RBCC Red Blood Cell Collection

CD44 (LHR, MDU2, MDU3, MIC4) [Confidence: high (a blood group or CD marker)]
CD44 antigen (CDw44; Epican; Extracellular matrix receptor III; ECMR-III; GP90 lymphocyte homing/adhesion receptor; HUTCH-I; Heparan sulfate proteoglycan; Hermes antigen; Hyaluronate receptor; Phagocytic glycoprotein 1; PGP-1; Phagocytic glycoprotein I; PGP-I; CD44; Flags: Precursor)

hRBCD IPI00297160
IPI00297160 CD44 antigen CD44 antigen membrane n/a 2 2 2 2 n/a 1 n/a n/a n/a 3 n/a 1 2 n/a 1 1 1 1 2 Type I membrane protein n/a found at its expected molecular weight found at molecular weight

BGMUT indian
383 indian CD44 CD44 137C, 207C, 255C, 326C, 716A In a (IN !) 137G>C; 207T>C; 255T>C; 326A>C; 716G>A R46P; A69A; H85H; Y109S; G239E In a+ b- Rare; Arabs, 11.8%; Iranians, 10.6%; South Asian Indians, 4%; Caucasians, Asians and Blacks, 0.1% 8636151 Telen et al. The R46P mutation is responsible for the phenotype. Blumenfeld OO, curator 2008-09-24 17:36:16.360 NA

Comments
Isoform P16070-7 was detected.

UniProt P16070
ID CD44_HUMAN Reviewed; 742 AA.
AC P16070; A5YRN9; B6EAT9; D3DR12; D3DR13; O95370; P22511; Q04858;
read moreAC Q13419; Q13957; Q13958; Q13959; Q13960; Q13961; Q13967; Q13968;
AC Q13980; Q15861; Q16064; Q16065; Q16066; Q16208; Q16522; Q86T72;
AC Q86Z27; Q8N694; Q92493; Q96J24; Q9H5A5; Q9UC28; Q9UC29; Q9UC30;
AC Q9UCB0; Q9UJ36;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 22-JAN-2014, entry version 175.
DE RecName: Full=CD44 antigen;
DE AltName: Full=CDw44;
DE AltName: Full=Epican;
DE AltName: Full=Extracellular matrix receptor III;
DE Short=ECMR-III;
DE AltName: Full=GP90 lymphocyte homing/adhesion receptor;
DE AltName: Full=HUTCH-I;
DE AltName: Full=Heparan sulfate proteoglycan;
DE AltName: Full=Hermes antigen;
DE AltName: Full=Hyaluronate receptor;
DE AltName: Full=Phagocytic glycoprotein 1;
DE Short=PGP-1;
DE AltName: Full=Phagocytic glycoprotein I;
DE Short=PGP-I;
DE AltName: CD_antigen=CD44;
DE Flags: Precursor;
GN Name=CD44; Synonyms=LHR, MDU2, MDU3, MIC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
RX PubMed=2466575; DOI=10.1016/0092-8674(89)90638-7;
RA Stamenkovic I., Amiot M., Pesando J.M., Seed B.;
RT "A lymphocyte molecule implicated in lymph node homing is a member of
RT the cartilage link protein family.";
RL Cell 56:1057-1062(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
RC TISSUE=Reticulocyte;
RX PubMed=1840487; DOI=10.1016/0006-291X(91)91009-2;
RA Harn H.-J., Isola N., Cooper D.L.;
RT "The multispecific cell adhesion molecule CD44 is represented in
RT reticulocyte cDNA.";
RL Biochem. Biophys. Res. Commun. 178:1127-1134(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10), AND VARIANT THR-479.
RX PubMed=1991450;
RA Stamenkovic I., Aruffo A., Amiot M., Seed B.;
RT "The hematopoietic and epithelial forms of CD44 are distinct
RT polypeptides with different adhesion potentials for hyaluronate-
RT bearing cells.";
RL EMBO J. 10:343-348(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 10 AND 11), AND VARIANT THR-479.
RC TISSUE=Myeloid leukemia cell;
RX PubMed=2056274; DOI=10.1084/jem.174.1.1;
RA Dougherty G.J., Lansdorp P.M., Cooper D.L., Humphries R.K.;
RT "Molecular cloning of CD44R1 and CD44R2, two novel isoforms of the
RT human CD44 lymphocyte 'homing' receptor expressed by hemopoietic
RT cells.";
RL J. Exp. Med. 174:1-5(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT THR-479.
RC TISSUE=Keratinocyte;
RX PubMed=1281868; DOI=10.1111/1523-1747.ep12614896;
RA Kugelman L.C., Ganguly S., Haggerty J.G., Weissman S.M.,
RA Milstone L.M.;
RT "The core protein of epican, a heparan sulfate proteoglycan on
RT keratinocytes, is an alternative form of CD44.";
RL J. Invest. Dermatol. 99:886-891(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANTS
RP ARG-417 AND THR-479.
RC TISSUE=Lymphoblast;
RX PubMed=1465456; DOI=10.1073/pnas.89.24.12160;
RA Screaton G.R., Bell M.V., Jackson D.G., Cornelis F.B., Gerth U.,
RA Bell J.I.;
RT "Genomic structure of DNA encoding the lymphocyte homing receptor CD44
RT reveals at least 12 alternatively spliced exons.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:12160-12164(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-417; THR-479
RP AND HIS-494.
RX PubMed=7508842;
RA Gunthert U.;
RT "CD44: a multitude of isoforms with diverse functions.";
RL Curr. Top. Microbiol. Immunol. 184:47-63(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 13 AND 14), AND VARIANT
RP THR-479.
RC TISSUE=Mammary carcinoma;
RX PubMed=8352881; DOI=10.1002/mc.2940070403;
RA Tanabe K.K., Nishi T., Saya H.;
RT "Novel variants of CD44 arising from alternative splicing: changes in
RT the CD44 alternative splicing pattern of MCF-7 breast carcinoma cells
RT treated with hyaluronidase.";
RL Mol. Carcinog. 7:212-220(1993).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 19).
RX PubMed=10933060; DOI=10.1038/sj.neo.7900045;
RA Chiu R.K., Carpenito C., Dougherty S.T., Hayes G.M., Dougherty G.J.;
RT "Identification and characterization of CD44RC, a novel alternatively
RT spliced soluble CD44 isoform that can potentiate the hyaluronan
RT binding activity of cell surface CD44.";
RL Neoplasia 1:446-452(1999).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
RC TISSUE=Articular cartilage;
RA Bosch P.P., Stevens J.W., Buckwalter J.A., Midura R.J.;
RT "CD44 in normal and neoplastic human cartilage.";
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 10 AND 12), AND VARIANT THR-479.
RC TISSUE=Colon adenocarcinoma, and Retinal pigment epithelium;
RA Wiebe G.J., Freund D., Corbeil D.;
RT "Sequence analysis of the human CD44 antigen.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11).
RA Xiang Q., Wang J., Fan C., He X., Huang L., Zhu H., Qiu X., Luo W.;
RT "Sequence analysis of a novel human CD44 variant.";
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 18).
RA Fang X., Xu W., Zhang X.;
RT "Construction of human CD44 eukaryotic vector and its expression in
RT mammary carcinoma cells MCF-7.";
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 12).
RC TISSUE=Spinal cord;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [16]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 12), AND
RP VARIANTS ARG-417 AND THR-479.
RC TISSUE=Pancreas, and Retinal pigment epithelium;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-22.
RC TISSUE=Lymphoblast;
RX PubMed=1922057;
RA Shtivelman E., Bishop J.M.;
RT "Expression of CD44 is repressed in neuroblastoma cells.";
RL Mol. Cell. Biol. 11:5446-5453(1991).
RN [19]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-742 (ISOFORM 15).
RX PubMed=2466576; DOI=10.1016/0092-8674(89)90639-9;
RA Goldstein L.A., Zhou D.F.H., Picker L.J., Minty C.N., Bargatze R.F.,
RA Ding J.F., Butcher E.C.;
RT "A human lymphocyte homing receptor, the hermes antigen, is related to
RT cartilage proteoglycan core and link proteins.";
RL Cell 56:1063-1072(1989).
RN [20]
RP PROTEIN SEQUENCE OF 55-108.
RC TISSUE=Glial tumor;
RX PubMed=7527301; DOI=10.1007/s002620050131;
RA Okada H., Yoshida J., Seo H., Wakabayashi T., Sugita K., Hagiwara M.;
RT "Anti-(glioma surface antigen) monoclonal antibody G-22 recognizes
RT overexpressed CD44 in glioma cells.";
RL Cancer Immunol. Immunother. 39:313-317(1994).
RN [21]
RP PROTEIN SEQUENCE OF 67-89.
RC TISSUE=Peripheral blood;
RX PubMed=7508992;
RA Shepley M.P., Racaniello V.R.;
RT "A monoclonal antibody that blocks poliovirus attachment recognizes
RT the lymphocyte homing receptor CD44.";
RL J. Virol. 68:1301-1308(1994).
RN [22]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 184-625 (ISOFORM 10), AND VARIANT
RP THR-479.
RC TISSUE=Foreskin;
RX PubMed=2007624; DOI=10.1083/jcb.113.1.207;
RA Brown T.A., Bouchard T., St John T., Wayner E., Carter W.G.;
RT "Human keratinocytes express a new CD44 core protein (CD44E) as a
RT heparan-sulfate intrinsic membrane proteoglycan with additional
RT exons.";
RL J. Cell Biol. 113:207-221(1991).
RN [23]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 221-267.
RX PubMed=8148709;
RA Matsumura Y., Hanbury D., Smith J., Tarin D.;
RT "Non-invasive detection of malignancy by identification of unusual
RT CD44 gene activity in exfoliated cancer cells.";
RL BMJ 308:619-624(1994).
RN [24]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 267-603 (ISOFORM 1), AND VARIANT
RP ARG-417.
RC TISSUE=Lung;
RX PubMed=1717145;
RA Hofmann M., Rudy W., Zoeller M., Toelg C., Ponta H., Herrlich P.,
RA Guenthert U.;
RT "CD44 splice variants confer metastatic behavior in rats: homologous
RT sequences are expressed in human tumor cell lines.";
RL Cancer Res. 51:5292-5297(1991).
RN [25]
RP REVIEW ON FUNCTION, AND POST-TRANSLATIONAL MODIFICATIONS.
RX PubMed=12511867; DOI=10.1038/nrm1004;
RA Ponta H., Sherman L., Herrlich P.A.;
RT "CD44: from adhesion molecules to signalling regulators.";
RL Nat. Rev. Mol. Cell Biol. 4:33-45(2003).
RN [26]
RP PHOSPHORYLATION AT SER-706.
RX PubMed=9580567;
RA Peck D., Isacke C.M.;
RT "Hyaluronan-dependent cell migration can be blocked by a CD44
RT cytoplasmic domain peptide containing a phosphoserine at position
RT 325.";
RL J. Cell Sci. 111:1595-1601(1998).
RN [27]
RP PHOSPHORYLATION AT SER-672.
RX PubMed=12032545; DOI=10.1038/ncb797;
RA Legg J.W., Lewis C.A., Parsons M., Ng T., Isacke C.M.;
RT "A novel PKC-regulated mechanism controls CD44 ezrin association and
RT directional cell motility.";
RL Nat. Cell Biol. 4:399-407(2002).
RN [28]
RP GLYCOSYLATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=12883358; DOI=10.1097/00008390-200308000-00001;
RA Bartolazzi A.;
RT "CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage
RT are regulated at post-translational level in cells of melanocytic
RT lineage.";
RL Melanoma Res. 13:325-337(2003).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686 AND SER-706, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [31]
RP FUNCTION.
RX PubMed=16541107; DOI=10.1038/sj.emboj.7601039;
RA Vikesaa J., Hansen T.V., Joenson L., Borup R., Wewer U.M.,
RA Christiansen J., Nielsen F.C.;
RT "RNA-binding IMPs promote cell adhesion and invadopodia formation.";
RL EMBO J. 25:1456-1468(2006).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706, AND MASS
RP SPECTROMETRY.
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [35]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-110, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686 AND SER-706, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [39]
RP GLYCOSYLATION AT THR-637 AND THR-638, STRUCTURE OF CARBOHYDRATES, AND
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.M111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of
RT N-and O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-178, STRUCTURE BY NMR OF
RP 20-178, AND INTERACTION WITH HA.
RX PubMed=14992719; DOI=10.1016/S1097-2765(04)00080-2;
RA Teriete P., Banerji S., Noble M., Blundell C.D., Wright A.J.,
RA Pickford A.R., Lowe E., Mahoney D.J., Tammi M.I., Kahmann J.D.,
RA Campbell I.D., Day A.J., Jackson D.G.;
RT "Structure of the regulatory hyaluronan binding domain in the
RT inflammatory leukocyte homing receptor CD44.";
RL Mol. Cell 13:483-496(2004).
RN [42]
RP STRUCTURE BY NMR OF 20-178 IN COMPLEX WITH HA.
RX PubMed=17085435; DOI=10.1074/jbc.M608425200;
RA Takeda M., Ogino S., Umemoto R., Sakakura M., Kajiwara M.,
RA Sugahara K.N., Hayasaka H., Miyasaka M., Terasawa H., Shimada I.;
RT "Ligand-induced structural changes of the CD44 hyaluronan-binding
RT domain revealed by NMR.";
RL J. Biol. Chem. 281:40089-40095(2006).
RN [43]
RP VARIANT BLOOD GROUP INDIAN PRO-46.
RX PubMed=8636151; DOI=10.1074/jbc.271.12.7147;
RA Telen M.J., Udani M., Washington M.K., Levesque M.C., Lloyd E.,
RA Rao N.;
RT "A blood group-related polymorphism of CD44 abolishes a hyaluronan-
RT binding consensus sequence without preventing hyaluronan binding.";
RL J. Biol. Chem. 271:7147-7153(1996).
CC -!- FUNCTION: Receptor for hyaluronic acid (HA). Mediates cell-cell
CC and cell-matrix interactions through its affinity for HA, and
CC possibly also through its affinity for other ligands such as
CC osteopontin, collagens, and matrix metalloproteinases (MMPs).
CC Adhesion with HA plays an important role in cell migration, tumor
CC growth and progression. In cancer cells, may play an important
CC role in invadopodia formation. Also involved in lymphocyte
CC activation, recirculation and homing, and in hematopoiesis.
CC Altered expression or dysfunction causes numerous pathogenic
CC phenotypes. Great protein heterogeneity due to numerous
CC alternative splicing and post-translational modification events.
CC -!- SUBUNIT: Interacts with PKN2. Interacts with TIAM1 and TIAM2 (By
CC similarity). Interacts with HA, as well as other
CC glycosaminoglycans, collagen, laminin, and fibronectin via its N-
CC terminal segment. Interacts with ANK, the ERM proteins (VIL2, RDX
CC and MSN), and NF2 via its C-terminal segment.
CC -!- INTERACTION:
CC P18011:ipaB (xeno); NbExp=4; IntAct=EBI-490245, EBI-490239;
CC Q9UPY5:SLC7A11; NbExp=4; IntAct=EBI-490245, EBI-3843348;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Note=Colocalizes with actin in membrane protrusions at
CC wounding edges (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=19;
CC Comment=Additional isoforms seem to exist. Additional isoforms
CC are produced by alternative splicing of 10 out of 19 exons
CC within the extracellular domain. Additional diversity is
CC generated through the utilization of internal splice donor and
CC acceptor sites within 2 of the exons. A variation in the
CC cytoplasmic domain was shown to result from the alternative
CC splicing of 2 exons. Isoform CD44 is expected to be expressed in
CC normal cells. Splice variants have been found in many tumor cell
CC lines. Exons 5, 6, 7, 8, 9, 10, 11, 13, 14 and 19 are
CC alternatively spliced. Experimental confirmation may be lacking
CC for some isoforms;
CC Name=1; Synonyms=CD44;
CC IsoId=P16070-1; Sequence=Displayed;
CC Note=Corresponds to the largest isoform;
CC Name=2; Synonyms=CD44SP;
CC IsoId=P16070-2; Sequence=VSP_005303, VSP_005304;
CC Name=3;
CC IsoId=P16070-3; Sequence=VSP_005305, VSP_005306;
CC Note=Alternative splice donor/acceptor on exon 5;
CC Name=4; Synonyms=Epidermal;
CC IsoId=P16070-4; Sequence=VSP_005307, VSP_005308;
CC Note=Lacks exon 6;
CC Name=5;
CC IsoId=P16070-5; Sequence=VSP_005313;
CC Note=Alternative splice donor/acceptor on exon 7;
CC Name=6;
CC IsoId=P16070-6; Sequence=VSP_005314, VSP_005315;
CC Note=Lacks exon 10;
CC Name=7;
CC IsoId=P16070-7; Sequence=VSP_005316, VSP_005317;
CC Note=Lacks exon 13;
CC Name=8;
CC IsoId=P16070-8; Sequence=VSP_005318, VSP_005319;
CC Note=Lacks exon 14;
CC Name=9;
CC IsoId=P16070-9; Sequence=VSP_005320, VSP_005321;
CC Note=Lacks exon 19;
CC Name=10; Synonyms=CD44E, CD44R1, Epithelial, Keratinocyte;
CC IsoId=P16070-10; Sequence=VSP_005309, VSP_005310;
CC Note=Lacks exons 6-11;
CC Name=11; Synonyms=CD44R2;
CC IsoId=P16070-11; Sequence=VSP_022797;
CC Note=Lacks exons 6-13;
CC Name=12; Synonyms=CDw44, Reticulocyte;
CC IsoId=P16070-12; Sequence=VSP_005311, VSP_005312;
CC Note=Lacks exons 6-14;
CC Name=13; Synonyms=CD44R4;
CC IsoId=P16070-13; Sequence=VSP_005309, VSP_005310, VSP_005318,
CC VSP_005319;
CC Note=Lacks exons 6-11 and exon 14;
CC Name=14; Synonyms=CD44R5;
CC IsoId=P16070-14; Sequence=VSP_005309, VSP_005310, VSP_005316,
CC VSP_005317, VSP_005318, VSP_005319;
CC Note=Lacks exons 6-11, exon 13 and exon 14;
CC Name=15; Synonyms=Hermes;
CC IsoId=P16070-15; Sequence=VSP_005311, VSP_005312, VSP_005320,
CC VSP_005321;
CC Note=Lacks exons 6-14 and exon 19;
CC Name=16;
CC IsoId=P16070-16; Sequence=VSP_005305, VSP_005306, VSP_005314,
CC VSP_005315;
CC Note=Alternative splice donor/acceptor on exon 5 and lacks exon
CC 10;
CC Name=17;
CC IsoId=P16070-17; Sequence=VSP_005313, VSP_005314, VSP_005315;
CC Note=Alternative splice donor/acceptor on exon 7 and lacks exon
CC 10;
CC Name=18;
CC IsoId=P16070-18; Sequence=VSP_005311, VSP_005312, VSP_043575;
CC Note=No experimental confirmation available;
CC Name=19; Synonyms=CD44RC;
CC IsoId=P16070-19; Sequence=VSP_043870, VSP_043871;
CC Note=Soluble isoform, has enhanced hyaluronan binding;
CC -!- TISSUE SPECIFICITY: Isoform 10 (epithelial isoform) is expressed
CC by cells of epithelium and highly expressed by carcinomas.
CC Expression is repressed in neuroblastoma cells.
CC -!- DOMAIN: The lectin-like LINK domain is responsible for hyaluronan
CC binding (By similarity).
CC -!- PTM: Proteolytically cleaved in the extracellular matrix by
CC specific proteinases (possibly MMPs) in several cell lines and
CC tumors.
CC -!- PTM: N- and O-glycosylated. O-glycosylation contains more-or-less-
CC sulfated chondroitin sulfate glycans, whose number may affect the
CC accessibility of specific proteinases to their cleavage site(s).
CC It is uncertain if O-glycosylation occurs on Thr-637 or Thr-638.
CC -!- PTM: Phosphorylated; activation of PKC results in the
CC dephosphorylation of Ser-706 (constitutive phosphorylation site),
CC and the phosphorylation of Ser-672.
CC -!- POLYMORPHISM: CD44 is responsible for the Indian blood group
CC system. The molecular basis of the In(A)=In1/In(B)=In2 blood group
CC antigens is a single variation in position 46; In(B), the most
CC frequent allele, has Arg-46.
CC -!- SIMILARITY: Contains 1 Link domain.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=indian";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CD44 entry;
CC URL="http://en.wikipedia.org/wiki/CD44";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CD44ID980CH11p13.html";
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; M24915; AAA35674.1; -; mRNA.
DR EMBL; M59040; AAA51950.1; -; mRNA.
DR EMBL; X55150; CAA38951.1; -; mRNA.
DR EMBL; X56794; CAA40133.1; -; mRNA.
DR EMBL; X66733; CAA47271.1; -; mRNA.
DR EMBL; L05423; AAB13622.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05409; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13622.1; JOINED; Genomic_DNA.
DR EMBL; L05423; AAB13623.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05411; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05412; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05414; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05415; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05416; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05417; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05418; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05419; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13623.1; JOINED; Genomic_DNA.
DR EMBL; L05424; AAB13624.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13624.1; JOINED; Genomic_DNA.
DR EMBL; L05424; AAB13625.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05411; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05412; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05414; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05416; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05417; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05418; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05419; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13625.1; JOINED; Genomic_DNA.
DR EMBL; L05424; AAB13626.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05411; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05412; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05414; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05416; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05417; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05418; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05419; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13626.1; JOINED; Genomic_DNA.
DR EMBL; L05424; AAB13627.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05417; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05418; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13627.1; JOINED; Genomic_DNA.
DR EMBL; L05424; AAB13628.1; -; Genomic_DNA.
DR EMBL; L05407; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05408; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05410; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05411; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05412; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05414; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05415; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05416; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05417; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05418; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05419; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05420; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05421; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; L05422; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; M69215; AAB13628.1; JOINED; Genomic_DNA.
DR EMBL; AJ251595; CAB61878.1; -; mRNA.
DR EMBL; S66400; AAB27917.1; -; mRNA.
DR EMBL; S66400; AAB27918.2; -; mRNA.
DR EMBL; S66400; AAB27919.1; -; mRNA.
DR EMBL; AF098641; AAC70782.1; -; mRNA.
DR EMBL; U40373; AAA82949.1; -; mRNA.
DR EMBL; AY101192; AAM50040.1; -; mRNA.
DR EMBL; AY101193; AAM50041.1; -; mRNA.
DR EMBL; EF581837; ABQ59315.1; -; mRNA.
DR EMBL; FJ216964; ACI46596.1; -; mRNA.
DR EMBL; AL832642; CAD89965.1; -; mRNA.
DR EMBL; AL133330; CAC10347.1; -; Genomic_DNA.
DR EMBL; AL136989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68147.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68148.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68149.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68151.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68152.1; -; Genomic_DNA.
DR EMBL; BC004372; AAH04372.1; -; mRNA.
DR EMBL; BC067348; AAH67348.1; -; mRNA.
DR EMBL; M25078; AAA36138.1; -; mRNA.
DR EMBL; X55938; CAA39404.1; -; mRNA.
DR EMBL; S72928; AAB30429.1; -; Genomic_DNA.
DR EMBL; X62739; CAA44602.1; -; mRNA.
DR PIR; A47195; A47195.
DR PIR; I37369; I37369.
DR PIR; I77371; I77371.
DR PIR; I77372; I77372.
DR PIR; JH0417; JH0417.
DR PIR; JH0518; JH0518.
DR PIR; S13530; S13530.
DR PIR; S24222; S24222.
DR RefSeq; NP_000601.3; NM_000610.3.
DR RefSeq; NP_001001389.1; NM_001001389.1.
DR RefSeq; NP_001001390.1; NM_001001390.1.
DR RefSeq; NP_001001391.1; NM_001001391.1.
DR RefSeq; NP_001001392.1; NM_001001392.1.
DR RefSeq; NP_001189484.1; NM_001202555.1.
DR RefSeq; NP_001189485.1; NM_001202556.1.
DR RefSeq; NP_001189486.1; NM_001202557.1.
DR RefSeq; XP_005253298.1; XM_005253241.1.
DR UniGene; Hs.502328; -.
DR PDB; 1POZ; NMR; -; A=20-178.
DR PDB; 1UUH; X-ray; 2.20 A; A/B=20-178.
DR PDB; 2I83; NMR; -; A=20-178.
DR PDBsum; 1POZ; -.
DR PDBsum; 1UUH; -.
DR PDBsum; 2I83; -.
DR ProteinModelPortal; P16070; -.
DR SMR; P16070; 20-178.
DR DIP; DIP-1121N; -.
DR IntAct; P16070; 14.
DR MINT; MINT-5000740; -.
DR DrugBank; DB00070; Hyaluronidase.
DR PhosphoSite; P16070; -.
DR DMDM; 308153615; -.
DR SWISS-2DPAGE; P16070; -.
DR PaxDb; P16070; -.
DR PRIDE; P16070; -.
DR DNASU; 960; -.
DR Ensembl; ENST00000263398; ENSP00000263398; ENSG00000026508.
DR Ensembl; ENST00000278386; ENSP00000278386; ENSG00000026508.
DR Ensembl; ENST00000352818; ENSP00000309732; ENSG00000026508.
DR Ensembl; ENST00000360158; ENSP00000353280; ENSG00000026508.
DR Ensembl; ENST00000415148; ENSP00000389830; ENSG00000026508.
DR Ensembl; ENST00000428726; ENSP00000398632; ENSG00000026508.
DR Ensembl; ENST00000433892; ENSP00000392331; ENSG00000026508.
DR Ensembl; ENST00000434472; ENSP00000404447; ENSG00000026508.
DR Ensembl; ENST00000437706; ENSP00000403990; ENSG00000026508.
DR Ensembl; ENST00000449691; ENSP00000391008; ENSG00000026508.
DR GeneID; 960; -.
DR KEGG; hsa:960; -.
DR UCSC; uc001mvu.3; human.
DR CTD; 960; -.
DR GeneCards; GC11P035116; -.
DR HGNC; HGNC:1681; CD44.
DR HPA; CAB000112; -.
DR HPA; CAB000316; -.
DR HPA; HPA005785; -.
DR MIM; 107269; gene.
DR MIM; 172290; gene.
DR MIM; 609027; phenotype.
DR neXtProt; NX_P16070; -.
DR PharmGKB; PA26221; -.
DR eggNOG; NOG41023; -.
DR HOVERGEN; HBG003850; -.
DR InParanoid; P16070; -.
DR KO; K06256; -.
DR OMA; SHPMGRG; -.
DR OrthoDB; EOG77HDFT; -.
DR PhylomeDB; P16070; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; CD44; human.
DR EvolutionaryTrace; P16070; -.
DR GeneWiki; CD44; -.
DR GenomeRNAi; 960; -.
DR NextBio; 4000; -.
DR PRO; PR:P16070; -.
DR ArrayExpress; P16070; -.
DR Bgee; P16070; -.
DR Genevestigator; P16070; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
DR GO; GO:0005518; F:collagen binding; NAS:UniProtKB.
DR GO; GO:0005540; F:hyaluronic acid binding; IDA:UniProtKB.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; IDA:UniProtKB.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
DR GO; GO:0051216; P:cartilage development; IEP:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; NAS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0070487; P:monocyte aggregation; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; IMP:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0002246; P:wound healing involved in inflammatory response; IEA:Ensembl.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR016186; C-type_lectin-like.
DR InterPro; IPR016187; C-type_lectin_fold.
DR InterPro; IPR001231; CD44_antigen.
DR InterPro; IPR000538; Link.
DR Pfam; PF00193; Xlink; 1.
DR PRINTS; PR00658; CD44.
DR PRINTS; PR01265; LINKMODULE.
DR SMART; SM00445; LINK; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS01241; LINK_1; 1.
DR PROSITE; PS50963; LINK_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood group antigen;
KW Cell adhesion; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW Phosphoprotein; Polymorphism; Proteoglycan;
KW Pyrrolidone carboxylic acid; Receptor; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 20 By similarity.
FT CHAIN 21 742 CD44 antigen.
FT /FTId=PRO_0000026687.
FT TOPO_DOM 21 649 Extracellular (Potential).
FT TRANSMEM 650 670 Helical; (Potential).
FT TOPO_DOM 671 742 Cytoplasmic (Potential).
FT DOMAIN 32 120 Link.
FT REGION 224 649 Stem.
FT COMPBIAS 150 158 Arg/Lys-rich (basic).
FT BINDING 41 41 Hyaluronan (By similarity).
FT BINDING 78 78 Hyaluronan (By similarity).
FT BINDING 79 79 Hyaluronan (By similarity).
FT BINDING 105 105 Hyaluronan (By similarity).
FT MOD_RES 21 21 Pyrrolidone carboxylic acid (Probable).
FT MOD_RES 672 672 Phosphoserine; by PKC.
FT MOD_RES 686 686 Phosphoserine.
FT MOD_RES 697 697 Phosphoserine (By similarity).
FT MOD_RES 706 706 Phosphoserine.
FT CARBOHYD 25 25 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 57 57 N-linked (GlcNAc...).
FT CARBOHYD 100 100 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 110 110 N-linked (GlcNAc...).
FT CARBOHYD 120 120 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 350 350 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 548 548 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 599 599 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 636 636 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 637 637 O-linked (GalNAc...); or Thr-638.
FT CARBOHYD 638 638 O-linked (GalNAc...); or Thr-637.
FT DISULFID 28 129 By similarity.
FT DISULFID 53 118 By similarity.
FT DISULFID 77 97 By similarity.
FT VAR_SEQ 23 29 DLNITCR -> GVGRRKS (in isoform 2).
FT /FTId=VSP_005303.
FT VAR_SEQ 30 742 Missing (in isoform 2).
FT /FTId=VSP_005304.
FT VAR_SEQ 78 139 RYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYC
FT FNASAPPEEDCTSVTDLPNAF -> SLHCSQQSKKVWAEEK
FT ASDQQWQWSCGGQKAKWTQRRGQQVSGNGAFGEQGVVRNSR
FT PVYDS (in isoform 19).
FT /FTId=VSP_043870.
FT VAR_SEQ 140 742 Missing (in isoform 19).
FT /FTId=VSP_043871.
FT VAR_SEQ 192 192 G -> A (in isoform 3 and isoform 16).
FT /FTId=VSP_005305.
FT VAR_SEQ 193 223 Missing (in isoform 3 and isoform 16).
FT /FTId=VSP_005306.
FT VAR_SEQ 223 535 Missing (in isoform 11).
FT /FTId=VSP_022797.
FT VAR_SEQ 223 223 T -> N (in isoform 10, isoform 13 and
FT isoform 14).
FT /FTId=VSP_005309.
FT VAR_SEQ 223 223 T -> R (in isoform 12, isoform 15 and
FT isoform 18).
FT /FTId=VSP_005311.
FT VAR_SEQ 223 223 T -> S (in isoform 4).
FT /FTId=VSP_005307.
FT VAR_SEQ 224 604 Missing (in isoform 12, isoform 15 and
FT isoform 18).
FT /FTId=VSP_005312.
FT VAR_SEQ 224 472 Missing (in isoform 10, isoform 13 and
FT isoform 14).
FT /FTId=VSP_005310.
FT VAR_SEQ 224 266 Missing (in isoform 4).
FT /FTId=VSP_005308.
FT VAR_SEQ 266 273 Missing (in isoform 5 and isoform 17).
FT /FTId=VSP_005313.
FT VAR_SEQ 385 385 I -> T (in isoform 6, isoform 16 and
FT isoform 17).
FT /FTId=VSP_005314.
FT VAR_SEQ 386 428 Missing (in isoform 6, isoform 16 and
FT isoform 17).
FT /FTId=VSP_005315.
FT VAR_SEQ 506 506 Q -> R (in isoform 7 and isoform 14).
FT /FTId=VSP_005316.
FT VAR_SEQ 507 535 Missing (in isoform 7 and isoform 14).
FT /FTId=VSP_005317.
FT VAR_SEQ 536 536 N -> R (in isoform 8, isoform 13 and
FT isoform 14).
FT /FTId=VSP_005318.
FT VAR_SEQ 537 604 Missing (in isoform 8, isoform 13 and
FT isoform 14).
FT /FTId=VSP_005319.
FT VAR_SEQ 605 625 Missing (in isoform 18).
FT /FTId=VSP_043575.
FT VAR_SEQ 675 675 R -> S (in isoform 9 and isoform 15).
FT /FTId=VSP_005320.
FT VAR_SEQ 676 742 Missing (in isoform 9 and isoform 15).
FT /FTId=VSP_005321.
FT VARIANT 46 46 R -> P (in In(A) antigen).
FT /FTId=VAR_006490.
FT VARIANT 393 393 T -> M (in dbSNP:rs11607491).
FT /FTId=VAR_030325.
FT VARIANT 417 417 K -> R (in dbSNP:rs9666607).
FT /FTId=VAR_021147.
FT VARIANT 479 479 I -> T (in dbSNP:rs1467558).
FT /FTId=VAR_030326.
FT VARIANT 494 494 D -> H (in dbSNP:rs12273397).
FT /FTId=VAR_030327.
FT CONFLICT 26 26 I -> M (in Ref. 10; AAA82949).
FT CONFLICT 109 109 S -> Y (in Ref. 1; AAA35674, 2; AAA51950,
FT 3; CAA38951 and 7; CAB61878).
FT CONFLICT 221 221 A -> R (in Ref. 3; CAA38951).
FT CONFLICT 241 241 T -> A (in Ref. 7; CAB61878).
FT CONFLICT 410 410 E -> V (in Ref. 5; CAA47271).
FT CONFLICT 494 494 D -> N (in Ref. 7; CAB61878).
FT CONFLICT 555 555 T -> H (in Ref. 3; CAA38951).
FT CONFLICT 620 620 G -> E (in Ref. 1; AAA35674).
FT CONFLICT 697 697 S -> I (in Ref. 11; AAM50041 and 16;
FT AAH67348).
FT STRAND 21 26
FT STRAND 33 38
FT HELIX 46 55
FT STRAND 57 59
FT HELIX 63 70
FT TURN 71 73
FT STRAND 80 82
FT STRAND 85 92
FT HELIX 98 100
FT STRAND 103 106
FT STRAND 109 111
FT STRAND 114 119
FT STRAND 121 123
FT STRAND 125 128
FT STRAND 130 132
FT STRAND 139 148
FT TURN 150 152
FT STRAND 154 160
FT HELIX 165 168
SQ SEQUENCE 742 AA; 81538 MW; BB9B66B19B970349 CRC64;
MDKFWWHAAW GLCLVPLSLA QIDLNITCRF AGVFHVEKNG RYSISRTEAA DLCKAFNSTL
PTMAQMEKAL SIGFETCRYG FIEGHVVIPR IHPNSICAAN NTGVYILTSN TSQYDTYCFN
ASAPPEEDCT SVTDLPNAFD GPITITIVNR DGTRYVQKGE YRTNPEDIYP SNPTDDDVSS
GSSSERSSTS GGYIFYTFST VHPIPDEDSP WITDSTDRIP ATTLMSTSAT ATETATKRQE
TWDWFSWLFL PSESKNHLHT TTQMAGTSSN TISAGWEPNE ENEDERDRHL SFSGSGIDDD
EDFISSTIST TPRAFDHTKQ NQDWTQWNPS HSNPEVLLQT TTRMTDVDRN GTTAYEGNWN
PEAHPPLIHH EHHEEEETPH STSTIQATPS STTEETATQK EQWFGNRWHE GYRQTPKEDS
HSTTGTAAAS AHTSHPMQGR TTPSPEDSSW TDFFNPISHP MGRGHQAGRR MDMDSSHSIT
LQPTANPNTG LVEDLDRTGP LSMTTQQSNS QSFSTSHEGL EEDKDHPTTS TLTSSNRNDV
TGGRRDPNHS EGSTTLLEGY TSHYPHTKES RTFIPVTSAK TGSFGVTAVT VGDSNSNVNR
SLSGDQDTFH PSGGSHTTHG SESDGHSHGS QEGGANTTSG PIRTPQIPEW LIILASLLAL
ALILAVCIAV NSRRRCGQKK KLVINSGNGA VEDRKPSGLN GEASKSQEMV HLVNKESSET
PDQFMTADET RNLQNVDMKI GV
//

MIM 107269
*RECORD*
*FIELD* NO
107269
*FIELD* TI
*107269 CD44 ANTIGEN; CD44
;;HERMES ANTIGEN;;
Pgp1;;
MDU3;;
INLU-RELATED p80 GLYCOPROTEIN
read more*FIELD* TX

DESCRIPTION

CD44 is an integral cell membrane glycoprotein with a postulated role in
matrix adhesion lymphocyte activation and lymph node homing (Aruffo et
al., 1990).

CLONING

Telen et al. (1983) used a murine monoclonal antibody (A3D8) to identify
an erythrocyte antigen inhibited by the In(Lu) gene. Telen et al. (1984)
showed that the A3D8 antigenic property resides on an 80-kD red cell
membrane protein which is present in only trace amounts in In(Lu)
Lu(a-b-) red cells (INLU; 111150). Haynes (1986) had evidence that the
A1G3 and A3D8 monoclonal antibodies bind to different epitopes on the
same 80-kD molecule. The monoclonal antibody A3D8 recognized an antigen
officially called MDU3, for 'monoclonal Duke University, 3,' or CD44.
Telen (1992) knew of no evidence that the INLU and CD44 (MDU3) genes are
the same.

By screening cDNA libraries prepared from hemopoietic cell lines,
Stamenkovic et al. (1989) isolated CD44 clones. Immunoprecipitation of
CD44 from transfected COS cells and cultured cell lines detected
cell-specific expression of an 80- to 90-kD protein and a 160-kD
protein. Several minor forms of 52 to 200 kD were variably present in
different cell types. RNA blot analysis revealed transcripts of 1.6,
2.2, and 5.0 kb in hemopoietic cell lines. RNA blot analysis of
carcinoma cell lines revealed 3 patterns of expression: the first,
exemplified by melanoma cell lines, was identical to the hemopoietic
cell pattern associated with the 80- to 90-kD isoform; the second,
exemplified by a colon carcinoma cell line, showed transcripts of 2.0,
2.6, and 5.6 kb associated with the 160-kD isoform; and the third,
exemplified by another colon carcinoma cell line, was a composite of the
first 2 patterns. All primary carcinoma specimens examined showed
prevalent CD44 transcripts of either hemopoietic or composite type. The
CD44 cDNA encodes a 361-amino acid protein with a 20-residue secretory
signal peptide, a 248-residue extracellular N-terminal domain with
multiple N- and O-linked glycosylation sites, a 21-amino acid
transmembrane domain, and a 72-residue hydrophilic cytoplasmic domain.
The mature protein has a calculated molecular mass of 37 kD. Sequence
analysis suggested homology with chicken and rat cartilage link proteins
(HAPLN1; 115435).

Stefanova et al. (1989) demonstrated that the lymphocyte homing receptor
is identical to the human leukocyte surface glycoprotein called CDw44,
on the basis of studies at the Third International Workshop on Human
Leukocyte Differentiation Antigens. It also appears to be identical to
the Pgp-1 glycoprotein of Omary et al. (1988).

GENE FAMILY

A table of all the CD antigens was provided by Schlossman et al. (1994)
with a list of the common names, the size in kilodaltons, and the nature
of the protein (adhesion, myeloid, platelet, and B cell, T cell, etc.).

GENE STRUCTURE

Screaton et al. (1992) found that the CD44 gene contains 19 exons
spanning 50 kb of genomic DNA. They identified 10 alternatively spliced
exons within the extracellular domain, including 1 exon that had not
previously been reported. In addition to the inclusion or exclusion of
whole exons, additional diversity was 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. Thus the genomic structure of CD44 is
remarkably complex, and alternative splicing is the basis of its
structural and functional diversity.

Nedvetzki et al. (2003) noted that human CD44 isoforms are generated
from 9 variant exons (v2 to v10) inserted in different combinations
between 2 constant regions consisting of 5 exons at the N terminus and 4
exons at the C terminus (constant exon 19 is noncoding). Direct splicing
of constant exon 5 to constant exon 16, thereby skipping the variant
exons, generates the standard CD44 isoform.

GENE FUNCTION

Aruffo et al. (1990) demonstrated that CD44 is the main cell surface
receptor for hyaluronate. Mature lymphocytes in the circulation migrate
selectively from the bloodstream to different lymphatic tissues through
specialized high endothelial venules (HEV). Molecules on the surface of
lymphocytes called homing receptors interact specifically with HEV and
play a central role in the migration.

Splice variants of the glycoprotein CD44 may be associated with
metastases and therefore may be useful in the early detection of
metastatic potential in surgical biopsy specimens, as well as in the
early diagnosis of cancer in screening programs, assessment of remaining
disease, and early detection of recurrence (Matsumura and Tarin, 1992).
Mayer et al. (1993) found that expression of CD44, which is not found in
normal gastric mucosa and is found in only 49% of primary tumors, was
associated with distant metastases at time of diagnosis and with tumor
recurrence and increased mortality from gastric cancer.

Weber et al. (1996) noted that the CD44 gene encodes a transmembrane
protein that is expressed as a family of molecular isoforms generated
from alternative RNA splicing and posttranslational modifications.
Certain CD44 isoforms that regulate activation and migration of
lymphocytes and macrophages may also enhance local growth and metastatic
spread of tumor cells. One ligand of CD44 is hyaluronic acid, binding of
which to the NH2-terminal domain of CD44 enhances cellular aggregation
and tumor cell growth. (Krainer et al. (1991) referred to CD44 as a
'hyaladherin' -- see 601269.) Weber et al. (1996) demonstrated that
another ligand is osteopontin (166490). Osteopontin induces cellular
chemotaxis but not homotypic aggregation of cells, whereas the inverse
is true for the interaction between CD44 and hyaluronate. The
alternative responses to CD44 ligation may be exploited by tumor cells
to allow OPN-mediated metastatic spread and hyaluronate-dependent growth
in newly colonized tissues in the process of tumor metastasis.

Sherman et al. (1998) investigated the role of CD44 proteins in early
limb development. Members of this family of transmembrane glycoproteins
are expressed by cells of the limb bud, including those of the apical
ectodermal ridge (AER). Distinct CD44 variants are generated from a
single gene by alternative RNA splicing of up to 10 variant exons and by
extensive posttranslational modifications. The amino acid sequences
encoded by these variant exons are located in the extracellular portion
of the protein near the transmembrane domain. A standard form of CD44
lacking these variant sequences is expressed by numerous cell types and
is the smallest CD44 protein. It carries no variant exon sequences.
Splice variants are expressed in only a limited number of tissues and in
certain tumors. Signals from the AER of the developing vertebrate limb,
including fibroblast growth factor-8 (600483), can maintain limb
mesenchymal cells in proliferative state. Sherman et al. (1998) reported
that a specific CD44 splice variant is crucial for the proliferation of
these mesenchymal cells. Epitopes carried by this variant colocalize
temporally and spatially with FGF8 in the AER throughout early limb
development. A splice variant containing the same sequence expressed on
model cells binds both FGF4 (164980) and FGF8 and stimulates mesenchymal
cells in vitro. Sherman et al. (1998) found that when applied to the
AER, an antibody against a specific CD44 epitope blocked FGF
presentation and inhibited limb outgrowth. Therefore, CD44 is necessary
for limb development and functions in a novel growth factor presentation
mechanism likely relevant to other physiologic and pathologic situations
in which a cell surface protein presents a signaling molecule to a
neighboring cell.

Cywes and Wessels (2001) demonstrated that CD44-dependent group A
Streptococcus binding to polarized monolayers of human keratinocytes
induced marked cytoskeletal rearrangements manifested by membrane
ruffling and disruption of intercellular junctions. Transduction of the
signal induced by group A Streptococcus binding to CD44 on the
keratinocyte surface involved Rac1 (602048) and the cytoskeleton linker
protein ezrin (123900), as well as tyrosine phosphorylation of cellular
proteins. Studies of bacterial translocation in 2 models of human skin
indicated that cell signaling triggered by interaction of the group A
Streptococcus capsule with CD44 opened intercellular junctions and
promoted tissue penetration by group A Streptococcus through a
paracellular route. Cywes and Wessels (2001) concluded that their
results support a model of host cytoskeleton manipulation and tissue
invasion by an extracellular bacterial pathogen.

Nedvetzki et al. (2003) identified a CD44 variant, designated CD44vRA,
in synovial fluid aspirated from 23 of 30 patients with rheumatoid
arthritis (RA; 180300). Sequence analysis showed that the CD44vRA
isoform contains an intron-derived CAG trinucleotide inclusion 5-prime
to constant exon 5 within the CD44v3-v10 isoform. Functional expression
studies in human cells showed that the CD44vRA variant interacted with
FGF2 (134920) via the heparan sulfate on exon v3 in a way that enhanced
binding and activation of soluble FGFR1 (136350) to a greater extent
than CD44v3-v10. Synovial fluid cells from RA patients bound soluble
FGFR1 more intensively than control cells. Nedvetzki et al. (2003)
postulated that activation of FGFR1 may play a role in the RA
inflammatory process.

In a mouse hindlimb model of arteriogenesis, van Royen et al. (2004)
found that Cd44 expression increased strongly during collateral vessel
growth in wildtype mice and that arteriogenesis was severely impaired in
Cd44 -/- mice. The defective arteriogenesis was accompanied by reduced
leukocyte trafficking to sites of collateral artery growth and reduced
expression of FGF2 and platelet-derived growth factor-B protein (PDGFB;
190040). In 14 consecutive patients with single-vessel coronary artery
disease, van Royen et al. (2004) found that the maximal expression of
CD44 on activated monocytes was reduced in patients with poor
collateralization compared to patients with good collateralization. Van
Royen et al. (2004) concluded that CD44 plays a pivotal role in
arteriogenesis.

By analyzing a human breast cancer cell line transduced with a micro RNA
(miRNA) expression library, Huang et al. (2008) found that human miR373
(611954) and miR520C stimulated cell migration and invasion in vitro and
in vivo. Using expression array analysis, they found that the migration
phenotype of miR373- and miR520C-expressing cells depended on
suppression of CD44. Upregulation of miR373 correlated inversely with
CD44 expression in breast cancer metastasis samples. The authors noted
that increased expression of the most common CD44 isoform correlates
with overall survival of breast cancer patients.

Godar et al. (2008) found that p53 (TP53; 191170) negatively regulated
CD44 expression in normal human mammary epithelial cells by binding to a
noncanonical p53-binding sequence in the CD44 promoter. Inhibition of
CD44 enabled the cells to respond to stress-induced, p53-dependent
cytostatic and apoptotic signals that would have otherwise been blocked
by CD44. In the absence of p53, CD44 promoted growth in a highly
tumorigenic mammary epithelial cell line. In both normal and tumorigenic
cell lines, p63 (TP63; 603273) positively regulated CD44 expression.

MAPPING

Francke et al. (1983) showed that the antigens defined by monoclonal
antibodies A3D8 and A1G3 are determined by genes on 11p.

The mouse monoclonal antibody Hermes-3 recognizes the 85- to 95-kD human
lymphocyte homing receptor. Using mouse-human T-lymphocyte hybrids and
hybrids of Chinese hamster ovary cells with human amniotic fibroblasts,
Ala-Kapee et al. (1989) found that Hermes-3 expression, as demonstrated
by indirect immunofluorescence and immunoprecipitation, was determined
by 11pter-p13. Forsberg et al. (1989) refined the assignment of the
lymphocyte homing receptor gene to 11pter-p13 by study of Chinese
hamster-human cell hybrids in which the human parent cells had various
deletions of human chromosome 11. Although CD44 may have function as a
lymphocyte homing receptor, the gene that maps to chromosome 11 is
distinct from the lymph node homing receptor located on chromosome 1
(153240) (Seldin, 1990). In the mouse, the corresponding gene has been
referred to as Ly-24.

Cianfriglia et al. (1992) mapped a drug-sensitivity marker, MC56, to
11pter-p13. Identity of the protein to the CD44 antigen, suggested on
other grounds, was supported by the map location.

MOLECULAR GENETICS

The Indian blood group (609027) comprises 2 antigens, In(a) and In(b),
which reside on CD44. By RT-PCR analysis of cDNA extracted from
In(a+b-)-transformed B lymphocytes, Telen et al. (1996) identified the
CD44 polymorphism that causes the In(b-) phenotype. The polymorphism
results in an arg46-to-pro change (R46P; 107269.0001), removing the
basically charged amino acid at the C terminus of the hyaluronan
(HA)-binding motif of CD44. In previous studies using chimeric proteins,
arg46 was shown to be crucial for HA binding by CD44 (Yang et al.,
1994). However, Telen et al. (1996) demonstrated that the R46P change
does not reduce HA binding to CD44.

ANIMAL MODEL

Schmits et al. (1997) generated mice deficient in all known isoforms of
Cd44 by targeting exons encoding the invariant N-terminal region of the
molecule. Mice were born in mendelian ratio without any obvious
developmental or neurologic deficits. Hematologic impairment was
evidenced by altered tissue distribution of myeloid progenitors with
increased levels of colony-forming unit-granulocyte-macrophage in bone
marrow and reduced numbers in spleen. Fetal liver colony-forming
unit-spleen and granulocyte colony-stimulating factor mobilization
assays, together with reduced colony-forming unit-granulocyte-macrophage
in peripheral blood, suggested that progenitor egress from the bone
marrow was defective. Mice also developed exaggerated granuloma
responses to Cryotosporidium parvum infection. Tumor studies showed that
SV40-transformed Cd44-deficient fibroblasts were highly tumorigenic in
nude mice, whereas reintroduction of Cd44 expression into these
fibroblasts resulted in a dramatic inhibition of tumor growth.

Teder et al. (2002) studied the role of Cd44 in lung inflammation by
using the Cd44-deficient mice generated by Schmits et al. (1997). After
intratracheal administration of bleomycin, 75% of Cd44-deficient mice
died by day 14. They developed unremitting inflammation, characterized
by impaired clearance of apoptotic neutrophils, persistent accumulation
of hyaluronan fragments at the site of the tissue injury, and impaired
activation of transforming growth factor beta-1 (190180). This phenotype
was partially reversed by reconstitution with Cd44+ cells, thus
demonstrating a critical role for this receptor in resolving lung
inflammation.

Using immunohistochemistry, Leemans et al. (2003) confirmed that
Cd44-high cells accumulated in mouse lungs following intranasal
infection with Mycobacterium tuberculosis. Cd44 -/- mice, however, had a
50% reduction in pulmonary macrophages 2 weeks after infection, although
the absolute numbers of leukocytes were unchanged. By 5 weeks after
infection, a significant reduction in Cd4 (186940)-positive lymphocyte
numbers was observed in mutant mice. At both time points, the
Cd44-deficient mice displayed disorganized granulomas containing
predominantly polymorphonuclear neutrophils rather than well-demarcated
granulomas consisting of lymphocytes and macrophages. Splenocytes were
more numerous in mice lacking Cd44, and they secreted significantly more
Ifng (147570) in response to antigen-specific stimulation than
splenocytes of wildtype mice. Flow cytometric analysis showed that human
CD44 bound to M. tuberculosis, and Cd44 -/- mouse macrophages contained
fewer bacteria than wildtype macrophages. The mutant mice allowed
greater replication of M. tuberculosis in lung and liver and had reduced
survival compared with wildtype mice. Leemans et al. (2003) proposed
that CD44 mediates resistance to mycobacterial infection by promoting
binding and phagocytosis by macrophages and by recruiting these cells to
the site of infection.

TNF (191160) is a major inducer of chronic inflammation, and its
overexpression leads to chronic inflammatory arthritis. Hayer et al.
(2005) crossed Cd44 -/- mice with mice transgenic for human TNF and
found that destruction of joints and progressive crippling was far more
severe in Cd44 -/- transgenic mice than in transgenic mice expressing
Cd44. Cd44 -/- transgenic mice exhibited increased systemic bone
resorption due to an increase in the number, size, and activity of
osteoclasts. Bone formation and osteoblast differentiation were not
affected. Cd44 -/- osteoclasts had an enhanced response to TNF that was
associated with increased activation of p38 (MAPK14; 600289). Hayer et
al. (2005) concluded that CD44 is a critical inhibitor of TNF-induced
joint destruction and inflammatory bone loss.

Krause et al. (2006) found that mice lacking Cd44 were as susceptible as
wildtype mice to murine chronic myeloid leukemia (CML; 608232) after
challenge with BCR-ABL virus. However, bone marrow cells from Cd44 -/-
mice transduced with the virus showed defective homing to recipient bone
marrow, resulting in decreased engraftment and reduced CML-like disease.
In contrast, Cd44 was dispensable for induction of B-lymphoblastic
leukemia-like disease. Krause et al. (2006) concluded that CD44 is
required for leukemic stem cells that initiate CML.

Jin et al. (2006) found that treatment with activating monoclonal
antibodies to CD44 markedly reduced leukemic repopulation in nonobese
diabetic (NOD)/severe combined immunodeficiency (SCID) mice challenged
with human acute myeloid leukemia (AML; 601626) cells. Absence of
leukemia following serial tumor transplantation experiments in mice
demonstrated direct targeting of AML leukemic stem cells (LSCs).
Treatment of engrafted mice with anti-CD44 reduced the number of Cd34
(142230)-positive/Cd38 (107270)-negative primitive stem cells and
increased the number of Cd14 (158120)-positive monocytic cells.
Anti-CD44 treatment also diminished the homing capacity of SCID
leukemia-initiating cells to bone marrow and spleen. Jin et al. (2006)
concluded that CD44 is a key regulator of AML LSCs, which require a
niche to maintain their stem cell properties. They suggested that CD44
targeting may help eliminate quiescent AML LSCs.

*FIELD* AV
.0001
INDIAN BLOOD GROUP SYSTEM POLYMORPHISM
CD44, ARG46PRO

The Indian blood group (609027) comprises 2 antigens, In(a) and In(b),
which reside on CD44. By RT-PCR analysis of cDNA extracted from
In(a+b-)-transformed B lymphocytes, Telen et al. (1996) identified the
CD44 polymorphism that causes the In(b-) phenotype. The G-to-C change at
nucleotide 252 results in an arg46-to-pro change (R46P), removing the
basically charged amino acid at the C terminus of the hyaluronan
(HA)-binding motif of CD44. In previous studies using chimeric proteins,
arg46 was shown to be crucial for HA binding by CD44 (Yang et al.,
1994). However, Telen et al. (1996) demonstrated that the R46P change
does not reduce HA binding to CD44.

*FIELD* SA
Forsberg et al. (1989)
*FIELD* RF
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of gene for human lymphocyte homing receptor to the short arm of chromosome
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2. Aruffo, A.; Stamenkovic, I.; Melnick, M.; Underhill, C. B.; Seed,
B.: CD44 is the principal cell surface receptor for hyaluronate. Cell 61:
1303-1313, 1990.

3. Cianfriglia, M.; Viora, M.; Tombesi, M.; Merendino, N.; Esposito,
G.; Samoggia, P.; Forsberg, U. H.; Schroder, J.: The gene encoding
for MC56 determinant (drug-sensitivity marker) is located on the short
arm of human chromosome 11. Int. J. Cancer 52: 585-587, 1992.

4. Cywes, C.; Wessels, M. R.: Group A Streptococcus tissue invasion
by CD44-mediated cell signalling. Nature 414: 648-652, 2001.

5. Forsberg, U. H.; Ala-Kapee, M. M.; Jalkanen, S.; Andersson, L.
C.; Schroder, J.: The gene for human lymphocyte homing receptor is
located on chromosome 11. Europ. J. Immun. 19: 409-412, 1989.

6. Forsberg, U. H.; Jalkanen, S.; Schroder, J.: Assignment of the
human lymphocyte homing receptor gene to the short arm of chromosome
11. Immunogenetics 29: 405-407, 1989.

7. Francke, U.; Foellmer, B. E.; Haynes, B. F.: Chromosome mapping
of human cell surface molecules: monoclonal anti-human lymphocyte
antibodies 4F2, A3D8, and A1G3 define antigens controlled by different
regions of chromosome 11. Somat. Cell Genet. 9: 333-344, 1983.

8. Godar, S.; Ince, T. A.; Bell, G. W.; Feldser, D.; Donaher, J. L.;
Bergh, J.; Liu, A.; Miu, K.; Watnick, R. S.; Reinhardt, F.; McAllister,
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functions of p53 depend on its repression of CD44 expression. Cell 134:
62-73, 2008.

9. Hayer, S.; Steiner, G.; Gortz, B.; Reiter, E.; Tohidast-Akrad,
M.; Amling, M.; Hoffmann, O.; Redlich, K.; Zwerina, J.; Skriner, K.;
Hilberg, F.; Wagner, E. F.; Smolen, J. S.; Schett, G.: CD44 is a
determinant of inflammatory bone loss. J. Exp. Med. 201: 903-914,
2005.

10. Haynes, B. F.: Personal Communication. Durham, N. C. 2/28/1986.

11. Huang, Q.; Gumireddy, K.; Schrier, M.; le Sage, C.; Nagel, R.;
Nair, S.; Egan, D. A.; Li, A.; Huang, G.; Klein-Szanto, A. J.; Gimotty,
P. A.; Katsaros, D.; Coukos, G.; Zhang, L.; Pure, E.; Agami, R.:
The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nature
Cell Biol. 10: 202-210, 2008.

12. Jin, L.; Hope, K. J.; Zhai, Q.; Smadja-Joffe, F.; Dick, J. E.
: Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nature
Med. 12: 1167-1174, 2006.

13. Krainer, A. R.; Mayeda, A.; Kozak, D.; Binns, G.: Functional
expression of cloned human splicing factor SF2: homology to RNA-binding
proteins, U1 70K, and Drosophila splicing regulators. Cell 66: 383-394,
1991.

14. Krause, D. S.; Lazarides, K.; von Andrian, U. H.; Van Etten, R.
A.: Requirement for CD44 in homing and engraftment of BCR-ABL-expressing
leukemic stem cells. Nature Med. 12: 1175-1180, 2006.

15. Leemans, J. C.; Florquin, S.; Heikens, M.; Pals, S. T.; van der
Neut, R.; van der Poll, T.: CD44 is a macrophage binding site for
Mycobacterium tuberculosis that mediates macrophage recruitment and
protective immunity against tuberculosis. J. Clin. Invest. 111:
681-689, 2003.

16. Matsumura, Y.; Tarin, D.: Significance of CD44 gene products
for cancer diagnosis and disease evaluation. Lancet 340: 1053-1058,
1992.

17. Mayer, B.; Jauch, K. W.; Gunthert, U.; Figdor, C. G.; Schildberg,
F. W.; Funke, I.; Johnson, J. P.: De-novo expression of CD44 and
survival in gastric cancer. Lancet 342: 1019-1022, 1993.

18. Nedvetzki, S.; Golan, I.; Assayag, N.; Gonen, E.; Caspi, D.; Gladnikoff,
M.; Yayon, A.; Naor, D.: A mutation in a CD44 variant of inflammatory
cells enhances the mitogenic interaction of FGF with its receptor. J.
Clin. Invest. 111: 1211-1220, 2003.

19. Omary, M. B.; Trowbridge, I. S.; Letarte, M.; Kagnoff, M. F.;
Isacke, C. M.: Structural heterogeneity of human Pgp-1 and its relationship
with p85. Immunogenetics 27: 460-464, 1988.

20. Schlossman, S. F.; Boumsell, L.; Gilks, W.; Harlan, J. M.; Kishimoto,
T.; Morimoto, C.; Ritz, J.; Shaw, S.; Silverstein, R. L.; Springer,
T. A.; Tedder, T. F.; Todd, R. F.: CD antigens 1993. Immun. Today 15:
98-99, 1994.

21. Schmits, R.; Filmus, J.; Gerwin, N.; Senaldi, G.; Kiefer, F.;
Kundig, T.; Wakeham, A.; Shahinian, A.; Catzavelos, C.; Rak, J.; Furlonger,
C.; Zakarian, A.; Simard, J. J.; Ohashi, P. S.; Paige, C. J.; Gutierrez-Romas,
J. C.; Mak, T. W.: CD44 regulates hematopoietic progenitor distribution,
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22. Screaton, G. R.; Bell, M. V.; Jackson, D. G.; Cornelis, F. B.;
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homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc.
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23. Seldin, M. F.: Personal Communication. Durham, N. C. 9/19/1990.

24. Sherman, L.; Wainwright, D.; Ponta, H.; Herrlich, P.: A splice
variant of CD44 expressed in the apical ectodermal ridge presents
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25. 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.

26. Stefanova, I.; Hilgert, I.; Bazil, V.; Kristofova, H.; Horejsi,
V.: Human leucocyte surface glycoprotein CDw44 and lymphocyte homing
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27. Teder, P.; Vandivier, R. W.; Jiang, D.; Liang, J.; Cohn, L.; Pure,
E.; Henson, P. M.; Noble, P. W.: Resolution of lung inflammation
by CD44. Science 296: 155-158, 2002.

28. Telen, M. J.: Personal Communication. Durham, N. C. 12/30/1992.

29. Telen, M. J.; Eisenbarth, G. S.; Haynes, B. F.: Human erythrocyte
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30. Telen, M. J.; Palker, T. J.; Haynes, B. F.: Human erythrocyte
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1984.

31. 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.

32. van Royen, N.; Voskuil, M.; Hoefer, I.; Jost, M.; de Graaf, S.;
Hedwig, F.; Andert, J.-P.; Wormhoudt, T. A. M.; Hua, J.; Hartmann,
S.; Bode, C.; Buschmann, I.; Schaper, W.; van der Neut, R.; Piek,
J. J.; Pals, S. T.: CD44 regulates arteriogenesis in mice and is
differentially expressed in patients with poor and good collateralization. Circulation 109:
1647-1652, 2004.

33. Weber, G. F.; Ashkar, S.; Glimcher, M. J.; Cantor, H.: Receptor-ligand
interaction between CD44 and osteopontin (Eta-1). Science 271: 509-512,
1996.

34. Yang, B.; Yang, B. L.; Savani, R. C.; Turley, E. A.: Identification
of a common hyaluronan binding motif in the hyaluronan binding proteins
RHAMM, CD44 and link protein. EMBO J. 13: 286-296, 1994.

*FIELD* CN
Patricia A. Hartz - updated: 11/5/2008
Patricia A. Hartz - updated: 10/28/2008
Cassandra L. Kniffin - updated: 11/26/2007
Paul J. Converse - updated: 10/27/2006
Paul J. Converse - updated: 10/26/2006
Marla J. F. O'Neill - updated: 1/31/2006
Paul J. Converse - updated: 2/25/2005
Paul J. Converse - updated: 11/15/2004
Ada Hamosh - updated: 4/9/2002
Ada Hamosh - updated: 1/9/2002
Victor A. McKusick - updated: 4/25/1998
Alan F. Scott - updated: 5/21/1996

*FIELD* CD
Victor A. McKusick: 9/25/1990

*FIELD* ED
mgross: 10/14/2013
wwang: 8/17/2011
mgross: 11/7/2008
terry: 11/5/2008
mgross: 10/30/2008
terry: 10/28/2008
wwang: 12/28/2007
ckniffin: 11/26/2007
mgross: 1/29/2007
mgross: 11/17/2006
terry: 10/27/2006
mgross: 10/26/2006
wwang: 2/3/2006
terry: 1/31/2006
terry: 12/21/2005
mgross: 2/25/2005
mgross: 11/15/2004
joanna: 11/15/2004
cwells: 4/11/2002
cwells: 4/10/2002
terry: 4/9/2002
alopez: 1/10/2002
terry: 1/9/2002
dkim: 7/24/1998
carol: 4/25/1998
terry: 4/25/1998
mark: 5/21/1996
terry: 5/21/1996
mark: 5/20/1996
mark: 2/10/1996
terry: 2/7/1996
terry: 7/29/1994
carol: 4/11/1994
warfield: 4/7/1994
carol: 9/8/1993
carol: 1/14/1993
carol: 1/13/1993

MIM 172290
*RECORD*
*FIELD* NO
172290
*FIELD* TI
172290 PHOSPHOGLYCOPROTEIN 1; PGP1
*FIELD* TX
Pgp-1 glycoprotein, as it is termed in the mouse, was first demonstrated
read morein that species. It is a polymorphic cell-surface antigen present in
many tissues and is coded by a gene on mouse chromosome 2. Isacke et al.
(1986) identified and characterized the homologous protein in man. In
both species, it is an abundant plasma membrane component of fibroblasts
and is uniformly distributed over the cell surface. It has a large
extracellular domain. It can be metabolically labeled with (32)P
exclusively on serine residues indicating that it is a transmembrane
glycoprotein (Isacke et al., 1986). Both this glycoprotein and the Thy-1
glycoprotein (188230) are abundant on mouse thymocytes but are not
expressed on human thymocytes.

*FIELD* RF
1. Isacke, C. M.; Sauvage, C. A.; Hyman, R.; Lesley, J.; Schulte,
R.; Trowbridge, I. S.: Identification and characterization of the
human Pgp-1 glycoprotein. Immunogenetics 23: 326-332, 1986.

*FIELD* CD
Victor A. McKusick: 10/16/1986

*FIELD* ED
dkim: 07/07/1998
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
reenie: 10/16/1986

MIM 609027
*RECORD*
*FIELD* NO
609027
*FIELD* TI
#609027 BLOOD GROUP, INDIAN SYSTEM; IN
;;INDIAN BLOOD GROUP SYSTEM; IN
*FIELD* TX
A number sign (#) is used with this entry because the Indian blood group
read moreantigens result from a polymorphism in the CD44 gene (107269).

DESCRIPTION

The Indian blood group comprises 2 antigens, In(a) and In(b). Most
individuals express the In(b) antigen (Giles, 1975). The rare event of
In(a) homozygosity is associated with production of alloantibody to
In(b) after transfusion or pregnancy (Telen et al., 1996). The In(a+b-)
phenotype is most common in Middle Eastern and South Asian populations
(Badakere et al., 1974).

BIOCHEMICAL FEATURES

By immunoblot analysis, Spring et al. (1988) determined that Indian
blood group antigens reside on CD44, an 80-kD erythrocyte membrane
N-glycan-containing glycoprotein. Immunofluorescence microscopy with
either mouse monoclonal antibody or human anti-In(b) demonstrated
expression on all peripheral blood leukocytes, but not on platelets.

MOLECULAR GENETICS

By RT-PCR analysis of cDNA extracted from In(a+b-)-transformed B
lymphocytes, Telen et al. (1996) identified the CD44 polymorphism that
causes the In(b-) phenotype. The polymorphism results in an arg46-to-pro
change (R46P; 107269.0001), removing the basically charged amino acid at
the C terminus of the hyaluronan (HA)-binding motif of CD44. In previous
studies using chimeric proteins, arg46 was shown to be crucial for HA
binding by CD44 (Yang et al., 1994). However, Telen et al. (1996)
demonstrated that the R46P change does not reduce HA binding to CD44.

*FIELD* RF
1. Badakere, S. S.; Parab, B. B.; Bhatia, H. M.: Further observations
on the In(a) (Indian) antigen in Indian populations. Vox Sang. 26:
400-401, 1974.

2. Giles, C. M.: Antithetical relationship of anti-In(a) with the
Salis antibody. Vox Sang. 29: 73-76, 1975.

3. Spring, F. A.; Dalchau, R.; Daniels, G. L.; Mallinson, G.; Judson,
P. A.; Parsons, S. F.; Fabre, J. W.; Anstee, D. J.: The In(a) and
In(b) blood group antigens are located on a glycoprotein of 80,000
MW (the CDw44 glycoprotein) whose expression is influenced by the
In(Lu) gene. Immunology 64: 37-43, 1988.

4. 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.

5. Yang, B.; Yang, B. L.; Savani, R. C.; Turley, E. A.: Identification
of a common hyaluronan binding motif in the hyaluronan binding proteins
RHAMM, CD44 and link protein. EMBO J. 13: 286-296, 1994.

*FIELD* CD
Paul J. Converse: 11/15/2004

*FIELD* ED
mgross: 10/14/2013
terry: 12/21/2005
mgross: 11/15/2004