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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)

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 a) cell migration b) 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 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 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: a) mucosa or tumors with well developed squamous differentiation b) colorectal carcinomas ~80% - well differentiated adenocarcinomas stain negatively with antibody - some splice variants may be associated with metastatic disease

Interactions

molecular events

Specific

CD44E (epithelial form)/CD44R1 CD44H (hematopoietic form) CD44R5 CD44SP

General

adhesion receptor cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein

Properties

SIZE: entity length = 742 aa MW = 82 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-20} N-glycosylation site {N25} Link {32-120} MOTIF: cysteine residue {C53} MODIFICATION: cysteine residue {C118} N-glycosylation site {N57} cysteine residue {C77} MODIFICATION: cysteine residue {C97} cysteine residue {C97} MODIFICATION: cysteine residue {C77} N-glycosylation site {N100} N-glycosylation site {N110} cysteine residue {C118} MODIFICATION: cysteine residue {C53} N-glycosylation site {N120} lysine-rich region {150-158} MOTIF: lysine residue (SEVERAL) Stem {224-649} MOTIF: N-glycosylation site {N350} N-glycosylation site {N548} N-glycosylation site {N599} N-glycosylation site {N636} transmembrane domain {650-670} Ser phosphorylation site {S672} Ser phosphorylation site {S686} Ser phosphorylation site {S697} Ser phosphorylation site {S706} Thr phosphorylation site {T720}

Database Correlations

OMIM correlations UniProt P16070 Pfam PF00193 Entrez Gene 960 Kegg hsa:960

References

  1. Webb DS et al LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science 249:1295 1990 PMID: 1697984
  2. Stossel TP. On the crawling of animal cells. Science. 1993 May 21;260(5111):1086-94. Review. PMID: 8493552
  3. Journal Watch 22(3):25, 2002 Cywes C & Wessels MR Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Nature 414:648, 2001 PMID: 11740562
  4. http://www.pathologyoutlines.com/cdmarkers.html 15 October 2002
  5. Entrez Gene :accession 960
  6. BGMUT; Note: Blood group antigen gene mutation database http://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=indian
  7. Wikipedia; Note: CD44 entry http://en.wikipedia.org/wiki/CD44
  8. UniProt :accession P16070

Component-of

molecular complex