Protein detail

CD44

CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44)

Entry name CD44	UniProt ID P16070	EVMP confidence score 0.88
Supporting publications (n) 64	Transmembrane count 1	Protein classification Blood group antigen proteinsCancer-related genesCD markersFDA approved drug targetsPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Protein Class (9)

Blood group antigen proteinsCancer-related genesCD markersFDA approved drug targetsPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsPredicted secreted proteinsTransporters

Protein Function (7)

Transporters
Predicted intracellular proteins
Blood group antigen proteins
CD markers
Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
FDA approved drug targets:Small molecule drugs

Transmembrane

650..670; Helical

Transmembrane Count

Ensembl

ENSG00000026508

Entrez Gene Symbol

CD44

Gene Synonym (9)

CD44RCSPG8HCELLINMC56MDU2MDU3MIC4Pgp1

Gene Description

CD44 molecule (Indian blood group)

Chromosome

Position

35138882-35232402

Supporting publications (n)

EVMP confidence score

0.88

Fluorescence & Localization2

Tissue Specifictestis

Function & Pathway6

Protein Function (7)

Transporters
Predicted intracellular proteins
Blood group antigen proteins
CD markers
Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
FDA approved drug targets:Small molecule drugs

Cellular Component (13)

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Molecular Function (5)

KEGG (6)

Reactome (20)

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Mediation Categories (6)

Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence81

Enzyme-Mediated Modification (12)

12 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
CD44	PRKCA	P17252	S	672	phosphorylation	PhosphoNetworksphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPProtMapperKEAphosphoELMPhosphoSitePhosphoSite_ProtMapper	KEA:12032545 phosphoELM:12032545
CD44	PRKCA	P17252	S	291	phosphorylation	MIMPKEAphosphoELM_MIMP	KEA:12032545
CD44	PRKCA	P17252	S	423	phosphorylation	KEA	KEA:12032545
CD44	PRKCA	P17252	S	629	phosphorylation	KEA	KEA:12032545
CD44	CAMK2A	Q9UQM7	S	706	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:11463356 ProtMapper:9580567 SIGNOR:9580567 SIGNOR:11463356
CD44	PRKACA	P17612	S	697	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	SIGNOR:16785995 ProtMapper:16785995
CD44	PRKCB	P05771	S	291	phosphorylation	MIMPphosphoELM_MIMP
CD44	PRKCG	P05129	S	291	phosphorylation	MIMPphosphoELM_MIMP
CD44	PRKCD	Q05655	S	291	phosphorylation	MIMPphosphoELM_MIMP
CD44	PRKCE	Q02156	S	291	phosphorylation	MIMPphosphoELM_MIMP

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Ligand-Receptor Signaling (65)

65 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
secreted	secreted	HPA_secretome	No	No	Yes	Yes	No
secreted	secreted	OmniPath	No	No	Yes	Yes	No
cell_surface	cell_surface	Surfaceome	No	No	Yes	Yes	No
cell_surface	cell_surface	connectomeDB2020	No	No	Yes	Yes	No
cell_surface	cell_surface	OmniPath	No	No	Yes	Yes	No
receptor	receptor	talklr	No	Yes	Yes	Yes	No
receptor	receptor	Cellinker	No	Yes	Yes	Yes	No
receptor	receptor	connectomeDB2020	No	Yes	Yes	Yes	No
receptor	receptor	iTALK	No	Yes	Yes	Yes	No
growth_factor	receptor	iTALK	No	Yes	Yes	Yes	No

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Regulatory Interaction Network (3)

3 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
ADA10	O14672	CD44	P16070	Yes	Yes	No	CellTalkDBSIGNOR	CellTalkDB:18971959 SIGNOR:26284334
KCC2A	Q9UQM7	CD44	P16070	Yes	Yes	No	WangphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperCui2007SIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	SIGNOR:9580567 SIGNOR:11463356 PhosphoSite:1281449 ProtMapper:11463356 ProtMapper:9580567 PhosphoSite:16785995 PhosphoSite:11463356 PhosphoSite:9580567 PhosphoSite:12032545 PhosphoSite:19582779 PhosphoSite:22865879
KAPCA	P17612	CD44	P16070	Yes	Yes	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperSIGNOR_ProtMapperPhosphoSite_ProtMapper	SIGNOR:16785995 ProtMapper:16785995

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential Ultracentrifugation	Western BlottingMass SpectrometryElisaFlow Cytometry	1	38014595

Sequence, Structure & Domains13

Sequences

Length

742

Mass

81,538

Sequence

MDKFWWHAAWGLCLVPLSLAQIDLNITCRFAGVFHVEKNGRYSISRTEAADLCKAFNSTLPTMAQMEKALSIGFETCRYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYCFNASAPPEEDCTSVTDLPNAFDGPITITIVNRDGTRYVQKGEYRTNPEDIYPSNPTDDDVSSGSSSERSSTSGGYIFYTFSTVHPIPDEDSPWITDSTDRIPATTLMSTSATATETATKRQETWDWFSWLFLPSESKNHLHTTTQMAGTSSNTISAGWEPNEENEDERDRHLSFSGSGIDDDEDFISSTISTTPRAFDHTKQNQDWTQWNPSHSNPEVLLQTTTRMTDVDRNGTTAYEGNWNPEAHPPLIHHEHHEEEETPHSTSTIQATPSSTTEETATQKEQWFGNRWHEGYRQTPKEDSHSTTGTAAASAHTSHPMQGRTTPSPEDSSWTDFFNPISHPMGRGHQAGRRMDMDSSHSITLQPTANPNTGLVEDLDRTGPLSMTTQQSNSQSFSTSHEGLEEDKDHPTTSTLTSSNRNDVTGGRRDPNHSEGSTTLLEGYTSHYPHTKESRTFIPVTSAKTGSFGVTAVTVGDSNSNVNRSLSGDQDTFHPSGGSHTTHGSESDGHSHGSQEGGANTTSGPIRTPQIPEWLIILASLLALALILAVCIAVNSRRRCGQKKKLVINSGNGAVEDRKPSGLNGEASKSQEMVHLVNKESSETPDQFMTADETRNLQNVDMKIGV

Alternative Products

Event=Alternative splicing; Named isoforms=19; Name=1; Synonyms=CD44; IsoId=P16070-1; Sequence=Displayed; Name=2; Synonyms=CD44SP; IsoId=P16070-2; Sequence=VSP_005303, VSP_005304; Name=3; IsoId=P16070-3; Sequence=VSP_005305, VSP_005306; Name=4; Synonyms=Epidermal; IsoId=P16070-4; Sequence=VSP_005307, VSP_005308; Name=5; IsoId=P16070-5; Sequence=VSP_005313; Name=6; IsoId=P16070-6; Sequence=VSP_005314, VSP_005315; Name=7; IsoId=P16070-7; Sequence=VSP_005316, VSP_005317; Name=8; IsoId=P16070-8; Sequence=VSP_005318, VSP_005319; Name=9; IsoId=P16070-9; Sequence=VSP_005320, VSP_005321; Name=10; Synonyms=CD44E, CD44R1, Epithelial, Keratinocyte; IsoId=P16070-10; Sequence=VSP_005309, VSP_005310; Name=11; Synonyms=CD44R2; IsoId=P16070-11; Sequence=VSP_022797; Name=12; Synonyms=CDw44, Reticulocyte; IsoId=P16070-12; Sequence=VSP_005311, VSP_005312; Name=13; Synonyms=CD44R4; IsoId=P16070-13; Sequence=VSP_005309, VSP_005310, VSP_005318, VSP_005319; Name=14; Synonyms=CD44R5; IsoId=P16070-14; Sequence=VSP_005309, VSP_005310, VSP_005316, VSP_005317, VSP_005318, VSP_005319; Name=15; Synonyms=Hermes; IsoId=P16070-15; Sequence=VSP_005311, VSP_005312, VSP_005320, VSP_005321; Name=16; IsoId=P16070-16; Sequence=VSP_005305, VSP_005306, VSP_005314, VSP_005315; Name=17; IsoId=P16070-17; Sequence=VSP_005313, VSP_005314, VSP_005315; Name=18; IsoId=P16070-18; Sequence=VSP_005311, VSP_005312, VSP_043575; Name=19; Synonyms=CD44RC; IsoId=P16070-19; Sequence=VSP_043870, VSP_043871

Alternative Sequence

23..29; DLNITCR -> GVGRRKS (in isoform 2); 30..742; Missing (in isoform 2); 78..139; RYGFIEGHVVIPRIHPNSICAANNTGVYILTSNTSQYDTYCFNASAPPEEDCTSVTDLPNAF -> SLHCSQQSKKVWAEEKASDQQWQWSCGGQKAKWTQRRGQQVSGNGAFGEQGVVRNSRPVYDS (in isoform 19); 140..742; Missing (in isoform 19); 192; G -> A (in isoform 3 and isoform 16); 193..223; Missing (in isoform 3 and isoform 16); 223..535; Missing (in isoform 11); 223; T -> N (in isoform 10, isoform 13 and isoform 14); 223; T -> R (in isoform 12, isoform 15 and isoform 18); 223; T -> S (in isoform 4); 224..604; Missing (in isoform 12, isoform 15 and isoform 18); 224..472; Missing (in isoform 10, isoform 13 and isoform 14); 224..266; Missing (in isoform 4); 266..273; Missing (in isoform 5 and isoform 17); 385; I -> T (in isoform 6, isoform 16 and isoform 17); 386..428; Missing (in isoform 6, isoform 16 and isoform 17); 506; Q -> R (in isoform 7 and isoform 14); 507..535; Missing (in isoform 7 and isoform 14); 536; N -> R (in isoform 8, isoform 13 and isoform 14); 537..604; Missing (in isoform 8, isoform 13 and isoform 14); 605..625; Missing (in isoform 18); 675; R -> S (in isoform 9 and isoform 15); 676..742; Missing (in isoform 9 and isoform 15)

3D Structural Models

Turn

150..152

Helix

46..55; 63..71; 98..100; 165..168

Beta Strand

21..26; 33..38; 57..59; 80..82; 85..92; 103..106; 109..111; 114..119; 121..123; 125..128; 130..132; 139..148; 154..160

3D Structure

NMR spectroscopy (2); X-ray crystallography (4)

Domain & Motif Annotations

Compositional Bias

179..189; Low complexity; 261..273; Polar residues; 386..396; Low complexity; 407..421; Basic and acidic residues; 422..435; Low complexity; 439..452; Polar residues; 476..489; Polar residues; 502..516; Low complexity; 528..539; Polar residues; 592..606; Polar residues; 619..629; Basic and acidic residues

Domain (CC)

The lectin-like LINK domain is responsible for hyaluronan binding.

Domain (FT)

32..120; Link

Region

160..189; Disordered; 224..649; Stem; 261..285; Disordered; 372..558; Disordered; 590..642; Disordered; 673..691; Required for interaction with EZR, MSN and RDX and for co-localization to microvilli

Clinical Relevance9

Disease Involvement (2)

Cancer-related genesFDA approved drug targets

Related Diseases (3)

Ovarian cancer Retinopathy Solid tumour/cancer

Biomarker

Phase 2; Phase 1

Drug Targets

FDA approved drug targets

Antibody (3)

CAB000112 CAB000316 HPA005785

Interaction Protein (2)

ENSG00000147065ENSG00000151012

Interaction Count

Interaction Dataset

intact_biogrid

Supporting Publications61

PMID	Title	Abstract
27564521	Concomitant Evaluation of a Panel of Exosome Proteins and MiRs for Qualification of Cultured Human Corneal Endothelial Cells.	Cultured HCECs sharing a CD44- phenotype of matured HCECs may be discriminated by measuring the amount of miRNAs or exosome in CS.
27758876	Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.	CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs.
28895255	UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/β-Catenin Pathway.	However, whether the state of p53 in MSCs can impact the bioactive molecule secretion of exosomes to promote cancer progression and the regulatory mechanism remains elusive. Our study aimed to investigate the regulation of ubiquitin protein ligase E3 component n-recognin 2 (UBR2) enriched in exosomes secreted by p53 deficient mouse bone marrow MSC (p53 © 2017 AlphaMed Press.
28928832	Downregulation of Rab27A contributes to metformin-induced suppression of breast cancer stem cells.	The present study demonstrated that the expression of RAB27A, member RAS oncogene family (Rab27a), which was reported to promote tumor progression by upregulating exocytosis of extracellular vesicles, was higher in mammosphere cells than in adherent MDA-MB-231 breast cancer cells.
29143228	Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients.	Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis.
30108515	Microgravity-Induced Alterations of Inflammation-Related Mechanotransduction in Endothelial Cells on Board SJ-10 Satellite.	Meanwhile, it also induced the depolymerization of actin filaments and microtubules, promoted the vimentin accumulation, restrained the collagen I and fibronectin deposition, regulated the mechanotransduction through focal adhesion kinase and Rho GTPases, and enhanced the exosome-mediated mRNA transfer.
30893511	Oncogenic and Non-Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis.	Importantly, valuable insights into oncogenic exosomes (362 unique proteins in comparison to non-malignant exosomes) of key metastatic regulatory factors and signaling molecules fundamental to pancreatic cancer progression (KRAS, CD44, EGFR) are provided. It is reported that oncogenic exosomes contain factors known to regulate the pre-metastatic niche (S100A4, F3, ITGβ5, ANXA1), clinically-relevant proteins which correlate with poor prognosis (CLDN1, MUC1) as well as protein networks involved in various cancer hallmarks including proliferation (CLU, CAV1), invasion (PODXL, ITGA3), metastasis (LAMP1, ST14) and immune surveillance escape (B2M).
30909497	CD44s Assembles Hyaluronan Coat on Filopodia and Extracellular Vesicles and Induces Tumorigenicity of MKN74 Gastric Carcinoma Cells.	Recent data has shown that CD44 and its principal ligand hyaluronan (HA) are carried by extracellular vesicles (EV) derived from stem and tumor cells, but the role of CD44 in EV shedding has not been studied so far.
31048929	Clinical impact of different exosomes' protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy.	Pancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression. We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4).
31184411	The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability.	The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34

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