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Reviewed, UniProtKB/Swiss-Prot P16070 (CD44_HUMAN)

Last modified July 22, 2008. Version 119. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length742 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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.

Ontologies

Keywords

   Biological processCell adhesion
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
   Molecular functionBlood group antigen
Receptor
   PTMGlycoprotein
Phosphoprotein
Proteoglycan
Pyrrolidone carboxylic acid
   Technical term3D-structure

Gene Ontology (GO)

   Biological processcell-cell adhesion Ref.17

Non-traceable author statement. Source: UniProtKB

cell-matrix adhesion Ref.17

Non-traceable author statement. Source: UniProtKB

   Cellular componentcell surface

Inferred from direct assay. Source: UniProtKB

integral to plasma membrane Ref.3

Non-traceable author statement. Source: UniProtKB

   Molecular functioncollagen binding

Non-traceable author statement. Source: UniProtKB

hyaluronic acid binding Ref.3

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ipaBP180114EBI-490245,EBI-490239From a different organism.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 742722CD44 antigen

Regions

Topological domain21 – 649629Extracellular Potential
Transmembrane650 – 67021 Potential
Topological domain671 – 74272Cytoplasmic Potential
Domain32 – 12089Link
Region224 – 649426Stem
Compositional bias150 – 1589Arg/Lys-rich (basic)

Amino acid modifications

Modified residue211Pyrrolidone carboxylic acid Probable
Modified residue6721Phosphoserine; by PKC
Modified residue6861Phosphoserine
Modified residue6971Phosphoserine
Modified residue7061Phosphoserine
Modified residue7201Phosphothreonine
Glycosylation251N-linked (GlcNAc...) Potential
Glycosylation571N-linked (GlcNAc...)
Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation1101N-linked (GlcNAc...) Potential
Glycosylation1201N-linked (GlcNAc...) Potential
Glycosylation3501N-linked (GlcNAc...) Potential
Glycosylation5481N-linked (GlcNAc...) Potential
Glycosylation5991N-linked (GlcNAc...) Potential
Glycosylation6361N-linked (GlcNAc...) Potential
Disulfide bond53 ↔ 118 By similarity
Disulfide bond77 ↔ 97 By similarity

Natural variations

Alternative sequence23 – 297DLNITCR → GVGRRKS in isoform 2.
Alternative sequence30 – 742713Missing in isoform 2.
Alternative sequence1921G → A in isoform 3 and isoform 16.
Alternative sequence193 – 22331Missing in isoform 3 and isoform 16.
Alternative sequence223 – 535313Missing in isoform 11.
Alternative sequence2231T → N in isoform 10, isoform 13 and isoform 14.
Alternative sequence2231T → R in isoform 12 and isoform 15.
Alternative sequence2231T → S in isoform 4.
Alternative sequence224 – 604381Missing in isoform 12 and isoform 15.
Alternative sequence224 – 472249Missing in isoform 10, isoform 13 and isoform 14.
Alternative sequence224 – 26643Missing in isoform 4.
Alternative sequence266 – 2738Missing in isoform 5 and isoform 17.
Alternative sequence3851I → T in isoform 6, isoform 16 and isoform 17.
Alternative sequence386 – 42843Missing in isoform 6, isoform 16 and isoform 17.
Alternative sequence5061Q → R in isoform 7 and isoform 14.
Alternative sequence507 – 53529Missing in isoform 7 and isoform 14.
Alternative sequence5361N → R in isoform 8, isoform 13 and isoform 14.
Alternative sequence537 – 60468Missing in isoform 8, isoform 13 and isoform 14.
Alternative sequence6751R → S in isoform 9 and isoform 15.
Alternative sequence676 – 74267Missing in isoform 9 and isoform 15.
Natural variant461R → P in In(A) antigen.
Natural variant3931T → M: dbSNP rs11607491.
Natural variant4171R → K: dbSNP rs9666607.
Natural variant4791T → I: dbSNP rs1467558.
Natural variant4941D → H: dbSNP rs12273397.

Experimental info

Sequence conflict261I → M in AAA82949. Ref.9
Sequence conflict1091S → Y in AAA35674. Ref.1
Sequence conflict1091S → Y in AAA51950. Ref.2
Sequence conflict1091S → Y in CAA38951. Ref.3
Sequence conflict1091S → Y in CAB61878. Ref.7
Sequence conflict2211A → R in CAA38951. Ref.3
Sequence conflict2411T → A in CAB61878. Ref.7
Sequence conflict4101E → V in CAA47271. Ref.5
Sequence conflict4941D → N in CAB61878. Ref.7
Sequence conflict5551T → H in CAA38951. Ref.3
Sequence conflict6201G → E in AAA35674. Ref.1
Sequence conflict6971S → I in AAM50041. Ref.10
Sequence conflict6971S → I in AAH67348. Ref.12

Secondary structure

............................ 742
Helix Strand Turn

Details...