EV MemProt Atlas

Basic Information13

Protein Names

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)

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

1

Ensembl

ENSG00000026508

Entrez Gene Symbol

CD44

Gene Synonym (9)

CD44RCSPG8HCELLINMC56MDU2MDU3MIC4Pgp1

Gene Description

CD44 molecule (Indian blood group)

Chromosome

11

Position

35138882-35232402

Supporting publications (n)

64

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)

Page 1 of 2

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	RPS6KA3	P51812	S	291	phosphorylation	KEA	KEA:17570479
CD44	SGK1	O00141	S	291	phosphorylation	KEA	KEA:17570479

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Ligand-Receptor Signaling (65)

65 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
other_receptor_family	receptor	HPMR	No	Yes	Yes	Yes	No
transferrin	receptor	HPMR	No	Yes	Yes	Yes	No
ecm_interaction	receptor	ICELLNET	No	Yes	Yes	Yes	No
receptor	receptor	OmniPath	No	Yes	Yes	Yes	No
extracellular	extracellular	HPMR	No	No	Yes	Yes	No
extracellular	extracellular	OmniPath	No	No	Yes	Yes	No
intracellular	intracellular	LOCATE	No	No	Yes	Yes	No
intracellular	intracellular	ComPPI	No	No	Yes	Yes	No
intracellular	intracellular	GO_Intercell	No	No	Yes	Yes	No
intracellular	intracellular	OmniPath	No	No	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

2

Interaction Dataset

intact_biogrid

Supporting Publications61

PMID	Title	Abstract
16229685	A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44.	By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-beta-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor a-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions.
22772984	MicroRNAs are exported from malignant cells in customized particles.	However, n-miRNAs of breast cancer cells associate with unconventional exosomes, which are larger than conventional exosomes and enriched in CD44, a protein relevant to breast cancer metastasis.
23230278	Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.	Additionally, we report for the first time in any extracellular vesicle study the colocalization of EpCAM, claudin-7, and CD44 in EpCAM-Exos. Here we describe the isolation, via sequential immunocapture using anti-A33- and anti-EpCAM-coupled magnetic beads, of two distinct populations of exosomes released from organoids derived from human colon carcinoma cell line LIM1863. Our observations are consistent with EpCAM- and A33-Exos being released from the apical and basolateral surfaces, respectively, and the EpCAM-Exos proteome profile with widely published stereotypical exosomes. The exosome populations (A33-Exos and EpCAM-Exos) could not be distinguished via electron microscopy and contained stereotypical exosome markers such as TSG101, Alix, and HSP70.
23767874	Biochemical and biological characterization of exosomes containing prominin-1/CD133.	Prom1-exo contained 154 proteins, including all of the 14 proteins most frequently expressed in exosomes, and multiple pro-metastatic proteins, including CD44, MAPK4K, GTP-binding proteins, ADAM10 and Annexin A2. With the goal to explore the mechanisms that govern proteo-lipidic-microRNA sorting in cancer exosomes and their potential contribution(s) to the metastatic phenotype, we here employed prominin-1-based immunomagnetic separation in combination with filtration and ultracentrifugation to purify prominin-1-expressing exosomes (prom1-exo) from melanoma and colon carcinoma cells.
24733759	The overexpression of a single oncogene (ERBB2/HER2) alters the proteomic landscape of extracellular vesicles.	However, despite its remarkable importance in oncology, the consequences of HER2 amplification over the extracellular vesicles (EVs) content have not yet been investigated.
25857718	Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.	As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes.
25928805	On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.	The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker) antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG) isotype control.
26754424	MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry.	No abstract available
26938523	The Role of CD44 and ERM Proteins in Expression and Functionality of P-glycoprotein in Breast Cancer Cells.	We have previously described the intercellular transfer of P-gp via extracellular vesicles (EVs) and proposed the involvement of a unique protein complex in regulating this process.
27419629	CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells.	No abstract available

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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