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Identification
HMDB Protein ID HMDBP01716
Secondary Accession Numbers
  • 7058
Name CD44 antigen
Synonyms
  1. CD44 antigen
  2. CDw44
  3. ECMR-III
  4. Epican
  5. Extracellular matrix receptor III
  6. GP90 lymphocyte homing/adhesion receptor
  7. HUTCH-I
  8. Heparan sulfate proteoglycan
  9. Hermes antigen
  10. Hyaluronate receptor
  11. PGP-1
  12. PGP-I
  13. Phagocytic glycoprotein 1
  14. Phagocytic glycoprotein I
Gene Name CD44
Protein Type Enzyme
Biological Properties
General Function Involved in binding
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. 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
binding
pattern binding
polysaccharide binding
glycosaminoglycan binding
hyaluronic acid binding
Process
cell adhesion
cellular process
Cellular Location
  1. Membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 11p13
SNPs CD44
Gene Sequence
>2229 bp
ATGGACAAGTTTTGGTGGCACGCAGCCTGGGGACTCTGCCTCGTGCCGCTGAGCCTGGCG
CAGATCGATTTGAATATAACCTGCCGCTTTGCAGGTGTATTCCACGTGGAGAAAAATGGT
CGCTACAGCATCTCTCGGACGGAGGCCGCTGACCTCTGCAAGGCTTTCAATAGCACCTTG
CCCACAATGGCCCAGATGGAGAAAGCTCTGAGCATCGGATTTGAGACCTGCAGGTATGGG
TTCATAGAAGGGCATGTGGTGATTCCCCGGATCCACCCCAACTCCATCTGTGCAGCAAAC
AACACAGGGGTGTACATCCTCACATACAACACCTCCCAGTATGACACATATTGCTTCAAT
GCTTCAGCTCCACCTGAAGAAGATTGTACATCAGTCACAGACCTGCCCAATGCCTTTGAT
GGACCAATTACCATAACTATTGTTAACCGTGATGGCACCCGCTATGTCCAGAAAGGAGAA
TACAGAACGAATCCTGAAGACATCTACCCCAGCAACCCTACTGATGATGACGTGAGCAGC
GGCTCCTCCAGTGAAAGGAGCAGCACTTCAGGAGGTTACATCTTTTACACCTTTTCTACT
GTACACCCCATCCCAGACGAAGACAGTCCCTGGATCACCGACAGCACAGACAGAATCCCT
GCTACCACTTTGATGAGCACTAGTGCTACAGCAACTGAGACAGCAACCAAGAGGCAAGAA
GCCTGGGATTGGTTTTCATGGTTGTTTCTACCATCAGAGTCAAAGAATCATCTTCACACA
ACAACACAAATGGCTGGTACGTCTTCAAATACCATCTCAGCAGGCTGGGAGCCAAATGAA
GAAAATGAAGATGAAAGAGACAGACACCTCAGTTTTTCTGGATCAGGCATTGATGATGAT
GAAGATTTTATCTCCAGCACCATTTCAACCACACCACGGGCCTTTGACCACACAAAACAG
AACCAGGACTGGACCCAGTGGAACCCAAGCCATTCAAATCCGGAAGTGCTACTTCAGACA
ACCACAAGGATGACTGATGTAGACAGAAATGGCACCACTGCTTATGAAGGAAACTGGAAC
CCAGAAGCACACCCTCCCCTCATTCACCATGAGCATCATGAGGAAGAAGAGACCCCACAT
TCTACAAGCACAATCCAGGCAACTCCTAGTAGTACAACGGAAGAAACAGCTACCCAGAAG
GAACAGTGGTTTGGCAACAGATGGCATGAGGGATATCGCCAAACACCCAGAGAAGACTCC
CATTCGACAACAGGGACAGCTGCAGCCTCAGCTCATACCAGCCATCCAATGCAAGGAAGG
ACAACACCAAGCCCAGAGGACAGTTCCTGGACTGATTTCTTCAACCCAATCTCACACCCC
ATGGGACGAGGTCATCAAGCAGGAAGAAGGATGGATATGGACTCCAGTCATAGTACAACG
CTTCAGCCTACTGCAAATCCAAACACAGGTTTGGTGGAAAATTTGGACAGGACAGGACCT
CTTTCAATGACAACGCAGCAGAGTAATTCTCAGAGCTTCTCTACATCACATGAAGGCTTG
GAAGAAGATAAAGACCATCCAACAACTTCTACTCTGACATCAAGCAATAGGAATGATGTC
ACAGGTGGAAGAAGAGACCCAAATCATTCTGAAGGCTCAACTACTTTACTGGAAGGTTAT
ACCTCTCATTACCCACACACGAAGGAAAGCAGGACCTTCATCCCAGTGACCTCAGCTAAG
ACTGGGTCCTTTGGAGTTACTGCAGTTACTGTTGGAGATTCCAACTCTAATGTCAATCGT
TCCTTATCAGGAGACCAAGACACATTCCACCCCAGTGGGGGGTCCCATACCACTCATGGA
TCTGAATCAGATGGACACTCACATGGGAGTCAAGAAGGTGGAGCAAACACAACCTCTGGT
CCTATAAGGACACCCCAAATTCCAGAATGGCTGATCATCTTGGCATCCCTCTTGGCCTTG
GCTTTGATTCTTGCAGTTTGCATTGCAGTCAACAGTCGAAGAAGGTGTGGGCAGAAGAAA
AAGCTAGTGATCAACAGTGGCAATGGAGCTGTGGAGGACAGAAAGCCAAGTGGACTCAAC
GGAGAGGCCAGCAAGTCTCAGGAAATGGTGCATTTGGTGAACAAGGAGTCGTCAGAAACT
CCAGACCAGTTTATGACAGCTGATGAGACAAGGAACCTGCAGAATGTGGACATGAAGATT
GGGGTGTAA
Protein Properties
Number of Residues 742
Molecular Weight 81537.0
Theoretical pI 5.0
Pfam Domain Function
Signals
  • 1-20
Transmembrane Regions
  • 650-670
Protein Sequence
>CD44 antigen
MDKFWWHAAWGLCLVPLSLAQIDLNITCRFAGVFHVEKNGRYSISRTEAADLCKAFNSTL
PTMAQMEKALSIGFETCRYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYCFN
ASAPPEEDCTSVTDLPNAFDGPITITIVNRDGTRYVQKGEYRTNPEDIYPSNPTDDDVSS
GSSSERSSTSGGYIFYTFSTVHPIPDEDSPWITDSTDRIPATTLMSTSATATETATKRQE
TWDWFSWLFLPSESKNHLHTTTQMAGTSSNTISAGWEPNEENEDERDRHLSFSGSGIDDD
EDFISSTISTTPRAFDHTKQNQDWTQWNPSHSNPEVLLQTTTRMTDVDRNGTTAYEGNWN
PEAHPPLIHHEHHEEEETPHSTSTIQATPSSTTEETATQKEQWFGNRWHEGYRQTPKEDS
HSTTGTAAASAHTSHPMQGRTTPSPEDSSWTDFFNPISHPMGRGHQAGRRMDMDSSHSIT
LQPTANPNTGLVEDLDRTGPLSMTTQQSNSQSFSTSHEGLEEDKDHPTTSTLTSSNRNDV
TGGRRDPNHSEGSTTLLEGYTSHYPHTKESRTFIPVTSAKTGSFGVTAVTVGDSNSNVNR
SLSGDQDTFHPSGGSHTTHGSESDGHSHGSQEGGANTTSGPIRTPQIPEWLIILASLLAL
ALILAVCIAVNSRRRCGQKKKLVINSGNGAVEDRKPSGLNGEASKSQEMVHLVNKESSET
PDQFMTADETRNLQNVDMKIGV
GenBank ID Protein 6491739
UniProtKB/Swiss-Prot ID P16070
UniProtKB/Swiss-Prot Entry Name CD44_HUMAN
PDB IDs
GenBank Gene ID AJ251595
GeneCard ID CD44
GenAtlas ID CD44
HGNC ID HGNC:1681
References
General References
  1. 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. [PubMed:19159218 ]
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  3. 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. [PubMed:18669648 ]
  4. 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. [PubMed:18691976 ]
  5. 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. [PubMed:17081983 ]
  6. 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. [PubMed:17974005 ]
  7. 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. [PubMed:16554811 ]
  8. 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. [PubMed:16335952 ]
  9. 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. [PubMed:19367720 ]
  10. 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. [PubMed:2466575 ]
  11. 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. [PubMed:1840487 ]
  12. 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. [PubMed:1991450 ]
  13. 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. [PubMed:2056274 ]
  14. 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. [PubMed:1281868 ]
  15. 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. [PubMed:1465456 ]
  16. Gunthert U: CD44: a multitude of isoforms with diverse functions. Curr Top Microbiol Immunol. 1993;184:47-63. [PubMed:7508842 ]
  17. 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. [PubMed:8352881 ]
  18. Shtivelman E, Bishop JM: Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol. 1991 Nov;11(11):5446-53. [PubMed:1922057 ]
  19. 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. [PubMed:2466576 ]
  20. 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. [PubMed:7527301 ]
  21. 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. [PubMed:7508992 ]
  22. 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. [PubMed:2007624 ]
  23. 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. [PubMed:8148709 ]
  24. 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. [PubMed:1717145 ]
  25. Ponta H, Sherman L, Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003 Jan;4(1):33-45. [PubMed:12511867 ]
  26. 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. [PubMed:9580567 ]
  27. 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. [PubMed:12032545 ]
  28. 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. [PubMed:12883358 ]
  29. 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. [PubMed:14992719 ]
  30. 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. [PubMed:17085435 ]
  31. 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. [PubMed:8636151 ]