Biotin--protein ligase

Details

Name

Biotin--protein ligase

Synonyms

• 6.3.4.-
• Biotin apo-protein ligase

Gene Name

HLCS

Organism

Humans

Amino acid sequence

>lcl|BSEQ0000317|Biotin--protein ligase
MEDRLHMDNGLVPQKIVSVHLQDSTLKEVKDQVSNKQAQILEPKPEPSLEIKPEQDGMEH
VGRDDPKALGEEPKQRRGSASGSEPAGDSDRGGGPVEHYHLHLSSCHECLELENSTIESV
KFASAENIPDLPYDYSSSLESVADETSPEREGRRVNLTGKAPNILLYVGSDSQEALGRFH
EVRSVLADCVDIDSYILYHLLEDSALRDPWTDNCLLLVIATRESIPEDLYQKFMAYLSQG
GKVLGLSSSFTFGGFQVTSKGALHKTVQNLVFSKADQSEVKLSVLSSGCRYQEGPVRLSP
GRLQGHLENEDKDRMIVHVPFGTRGGEAVLCQVHLELPPSSNIVQTPEDFNLLKSSNFRR
YEVLREILTTLGLSCDMKQVPALTPLYLLSAAEEIRDPLMQWLGKHVDSEGEIKSGQLSL
RFVSSYVSEVEITPSCIPVVTNMEAFSSEHFNLEIYRQNLQTKQLGKVILFAEVTPTTMR
LLDGLMFQTPQEMGLIVIAARQTEGKGRGGNVWLSPVGCALSTLLISIPLRSQLGQRIPF
VQHLMSVAVVEAVRSIPEYQDINLRVKWPNDIYYSDLMKIGGVLVNSTLMGETFYILIGC
GFNVTNSNPTICINDLITEYNKQHKAELKPLRADYLIARVVTVLEKLIKEFQDKGPNSVL
PLYYRYWVHSGQQVHLGSAEGPKVSIVGLDDSGFLQVHQEGGEVVTVHPDGNSFDMLRNL
ILPKRR

Number of residues

726

Molecular Weight

80759.345

Theoretical pI

5.34

GO Classification

Functions

ATP binding / biotin binding / biotin-[acetyl-CoA-carboxylase] ligase activity / biotin-[methylcrotonoyl-CoA-carboxylase] ligase activity / biotin-[methylmalonyl-CoA-carboxytransferase] ligase activity / biotin-[propionyl-CoA-carboxylase (ATP-hydrolyzing)] ligase activity / biotin-protein ligase activity / enzyme binding

Processes

biotin metabolic process / cell proliferation / histone biotinylation / histone modification / protein biotinylation / response to biotin / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process

Components

chromatin / cytoplasm / cytosol / mitochondrion / nuclear lamina / nuclear matrix

General Function

Enzyme binding

Specific Function

Post-translational modification of specific protein by attachment of biotin. Acts on various carboxylases such as acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl CoA carboxylase, and 3-methylcrotonyl CoA carboxylase.

Pfam Domain Function

• BPL_LplA_LipB (PF03099)
• BPL_C (PF02237)
• BPL_N (PF09825)

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0009975|Biotin--protein ligase (HLCS)
ATGGAAGATAGACTCCACATGGATAATGGACTGGTACCCCAAAAGATTGTGTCGGTGCAC
TTGCAGGACTCCACTCTGAAGGAAGTTAAGGATCAGGTCTCAAACAAGCAAGCCCAGATC
CTAGAGCCGAAGCCTGAACCTTCTCTTGAGATTAAGCCTGAGCAGGACGGTATGGAGCAT
GTTGGCAGAGATGACCCAAAGGCTCTTGGTGAAGAACCCAAACAAAGGAGAGGCAGTGCC
TCTGGGAGTGAGCCTGCTGGGGACAGTGACAGGGGAGGGGGCCCCGTTGAGCATTATCAC
CTCCATCTGTCTAGTTGCCACGAGTGTCTGGAACTTGAGAACAGCACCATTGAGTCAGTC
AAGTTTGCGTCTGCCGAGAACATTCCAGACCTTCCCTACGATTATAGCAGCAGTTTGGAG
AGTGTTGCTGATGAGACCTCCCCCGAAAGAGAAGGGAGGAGAGTCAACCTCACGGGAAAG
GCACCCAACATCCTCCTCTATGTGGGCTCCGACTCCCAGGAAGCCCTCGGCCGGTTCCAC
GAGGTCCGGTCTGTGCTGGCCGACTGTGTGGACATTGACAGTTATATTCTCTACCACCTG
CTGGAGGACAGTGCTCTCAGAGACCCGTGGACGGACAACTGTCTGCTGTTGGTCATTGCT
ACCAGGGAGTCCATTCCCGAAGACCTGTACCAGAAGTTCATGGCCTATCTTTCTCAGGGA
GGGAAGGTGTTGGGCCTGTCTTCATCCTTCACCTTTGGTGGCTTTCAGGTGACAAGCAAG
GGTGCACTGCACAAGACAGTCCAGAACTTGGTTTTCTCCAAGGCTGACCAGAGCGAGGTG
AAGCTCAGCGTCTTGAGCAGTGGCTGCAGGTACCAGGAAGGCCCCGTCCGGCTCAGCCCC
GGCAGGCTCCAGGGCCACCTGGAGAATGAGGACAAGGACAGGATGATTGTGCATGTGCCT
TTTGGAACTCGCGGGGGAGAAGCTGTTCTTTGCCAGGTGCACTTAGAACTACCTCCCAGC
TCCAACATAGTGCAAACTCCAGAAGATTTTAACTTGCTCAAGTCAAGCAATTTTAGAAGA
TACGAAGTCCTTAGAGAGATTCTGACAACCCTTGGCCTCAGCTGTGACATGAAACAAGTT
CCTGCCTTAACTCCTCTTTACTTGCTGTCAGCTGCGGAGGAAATCAGGGATCCTCTTATG
CAGTGGCTTGGGAAACATGTGGACTCCGAGGGAGAAATAAAATCCGGCCAGCTCTCTCTT
AGATTTGTTTCATCCTACGTGTCTGAAGTAGAAATAACCCCATCTTGTATACCTGTGGTG
ACCAACATGGAGGCCTTCTCATCAGAACATTTCAACTTAGAGATCTATCGCCAAAATCTG
CAGACCAAGCAGTTGGGGAAAGTAATTTTGTTTGCCGAAGTGACCCCCACAACGATGCGT
CTCCTGGATGGGCTGATGTTTCAGACACCGCAGGAAATGGGCTTAATAGTGATCGCGGCC
CGGCAGACCGAGGGCAAAGGACGGGGAGGGAATGTGTGGCTGAGCCCTGTGGGATGTGCT
CTTTCTACTCTGCTCATCTCCATTCCACTGAGATCCCAGCTGGGACAGAGGATCCCGTTT
GTCCAGCATCTGATGTCCGTGGCTGTCGTGGAAGCAGTGAGGTCCATTCCCGAGTATCAG
GATATCAACTTACGAGTGAAGTGGCCCAACGATATTTATTACAGTGACCTCATGAAGATC
GGCGGAGTTCTGGTTAACTCAACACTCATGGGAGAAACATTTTATATACTTATTGGCTGT
GGATTTAATGTGACTAACAGTAACCCTACCATCTGCATCAACGACCTCATCACAGAATAC
AATAAACAACACAAGGCAGAACTGAAGCCCTTAAGAGCCGATTATCTCATCGCCAGAGTC
GTGACTGTGCTGGAGAAACTGATCAAAGAGTTTCAGGACAAAGGGCCCAACAGCGTCCTT
CCCCTTTATTACCGATACTGGGTCCACAGTGGTCAGCAAGTCCATCTGGGCAGCGCAGAG
GGACCAAAGGTGTCCATCGTTGGCCTGGACGATTCTGGCTTCCTCCAGGTTCACCAGGAG
GGCGGCGAGGTTGTGACTGTGCACCCGGACGGCAACTCCTTCGACATGCTGAGAAACCTC
ATCCTCCCCAAACGGCGGTAA

Chromosome Location

21

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	P50747
UniProtKB Entry Name	BPL1_HUMAN
GenBank Protein ID	577625
GenBank Gene ID	D23672
GenAtlas ID	HLCS
HGNC ID	HGNC:4976

General References

1. Suzuki Y, Aoki Y, Ishida Y, Chiba Y, Iwamatsu A, Kishino T, Niikawa N, Matsubara Y, Narisawa K: Isolation and characterization of mutations in the human holocarboxylase synthetase cDNA. Nat Genet. 1994 Oct;8(2):122-8. [Article]
2. Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M: Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Genome Res. 1997 Jan;7(1):47-58. [Article]
3. Yang X, Aoki Y, Li X, Sakamoto O, Hiratsuka M, Kure S, Taheri S, Christensen E, Inui K, Kubota M, Ohira M, Ohki M, Kudoh J, Kawasaki K, Shibuya K, Shintani A, Asakawa S, Minoshima S, Shimizu N, Narisawa K, Matsubara Y, Suzuki Y: Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency. Hum Genet. 2001 Nov;109(5):526-34. Epub 2001 Oct 5. [Article]
4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
5. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. [Article]
6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
7. Dahmane N, Ghezala GA, Gosset P, Chamoun Z, Dufresne-Zacharia MC, Lopes C, Rabatel N, Gassanova-Maugenre S, Chettouh Z, Abramowski V, Fayet E, Yaspo ML, Korn B, Blouin JL, Lehrach H, Poutska A, Antonarakis SE, Sinet PM, Creau N, Delabar JM: Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome. Genomics. 1998 Feb 15;48(1):12-23. [Article]
8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
11. Aoki Y, Suzuki Y, Sakamoto O, Li X, Takahashi K, Ohtake A, Sakuta R, Ohura T, Miyabayashi S, Narisawa K: Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients. Biochim Biophys Acta. 1995 Dec 12;1272(3):168-74. [Article]
12. Dupuis L, Leon-Del-Rio A, Leclerc D, Campeau E, Sweetman L, Saudubray JM, Herman G, Gibson KM, Gravel RA: Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency. Hum Mol Genet. 1996 Jul;5(7):1011-6. [Article]
13. Aoki Y, Suzuki Y, Li X, Sakamoto O, Chikaoka H, Takita S, Narisawa K: Characterization of mutant holocarboxylase synthetase (HCS): a Km for biotin was not elevated in a patient with HCS deficiency. Pediatr Res. 1997 Dec;42(6):849-54. [Article]
14. Aoki Y, Li X, Sakamoto O, Hiratsuka M, Akaishi H, Xu L, Briones P, Suormala T, Baumgartner ER, Suzuki Y, Narisawa K: Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency. Hum Genet. 1999 Feb;104(2):143-8. [Article]
15. Sakamoto O, Suzuki Y, Li X, Aoki Y, Hiratsuka M, Suormala T, Baumgartner ER, Gibson KM, Narisawa K: Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. Pediatr Res. 1999 Dec;46(6):671-6. [Article]
16. Morrone A, Malvagia S, Donati MA, Funghini S, Ciani F, Pela I, Boneh A, Peters H, Pasquini E, Zammarchi E: Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency. Am J Med Genet. 2002 Jul 22;111(1):10-8. [Article]
17. Tang NL, Hui J, Yong CK, Wong LT, Applegarth DA, Vallance HD, Law LK, Fung SL, Mak TW, Sung YM, Cheung KL, Fok TF: A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency. Clin Biochem. 2003 Mar;36(2):145-9. [Article]
18. Suzuki Y, Yang X, Aoki Y, Kure S, Matsubara Y: Mutations in the holocarboxylase synthetase gene HLCS. Hum Mutat. 2005 Oct;26(4):285-90. [Article]
19. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]
20. Bailey LM, Ivanov RA, Jitrapakdee S, Wilson CJ, Wallace JC, Polyak SW: Reduced half-life of holocarboxylase synthetase from patients with severe multiple carboxylase deficiency. Hum Mutat. 2008 Jun;29(6):E47-57. doi: 10.1002/humu.20766. [Article]
21. Tammachote R, Janklat S, Tongkobpetch S, Suphapeetiporn K, Shotelersuk V: Holocarboxylase synthetase deficiency: novel clinical and molecular findings. Clin Genet. 2010 Jul;78(1):88-93. doi: 10.1111/j.1399-0004.2009.01357.x. Epub 2009 Dec 2. [Article]
22. De Castro M, Zand DJ, Lichter-Konecki U, Kirmse B: Severe neonatal holocarboxylase synthetase deficiency in west african siblings. JIMD Rep. 2015;20:1-4. doi: 10.1007/8904_2014_367. Epub 2015 Feb 18. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB00121	Biotin	approved, investigational, nutraceutical	unknown	substrate	Details