CD44 antigen

Details

Name
CD44 antigen
Synonyms
  • CDw44
  • ECMR-III
  • Epican
  • Extracellular matrix receptor III
  • GP90 lymphocyte homing/adhesion receptor
  • Heparan sulfate proteoglycan
  • Hermes antigen
  • HUTCH-I
  • Hyaluronate receptor
  • LHR
  • MDU2
  • MDU3
  • MIC4
  • PGP-1
  • PGP-I
  • Phagocytic glycoprotein 1
  • Phagocytic glycoprotein I
Gene Name
CD44
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037125|CD44 antigen
MDKFWWHAAWGLCLVPLSLAQIDLNITCRFAGVFHVEKNGRYSISRTEAADLCKAFNSTL
PTMAQMEKALSIGFETCRYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYCFN
ASAPPEEDCTSVTDLPNAFDGPITITIVNRDGTRYVQKGEYRTNPEDIYPSNPTDDDVSS
GSSSERSSTSGGYIFYTFSTVHPIPDEDSPWITDSTDRIPATTLMSTSATATETATKRQE
TWDWFSWLFLPSESKNHLHTTTQMAGTSSNTISAGWEPNEENEDERDRHLSFSGSGIDDD
EDFISSTISTTPRAFDHTKQNQDWTQWNPSHSNPEVLLQTTTRMTDVDRNGTTAYEGNWN
PEAHPPLIHHEHHEEEETPHSTSTIQATPSSTTEETATQKEQWFGNRWHEGYRQTPKEDS
HSTTGTAAASAHTSHPMQGRTTPSPEDSSWTDFFNPISHPMGRGHQAGRRMDMDSSHSIT
LQPTANPNTGLVEDLDRTGPLSMTTQQSNSQSFSTSHEGLEEDKDHPTTSTLTSSNRNDV
TGGRRDPNHSEGSTTLLEGYTSHYPHTKESRTFIPVTSAKTGSFGVTAVTVGDSNSNVNR
SLSGDQDTFHPSGGSHTTHGSESDGHSHGSQEGGANTTSGPIRTPQIPEWLIILASLLAL
ALILAVCIAVNSRRRCGQKKKLVINSGNGAVEDRKPSGLNGEASKSQEMVHLVNKESSET
PDQFMTADETRNLQNVDMKIGV
Number of residues
742
Molecular Weight
81537.025
Theoretical pI
5.0
GO Classification
Functions
collagen binding / hyaluronic acid binding / hyalurononglucosaminidase activity
Processes
blood coagulation / branching involved in prostate gland morphogenesis / branching involved in ureteric bud morphogenesis / carbohydrate metabolic process / cartilage development / cell-matrix adhesion / cellular response to fibroblast growth factor stimulus / cytokine-mediated signaling pathway / extracellular matrix disassembly / extracellular matrix organization / glycosaminoglycan metabolic process / hyaluronan catabolic process / hyaluronan metabolic process / interferon-gamma-mediated signaling pathway / leukocyte migration / monocyte aggregation / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of ERK1 and ERK2 cascade / positive regulation of gene expression / positive regulation of heterotypic cell-cell adhesion / positive regulation of monocyte aggregation / positive regulation of peptidyl-serine phosphorylation / positive regulation of peptidyl-tyrosine phosphorylation / single organismal cell-cell adhesion / small molecule metabolic process / Wnt signaling pathway / wound healing involved in inflammatory response
Components
basolateral plasma membrane / cell surface / cytoplasm / external side of plasma membrane / extracellular exosome / focal adhesion / Golgi apparatus / integral component of plasma membrane / macrophage migration inhibitory factor receptor complex / plasma membrane
General Function
Hyalurononglucosaminidase activity
Specific Function
Receptor for hyaluronic acid (HA). Mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression. In cancer cells, may play an important role in invadopodia formation. Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events. Receptor for LGALS9; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (By similarity).
Pfam Domain Function
Transmembrane Regions
650-670
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019066|CD44 antigen (CD44)
ATGGACAAGTTTTGGTGGCACGCAGCCTGGGGACTCTGCCTCGTGCCGCTGAGCCTGGCG
CAGATCGATTTGAATATAACCTGCCGCTTTGCAGGTGTATTCCACGTGGAGAAAAATGGT
CGCTACAGCATCTCTCGGACGGAGGCCGCTGACCTCTGCAAGGCTTTCAATAGCACCTTG
CCCACAATGGCCCAGATGGAGAAAGCTCTGAGCATCGGATTTGAGACCTGCAGGTATGGG
TTCATAGAAGGGCACGTGGTGATTCCCCGGATCCACCCCAACTCCATCTGTGCAGCAAAC
AACACAGGGGTGTACATCCTCACATCCAACACCTCCCAGTATGACACATATTGCTTCAAT
GCTTCAGCTCCACCTGAAGAAGATTGTACATCAGTCACAGACCTGCCCAATGCCTTTGAT
GGACCAATTACCATAACTATTGTTAACCGTGATGGCACCCGCTATGTCCAGAAAGGAGAA
TACAGAACGAATCCTGAAGACATCTACCCCAGCAACCCTACTGATGATGACGTGAGCAGC
GGCTCCTCCAGTGAAAGGAGCAGCACTTCAGGAGGTTACATCTTTTACACCTTTTCTACT
GTACACCCCATCCCAGACGAAGACAGTCCCTGGATCACCGACAGCACAGACAGAATCCCT
GCTACCACTTTGATGAGCACTAGTGCTACAGCAACTGAGACAGCAACCAAGAGGCAAGAA
ACCTGGGATTGGTTTTCATGGTTGTTTCTACCATCAGAGTCAAAGAATCATCTTCACACA
ACAACACAAATGGCTGGTACGTCTTCAAATACCATCTCAGCAGGCTGGGAGCCAAATGAA
GAAAATGAAGATGAAAGAGACAGACACCTCAGTTTTTCTGGATCAGGCATTGATGATGAT
GAAGATTTTATCTCCAGCACCATTTCAACCACACCACGGGCTTTTGACCACACAAAACAG
AACCAGGACTGGACCCAGTGGAACCCAAGCCATTCAAATCCGGAAGTGCTACTTCAGACA
ACCACAAGGATGACTGATGTAGACAGAAATGGCACCACTGCTTATGAAGGAAACTGGAAC
CCAGAAGCACACCCTCCCCTCATTCACCATGAGCATCATGAGGAAGAAGAGACCCCACAT
TCTACAAGCACAATCCAGGCAACTCCTAGTAGTACAACGGAAGAAACAGCTACCCAGAAG
GAACAGTGGTTTGGCAACAGATGGCATGAGGGATATCGCCAAACACCCAAAGAAGACTCC
CATTCGACAACAGGGACAGCTGCAGCCTCAGCTCATACCAGCCATCCAATGCAAGGAAGG
ACAACACCAAGCCCAGAGGACAGTTCCTGGACTGATTTCTTCAACCCAATCTCACACCCC
ATGGGACGAGGTCATCAAGCAGGAAGAAGGATGGATATGGACTCCAGTCATAGTATAACG
CTTCAGCCTACTGCAAATCCAAACACAGGTTTGGTGGAAGATTTGGACAGGACAGGACCT
CTTTCAATGACAACGCAGCAGAGTAATTCTCAGAGCTTCTCTACATCACATGAAGGCTTG
GAAGAAGATAAAGACCATCCAACAACTTCTACTCTGACATCAAGCAATAGGAATGATGTC
ACAGGTGGAAGAAGAGACCCAAATCATTCTGAAGGCTCAACTACTTTACTGGAAGGTTAT
ACCTCTCATTACCCACACACGAAGGAAAGCAGGACCTTCATCCCAGTGACCTCAGCTAAG
ACTGGGTCCTTTGGAGTTACTGCAGTTACTGTTGGAGATTCCAACTCTAATGTCAATCGT
TCCTTATCAGGAGACCAAGACACATTCCACCCCAGTGGGGGGTCCCATACCACTCATGGA
TCTGAATCAGATGGACACTCACATGGGAGTCAAGAAGGTGGAGCAAACACAACCTCTGGT
CCTATAAGGACACCCCAAATTCCAGAATGGCTGATCATCTTGGCATCCCTCTTGGCCTTG
GCTTTGATTCTTGCAGTTTGCATTGCAGTCAACAGTCGAAGAAGGTGTGGGCAGAAGAAA
AAGCTAGTGATCAACAGTGGCAATGGAGCTGTGGAGGACAGAAAGCCAAGTGGACTCAAC
GGAGAGGCCAGCAAGTCTCAGGAAATGGTGCATTTGGTGAACAAGGAGTCGTCAGAAACT
CCAGACCAGTTTATGACAGCTGATGAGACAAGGAACCTGCAGAATGTGGACATGAAGATT
GGGGTGTAA
Chromosome Location
11
Locus
11p13
External Identifiers
ResourceLink
UniProtKB IDP16070
UniProtKB Entry NameCD44_HUMAN
GenBank Protein ID180197
GenBank Gene IDM24915
GenAtlas IDCD44
HGNC IDHGNC:1681
General References
  1. Stamenkovic I, Amiot M, Pesando JM, Seed B: A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057-62. [Article]
  2. Harn HJ, Isola N, Cooper DL: The multispecific cell adhesion molecule CD44 is represented in reticulocyte cDNA. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1127-34. [Article]
  3. Stamenkovic I, Aruffo A, Amiot M, Seed B: The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343-8. [Article]
  4. Dougherty GJ, Landorp PM, Cooper DL, Humphries RK: Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells. J Exp Med. 1991 Jul 1;174(1):1-5. [Article]
  5. Kugelman LC, Ganguly S, Haggerty JG, Weissman SM, Milstone LM: The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44. J Invest Dermatol. 1992 Dec;99(6):886-91. [Article]
  6. Screaton GR, Bell MV, Jackson DG, Cornelis FB, Gerth U, Bell JI: Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160-4. [Article]
  7. Gunthert U: CD44: a multitude of isoforms with diverse functions. Curr Top Microbiol Immunol. 1993;184:47-63. [Article]
  8. Tanabe KK, Nishi T, Saya H: Novel variants of CD44 arising from alternative splicing: changes in the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells treated with hyaluronidase. Mol Carcinog. 1993;7(4):212-20. [Article]
  9. Chiu RK, Carpenito C, Dougherty ST, Hayes GM, Dougherty GJ: Identification and characterization of CD44RC, a novel alternatively spliced soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell surface CD44. Neoplasia. 1999 Nov;1(5):446-52. [Article]
  10. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  11. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  12. 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]
  13. Shtivelman E, Bishop JM: Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol. 1991 Nov;11(11):5446-53. [Article]
  14. Goldstein LA, Zhou DF, Picker LJ, Minty CN, Bargatze RF, Ding JF, Butcher EC: A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063-72. [Article]
  15. Okada H, Yoshida J, Seo H, Wakabayashi T, Sugita K, Hagiwara M: Anti-(glioma surface antigen) monoclonal antibody G-22 recognizes overexpressed CD44 in glioma cells. Cancer Immunol Immunother. 1994 Nov;39(5):313-7. [Article]
  16. Shepley MP, Racaniello VR: A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44. J Virol. 1994 Mar;68(3):1301-8. [Article]
  17. Brown TA, Bouchard T, St John T, Wayner E, Carter WG: Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol. 1991 Apr;113(1):207-21. [Article]
  18. Matsumura Y, Hanbury D, Smith J, Tarin D: Non-invasive detection of malignancy by identification of unusual CD44 gene activity in exfoliated cancer cells. BMJ. 1994 Mar 5;308(6929):619-24. [Article]
  19. Hofmann M, Rudy W, Zoller M, Tolg C, Ponta H, Herrlich P, Gunthert U: CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res. 1991 Oct 1;51(19):5292-7. [Article]
  20. Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003 Jan;4(1):33-45. [Article]
  21. Peck D, Isacke CM: Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325. J Cell Sci. 1998 Jun;111 ( Pt 11):1595-601. [Article]
  22. Legg JW, Lewis CA, Parsons M, Ng T, Isacke CM: A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility. Nat Cell Biol. 2002 Jun;4(6):399-407. [Article]
  23. Gasbarri A, Del Prete F, Girnita L, Martegani MP, Natali PG, Bartolazzi A: CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage. Melanoma Res. 2003 Aug;13(4):325-37. [Article]
  24. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [Article]
  25. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  26. Vikesaa J, Hansen TV, Jonson L, Borup R, Wewer UM, Christiansen J, Nielsen FC: RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006 Apr 5;25(7):1456-68. Epub 2006 Mar 16. [Article]
  27. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [Article]
  28. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  29. 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]
  30. 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]
  31. Vepachedu R, Karim Z, Patel O, Goplen N, Alam R: Unc119 protects from Shigella infection by inhibiting the Abl family kinases. PLoS One. 2009;4(4):e5211. doi: 10.1371/journal.pone.0005211. Epub 2009 Apr 17. [Article]
  32. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  33. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  34. 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]
  35. Halim A, Nilsson J, Ruetschi U, Hesse C, Larson G: Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD. Mol Cell Proteomics. 2012 Apr;11(4):M111.013649. doi: 10.1074/mcp.M111.013649. Epub 2011 Dec 14. [Article]
  36. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  37. 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]
  38. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  39. Teriete P, Banerji S, Noble M, Blundell CD, Wright AJ, Pickford AR, Lowe E, Mahoney DJ, Tammi MI, Kahmann JD, Campbell ID, Day AJ, Jackson DG: Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. Mol Cell. 2004 Feb 27;13(4):483-96. [Article]
  40. Takeda M, Ogino S, Umemoto R, Sakakura M, Kajiwara M, Sugahara KN, Hayasaka H, Miyasaka M, Terasawa H, Shimada I: Ligand-induced structural changes of the CD44 hyaluronan-binding domain revealed by NMR. J Biol Chem. 2006 Dec 29;281(52):40089-95. Epub 2006 Nov 2. [Article]
  41. Telen MJ, Udani M, Washington MK, Levesque MC, Lloyd E, Rao N: A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding. J Biol Chem. 1996 Mar 22;271(12):7147-53. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08818Hyaluronic acidapproved, vet_approvedyesbinderDetails
DB06550BivatuzumabinvestigationalunknownDetails