CD44; phagocytic glycoprotein I; PGP-1; HUTCH-I; extracellular matrix receptor-III; ECMR-III; GP90 lymphocyte homing/adhesion receptor; Hermes antigen; hyaluronate receptor; heparan sulfate proteoglycan; epican; CDw44 (LHR, MDU2, MDU3, MIC4)
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Function
- receptor for hyaluronic acid
- mediates cell-cell & cell-matrix interactions through affinity for hyaluronic acid, & possibly also through affinity for other ligands including osteopontin, collagens, & matrix metalloproteinases
- adhesion with hyaluronic acid plays a role in
- cell migration
- tumor growth & progression
- role in lymphocyte activation, recirculation & homing, & in hematopoiesis
- altered expression or dysfunction causes numerous pathogenic phenotypes
- great protein heterogeneity due to numerous alternative splicing & post-translational modifications
- interacts with hyaluronic acid, as well as other glycosaminoglycans, collagen, laminin, & fibronectin via its N-terminal segment
- interacts with ANK, the ERM proteins (VIL2, RDX & MSN), & NF2 via its C-terminal segment
- proteolytically cleaved in the extracellular matrix by specific proteinases (possibly matrix metalloproteinases) in several cell lines & tumors
- phosphorylated
- activation of PKC results in dephosphorylation of Ser-706 (constitutive phosphorylation site), & phosphorylation of Ser-672
Structure
- N-glycosylated
- O-glycosylated; contains more-or-less-sulfated chondroitin sulfate glycans, whose number may affect the accessibility of specific proteinases to their cleavage site(s)
- contains 1 link domain
Compartment
membrane
Alternative splicing
named isoforms=17
Additional isoforms seem to exist
Expression
- epithelial isoform (CD44E) is expressed by cells of epithelium & highly expressed by carcinomas
- hematopoietic isoform (CD44H) is expressed by cells of mesodermal origin
- white blood cells
- red blood cells
- stomach
- colon
- breast
- uterus
- platelets, hepatocytes, cardiac muscle, kidney, tubular epithelium, testis & normal glandular epithelium stain negatively with antibody
Pathology
- host receptor for bacterial capsule hyaluronate of group A Streptococcus[3]; bacterial attachment results in a breakdown of intercellular junctions allowing penetration of bacteria into tissue
- expressed in:
- mucosa or tumors with well developed squamous differentiation
- colorectal carcinomas ~80%
- well differentiated adenocarcinomas stain negatively with antibody
- some splice variants may be associated with metastatic disease
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
More general terms
More specific terms
References
- ↑ Webb DS et al LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science 249:1295 1990 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1697984
- ↑ Stossel TP. On the crawling of animal cells. Science. 1993 May 21;260(5111):1086-94. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8493552
- ↑ 3.0 3.1 Journal Watch 22(3):25, 2002 Cywes C & Wessels MR Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Nature 414:648, 2001 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/11740562
- ↑ <Internet> http://www.pathologyoutlines.com/cdmarkers.html 15 October 2002
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=960
- ↑ BGMUT; Note: Blood group antigen gene mutation database http://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=indian
- ↑ Wikipedia; Note: CD44 entry http://en.wikipedia.org/wiki/CD44
- ↑ UniProt http://www.uniprot.org/uniprot/P16070.html
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:960
- OMIM: https://mirror.omim.org/entry/107269
- OMIM: https://mirror.omim.org/entry/172290
- OMIM: https://mirror.omim.org/entry/609027
- UniProt: http://www.uniprot.org/uniprot/P16070.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=960