T-cell surface glycoprotein CD4

Details

Name
T-cell surface glycoprotein CD4
Synonyms
  • T-cell surface antigen T4/Leu-3
Gene Name
CD4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0019431|T-cell surface glycoprotein CD4
MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIK
ILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQL
LVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSG
TWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWW
QAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLA
LEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWV
LNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCV
RCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI
Number of residues
458
Molecular Weight
51110.205
Theoretical pI
10.24
GO Classification
Functions
coreceptor activity / enzyme binding / extracellular matrix structural constituent / glycoprotein binding / MHC class II protein binding / protein homodimerization activity / protein kinase binding / receptor activity / transmembrane signaling receptor activity / virus receptor activity / zinc ion binding
Processes
adaptive immune response / cell surface receptor signaling pathway / cytokine production / defense response to Gram-negative bacterium / entry into host cell / enzyme linked receptor protein signaling pathway / immune response / induction by virus of host cell-cell fusion / innate immune response / maintenance of protein location in cell / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 biosynthetic process / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of protein kinase activity / regulation of defense response to virus by virus / regulation of T cell activation / signal transduction / T cell costimulation / T cell differentiation / T cell receptor signaling pathway / T cell selection / transmembrane receptor protein tyrosine kinase signaling pathway / viral process
Components
early endosome / endoplasmic reticulum lumen / endoplasmic reticulum membrane / external side of plasma membrane / integral component of membrane / membrane raft / plasma membrane / T cell receptor complex
General Function
Zinc ion binding
Specific Function
Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts.(Microbial infection) Acts as a receptor for human immunodeficiency virus-1 (PubMed:2214026, PubMed:16331979, PubMed:9641677). Down-regulated by HIV-1 Vpu (PubMed:17346169). Acts as a receptor for Human Herpes virus 7/HHV-7 (PubMed:7909607).
Pfam Domain Function
Transmembrane Regions
397-418
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019432|T-cell surface glycoprotein CD4 (CD4)
ATGAACCGGGGAGTCCCTTTTAGGCACTTGCTTCTGGTGCTGCAACTGGCGCTCCTCCCA
GCAGCCACTCAGGGAAAGAAAGTGGTGCTGGGCAAAAAAGGGGATACAGTGGAACTGACC
TGTACAGCTTCCCAGAAGAAGAGCATACAATTCCACTGGAAAAACTCCAACCAGATAAAG
ATTCTGGGAAATCAGGGCTCCTTCTTAACTAAAGGTCCATCCAAGCTGAATGATCGCGCT
GACTCAAGAAGAAGCCTTTGGGACCAAGGAAACTTTCCCCTGATCATCAAGAATCTTAAG
ATAGAAGACTCAGATACTTACATCTGTGAAGTGGAGGACCAGAAGGAGGAGGTGCAATTG
CTAGTGTTCGGATTGACTGCCAACTCTGACACCCACCTGCTTCAGGGGCAGAGCCTGACC
CTGACCTTGGAGAGCCCCCCTGGTAGTAGCCCCTCAGTGCAATGTAGGAGTCCAAGGGGT
AAAAACATACAGGGGGGGAAGACCCTCTCCGTGTCTCAGCTGGAGCTCCAGGATAGTGGC
ACCTGGACATGCACTGTCTTGCAGAACCAGAAGAAGGTGGAGTTCAAAATAGACATCGTG
GTGCTAGCTTTCCAGAAGGCCTCCAGCATAGTCTATAAGAAAGAGGGGGAACAGGTGGAG
TTCTCCTTCCCACTCGCCTTTACAGTTGAAAAGCTGACGGGCAGTGGCGAGCTGTGGTGG
CAGGCGGAGAGGGCTTCCTCCTCCAAGTCTTGGATCACCTTTGACCTGAAGAACAAGGAA
GTGTCTGTAAAACGGGTTACCCAGGACCCTAAGCTCCAGATGGGCAAGAAGCTCCCGCTC
CACCTCACCCTGCCCCAGGCCTTGCCTCAGTATGCTGGCTCTGGAAACCTCACCCTGGCC
CTTGAAGCGAAAACAGGAAAGTTGCATCAGGAAGTGAACCTGGTGGTGATGAGAGCCACT
CAGCTCCAGAAAAATTTGACCTGTGAGGTGTGGGGACCCACCTCCCCTAAGCTGATGCTG
AGTTTGAAACTGGAGAACAAGGAGGCAAAGGTCTCGAAGCGGGAGAAGGCGGTGTGGGTG
CTGAACCCTGAGGCGGGGATGTGGCAGTGTCTGCTGAGTGACTCGGGACAGGTCCTGCTG
GAATCCAACATCAAGGTTCTGCCCACATGGTCCACCCCGGTGCAGCCAATGGCCCTGATT
GTGCTGGGGGGCGTCGCCGGCCTCCTGCTTTTCATTGGGCTAGGCATCTTCTTCTGTGTC
AGGTGCCGGCACCGAAGGCGCCAAGCAGAGCGGATGTCTCAGATCAAGAGACTCCTCAGT
GAGAAGAAGACCTGCCAGTGTCCTCACCGGTTTCAGAAGACATGTAGCCCCATTTGA
Chromosome Location
12
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP01730
UniProtKB Entry NameCD4_HUMAN
GenBank Gene IDBC025782
GenAtlas IDCD4
HGNC IDHGNC:1678
General References
  1. Maddon PJ, Littman DR, Godfrey M, Maddon DE, Chess L, Axel R: The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell. 1985 Aug;42(1):93-104. [Article]
  2. Littman DR, Maddon PJ, Axel R: Corrected CD4 sequence. Cell. 1988 Nov 18;55(4):541. [Article]
  3. Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, Malley T, Gibbs RA: A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13. Genome Res. 1996 Apr;6(4):314-26. [Article]
  4. Ansari-Lari MA, Shen Y, Muzny DM, Lee W, Gibbs RA: Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination. Genome Res. 1997 Mar;7(3):268-80. [Article]
  5. Hodge TW, Sasso DR, McDougal JS: Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240. Hum Immunol. 1991 Feb;30(2):99-104. [Article]
  6. 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]
  7. 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]
  8. Fomsgaard A, Hirsch VM, Johnson PR: Cloning and sequences of primate CD4 molecules: diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus. Eur J Immunol. 1992 Nov;22(11):2973-81. [Article]
  9. Carr SA, Hemling ME, Folena-Wasserman G, Sweet RW, Anumula K, Barr JR, Huddleston MJ, Taylor P: Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry. J Biol Chem. 1989 Dec 15;264(35):21286-95. [Article]
  10. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [Article]
  11. Lederman S, DeMartino JA, Daugherty BL, Foeldvari I, Yellin MJ, Cleary AM, Berkowitz N, Lowy I, Braunstein NS, Mark GE, et al.: A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4. Mol Immunol. 1991 Nov;28(11):1171-81. [Article]
  12. Crise B, Buonocore L, Rose JK: CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor. J Virol. 1990 Nov;64(11):5585-93. [Article]
  13. Spellman MW, Leonard CK, Basa LJ, Gelineo I, van Halbeek H: Carbohydrate structures of recombinant soluble human CD4 expressed in Chinese hamster ovary cells. Biochemistry. 1991 Mar 5;30(9):2395-406. [Article]
  14. Crise B, Rose JK: Identification of palmitoylation sites on CD4, the human immunodeficiency virus receptor. J Biol Chem. 1992 Jul 5;267(19):13593-7. [Article]
  15. Aiken C, Konner J, Landau NR, Lenburg ME, Trono D: Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell. 1994 Mar 11;76(5):853-64. [Article]
  16. Lusso P, Secchiero P, Crowley RW, Garzino-Demo A, Berneman ZN, Gallo RC: CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3872-6. [Article]
  17. Zeitlmann L, Sirim P, Kremmer E, Kolanus W: Cloning of ACP33 as a novel intracellular ligand of CD4. J Biol Chem. 2001 Mar 23;276(12):9123-32. Epub 2000 Dec 11. [Article]
  18. Fragoso R, Ren D, Zhang X, Su MW, Burakoff SJ, Jin YJ: Lipid raft distribution of CD4 depends on its palmitoylation and association with Lck, and evidence for CD4-induced lipid raft aggregation as an additional mechanism to enhance CD3 signaling. J Immunol. 2003 Jan 15;170(2):913-21. [Article]
  19. Sharma D, Balamurali MM, Chakraborty K, Kumaran S, Jeganathan S, Rashid U, Ingallinella P, Varadarajan R: Protein minimization of the gp120 binding region of human CD4. Biochemistry. 2005 Dec 13;44(49):16192-202. [Article]
  20. Lindwasser OW, Chaudhuri R, Bonifacino JS: Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses. Curr Mol Med. 2007 Mar;7(2):171-84. [Article]
  21. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
  22. Wang JH, Yan YW, Garrett TP, Liu JH, Rodgers DW, Garlick RL, Tarr GE, Husain Y, Reinherz EL, Harrison SC: Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature. 1990 Nov 29;348(6300):411-8. [Article]
  23. Ryu SE, Kwong PD, Truneh A, Porter TG, Arthos J, Rosenberg M, Dai XP, Xuong NH, Axel R, Sweet RW, et al.: Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419-26. [Article]
  24. Wu H, Kwong PD, Hendrickson WA: Dimeric association and segmental variability in the structure of human CD4. Nature. 1997 May 29;387(6632):527-30. [Article]
  25. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA: Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998 Jun 18;393(6686):648-59. [Article]
  26. Garron ML, Arthos J, Guichou JF, McNally J, Cicala C, Arold ST: Structural basis for the interaction between focal adhesion kinase and CD4. J Mol Biol. 2008 Feb 1;375(5):1320-8. Epub 2007 Nov 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12698Ibalizumabapproved, investigationalunknownantagonistDetails
DB06241ClenoliximabinvestigationalunknownDetails
DB00098Antithymocyte immunoglobulin (rabbit)approvedyesDetails