acid sequence of human serum albumin. FEBS Lett. 1975 Oct 15;58(1):134-7. [PubMed Link Image]
  8. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  9. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
  10. Minchiotti L, Galliano M, Stoppini M, Ferri G, Crespeau H, Rochu D, Porta F: Two alloalbumins with identical electrophoretic mobility are produced by differently charged amino acid substitutions. Biochim Biophys Acta. 1992 Mar 12;1119(3):232-8. [PubMed Link Image]
  11. 1518850 Carlson J, Sakamoto Y, Laurell CB, Madison J, Watkins S, Putnam FW: Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8225-9.
  12. 1630489 He XM, Carter DC: Atomic structure and chemistry of human serum albumin. Nature. 1992 Jul 16;358(6383):209-15.
  13. 1859851 Peach RJ, Brennan SO: Structural characterization of a glycoprotein variant of human serum albumin: albumin Casebrook (494 Asp----Asn). Biochim Biophys Acta. 1991 Jul 26;1097(1):49-54.
  14. 1946412 Madison J, Arai K, Sakamoto Y, Feld RD, Kyle RA, Watkins S, Davis E, Matsuda Y, Amaki I, Putnam FW: Genetic variants of serum albumin in Americans and Japanese. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9853-7.
  15. 2068071 Watkins S, Madison J, Davis E, Sakamoto Y, Galliano M, Minchiotti L, Putnam FW: A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5959-63.
  16. 2104980 Brennan SO, Myles T, Peach RJ, Donaldson D, George PM: Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. Proc Natl Acad Sci U S A. 1990 Jan;87(1):26-30.
  17. 2247440 Galliano M, Minchiotti L, Porta F, Rossi A, Ferri G, Madison J, Watkins S, Putnam FW: Mutations in genetic variants of human serum albumin found in Italy. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8721-5.
  18. 2374930 Carter DC, He XM: Structure of human serum albumin. Science. 1990 Jul 20;249(4966):302-3.
  19. 2404284 Arai K, Madison J, Shimizu A, Putnam FW: Point substitutions in albumin genetic variants from Asia. Proc Natl Acad Sci U S A. 1990 Jan;87(1):497-501.
  20. 2419329 Urano Y, Watanabe K, Sakai M, Tamaoki T: The human albumin gene. Characterization of the 5' and 3' flanking regions and the polymorphic gene transcripts. J Biol Chem. 1986 Mar 5;261(7):3244-51.
  21. 2437111 Carraway RE, Mitra SP, Cochrane DE: Structure of a biologically active neurotensin-related peptide obtained from pepsin-treated albumin(s). J Biol Chem. 1987 May 5;262(13):5968-73.
  22. 2727704 Carter DC, He XM, Munson SH, Twigg PD, Gernert KM, Broom MB, Miller TY: Three-dimensional structure of human serum albumin. Science. 1989 Jun 9;244(4909):1195-8.
  23. 2762316 Arai K, Madison J, Huss K, Ishioka N, Satoh C, Fujita M, Neel JV, Sakurabayashi I, Putnam FW: Point substitutions in Japanese alloalbumins. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6092-6.
  24. 2911589 Arai K, Ishioka N, Huss K, Madison J, Putnam FW: Identical structural changes in inherited albumin variants from different populations. Proc Natl Acad Sci U S A. 1989 Jan;86(2):434-8.
  25. 3009475 Minghetti PP, Ruffner DE, Kuang WJ, Dennison OE, Hawkins JW, Beattie WG, Dugaiczyk A: Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747-57.
  26. 3087352 Mogard MH, Kobayashi R, Chen CF, Lee TD, Reeve JR Jr, Shively JE, Walsh JH: The amino acid sequence of kinetensin, a novel peptide isolated from pepsin-treated human plasma: homology with human serum albumin, neurotensin and angiotensin. Biochem Biophys Res Commun. 1986 May 14;136(3):983-8.
  27. 3474609 Takahashi N, Takahashi Y, Blumberg BS, Putnam FW: Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413-7.
  28. 3479777 Takahashi N, Takahashi Y, Isobe T, Putnam FW, Fujita M, Satoh C, Neel JV: Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001-5.
  29. 3828358 Brennan SO, Herbert P: Albumin Canterbury (313 Lys----Asn). A point mutation in the second domain of serum albumin. Biochim Biophys Acta. 1987 Apr 8;912(2):191-7.
  30. 6171778 Lawn RM, Adelman J, Bock SC, Franke AE, Houck CM, Najarian RC, Seeburg PH, Wion KL: The sequence of human serum albumin cDNA and its expression in E. coli. Nucleic Acids Res. 1981 Nov 25;9(22):6103-114.
  31. 6275391 Dugaiczyk A, Law SW, Dennison OE: Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci U S A. 1982 Jan;79(1):71-5.
  32. 656055 Jacobsen C: Lysine residue 240 of human serum albumin is involved in high-affinity binding of bilirubin. Biochem J. 1978 May 1;171(2):453-9.
  33. 7852505 Rushbrook JI, Becker E, Schussler GC, Divino CM: Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7.
  34. 7895732 Corbett JM, Wheeler CH, Baker CS, Yacoub MH, Dunn MJ: The human myocardial two-dimensional gel protein database: update 1994. Electrophoresis. 1994 Nov;15(11):1459-65.
  35. 7902134 Galliano M, Minchiotti L, Iadarola P, Stoppini M, Giagnoni P, Watkins S, Madison J, Putnam FW: Protein and DNA sequence analysis of a 'private' genetic variant: albumin Ortonovo (Glu-505-->Lys). Biochim Biophys Acta. 1993 Nov 25;1225(1):27-32.
  36. 8022807 Madison J, Galliano M, Watkins S, Minchiotti L, Porta F, Rossi A, Putnam FW: Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6476-80.
  37. 8048949 Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S: An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7.
  38. 8347685 Brennan SO, Fellowes AP: Albumin Hawkes Bay; a low level variant caused by loss of a sulphydryl group at position 177. Biochim Biophys Acta. 1993 Aug 4;1182(1):46-50.
  39. 8513793 Minchiotti L, Galliano M, Zapponi MC, Tenni R: The structural characterization and bilirubin-binding properties of albumin Herborn, a [Lys240-->Glu] albumin mutant. Eur J Biochem. 1993 Jun 1;214(2):437-44.
  40. 9329347 Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T: A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50.
  41. 955075 Walker JE: Lysine residue 199 of human serum albumin is modified by acetylsalicyclic acid. FEBS Lett. 1976 Jul 15;66(2):173-5.
  42. 9589637 Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S: Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54.
  43. 9731778 Curry S, Mandelkow H, Brick P, Franks N: Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol. 1998 Sep;5(9):827-35.
Target 4 Drug References Not Available
Drug Target 5 [top]
Target 5 ID 594
Target 5 Name Thyroxine-binding globulin
Target 5 Synonyms
  1. Serpin A7
  2. T4-binding globulin
  3. Thyroxine-binding globulin precursor
Target 5 Gene Name SERPINA7
Target 5 Protein Sequence >Thyroxine-binding globulin precursor 
MSPFLYLVLLVLGLHATIHCASPEGKVTACHSSQPNATLYKMSSINADFAFNLYRRFTVE
TPDKNIFFSPVSISAALVMLSFGACCSTQTEIVETLGFNLTDTPMVEIQHGFQHLICSLN
FPKKELELQIGNALFIGKHLKPLAKFLNDVKTLYETEVFSTDFSNISAAKQEINSHVEMQ
TKGKVVGLIQDLKPNTIMVLVNYIHFKAQWANPFDPSKTEDSSSFLIDKTTTVQVPMMHQ
MEQYYHLVDMELNCTVLQMDYSKNALALFVLPKEGQMESVEAAMSSKTLKKWNRLLQKGW
VDLFVPKFSISATYDLGATLLKMGIQHAYSENADFSGLTEDNGLKLSNAAHKAVLHIGEK
GTEAAAVPEVELSDQPENTFLHPIIQIDRSFMLLILERSTRSILFLGKVVNPTEA
Target 5 Number of Residues 421
Target 5 Molecular Weight 46325
Target 5 Theoretical pI 6.27
Target 5 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 5 General Function Involved in serine-type endopeptidase inhibitor activity
Target 5 Specific Function Major thyroid hormone transport protein in serum
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • 1-20
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 338697 Link Image
Target 5 UniProtKB/Swiss-Prot ID P05543 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name THBG_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Secreted protein
Target 5 Gene Sequence >1248 bp 
ATGTCACCATTCCTGTACCTGGTTCTCTTGGTACTTGGGCTTCATGCTACAATCCACTGT
GCATCACCTGAAGGCAAAGTAACAGCCTGCCATTCATCCCAACCAAATGCCACTCTCTAC
AAGATGTCATCCATTAATGCTGACTTTGCATTCAATCTGTACCGGAGGTTCACTGTGGAG
ACCCCAGATAAGAACATCTTCTTTTCCCCTGTGAGCATTTCTGCAGCTTTGGTTATGCTT
TCCTTTGGGGCCTGCTGCAGCACCCAAACTGAGATTGTGGAGACCTTGGGGTTCAACCTC
ACAGACACTCCAATGGTAGAGATCCAGCATGGCTTCCAGCATCTGATCTGTTCACTGAAT
TTTCCAAAGAAGGAACTGGAATTGCAGATAGGAAATGCCCTCTTCATTGGCAAGCATCTG
AAACCACTGGCAAAGTTCTTGAATGATGTCAAGACCCTCTATGAGACTGAAGTCTTTTCT
ACCGACTTCTCCAACATTTCTGCAGCCAAGCAGGAGATTAACAGTCATGTGGAGATGCAA
ACCAAAGGGAAAGTTGTGGGTCTAATTCAAGACCTCAAGCCAAACACCACTATGGTCTTA
GTGAACTATATTCACTTTAAAGCCCAGTGGGCAAATCCTTTTGATCCATCCAAGACAGAA
GACAGTTCCAGCTTCTTAATAGACAAGACCACCACTGTTCAAGTGCCCATGATGCACCAG
ATGGAACAATACTATCACCTAGTGGATATGGAATTGAACTGCACAGTTCTGCAAATGGAC
TACAGCAAGAATGCTCTGGCACTCTTTGTTCTTCCCAAGGAGGGACAGATGGAGTCAGTG
GAAGCTGCCATGTCATCTAAAACACTGAAGAAGTGGAACCGCTTACTACAGAAGGGATGG
GTTGACTTGTTTGTTCCAAAGTTTTCCATTTCTGCCACATATGACCTTGGAGCCACACTT
TTGAAGATGGGCATTCAGCATGCCTATTCTGAAAATGCTGATTTTTCTGGACTCACAGAG
GACAATGGTCTGAAACTTTCCAATGCTGCCCATAAGGCTGTGCTGCACATTGGTGAAAAG
GGAACTGAAGCTGCAGCTGTCCCTGAAGTTGAACTTTCGGATCAGCCTGAAAACACTTTC
CTACACCCTATTATCCAAATTGATAGATCTTTCATGTTGTTGATTTTGGAGAGAAGCACA
AGGAGTATTCTCTTTCTAGGGAAAGTTGTGAACCCAACGGAAGCGTAG
Target 5 GenBank Gene ID
Target 5 GeneCard ID SERPINA7 Link Image
Target 5 GenAtlas ID SERPINA7 Link Image
Target 5 HGNC ID HGNC:11583 Link Image
Target 5 Chromosome Location X
Target 5 Locus Xq22.2
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Shirotani T, Kishikawa H, Wake N, Miyamura N, Hashimoto Y, Motoyoshi S, Yamaguchi K, Shichiri M: Thyroxine-binding globulin variant (TBG-Kumamoto): identification of a point mutation and genotype analysis of its family. Endocrinol Jpn. 1992 Dec;39(6):577-84. [PubMed Link Image]
  2. Bertenshaw R, Sarne D, Tornari J, Weinberg M, Refetoff S: Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions. Biochim Biophys Acta. 1992 Aug 25;1139(4):307-10. [PubMed Link Image]
  3. Bertenshaw R, Takeda K, Refetoff S: Sequencing of the variant thyroxine-binding globulin (TBG)-Quebec reveals two nucleotide substitutions. Am J Hum Genet. 1991 Apr;48(4):741-4. [PubMed Link Image]
  4. Janssen OE, Takeda K, Refetoff S: Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency. Hum Genet. 1991 Jun;87(2):119-22. [PubMed Link Image]
  5. Waltz MR, Pullman TN, Takeda K, Sobieszczyk P, Refetoff S: Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks. J Endocrinol Invest. 1990 Apr;13(4):343-9. [PubMed Link Image]
  6. Mori Y, Takeda K, Charbonneau M, Refetoff S: Replacement of Leu227 by Pro in thyroxine-binding globulin (TBG) is associated with complete TBG deficiency in three of eight families with this inherited defect. J Clin Endocrinol Metab. 1990 Mar;70(3):804-9. [PubMed Link Image]
  7. Takeda K, Mori Y, Sobieszczyk S, Seo H, Dick M, Watson F, Flink IL, Seino S, Bell GI, Refetoff S: Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties. J Clin Invest. 1989 Apr;83(4):1344-8. [PubMed Link Image]
  8. Mori Y, Seino S, Takeda K, Flink IL, Murata Y, Bell GI, Refetoff S: A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule. Mol Endocrinol. 1989 Mar;3(3):575-9. [PubMed Link Image]
  9. Flink IL, Bailey TJ, Gustafson TA, Markham BE, Morkin E: Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7708-12. [PubMed Link Image]
  10. Cheng SY: Partial amino acid sequence of human thyroxine-binding globulin. Further evidence for a single polypeptide chain. Biochem Biophys Res Commun. 1977 Dec 21;79(4):1212-8. [PubMed Link Image]
  11. 8232304 Hayashi Y, Mori Y, Janssen OE, Sunthornthepvarakul T, Weiss RE, Takeda K, Weinberg M, Seo H, Bell GI, Refetoff S: Human thyroxine-binding globulin gene: complete sequence and transcriptional regulation. Mol Endocrinol. 1993 Aug;7(8):1049-60.
  12. 8268226 Akbari MT, Kapadi A, Farmer MJ, Fitch NJ, McCann KP, Kordestani S, Flink IL, Sheppard MC, Ramsden DB: The structure of the human thyroxine binding globulin (TBG) gene. Biochim Biophys Acta. 1993 Dec 14;1216(3):446-54.
Target 5 Drug References
  1. Klieber MA, Underhill C, Hammond GL, Muller YA: Corticosteroid-binding Globulin, a Structural Basis for Steroid Transport and Proteinase-triggered Release. J Biol Chem. 2007 Oct 5;282(40):29594-603. Epub 2007 Jul 19. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 758
Target 6 Name Thyroid hormone receptor alpha
Target 6 Synonyms
  1. C-erbA-alpha
  2. EAR-7
  3. EAR7
  4. c-erbA-1
Target 6 Gene Name THRA
Target 6 Protein Sequence >Thyroid hormone receptor alpha 
MEQKPSKVECGSDPEENSARSPDGKRKRKNGQCSLKTSMSGYIPSYLDKDEQCVVCGDKA
TGYHYRCITCEGCKGFFRRTIQKNLHPTYSCKYDSCCVIDKITRNQCQLCRFKKCIAVGM
AMDLVLDDSKRVAKRKLIEQNRERRRKEEMIRSLQQRPEPTPEEWDLIHIATEAHRSTNA
QGSHWKQRRKFLPDDIGQSPIVSMPDGDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFS
ELPCEDQIILLKGCCMEIMSLRAAVRYDPESDTLTLSGEMAVKREQLKNGGLGVVSDAIF
ELGKSLSAFNLDDTEVALLQAVLLMSTDRSGLLCVDKIEKSQEAYLLAFEHYVNHRKHNI
PHFWPKLLMKEREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQL
GEAGSLQGPVLQHQSPKSPQQRLLELLHRSGILHARAVCGEDDSSEADSPSSSEEEPEVC
EDLAGNAASP
Target 6 Number of Residues 498
Target 6 Molecular Weight 54816
Target 6 Theoretical pI 6.85
Target 6 GO Classification
Function
thyroid hormone receptor activity
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 6 General Function Involved in transcription factor activity
Target 6 Specific Function Nuclear hormone receptor. High affinity receptor for triiodothyronine
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Pfam Domain Function
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • None
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 825639 Link Image
Target 6 UniProtKB/Swiss-Prot ID P10827 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name THA_HUMAN Link Image
Target 6 PDB ID 1NAV Link Image
Target 6 PDB File Show
Target 6 3D Structure
Target 6 Cellular Location
  • Nucleus
Target 6 Gene Sequence >1473 bp 
ATGGAACAGAAGCCAAGCAAGGTGGAGTGTGGGTCAGACCCAGAGGAGAACAGTGCCAGG
TCACCAGATGGAAAGCGAAAAAGAAAGAACGGCCAATGTTCCCTGAAAACCAGCATGTCA
GGGTATATCCCTAGTTACCTGGACAAAGACGAGCAGTGTGTCGTGTGTGGGGACAAGGCA
ACTGGTTATCACTACCGCTGTATCACTTGTGAGGGCTGCAAGGGCTTCTTTCGCCGCACA
ATCCAGAAGAACCTCCATCCCACCTATTCCTGCAAATATGACAGCTGCTGTGTCATTGAC
AAGATCACCCGCAATCAGTGCCAGCTGTGCCGCTTCAAGAAGTGCATCGCCGTGGGCATG
GCCATGGACTTGGTTCTAGATGACTCGAAGCGGGTGGCCAAGCGTAAGCTGATTGAGCAG
AACCGGGAGCGGCGGCGGAAGGAGGAGATGATCCGATCACTGCAGCAGCGACCAGAGCCC
ACTCCTGAAGAGTGGGATCTGATCCACATTGCCACAGAGGCCCATCGCAGCACCAATGCC
CAGGGCAGCCATTGGAAACAGAGGCGGAAATTCCTGCCCGATGACATTGGCCAGTCACCC
ATTGTCTCCATGCCGGACGGAGACAAGGTGGACCTGGAAGCCTTCAGCGAGTTTACCAAG
ATCATCACCCCGGCCATCACCCGTGTGGTGGACTTTGCCAAAAAACTGCCCATGTTCTCC
GAGCTGCCTTGCGAAGACCAGATCATCCTCCTGAAGGGGTGCTGCATGGAGATCATGTCC
CTGCGGGCGGCTGTCCGCTACGACCCTGAGAGCGACACCCTGACGCTGAGTGGGGAGATG
GCTGTCAAGCGGGAGCAGCTCAAGAATGGCGGCCTGGGCGTAGTCTCCGACGCCATCTTT
GAACTGGGCAAGTCACTCTCTGCCTTTAACCTGGATGACACGGAAGTGGCTCTGCTGCAG
GCTGTGCTGCTAATGTCAACAGACCGCTCGGGCCTGCTGTGTGTGGACAAGATCGAGAAG
AGTCAGGAGGCGTACCTGCTGGCGTTCGAGCACTACGTCAACCACCGCAAACACAACATT
CCGCACTTCTGGCCCAAGCTGCTGATGAAGGAGAGAGAAGTGCAGAGTTCGATTCTGTAC
AAGGGGGCAGCGGCAGAAGGCCGGCCGGGCGGGTCACTGGGCGTCCACCCGGAAGGACAG
CAGCTTCTCGGAATGCATGTTGTTCAGGGTCCGCAGGTCCGGCAGCTTGAGCAGCAGCTT
GGTGAAGCGGGAAGTCTCCAAGGGCCGGTTCTTCAGCACCAGAGCCCGAAGAGCCCGCAG
CAGCGTCTCCTGGAGCTGCTCCACCGAAGCGGAATTCTCCATGCCCGAGCGGTCTGTGGG
GAAGACGACAGCAGTGAGGCGGACTCCCCGAGCTCCTCTGAGGAGGAACCGGAGGTCTGC
GAGGACCTGGCAGGCAATGCAGCCTCTCCCTGA
Target 6 GenBank Gene ID
Target 6 GeneCard ID THRA Link Image
Target 6 GenAtlas ID THRA Link Image
Target 6 HGNC ID HGNC:11796 Link Image
Target 6 Chromosome Location 17
Target 6 Locus 17q11.2
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. [PubMed Link Image]
  2. Laudet V, Begue A, Henry-Duthoit C, Joubel A, Martin P, Stehelin D, Saule S: Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene. Nucleic Acids Res. 1991 Mar 11;19(5):1105-12. [PubMed Link Image]
  3. Nakai A, Sakurai A, Bell GI, DeGroot LJ: Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues. Mol Endocrinol. 1988 Nov;2(11):1087-92. [PubMed Link Image]
  4. Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T: Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989 Apr 7;57(1):31-9. [PubMed Link Image]
  5. Nakai A, Seino S, Sakurai A, Szilak I, Bell GI, DeGroot LJ: Characterization of a thyroid hormone receptor expressed in human kidney and other tissues. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2781-5. [PubMed Link Image]
  6. Benbrook D, Pfahl M: A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788-91. [PubMed Link Image]
  7. Pfahl M, Benbrook D: Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor. Nucleic Acids Res. 1987 Nov 25;15(22):9613. [PubMed Link Image]
  8. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed Link Image]
Target 6 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 2405
Target 7 Name Transthyretin
Target 7 Synonyms
  1. Prealbumin
  2. TBPA
  3. Transthyretin precursor
Target 7 Gene Name Ttr
Target 7 Protein Sequence >Transthyretin precursor 
MASLRLFLLCLAGLIFASEAGPGGAGESKCPLMVKVLDAVRGSPAVDVAVKVFKKTADGS
WEPFASGKTAESGELHGLTTDEKFTEGVYRVELDTKSYWKALGISPFHEYAEVVFTANDS
GHRHYTIAALLSPYSYSTTAVVSNPQN
Target 7 Number of Residues 149
Target 7 Molecular Weight 15720
Target 7 Theoretical pI 6.10
Target 7 GO Classification
Function
binding
steroid binding
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 7 General Function Involved in steroid binding
Target 7 Specific Function Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
Target 7 Pathways Not Available
Target 7 Reactions Not Available
Target 7 Pfam Domain Function
Target 7 Signals
  • 1-20
Target 7 Transmembrane Regions
  • None
Target 7 Essentiality Essential
Target 7 GenBank ID Protein 205982 Link Image
Target 7 UniProtKB/Swiss-Prot ID P02767 Link Image
Target 7 UniProtKB/Swiss-Prot Entry Name TTHY_RAT Link Image
Target 7 PDB ID 1KGI Link Image
Target 7 PDB File Show
Target 7 3D Structure
Target 7 Cellular Location
  • Secreted protein
Target 7 Gene Sequence >444 bp 
ATGGCTTCCCTTCGCCTGTTCCTCCTCTGCCTCGCTGGACTGATATTTGCGTCTGAAGCT
GGCCCTGGGGGTGCTGGAGAATCCAAGTGTCCTCTGATGGTCAAAGTCCTGGATGCTGTC
CGAGGCAGCCCTGCTGTCGATGTGGCCGTGAAAGTGTTCAAAAGGACTGCAGACGGAAGC
TGGGAGCCGTTTGCCTCTGGGAAGACCGCCGAGTCTGGAGAGCTGCACGGGCTCACCACA
GATGAGAAGTTCACGGAAGGGGTGTACAGGGTAGAACTGGACACCAAATCATACTGGAAG
GCTCTTGGCATTTCCCCATTCCATGAATACGCAGAGGTGGTTTTCACAGCCAATGACTCT
GGTCATCGCCACTACACCATCGCAGCCCTGCTCAGCCCGTACTCCTACAGCACCACTGCT
GTCGTCAGTAACCCCCAGAACTGA
Target 7 GenBank Gene ID
Target 7 GeneCard ID Not Available
Target 7 GenAtlas ID Not Available
Target 7 HGNC ID Not Available
Target 7 Chromosome Location Not Available
Target 7 Locus Not Available
Target 7 SNPs SNPJam Report Link Image
Target 7 General References
  1. Duan W, Cole T, Schreiber G: Cloning and nucleotide sequencing of transthyretin (prealbumin) cDNA from rat choroid plexus and liver. Nucleic Acids Res. 1989 May 25;17(10):3979. [PubMed Link Image]
  2. Fung WP, Thomas T, Dickson PW, Aldred AR, Milland J, Dziadek M, Power B, Hudson P, Schreiber G: Structure and expression of the rat transthyretin (prealbumin) gene. J Biol Chem. 1988 Jan 5;263(1):480-8. [PubMed Link Image]
  3. Dickson PW, Howlett GJ, Schreiber G: Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence, and gene expression in liver and brain. J Biol Chem. 1985 Jul 5;260(13):8214-9. [PubMed Link Image]
  4. Sundelin J, Melhus H, Das S, Eriksson U, Lind P, Tragardh L, Peterson PA, Rask L: The primary structure of rabbit and rat prealbumin and a comparison with the tertiary structure of human prealbumin. J Biol Chem. 1985 May 25;260(10):6481-7. [PubMed Link Image]
  5. Navab M, Mallia AK, Kanda Y, Goodman DS: Rat plasma prealbumin. Isolation and partial characterization. J Biol Chem. 1977 Jul 25;252(14):5100-6. [PubMed Link Image]
  6. Wojtczak A: Crystal structure of rat transthyretin at 2.5 A resolution: first report on a unique tetrameric structure. Acta Biochim Pol. 1997;44(3):505-17. [PubMed Link Image]
Target 7 Drug References Not Available
Drug Target 8 [top]
Target 8 ID 4334
Target 8 Name Transthyretin
Target 8 Synonyms
  1. Transthyretin precursor
Target 8 Gene Name Not Available
Target 8 Protein Sequence >Transthyretin 
MLQPLHCLLLASAVLLCNTAPTPTDKHGGSDTRCPLMVKILDAVKGTPAGSVALKVSQKT
ADGGWTQIATGVTDATGEIHNLITEQQFPAGVYRVEFDTKAYWTNQGSTPFHEVAEVVFD
AHPEGHRHYTLALLLSPFSYTTTAVVSSVRE
Target 8 Number of Residues 153
Target 8 Molecular Weight 16235
Target 8 Theoretical pI 6.38
Target 8 GO Classification
Function
binding
steroid binding
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 8 General Function Involved in steroid binding
Target 8 Specific Function Not Available
Target 8 Pathways Not Available
Target 8 Reactions Not Available
Target 8 Pfam Domain Function
Target 8 Signals
  • 1-19
Target 8 Transmembrane Regions
  • None
Target 8 Essentiality Essential
Target 8 GenBank ID Protein Not Available
Target 8 UniProtKB/Swiss-Prot ID Q9PTT3 Link Image
Target 8 UniProtKB/Swiss-Prot Entry Name Q9PTT3_SPAAU Link Image
Target 8 PDB ID 1SN5 Link Image
Target 8 PDB File Show
Target 8 3D Structure
Target 8 Cellular Location Not Available
Target 8 Gene Sequence >456 bp 
ATGCTGCAGCCTCTGCACTGTCTGCTTCTAGCCTCCGCCGTGCTGCTCTGCAACACCGCC
CCCACCCCCACGGACAAACATGGAGGCTCAGACACCAGGTGTCCTCTGATGGTAAAAATC
CTGGACGCAGTGAAAGGGACTCCAGCCGGATCAGTGGCACTCAAAGTGTCTCAGAAGACT
GCTGATGGAGGGTGGACACAGATTGCGACCGGAGTGACAGATGCCACTGGGGAGATCCAC
AATCTGATCACAGAGCAGCAGTTCCCAGCAGGAGTGTATCGTGTTGAGTTTGACACCAAA
GCTTACTGGACGAATCAGGGCAGCACGCCGTTCCATGAAGTAGCTGAGGTGGTGTTTGAC
GCCCATCCTGAAGGCCATCGTCACTACACCTTGGCTCTGCTGCTCAGTCCGTTCTCCTAC
ACCACCACCGCCGTGGTCTCCAGCGTACGCGAGTGA
Target 8 GenBank Gene ID
Target 8 GeneCard ID Not Available
Target 8 GenAtlas ID Not Available
Target 8 HGNC ID Not Available
Target 8 Chromosome Location Not Available
Target 8 Locus Not Available
Target 8 SNPs Not Available
Target 8 General References
  1. Funkenstein B, Perrot V, Brown CL: Cloning of putative piscine (Sparus aurata) transthyretin: developmental expression and tissue distribution. Mol Cell Endocrinol. 1999 Nov 25;157(1-2):67-73. [PubMed Link Image]
Target 8 Drug References Not Available

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.