CD44_CANLF
ID CD44_CANLF Reviewed; 351 AA.
AC Q28284;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, 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; Fragment;
GN Name=CD44;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Beagle; TISSUE=Thymus;
RX PubMed=7514890; DOI=10.1016/0167-4781(94)90111-2;
RA Milde K.F., Alejandro R., Mintz D.H., Pastori R.L.;
RT "Molecular cloning of the canine CD44 antigen cDNA.";
RL Biochim. Biophys. Acta 1218:112-114(1994).
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 -!- TISSUE SPECIFICITY: Lymph nodes.
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-320 (constitutive phosphorylation site), and the phosphorylation
CC of Ser-286. {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; Z27115; CAA81630.1; -; mRNA.
DR PIR; S45305; S45305.
DR AlphaFoldDB; Q28284; -.
DR SMR; Q28284; -.
DR PaxDb; Q28284; -.
DR eggNOG; ENOG502RX7Q; Eukaryota.
DR InParanoid; Q28284; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
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:0035692; C:macrophage migration inhibitory factor receptor complex; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:GOC.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
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;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL <1..13
FT /evidence="ECO:0000255"
FT CHAIN 14..>351
FT /note="CD44 antigen"
FT /id="PRO_0000026684"
FT TOPO_DOM 14..263
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..>351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..113
FT /note="Link"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT REGION 143..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..263
FT /note="Stem"
FT REGION 287..305
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 329..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 196..211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..234
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 34
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 71
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT MOD_RES 286
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15379"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 21..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 46..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 70..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT NON_TER 1
FT NON_TER 351
SQ SEQUENCE 351 AA; 38066 MW; E73387E70E20C0E0 CRC64;
LAWGLCLLRL SLAQIDLNIT CRYAGVFHVE KNGRYSISRT AAADLCKAFN STLPTMAQME
RALSVGFETC RYGFIEGHVV IPRIQPNAIC AANHTGVYIL ISNTSQYDTY CFNASAPPEE
DCTSVTHLPN AFDGPITITI VNRDGTRYSQ KGEYRTNPED INPSNPTDDD VSSGSSSERS
TSAGYNIFHT HLPTAYPTED QDSSRVSSNS DHTPITKDHD SSVHPSERSH TTHGSESAGH
SSGSQEGGAN TTSGPMRKPQ IPEWLIILAS LLALALILAV CIAVNSRRRC GQKKKLVINN
GNGAVGDRKP SGINGEASKS QEMVHLVNKE PSETPDQYTT ADETRNLQNV D
