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)
receptor	receptor	CellPhoneDB	No	Yes	Yes	Yes	No
receptor	receptor	GO_Intercell	No	Yes	Yes	Yes	No
receptor	receptor	HPMR	No	Yes	Yes	Yes	No
receptor	receptor	ICELLNET	No	Yes	Yes	Yes	No
receptor	receptor	CellChatDB	No	Yes	Yes	Yes	No
receptor	receptor	CellTalkDB	No	Yes	Yes	Yes	No
receptor	receptor	Ramilowski2015	No	Yes	Yes	Yes	No
receptor	receptor	LRdb	No	Yes	Yes	Yes	No
proteoglycan	receptor	OmniPath	No	Yes	Yes	Yes	No
cytokine_receptor	receptor	CellPhoneDB	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
31473497	Exosomes in specific fractions of the boar ejaculate contain CD44: A marker for epididymosomes?	Noteworthy, these pig SP-exosomes were CD44-bearing when analysed by FC, with bands detected by western blotting (WB) at the expected 85 kD size. The findings pave for the selective isolation of exosomes in functional studies of their function when interacting with spermatozoa, the oocyte and/or the female genitalia, including hyaluronan-CD44 interplay.
31485223	The Pancreatic Cancer-Initiating Cell Marker CD44v6 Affects Transcription, Translation, and Signaling: Consequences for Exosome Composition and Delivery.	Due to the association of CD44v6 with Tspan8 in internalization prone tetraspanin-enriched membrane domains (TEM) and the engagement of Tspan8 in exosome biogenesis, most CD44v6-dependent changes were transferred into TEX such that the input of CD44v6 to TEX activities becomes largely waved in both a CD44v6kd and a Tspan8kd.
31676071	Disruption of Core 1-mediated O-glycosylation oppositely regulates CD44 expression in human colon cancer cells and tumor-derived exosomes.	CD44 in exosomes might be a potential biomarker of aberrant O-glycosylation. CD63 immunoaffinity-purified exosomes are examined for CD44 expression by flow cytometric analyses. Exosomes derived from LS174T and LSC human colon cancer cell lines were isolated from cell culture supernatant and pulled down using tetraspanin-specific antibody CD63 immunoaffinity magnetic beads. In this research, we aimed to investigate whether CD44 expression in cells and exosomes can be influenced by disruption of Core 1-mediated O-glycosylation. The percentages of CD44 in exosomes derived from abnormally O-glycosylated cells are significantly higher compared with those derived from normal ones, however, which is surprisingly contrary to the cellular expression levels of CD44.
31786017	Electrochemical immunosensing of nanovesicles as biomarkers for breast cancer.	To achieve that, the exosomes were preconcentrated from cell-culture supernatant (and eventually in human serum) on magnetic particles modified with antibodies against the general tetraspanins CD9, CD63 and CD81, as well as specific receptors of cancer (CD24, CD44, CD54, CD326 and CD340).
31806995	Checkpoint CD47 Function On Tumor Metastasis And Immune Therapy.	Meanwhile, tumor cells express high CD47 protein which may secrete exosomes with high CD47 expression. The high CD47 expression-exosomes could serve the tumor metastasis process and provide transfer convenience for tumors on the microenvironment.
31820036	HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.	No abstract available
31894881	Chicken seminal fluid lacks CD9- and CD44-bearing extracellular vesicles.	In the present study, sperm-free SF from Red Jungle Fowl, White Leghorn and an advanced intercross (AIL, 12th generation) were studied using flow cytometry of the membrane marker tetraspanin CD9, Western blotting of the membrane receptor CD44 and electron microscopy in non-enriched (whole SF) or enriched fractions obtained by precipitation using a commercial kit (Total Exosome Precipitation Solution). Its complex proteome might either be free or linked to extracellular vesicles (EVs) as it is the case in mammals, where EVs depict the tetraspanin CD9; and where those EVs derived from the epididymis (epididymosomes) also present the receptor CD44.
32054015	Matrix Effect in the Isolation of Breast Cancer-Derived Nanovesicles by Immunomagnetic Separation and Electrochemical Immunosensing-A Comparative Study.	Based on this study, the exosomes were preconcentrated by immunomagnetic separation on antiCD81-modified magnetic particles in order to achieve further magnetic actuation on the surface of the electrode for the electrochemical readout.
32642575	CD44v8-10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients.	In this study, we examined CD44 protein and mRNA expression in cell lysates and exosomes isolated from prostate cancer cells, evaluated the effect of CD44v8-10 knockdown on docetaxel sensitivity and measured CD44 mRNA copy numbers contained in serum exosomes in prostate cancer patients. The CD44v8-10 mRNA copy numbers in serum exosomes were higher in docetaxel-resistant patients than in docetaxel-naïve patients and control males (median 46, 12 and 17 copies/mL serum, respectively, CD44v8-10 may be involved in docetaxel resistance in prostate cancer and serum exosomal CD44v8-10 mRNA could be a diagnostic marker for docetaxel-resistant CRPC. The levels of CD44v8-10 protein and mRNA in cell lysates and exosomes were higher in PC-3R cells than in PC-3 cells. We hypothesized that CD44 in serum exosomes could be a diagnostic marker for docetaxel resistance in CRPC patients.
32760666	Enrichment of CD44 in Exosomes From Breast Cancer Cells Treated With Doxorubicin Promotes Chemoresistance.	No abstract available

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