CD44_RAT
ID CD44_RAT Reviewed; 503 AA.
AC P26051; Q99021;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 160.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=BDIX; TISSUE=Pancreas;
RX PubMed=1707342; DOI=10.1016/0092-8674(91)90403-l;
RA Guenthert U., Hofmann M., Rudy W., Reber S., Zoeller M., Haussmann I.,
RA Matzku S., Wenzel A., Ponta H., Herrlich P.;
RT "A new variant of glycoprotein CD44 confers metastatic potential to rat
RT carcinoma cells.";
RL Cell 65:13-24(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Stevens J.W., Midura R.J.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SULFATION AT TYR-288.
RX PubMed=9692903; DOI=10.1046/j.1432-1327.1998.2550074.x;
RA Sleeman J.P., Rahmsdorf U., Steffen A., Ponta H., Herrlich P.;
RT "CD44 variant exon v5 encodes a tyrosine that is sulphated.";
RL Eur. J. Biochem. 255:74-80(1998).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447; THR-451 AND SER-467, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=2; Synonyms=Long, Meta-1;
CC IsoId=P26051-1; Sequence=Displayed;
CC Name=1; Synonyms=Short;
CC IsoId=P26051-2; Sequence=VSP_005330;
CC -!- DOMAIN: The lectin-like LINK domain is responsible for hyaluronan
CC binding. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P16070}.
CC -!- PTM: O-glycosylated; contains chondroitin sulfate glycans which can be
CC more or less sulfated. {ECO:0000250|UniProtKB:P16070}.
CC -!- PTM: Phosphorylated; activation of PKC results in the dephosphorylation
CC of Ser-467 (constitutive phosphorylation site), and the phosphorylation
CC of Ser-433. {ECO:0000250}.
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DR EMBL; M61875; AAA53532.1; -; mRNA.
DR EMBL; M61874; AAA53534.1; -; mRNA.
DR EMBL; U52179; AAA97915.1; -; mRNA.
DR EMBL; U46957; AAA92920.1; -; mRNA.
DR PIR; B38745; B38745.
DR RefSeq; XP_006234693.1; XM_006234631.3.
DR AlphaFoldDB; P26051; -.
DR SMR; P26051; -.
DR BioGRID; 247441; 1.
DR CORUM; P26051; -.
DR IntAct; P26051; 1.
DR GlyGen; P26051; 8 sites.
DR iPTMnet; P26051; -.
DR PhosphoSitePlus; P26051; -.
DR GeneID; 25406; -.
DR UCSC; RGD:2307; rat. [P26051-1]
DR CTD; 960; -.
DR RGD; 2307; Cd44.
DR eggNOG; ENOG502RX7Q; Eukaryota.
DR InParanoid; P26051; -.
DR PhylomeDB; P26051; -.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-216083; Integrin cell surface interactions.
DR Reactome; R-RNO-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P26051; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0042995; C:cell projection; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:RGD.
DR GO; GO:0005540; F:hyaluronic acid binding; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISO:RGD.
DR GO; GO:0001955; P:blood vessel maturation; IEP:RGD.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; ISO:RGD.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; IMP:RGD.
DR GO; GO:0016477; P:cell migration; IMP:RGD.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISO:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:GOC.
DR GO; GO:0030214; P:hyaluronan catabolic process; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0034238; P:macrophage fusion; IMP:RGD.
DR GO; GO:0070487; P:monocyte aggregation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; ISO:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0002906; P:negative regulation of mature B cell apoptotic process; ISO:RGD.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; IMP:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; ISO:RGD.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IMP:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0001558; P:regulation of cell growth; IDA:RGD.
DR GO; GO:2000392; P:regulation of lamellipodium morphogenesis; ISS:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0042110; P:T cell activation; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
DR GO; GO:0002246; P:wound healing involved in inflammatory response; ISO:RGD.
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; 1.
DR PANTHER; PTHR10225:SF6; PTHR10225:SF6; 1.
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 Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Proteoglycan;
KW Receptor; Reference proteome; Signal; Sulfation; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT CHAIN 22..503
FT /note="CD44 antigen"
FT /id="PRO_0000026691"
FT TOPO_DOM 22..410
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..124
FT /note="Link"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT REGION 172..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..410
FT /note="Stem"
FT REGION 232..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 434..452
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 179..207
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 44
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 82
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT BINDING 108
FT /ligand="hyaluronan"
FT /ligand_id="ChEBI:CHEBI:132153"
FT /evidence="ECO:0000250"
FT MOD_RES 288
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:9692903"
FT MOD_RES 433
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P16070"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15379"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 60
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 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 56..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DISULFID 80..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT VAR_SEQ 224..385
FT /note="IATTPWVSAHTKQNQERTQWNPIHSNPEVLLQTTTRMTDIDRNSTSAHGENW
FT TQEPQPPFNNHEYQDEEETPHATSTTWADPNSTTEEAATQKEKWFENEWQGKNPPTPSE
FT DSHVTEGTTASAHNNHPSQRMTTQSQEDVSWTDFFDPISHPMGQGHQTESK -> SDGD
FT SSMDPRGGFDTVTHGSELA (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:1707342, ECO:0000303|Ref.2"
FT /id="VSP_005330"
FT CONFLICT 74
FT /note="R -> S (in Ref. 2; AAA97915/AAA92920)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 55946 MW; FB489D009BD4EE22 CRC64;
MDKVWWHTAW GLLCLLQLSL AQQQIDLNIT CRYAGVFHVE KNGRYSISRT EAADLCEAFN
TTLPTMAQME LALRKGFETC RYGFIEGHVV IPRIHPNAIC AANNTGVYIL LASNTSHYDT
YCFNASAPLE EDCTSVTDLP NSFDGPVTIT IVNRDGTRYS KKGEYRTHQE DIDASNIIDE
DVSSGSTIEK STPEGYILHT DLPTSQPTGD RDDAFFIGST LATIATTPWV SAHTKQNQER
TQWNPIHSNP EVLLQTTTRM TDIDRNSTSA HGENWTQEPQ PPFNNHEYQD EEETPHATST
TWADPNSTTE EAATQKEKWF ENEWQGKNPP TPSEDSHVTE GTTASAHNNH PSQRMTTQSQ
EDVSWTDFFD PISHPMGQGH QTESKGHSSG NQDSGVTTTS GPARRPQIPE WLIILASLLA
LALILAVCIA VNSRRRCGQK KKLVINSGNG TVEDRKPSEL NGEASKSQEM VHLVNKEPTE
TPDQFMTADE TRNLQSVDMK IGV
