[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
DOI=10.1016/0092-8674(89)90638-7; PubMed=2466575 [NCBI, ExPASy, EBI, Israel, Japan]
Stamenkovic I.,
Amiot M.,
Pesando J.M.,
Seed B.;
"A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family.";
Cell 56:1057-1062(1989).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
TISSUE=Reticulocyte;
DOI=10.1016/0006-291X(91)91009-2; PubMed=1840487 [NCBI, ExPASy, EBI, Israel, Japan]
Harn H.-J.,
Isola N.,
Cooper D.L.;
"The multispecific cell adhesion molecule CD44 is represented in reticulocyte cDNA.";
Biochem. Biophys. Res. Commun. 178:1127-1134(1991).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10).
PubMed=1991450 [NCBI, ExPASy, EBI, Israel, Japan]
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. 10:343-348(1991).
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[4]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 10 AND 11).
TISSUE=Myeloid leukemia cell;
DOI=10.1084/jem.174.1.1; PubMed=2056274 [NCBI, ExPASy, EBI, Israel, Japan]
Dougherty G.J.,
Lansdorp P.M.,
Cooper D.L.,
Humphries R.K.;
"Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte 'homing' receptor expressed by hemopoietic cells.";
J. Exp. Med. 174:1-5(1991).
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[5]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT LYS-417.
TISSUE=Keratinocyte;
DOI=10.1111/1523-1747.ep12614896; PubMed=1281868 [NCBI, ExPASy, EBI, Israel, Japan]
Kugelman L.C.,
Ganguly S.,
Haggerty J.G.,
Weissman S.M.,
Milstone L.M.;
"The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44.";
J. Invest. Dermatol. 99:886-891(1992).
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[6]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
TISSUE=Lymphoblast;
DOI=10.1073/pnas.89.24.12160; PubMed=1465456 [NCBI, ExPASy, EBI, Israel, Japan]
Screaton G.R.,
Bell M.V.,
Jackson D.G.,
Cornelis F.B.,
Gerth U.,
Bell J.I.;
"Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons.";
Proc. Natl. Acad. Sci. U.S.A. 89:12160-12164(1992).
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[7]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-494.
PubMed=7508842 [NCBI, ExPASy, EBI, Israel, Japan]
Gunthert U.;
"CD44: a multitude of isoforms with diverse functions.";
Curr. Top. Microbiol. Immunol. 184:47-63(1993).
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[8]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 13 AND 14).
TISSUE=Mammary carcinoma;
DOI=10.1002/mc.2940070403; PubMed=8352881 [NCBI, ExPASy, EBI, Israel, Japan]
Tanabe K.K.,
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. 7:212-220(1993).
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[9]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
TISSUE=Articular cartilage;
Bosch P.P.,
Stevens J.W.,
Buckwalter J.A.,
Midura R.J.;
"CD44 in normal and neoplastic human cartilage.";
Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
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[10]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 10 AND 12).
TISSUE=Colon adenocarcinoma, and Retinal pigment epithelium;
Wiebe G.J.,
Freund D.,
Corbeil D.;
"Sequence analysis of the human CD44 antigen.";
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
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[11]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11).
Xiang Q.,
Wang J.,
Fan C.,
He X.,
Huang L.,
Zhu H.,
Qiu X.,
Luo W.;
"Sequence analysis of a novel human CD44 variant.";
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
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[12]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12).
TISSUE=Spinal cord;
DOI=10.1186/1471-2164-8-399; PubMed=17974005 [NCBI, ExPASy, EBI, Israel, Japan]
Bechtel S.,
Rosenfelder H.,
Duda A.,
Schmidt C.P.,
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 8:399-399(2007).
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[13]
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NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-417 AND ILE-479.
DOI=10.1038/nature04632; PubMed=16554811 [NCBI, ExPASy, EBI, Israel, Japan]
Taylor T.D.,
Noguchi H.,
Totoki Y.,
Toyoda A.,
Kuroki Y.,
Dewar K.,
Lloyd C.,
Itoh T.,
Takeda T.,
Kim D.-W.,
She X.,
Barlow K.F.,
Bloom T.,
Bruford E.,
Chang J.L.,
Cuomo C.A.,
Eichler E.,
FitzGerald M.G.,
Jaffe D.B., ![]()
LaButti K.,
Nicol R.,
Park H.-S.,
Seaman C.,
Sougnez C.,
Yang X.,
Zimmer A.R.,
Zody M.C.,
Birren B.W.,
Nusbaum C.,
Fujiyama A.,
Hattori M.,
Rogers J.,
Lander E.S.,
Sakaki Y.;
"Human chromosome 11 DNA sequence and analysis including novel gene identification.";
Nature 440:497-500(2006).
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[14]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 12).
TISSUE=Pancreas, and Retinal pigment epithelium;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[15]
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NUCLEOTIDE SEQUENCE [MRNA] OF 1-22.
TISSUE=Lymphoblast;
PubMed=1922057 [NCBI, ExPASy, EBI, Israel, Japan]
Shtivelman E.,
Bishop J.M.;
"Expression of CD44 is repressed in neuroblastoma cells.";
Mol. Cell. Biol. 11:5446-5453(1991).
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[16]
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NUCLEOTIDE SEQUENCE [MRNA] OF 2-742 (ISOFORM 15).
DOI=10.1016/0092-8674(89)90639-9; PubMed=2466576 [NCBI, ExPASy, EBI, Israel, Japan]
Goldstein L.A.,
Zhou D.F.H.,
Picker L.J.,
Minty C.N.,
Bargatze R.F.,
Ding J.F.,
Butcher E.C.;
"A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins.";
Cell 56:1063-1072(1989).
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[17]
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PROTEIN SEQUENCE OF 55-108.
TISSUE=Glial tumor;
DOI=10.1007/s002620050131; PubMed=7527301 [NCBI, ExPASy, EBI, Israel, Japan]
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. 39:313-317(1994).
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[18]
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NUCLEOTIDE SEQUENCE [MRNA] OF 184-625 (ISOFORM 10).
TISSUE=Foreskin;
DOI=10.1083/jcb.113.1.207; PubMed=2007624 [NCBI, ExPASy, EBI, Israel, Japan]
Brown T.A.,
Bouchard T.,
St John T.,
Wayner E.,
Carter W.G.;
"Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons.";
J. Cell Biol. 113:207-221(1991).
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[19]
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NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 221-267.
PubMed=8148709 [NCBI, ExPASy, EBI, Israel, Japan]
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 308:619-624(1994).
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[20]
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NUCLEOTIDE SEQUENCE [MRNA] OF 267-603 (ISOFORM 1).
TISSUE=Lung;
PubMed=1717145 [NCBI, ExPASy, EBI, Israel, Japan]
Hofmann M.,
Rudy W.,
Zoeller M.,
Toelg C.,
Ponta H.,
Herrlich P.,
Guenthert U.;
"CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines.";
Cancer Res. 51:5292-5297(1991).
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[21]
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REVIEW ON FUNCTION, AND POST-TRANSLATIONAL MODIFICATIONS.
DOI=10.1038/nrm1004; PubMed=12511867 [NCBI, ExPASy, EBI, Israel, Japan]
Ponta H.,
Sherman L.,
Herrlich P.A.;
"CD44: from adhesion molecules to signalling regulators.";
Nat. Rev. Mol. Cell Biol. 4:33-45(2003).
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[22]
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PHOSPHORYLATION AT SER-706.
PubMed=9580567 [NCBI, ExPASy, EBI, Israel, Japan]
Peck D.,
Isacke C.M.;
"Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325.";
J. Cell Sci. 111:1595-1601(1998).
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[23]
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PHOSPHORYLATION AT SER-672.
DOI=10.1038/ncb797; PubMed=12032545 [NCBI, ExPASy, EBI, Israel, Japan]
Legg J.W.,
Lewis C.A.,
Parsons M.,
Ng T.,
Isacke C.M.;
"A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility.";
Nat. Cell Biol. 4:399-407(2002).
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[24]
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GLYCOSYLATION, AND PROTEOLYTIC PROCESSING.
DOI=10.1097/00008390-200308000-00001; PubMed=12883358 [NCBI, ExPASy, EBI, Israel, Japan]
Bartolazzi A.;
"CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage.";
Melanoma Res. 13:325-337(2003).
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[25]
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GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan]
Liu T.,
Qian W.-J.,
Gritsenko M.A.,
Camp D.G. II,
Monroe M.E.,
Moore R.J.,
Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
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[26]
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PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686; SER-697; SER-706 AND THR-720, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V.,
Blagoev B.,
Gnad F.,
Macek B.,
Kumar C.,
Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
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[27]
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PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706, AND MASS SPECTROMETRY.
DOI=10.1016/j.molcel.2008.07.007; PubMed=18691976 [NCBI, ExPASy, EBI, Israel, Japan]
Daub H.,
Olsen J.V.,
Bairlein M.,
Gnad F.,
Oppermann F.S.,
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 31:438-448(2008).
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[28]
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PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686 AND SER-706, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N.,
Zhou C.,
Villen J.,
Beausoleil S.A.,
Bakalarski C.E.,
Elledge S.J.,
Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
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[29]
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GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-110, AND MASS SPECTROMETRY.
TISSUE=Liver;
DOI=10.1021/pr8008012; PubMed=19159218 [NCBI, ExPASy, EBI, Israel, Japan]
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. 8:651-661(2009).
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[30]
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X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-178, STRUCTURE BY NMR OF 20-178, AND INTERACTION WITH HA.
DOI=10.1016/S1097-2765(04)00080-2; PubMed=14992719 [NCBI, ExPASy, EBI, Israel, Japan]
Teriete P.,
Banerji S.,
Noble M.,
Blundell C.D.,
Wright A.J.,
Pickford A.R.,
Lowe E.,
Mahoney D.J.,
Tammi M.I.,
Kahmann J.D.,
Campbell I.D.,
Day A.J.,
Jackson D.G.;
"Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44.";
Mol. Cell 13:483-496(2004).
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[31]
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STRUCTURE BY NMR OF 20-178 IN COMPLEX WITH HA.
DOI=10.1074/jbc.M608425200; PubMed=17085435 [NCBI, ExPASy, EBI, Israel, Japan]
Takeda M.,
Ogino S.,
Umemoto R.,
Sakakura M.,
Kajiwara M.,
Sugahara K.N.,
Hayasaka H.,
Miyasaka M.,
Terasawa H.,
Shimada I.;
"Ligand-induced structural changes of the CD44 hyaluronan-binding domain revealed by NMR.";
J. Biol. Chem. 281:40089-40095(2006).
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[32]
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VARIANT BLOOD GROUP INDIAN PRO-46.
DOI=10.1074/jbc.271.12.7147; PubMed=8636151 [NCBI, ExPASy, EBI, Israel, Japan]
Telen M.J.,
Udani M.,
Washington M.K.,
Levesque M.C.,
Lloyd E.,
Rao N.;
"A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding.";
J. Biol. Chem. 271:7147-7153(1996).
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- 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.
- SUBUNIT: Interacts with HA, as well as other glycosaminoglycans, collagen, laminin, and fibronectin via its N-terminal segment. Interacts with ANK, the ERM proteins (VIL2, RDX and MSN), and NF2 via its C-terminal segment.
- INTERACTION:
P18011:ipaB (xeno); NbExp=4; IntAct=EBI-490245, EBI-490239;
- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
- ALTERNATIVE PRODUCTS:
17 named isoforms [FASTA] produced by alternative splicing. Additional isoforms seem to exist. Additional isoforms are produced by alternative splicing of 10 out of 19 exons within the extracellular domain. Additional diversity is generated through the utilization of internal splice donor and acceptor sites within 2 of the exons. A variation in the cytoplasmic domain was shown to result from the alternative splicing of 2 exons. Isoform CD44 is expected to be expressed in normal cells. Splice variants have been found in many tumor cell lines. Exons 5, 6, 7, 8, 9, 10, 11, 13, 14 and 19 are alternatively spliced. Experimental confirmation may be lacking for some isoforms.
| Name | CD44 |
| Isoform ID | P16070-1 |
| Note: Corresponds to the largest isoform. |
| This is the isoform sequence displayed in this entry. |
|
| |
| Name | 3 |
| Isoform ID | P16070-3 |
| Note: Alternative splice donor/acceptor on exon 5. |
| Features which should be applied to build the isoform sequence: VSP_005305, VSP_005306. |
|
|
| Name | 4 |
| Synonyms | Epidermal |
| Isoform ID | P16070-4 |
| Note: Lacks exon 6. |
| Features which should be applied to build the isoform sequence: VSP_005307, VSP_005308. |
|
|
| Name | 5 |
| Isoform ID | P16070-5 |
| Note: Alternative splice donor/acceptor on exon 7. |
| Features which should be applied to build the isoform sequence: VSP_005313. |
|
| | | | |
| Name | 10 |
| Synonyms | CD44E, CD44R1, Epithelial, Keratinocyte |
| Isoform ID | P16070-10 |
| Note: Lacks exons 6-11. |
| Features which should be applied to build the isoform sequence: VSP_005309, VSP_005310. |
|
|
| Name | 11 |
| Synonyms | CD44R2 |
| Isoform ID | P16070-11 |
| Note: Lacks exons 6-13. |
| Features which should be applied to build the isoform sequence: VSP_022797. |
|
|
| Name | 12 |
| Synonyms | CDw44, Reticulocyte |
| Isoform ID | P16070-12 |
| Note: Lacks exons 6-14. |
| Features which should be applied to build the isoform sequence: VSP_005311, VSP_005312. |
|
| | | | |
| Name | 17 |
| Isoform ID | P16070-17 |
| Note: Alternative splice donor/acceptor on exon 7 and lacks exon 10. |
| Features which should be applied to build the isoform sequence: VSP_005313, VSP_005314, VSP_005315. |
|
|
- TISSUE SPECIFICITY: An epithelial isoform (CD44E) is expressed by cells of epithelium and highly expressed by carcinomas. An hematopoietic isoform (CD44H) is expressed by cells of mesodermal origin. Expression is repressed in neuroblastoma cells.
- PTM: Proteolytically cleaved in the extracellular matrix by specific proteinases (possibly MMPs) in several cell lines and tumors.
- PTM: N-glycosylated.
- PTM: O-glycosylated; contains more-or-less-sulfated chondroitin sulfate glycans, whose number may affect the accessibility of specific proteinases to their cleavage site(s).
- PTM: Phosphorylated; activation of PKC results in the dephosphorylation of Ser-706 (constitutive phosphorylation site), and the phosphorylation of Ser-672.
- POLYMORPHISM: CD44 is responsible for the Indian blood group system. The molecular basis of the In(A)=In1/In(B)=In2 blood group antigens is a single variation in position 46; In(B), the most frequent allele, has Arg-46.
- SIMILARITY: Contains 1 Link domain.
- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation database; URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=indian";.
- WEB RESOURCE: Name=Wikipedia; Note=CD44 entry; URL="http://en.wikipedia.org/wiki/CD44";.
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