CD44 antigen precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    CD44 antigen
Alternative name(s):
    Phagocytic glycoprotein I
    PGP-1
    HUTCH-I
    Extracellular matrix receptor-III
      Short name=ECMR-III
    GP90 lymphocyte homing/adhesion receptor
    Hermes antigen
    Hyaluronate receptor
    Heparan sulfate proteoglycan
    Epican
    CDw44
    CD_antigen=CD44

Gene names

Name:	CD44
Synonyms:	LHR, MDU2, MDU3, MIC4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	742 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

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 structure	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.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	An epithelial CD44E) is expressed by cells of epithelium and highly expressed by carcinomas. An hematopoietic CD44H) is expressed by cells of mesodermal origin. Expression is repressed in neuroblastoma cells.
Post-translational modification	Proteolytically cleaved in the extracellular matrix by specific proteinases (possibly MMPs) in several cell lines and tumors. 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). 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.
Sequence similarities	Contains 1 Link domain.

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Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
Molecular function	Blood group antigen Receptor
PTM	Glycoprotein Phosphoprotein Proteoglycan Pyrrolidone carboxylic acid
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell-cell adhesion Ref.17 Non-traceable author statement. Source: UniProtKB cell-matrix adhesion Ref.17 Non-traceable author statement. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	collagen binding Non-traceable author statement. Source: UniProtKB hyaluronic acid binding Ref.3 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ipaB	P18011	4	EBI-490245,EBI-490239	From a different organism.

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Alternative products

This entry describes 17 isoforms produced by alternative splicing. [Align] [Select] Notes: 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.

Isoform CD44 (identifier: P16070-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Notes: Corresponds to the largest isoform.

Isoform 2 (identifier: P16070-2) Also known as: CD44SP; The sequence of this isoform differs from the canonical sequence as follows: 23-29: DLNITCR → GVGRRKS 30-742: Missing.

Isoform 3 (identifier: P16070-3) The sequence of this isoform differs from the canonical sequence as follows: 192-192: G → A 193-223: Missing.
Notes: Alternative splice donor/acceptor on exon 5.

Isoform 4 (identifier: P16070-4) Also known as: Epidermal; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → S 224-266: Missing.
Notes: Lacks exon 6.

Isoform 5 (identifier: P16070-5) The sequence of this isoform differs from the canonical sequence as follows: 266-273: Missing.
Notes: Alternative splice donor/acceptor on exon 7.

Isoform 6 (identifier: P16070-6) The sequence of this isoform differs from the canonical sequence as follows: 385-385: I → T 386-428: Missing.
Notes: Lacks exon 10.

Isoform 7 (identifier: P16070-7) The sequence of this isoform differs from the canonical sequence as follows: 506-506: Q → R 507-535: Missing.
Notes: Lacks exon 13.

Isoform 8 (identifier: P16070-8) The sequence of this isoform differs from the canonical sequence as follows: 536-536: N → R 537-604: Missing.
Notes: Lacks exon 14.

Isoform 9 (identifier: P16070-9) The sequence of this isoform differs from the canonical sequence as follows: 675-675: R → S 676-742: Missing.
Notes: Lacks exon 19.

Isoform 10 (identifier: P16070-10) Also known as: CD44E; CD44R1; Epithelial; Keratinocyte; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → N 224-472: Missing.
Notes: Lacks exons 6-11.

Isoform 11 (identifier: P16070-11) Also known as: CD44R2; The sequence of this isoform differs from the canonical sequence as follows: 223-535: Missing.
Notes: Lacks exons 6-13.

Isoform 12 (identifier: P16070-12) Also known as: CDw44; Reticulocyte; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → R 224-604: Missing.
Notes: Lacks exons 6-14.

Isoform 13 (identifier: P16070-13) Also known as: CD44R4; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → N 224-472: Missing. 536-536: N → R 537-604: Missing.
Notes: Lacks exons 6-11 and exon 14.

Isoform 14 (identifier: P16070-14) Also known as: CD44R5; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → N 224-472: Missing. 506-506: Q → R 507-535: Missing. 536-536: N → R 537-604: Missing.
Notes: Lacks exons 6-11, exon 13 and exon 14.

Isoform 15 (identifier: P16070-15) Also known as: Hermes; The sequence of this isoform differs from the canonical sequence as follows: 223-223: T → R 224-604: Missing. 675-675: R → S 676-742: Missing.
Notes: Lacks exons 6-14 and exon 19.

Isoform 16 (identifier: P16070-16) The sequence of this isoform differs from the canonical sequence as follows: 192-192: G → A 193-223: Missing. 385-385: I → T 386-428: Missing.
Notes: Alternative splice donor/acceptor on exon 5 and lacks exon 10.

Isoform 17 (identifier: P16070-17) The sequence of this isoform differs from the canonical sequence as follows: 266-273: Missing. 385-385: I → T 386-428: Missing.
Notes: Alternative splice donor/acceptor on exon 7 and lacks exon 10.