CD44_PAPHA
ID CD44_PAPHA Reviewed; 362 AA.
AC P14745;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 120.
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 Papio hamadryas (Hamadryas baboon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Papio.
OX NCBI_TaxID=9557;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 66-74.
RX PubMed=2471974; DOI=10.1073/pnas.86.12.4659;
RA Idzerda R.L., Carter W.G., Nottenburg C., Wayner E.A., Gallatin W.M.,
RA St John T.;
RT "Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion
RT receptor for high endothelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4659-4663(1989).
CC -!- FUNCTION: Cell-surface receptor that plays a role in cell-cell
CC interactions, cell adhesion and migration, helping them to sense and
CC respond to changes in the tissue microenvironment. Participates thereby
CC in a wide variety of cellular functions including the activation,
CC recirculation and homing of T-lymphocytes, hematopoiesis, inflammation
CC and response to bacterial infection. Engages, through its ectodomain,
CC extracellular matrix components such as hyaluronan/HA, collagen, growth
CC factors, cytokines or proteases and serves as a platform for signal
CC transduction by assembling, via its cytoplasmic domain, protein
CC complexes containing receptor kinases and membrane proteases. Such
CC effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and
CC phospholipase C that coordinate signaling pathways promoting calcium
CC mobilization and actin-mediated cytoskeleton reorganization essential
CC for cell migration and adhesion. {ECO:0000250|UniProtKB:P15379,
CC 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 -!- 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; M22452; AAA35385.1; -; mRNA.
DR AlphaFoldDB; P14745; -.
DR SMR; P14745; -.
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 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Cell projection; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Proteoglycan;
KW Receptor; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..362
FT /note="CD44 antigen"
FT /id="PRO_0000026690"
FT TOPO_DOM 21..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 32..120
FT /note="Link"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT REGION 160..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 225..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 COMPBIAS 165..186
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 41
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 105
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 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 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
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 28..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 53..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 77..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT CONFLICT 67
FT /note="E -> V (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 39379 MW; 578BFCE7C3D52FFF CRC64;
MDKFWWRAAW GLCLVQLSLA QIDLNITCRF EGIYHVEKNG RYSISRTEAA DLCKAFNSTL
PTMAQMEKAL SIGFETCRYG FIEGHVVIPR IHPNSICAAN NTGVYILTSN TSQYDTYCFN
ASAPPGEDCT SVTDLPNAFD GPITITIVNR DGTRYVKKGE YRTNPEDINP SSPTDDDVSS
GSSSERSSTL GGYIFYNHFS TSPPIPDEDG PWITDSTDRT PATRDQGAFD PSGGSHTTHG
SESAGHSHGS REGGANTTSG PLRTPQIPEW LIILASLLAL ALILAVCIAV NSRRRCGQKK
KLVINNGNGA VEDRKSSGLN GEASKSQEMV HLVNKESSET PDQFMTADET RNLQNVDMKI
GV
