CD44 antigen (CD44)
The protein contains 742 amino acids for an estimated molecular weight of 81538 Da.
Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). (updated: May 8, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| In(A) antigen | |
| dbSNP:rs11607491 | |
| dbSNP:rs9666607 | |
| dbSNP:rs1467558 | |
| dbSNP:rs12273397 |
Biological Process
Blood coagulation
Branching involved in prostate gland morphogenesis
Branching involved in ureteric bud morphogenesis
Carbohydrate metabolic process
Cartilage development
Cell adhesion
Cell migration
Cell-cell adhesion
Cell-matrix adhesion
Cellular response to fibroblast growth factor stimulus
Cytokine-mediated signaling pathway
Extracellular matrix disassembly
Extracellular matrix organization
Glycosaminoglycan metabolic process
Hyaluronan catabolic process
Hyaluronan metabolic process
Inflammatory response
Interferon-gamma-mediated signaling pathway
Leukocyte migration
Monocyte aggregation
Negative regulation of apoptotic process
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of DNA damage response, signal transduction by p53 class mediator
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Neutrophil degranulation
Pathogenesis
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of gene expression
Positive regulation of heterotypic cell-cell adhesion
Positive regulation of monocyte aggregation
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of peptidyl-tyrosine phosphorylation
Regulation of lamellipodium morphogenesis
Single organismal cell-cell adhesion
Small molecule metabolic process
T cell activation
Wnt signaling pathway
Wound healing involved in inflammatory response
Wound healing, spreading of cells
Cellular Component
Apical plasma membrane
Basolateral plasma membrane
Cell projection
Cell surface
Cytoplasm
Cytosol
External side of plasma membrane
Extracellular exosome
Focal adhesion
Golgi apparatus
Integral component of plasma membrane
Lamellipodium membrane
Macrophage migration inhibitory factor receptor complex
Microvillus
Plasma membrane
Secretory granule membrane
The reference OMIM entry for this protein is 107269
Cd44 antigen; cd44
Hermes antigen
Pgp1
Mdu3
Inlu-related p80 glycoprotein
DESCRIPTION
CD44 is an integral cell membrane glycoprotein with a postulated role in matrix adhesion lymphocyte activation and lymph node homing (Aruffo et al., 1990).CLONING
Telen et al. (1983) used a murine monoclonal antibody (A3D8) to identify an erythrocyte antigen inhibited by the In(Lu) gene. Telen et al. (1984) showed that the A3D8 antigenic property resides on an 80-kD red cell membrane protein which is present in only trace amounts in In(Lu) Lu(a-b-) red cells (INLU; 111150). Haynes (1986) had evidence that the A1G3 and A3D8 monoclonal antibodies bind to different epitopes on the same 80-kD molecule. The monoclonal antibody A3D8 recognized an antigen officially called MDU3, for 'monoclonal Duke University, 3,' or CD44. Telen (1992) knew of no evidence that the INLU and CD44 (MDU3) genes are the same. By screening cDNA libraries prepared from hemopoietic cell lines, Stamenkovic et al. (1989) isolated CD44 clones. Immunoprecipitation of CD44 from transfected COS cells and cultured cell lines detected cell-specific expression of an 80- to 90-kD protein and a 160-kD protein. Several minor forms of 52 to 200 kD were variably present in different cell types. RNA blot analysis revealed transcripts of 1.6, 2.2, and 5.0 kb in hemopoietic cell lines. RNA blot analysis of carcinoma cell lines revealed 3 patterns of expression: the first, exemplified by melanoma cell lines, was identical to the hemopoietic cell pattern associated with the 80- to 90-kD isoform; the second, exemplified by a colon carcinoma cell line, showed transcripts of 2.0, 2.6, and 5.6 kb associated with the 160-kD isoform; and the third, exemplified by another colon carcinoma cell line, was a composite of the first 2 patterns. All primary carcinoma specimens examined showed prevalent CD44 transcripts of either hemopoietic or composite type. The CD44 cDNA encodes a 361-amino acid protein with a 20-residue secretory signal peptide, a 248-residue extracellular N-terminal domain with multiple N- and O-linked glycosylation sites, a 21-amino acid transmembrane domain, and a 72-residue hydrophilic cytoplasmic domain. The mature protein has a calculated molecular mass of 37 kD. Sequence analysis suggested homology with chicken and rat cartilage link proteins (HAPLN1; 115435). Stefanova et al. (1989) demonstrated that the lymphocyte homing receptor is identical to the human leukocyte surface glycoprotein called CDw44, on the basis of studies at the Third International Workshop on Human Leukocyte Differentiation Antigens. It also appears to be identical to the Pgp-1 glycoprotein of Omary et al. (1988).GENE FAMILY
A table of all the CD antigens was provided by Schlossman et al. (1994) with a list of the common names, the size in kilodaltons, and the nature of the protein (adhesion, myeloid, platelet, and B cell, T cell, etc.).GENE STRUCTURE
Screaton et al. (1992) found that the CD44 gene contains 19 exons spanning 50 kb of genomic DNA. They identified 10 alternatively spliced exons within the extracellular domain, including 1 exon that had not previously been reported. In addition to the inclusion or exclusion of whole exons, additional diversity was 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. Thus the genomic structure of CD44 is remarkably complex, and alternative splicing is t ... More on the omim web siteThe reference OMIM entry for this protein is 609027
Blood group, indian system; in
Indian blood group system; in
A number sign (#) is used with this entry because the Indian blood group antigens result from a polymorphism in the CD44 gene (107269).
DESCRIPTION
The Indian blood group comprises 2 antigens, In(a) and In(b). Most individuals express the In(b) antigen (Giles, 1975). The rare event of In(a) homozygosity is associated with production of alloantibody to In(b) after transfusion or pregnancy (Telen et al., 1996). The In(a+b-) phenotype is most common in Middle Eastern and South Asian populations (Badakere et al., 1974).BIOCHEMICAL FEATURES
By immunoblot analysis, Spring et al. (1988) determined that Indian blood group antigens reside on CD44, an 80-kD erythrocyte membrane N-glycan-containing glycoprotein. Immunofluorescence microscopy with either mouse monoclonal antibody or human anti-In(b) demonstrated expression on all peripheral blood leukocytes, but not on platelets.MOLECULAR GENETICS
By RT-PCR analysis of cDNA extracted from In(a+b-)-transformed B lymphocytes, Telen et al. (1996) identified the CD44 polymorphism that causes the In(b-) phenotype. The polymorphism results in an arg46-to-pro change (R46P; 107269.0001), removing the basically charged amino acid at the C terminus of the hyaluronan (HA)-binding motif of CD44. In previous studies using chimeric proteins, arg46 was shown to be crucial for HA binding by CD44 (Yang et al., 1994). However, Telen et al. (1996) demonstrated that the R46P change does not reduce HA binding to CD44. ... More on the omim web siteThe reference OMIM entry for this protein is 172290
Phosphoglycoprotein 1; pgp1
Pgp-1 glycoprotein, as it is termed in the mouse, was first demonstrated in that species. It is a polymorphic cell-surface antigen present in many tissues and is coded by a gene on mouse chromosome 2. Isacke et al. (1986) identified and characterized the homologous protein in man. In both species, it is an abundant plasma membrane component of fibroblasts and is uniformly distributed over the cell surface. It has a large extracellular domain. It can be metabolically labeled with (32)P exclusively on serine residues indicating that it is a transmembrane glycoprotein (Isacke et al., 1986). Both this glycoprotein and the Thy-1 glycoprotein (188230) are abundant on mouse thymocytes but are not expressed on human thymocytes. ... More on the omim web site
July 2, 2021: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 2, 2021: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 2, 2021: Protein entry updated
Automatic update: OMIM entry 107269 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 107269 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 172290 was added.
April 11, 2021: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 609027 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 107269 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 172290 was added.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 4, 2019: Protein entry updated
Automatic update: OMIM entry 609027 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 107269 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 172290 was added.
June 7, 2019: Protein entry updated
Automatic update: OMIM entry 609027 was added.
May 12, 2019: Protein entry updated
Automatic update: model status changed
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 6, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 5, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 4, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
July 2, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
May 26, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 107269 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 172290 was added.
April 27, 2018: Protein entry updated
Automatic update: OMIM entry 609027 was added.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 107269 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed