CD44
CD44 antigen
Also known as: CD44_HUMAN, CD44R, CSPG8, HCELL, IN, MC56, MDU2, MDU3, MIC4, Pgp1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P16070
- Gene
- CD44
- Ensembl
- ENSG00000026508
- Chromosome
- 11
- Canonical length
- 742 aa
- Protein class
- Blood group antigen proteins, Cancer-related genes, CD markers, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters
- Subcellular location
- Golgi apparatus,Plasma membrane
- Secretome location
- Secreted to blood
OverviewNCBI Gene
The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
742 residues, UniProt reviewed canonical sequence.
>P16070|CD44
1 MDKFWWHAAW GLCLVPLSLA QIDLNITCRF AGVFHVEKNG RYSISRTEAA DLCKAFNSTL
61 PTMAQMEKAL SIGFETCRYG FIEGHVVIPR IHPNSICAAN NTGVYILTSN TSQYDTYCFN
121 ASAPPEEDCT SVTDLPNAFD GPITITIVNR DGTRYVQKGE YRTNPEDIYP SNPTDDDVSS
181 GSSSERSSTS GGYIFYTFST VHPIPDEDSP WITDSTDRIP ATTLMSTSAT ATETATKRQE
241 TWDWFSWLFL PSESKNHLHT TTQMAGTSSN TISAGWEPNE ENEDERDRHL SFSGSGIDDD
301 EDFISSTIST TPRAFDHTKQ NQDWTQWNPS HSNPEVLLQT TTRMTDVDRN GTTAYEGNWN
361 PEAHPPLIHH EHHEEEETPH STSTIQATPS STTEETATQK EQWFGNRWHE GYRQTPKEDS
421 HSTTGTAAAS AHTSHPMQGR TTPSPEDSSW TDFFNPISHP MGRGHQAGRR MDMDSSHSIT
481 LQPTANPNTG LVEDLDRTGP LSMTTQQSNS QSFSTSHEGL EEDKDHPTTS TLTSSNRNDV
541 TGGRRDPNHS EGSTTLLEGY TSHYPHTKES RTFIPVTSAK TGSFGVTAVT VGDSNSNVNR
601 SLSGDQDTFH PSGGSHTTHG SESDGHSHGS QEGGANTTSG PIRTPQIPEW LIILASLLAL
661 ALILAVCIAV NSRRRCGQKK KLVINSGNGA VEDRKPSGLN GEASKSQEMV HLVNKESSET
721 PDQFMTADET RNLQNVDMKI GVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CD44 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.61
- Highest tissue expression
- 470 nTPM
Expression across tissuesHPA
Tissue
- salivary gland: 470 nTPM
- skin: 351 nTPM
- bone marrow: 291 nTPM
- pancreas: 225 nTPM
- urinary bladder: 217 nTPM
- appendix: 206 nTPM
Single-cell type
- pancreatic acinar cells: 2,586 nCPM
- monocytes: 2,581 nCPM
- mast cells: 1,993 nCPM
- pancreatic duct cells: 1,846 nCPM
- basal keratinocytes: 1,693 nCPM
- neutrophils: 1,651 nCPM
Immune cell
- total PBMC: 438 nTPM
- classical monocyte: 404 nTPM
- non-classical monocyte: 358 nTPM
- NK-cell: 323 nTPM
- T-reg: 310 nTPM
- intermediate monocyte: 258 nTPM
Brain region
- hypothalamus: 253 nTPM
- medulla oblongata: 247 nTPM
- spinal cord: 245 nTPM
- white matter: 237 nTPM
- midbrain: 222 nTPM
- thalamus: 139 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CD44.
Disease | ImmuneIEDB
Conditions an epitope on CD44 was assayed in.
- rheumatoid arthritis B cell
ReferencesPubMed · IEDB
Publications for CD44 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
6 publications
- CD44 is required for the pathogenesis of experimental crescentic glomerulonephritis and collapsing focal segmental glomerulosclerosis.
2018 · Kidney Int · RCR 2.7 · 64 citations - RNA sequencing of microglia and monocyte-derived macrophages from mice with experimental autoimmune encephalomyelitis illustrates a changing phenotype with disease course.
2014 · J Neuroimmunol · RCR 2.1 · 75 citations - The neonatal Fc receptor (FcRn) is not required for IVIg or anti-CD44 monoclonal antibody-mediated amelioration of murine immune thrombocytopenia.
2011 · Blood · RCR 0.9 · 33 citations - The osteopontin - CD44 pathway is superfluous for the development of autoimmune myocarditis.
2006 · Eur J Immunol · RCR 0.3 · 15 citations - Anti-CD44 treatment does not prevent the extravasation of autopathogenic T cells to the thyroid in experimental autoimmune thyroiditis.
1999 · Immunology · RCR 0.3 · 13 citations
Show 1 more
- Expression of CD44 in synovium of rabbits with chronic arthritis induced by immunization with Escherichia coli.
2001 · J Rheumatol · RCR 0 · 1 citations
Reference: B cellIEDB
1 publication
- Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations
Reference: T cellIEDB
1 publication
- EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells.
2018 · PLoS One · RCR 1.2 · 34 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.66
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.84
- DepMap mean gene effect
- -0.07
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cartilage development
- cell adhesion
- cell migration
- cell-cell adhesion
- cell-matrix adhesion
- cellular response to fibroblast growth factor stimulus
- cytokine-mediated signaling pathway
- endocytosis
- hyaluronan catabolic process
- inflammatory response
- monocyte aggregation
- negative regulation of 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
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of heterotypic cell-cell adhesion
- positive regulation of monocyte aggregation
- regulation of lamellipodium morphogenesis
- T cell activation
- wound healing, spreading of cells
Molecular functions
- cargo receptor activity
- collagen binding
- hyaluronic acid binding
- transmembrane signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CD44 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CD44 as an antibody target. Whether an autoantibody or antibody against CD44 could matter depends on whether native CD44 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CD44 is annotated at the cell surface, where native CD44 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CD44 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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