Description
CD44
is a ubiquitously expressed protein that is the major receptor for hyaluronan
and exerts control over cell growth and migration (1‑3). Human CD44 has a
20 amino acid (aa) signal sequence, an extracellular domain (ECD) with a
100 aa hyaluronan‑binding disulfide‑stabilized link region and a 325‑530
aa stem region, a 21 aa transmembrane domain, and a 72 aa cytoplasmic
domain. CD44 transcripts undergo complex alternative splicing, and, within the
stem, ten variably spliced exons (v1‑10 corresponding to exons 6‑15; although
human CD44 lacks v1/exon 6) produce multiple protein isoforms (1‑4). The
standard or hematopoietic form, CD44H, does not include the variable segments
(1‑4). Cancer aggressiveness and T cell activation have been correlated
with expression of specific isoforms (1, 4, 5). Human CD44v5 contains
exon 10 and is associated with tumor progression and metastasis in many types
of cancer including breast, colon, lung, renal, skin, and ovarian tumors (6, 12).
With variable N‑ and O‑glycosylation and splicing within the stalk, CD44 can
range from 80 to 200 kDa (1). Within the N‑terminal invariant portion of the
ECD (aa 21‑222), human CD44 shares 76%, 76%, 86%, 83% and 79% identity with
corresponding mouse, rat, equine, canine and bovine CD44, respectively. The
many reported functions of CD44 fall within three categories (1). First, CD44
binds hyaluronan and other ligands within the extracellular matrix and can
function as a "platform" for growth factors and metalloproteinases.
Second, CD44 can function as a co‑receptor that modifies activity of receptors
including MET and the ERBB family of tyrosine kinases. Third, the CD44
intracellular domain links the plasma membrane to the actin cytoskeleton via
the ERM proteins, ezrin, radixin and moesin. CD44 can be synthesized in a
soluble form (6) or may be cleaved at multiple sites by either membrane‑type
matrix metalloproteinases, or ADAM proteases to produce soluble ectodomains (8,
9). The cellular portion may then undergo gamma secretase‑dependent
intramembrane cleavage to form an A beta‑like transmembrane portion and a
cytoplasmic signaling portion that affects gene expression (10, 11). These
cleavage events are thought to promote metastasis by enhancing tumor cell
motility and growth (1, 8). CD44v5 plays important role in cancer
progression involving in cell migration and invasion and is considered a
functional cancer biomarker (6, 12).
Bioinformatics
| Uniprot |
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| Product By Gene ID |
960 |
| Alternate Names |
- CD44 antigen
- CD44 molecule (Indian blood group)
- CD44
- CD44R
- CDw44
- cell surface glycoprotein CD44
- chondroitin sulfate proteoglycan 8
- CSPG8
- ECMR-III
- epican
- Extracellular matrix receptor III
- GP90 lymphocyte homing/adhesion receptor
- HCAM
- HCELL
- hematopoietic cell E- and L-selectin ligand
- Heparan sulfate proteoglycan
- Hermes antigen
- homing function and Indian blood group system
- HUTCH-I
- Hyaluronate receptor
- IN
- LHR
- MC56
- MDU2
- MDU2CD44 antigen (homing function and Indian blood group system)
- MDU3
- MDU3CDW44
- MIC4
- MIC4MGC10468
- MUTCH-I
- Pgp1
- PGP-1
- PGP-I
- Phagocytic glycoprotein 1
- Phagocytic glycoprotein I
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