CD44_CRIGR
ID CD44_CRIGR Reviewed; 362 AA.
AC P20944;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=CD44 antigen;
DE AltName: Full=Extracellular matrix receptor III;
DE Short=ECMR-III;
DE AltName: Full=GP90 lymphocyte homing/adhesion receptor;
DE AltName: Full=HUTCH-I;
DE AltName: Full=Hermes antigen;
DE AltName: Full=Hyaluronate receptor;
DE AltName: Full=Phagocytic glycoprotein 1;
DE Short=PGP-1;
DE AltName: Full=Phagocytic glycoprotein I;
DE Short=PGP-I;
DE AltName: CD_antigen=CD44;
DE Flags: Precursor;
GN Name=CD44;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1694723; DOI=10.1016/0092-8674(90)90694-a;
RA Aruffo A., Stamenkovic I., Melnick M., Underhill C.B., Seed B.;
RT "CD44 is the principal cell surface receptor for hyaluronate.";
RL Cell 61:1303-1313(1990).
CC -!- FUNCTION: Cell-surface receptor that plays a role in cell-cell
CC interactions, as well as cell adhesion and migration, helping them to
CC sense and respond to changes in the tissue microenvironment.
CC Participates thereby in a wide variety of cellular functions including
CC the activation, recirculation and homing of T-lymphocytes,
CC hematopoiesis, inflammation and response to bacterial infection.
CC Engages, through its ectodomain, extracellular matrix components such
CC as hyaluronan/HA, collagen, growth factors, cytokines or proteases and
CC serves as a platform for signal transduction by assembling, via its
CC cytoplasmic domain, protein complexes containing receptor kinases and
CC membrane proteases. Such effectors include PKN2, the RhoGTPases RAC1
CC and RHOA, Rho-kinases and phospholipase C that coordinate signaling
CC pathways promoting calcium mobilization and actin-mediated cytoskeleton
CC reorganization essential for cell migration and adhesion.
CC {ECO:0000250|UniProtKB:P15379, ECO:0000250|UniProtKB:P16070}.
CC -!- SUBUNIT: Interacts with PKN2 (By similarity). Interacts with TIAM1 and
CC TIAM2 (By similarity). Interacts with HA, as well as other
CC glycosaminoglycans, collagen, laminin, and fibronectin via its N-
CC terminal segment. Interacts with UNC119. Interacts with PDPN (via
CC extracellular domain); this interaction is required for PDPN-mediated
CC directional migration and regulation of lamellipodia
CC extension/stabilization during cell spreading and migration (By
CC similarity). Interacts with RDX, EZR and MSN (By similarity). Interacts
CC with EGFR (By similarity). Interacts with CD74; this complex is
CC essential for the MIF-induced signaling cascade that results in B cell
CC survival (By similarity). {ECO:0000250|UniProtKB:P15379,
CC ECO:0000250|UniProtKB:P16070}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15379};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P15379}.
CC Cell projection, microvillus {ECO:0000250|UniProtKB:P15379}.
CC Note=Colocalizes with actin in membrane protrusions at wounding edges.
CC Co-localizes with RDX, EZR and MSN in microvilli.
CC {ECO:0000250|UniProtKB:P15379}.
CC -!- INDUCTION: By EBV.
CC -!- DOMAIN: The lectin-like LINK domain is responsible for hyaluronan
CC binding. {ECO:0000250}.
CC -!- PTM: Phosphorylated; activation of PKC results in the dephosphorylation
CC of Ser-326 (constitutive phosphorylation site), and the phosphorylation
CC of Ser-292. {ECO:0000250|UniProtKB:P16070}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P16070}.
CC -!- PTM: O-glycosylated; addition of the glycosaminoglycan chondroitin
CC sulfate, of sulfate, of phosphate to cytoplasmic domain serine
CC residues. {ECO:0000250|UniProtKB:P16070}.
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DR EMBL; M33827; AAA36967.1; -; mRNA.
DR PIR; A35616; A35616.
DR AlphaFoldDB; P20944; -.
DR SMR; P20944; -.
DR eggNOG; ENOG502RX7Q; Eukaryota.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0042995; C:cell projection; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031258; C:lamellipodium membrane; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005540; F:hyaluronic acid binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; ISS:UniProtKB.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR001231; CD44_antigen.
DR InterPro; IPR043210; CD44_antigen-like.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR000538; Link_dom.
DR PANTHER; PTHR10225; PTHR10225; 2.
DR PANTHER; PTHR10225:SF6; PTHR10225:SF6; 2.
DR Pfam; PF00193; Xlink; 1.
DR PRINTS; PR00658; CD44.
DR PRINTS; PR01265; LINKMODULE.
DR SMART; SM00445; LINK; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS01241; LINK_1; 1.
DR PROSITE; PS50963; LINK_2; 1.
PE 2: Evidence at transcript level;
KW Cell adhesion; Cell membrane; Cell projection; Disulfide bond;
KW Glycoprotein; Membrane; Phosphoprotein; Proteoglycan; Receptor; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..362
FT /note="CD44 antigen"
FT /id="PRO_0000026685"
FT TOPO_DOM 23..269
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 34..122
FT /note="Link"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT REGION 158..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..269
FT /note="Stem"
FT REGION 293..311
FT /note="Required for interaction with EZR, MSN and RDX and
FT for co-localization to microvilli"
FT /evidence="ECO:0000250|UniProtKB:P15379"
FT REGION 307..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..173
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..260
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..321
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 43
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT MOD_RES 292
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15379"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT CARBOHYD 27
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 55..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 79..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
SQ SEQUENCE 362 AA; 39775 MW; E89EB434E9EEC948 CRC64;
MDKFWWHAAW GLCLLPLSLA HEQIDLNITC RYAGVFHVEK NGRYSISRTE AADLCQAFNS
TLPTMDQMVM ALSKGFETCR YGFIEGHVVI PRIQPNAICA ANHTGVYILT SNTSHYDTYC
FNASAPLEED CTSVTDLPNS FEGPVTITIV NRDGTRYSKK GEYRTHQEDI DASNTTDDDV
SSGSSSEKST SGGYVFHTYL PTIHSTADQD DPYFIGSTMA TRDQDSSMDP RGNSLTVTDG
SKLTEHSSGN QDSGLNSTSR PGGKPRVPEW LIVLASLLAL ALILAVCIAV NSRRRCGQKK
KLVINSGNGK VEDRKPSELN GEASKSQEMV HLVNKEPSET PDQFMTADET RNLQNVDMKI
GV
