CRTAM_HUMAN
ID CRTAM_HUMAN Reviewed; 393 AA.
AC O95727; Q59EI1; Q6IRX2;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Cytotoxic and regulatory T-cell molecule;
DE AltName: Full=Class-I MHC-restricted T-cell-associated molecule;
DE AltName: CD_antigen=CD355;
DE Flags: Precursor;
GN Name=CRTAM {ECO:0000312|EMBL:AAC80267.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC80267.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP ARG-321.
RX PubMed=10811014; DOI=10.1002/jlb.67.5.725;
RA Kennedy J., Vicari A.P., Saylor V., Zurawski S.M., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Zlotnik A.;
RT "A molecular analysis of NKT cells: identification of a class-I restricted
RT T cell-associated molecule (CRTAM).";
RL J. Leukoc. Biol. 67:725-734(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAD93067.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain {ECO:0000312|EMBL:BAD93067.1};
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH70266.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-368.
RC TISSUE=Peripheral blood {ECO:0000312|EMBL:AAH70266.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CADM1, AND TISSUE SPECIFICITY.
RX PubMed=15811952; DOI=10.1182/blood-2005-02-0817;
RA Boles K.S., Barchet W., Diacovo T., Cella M., Colonna M.;
RT "The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell
RT responses through the cell-surface receptor CRTAM.";
RL Blood 106:779-786(2005).
RN [5] {ECO:0000305}
RP INTERACTION WITH CADM1.
RX PubMed=15781451; DOI=10.1074/jbc.m502095200;
RA Galibert L., Diemer G.S., Liu Z., Johnson R.S., Smith J.L., Walzer T.,
RA Comeau M.R., Rauch C.T., Wolfson M.F., Sorensen R.A.,
RA Van der Vuurst de Vries A.-R., Branstetter D.G., Koelling R.M.,
RA Scholler J., Fanslow W.C., Baum P.R., Derry J.M., Yan W.;
RT "Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and
RT is a ligand for class-I-restricted T-cell-associated molecule.";
RL J. Biol. Chem. 280:21955-21964(2005).
RN [6] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=16300832; DOI=10.1016/j.jneuroim.2005.09.017;
RA Patino-Lopez G., Hevezi P., Lee J., Willhite D., Verge G.M., Lechner S.M.,
RA Ortiz-Navarrete V., Zlotnik A.;
RT "Human class-I restricted T cell associated molecule is highly expressed in
RT the cerebellum and is a marker for activated NKT and CD8+ T lymphocytes.";
RL J. Neuroimmunol. 171:145-155(2006).
RN [7] {ECO:0007744|PDB:3RBG}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 18-117, SUBUNIT, AND DISULFIDE
RP BOND.
RX PubMed=23583034; DOI=10.1016/j.str.2013.02.022;
RA Rubinstein R., Ramagopal U.A., Nathenson S.G., Almo S.C., Fiser A.;
RT "Functional classification of immune regulatory proteins.";
RL Structure 21:766-776(2013).
RN [8] {ECO:0007744|PDB:4H5S}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 18-117, SUBUNIT, INTERACTION WITH
RP CADM1, DISULFIDE BOND, AND MUTAGENESIS OF PHE-56; THR-57; LYS-67 AND
RP TYR-101.
RX PubMed=23871486; DOI=10.1016/j.str.2013.06.006;
RA Zhang S., Lu G., Qi J., Li Y., Zhang Z., Zhang B., Fan Z., Yan J.,
RA Gao G.F.;
RT "Competition of cell adhesion and immune recognition: insights into the
RT interaction between CRTAM and nectin-like 2.";
RL Structure 21:1430-1439(2013).
CC -!- FUNCTION: Mediates heterophilic cell-cell adhesion which regulates the
CC activation, differentiation and tissue retention of various T-cell
CC subsets (By similarity). Interaction with CADM1 promotes natural killer
CC (NK) cell cytotoxicity and IFNG/interferon-gamma secretion by CD8+ T-
CC cells in vitro as well as NK cell-mediated rejection of tumors
CC expressing CADM1 in vivo (PubMed:15811952). Regulates CD8+ T-cell
CC proliferation in response to T-cell receptor (TCR) activation (By
CC similarity). Appears to be dispensable for CD8+ T-cell-mediated
CC cytotoxicity (By similarity). Interaction with SCRIB promotes the late
CC phase of cellular polarization of a subset of CD4+ T-cells, which in
CC turn regulates TCR-mediated proliferation and IFNG, IL17 and IL22
CC production (By similarity). By interacting with CADM1 on CD8+ dendritic
CC cells, regulates the retention of activated CD8+ T-cells within the
CC draining lymph node (By similarity). Required for the intestinal
CC retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent,
CC intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells (By
CC similarity). Interaction with CADM1 promotes the adhesion to gut-
CC associated CD103+ dendritic cells, which may facilitate the expression
CC of gut-homing and adhesion molecules on T-cells and the conversion of
CC CD4+ T-cells into CD4+ CD8+ T-cells (By similarity).
CC {ECO:0000250|UniProtKB:Q149L7, ECO:0000269|PubMed:15811952}.
CC -!- SUBUNIT: Monomer (PubMed:23583034). May form homodimer (via Ig-like V-
CC type domain) (PubMed:23583034, PubMed:23871486). Interacts (via Ig-like
CC V-type domain) with CADM1 (via Ig-like V-type domain); the interaction
CC competes with CRTAM homodimerization and CADM1 homodimerization
CC (PubMed:15781451, PubMed:15811952, PubMed:23871486). Interacts (via
CC PDZ-binding motif) with SCRIB (via PDZ domain 3); the interaction
CC promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (By
CC similarity). {ECO:0000250|UniProtKB:Q149L7,
CC ECO:0000269|PubMed:15781451, ECO:0000269|PubMed:15811952,
CC ECO:0000269|PubMed:23583034, ECO:0000269|PubMed:23871486}.
CC -!- INTERACTION:
CC O95727-1; Q9BY67: CADM1; NbExp=4; IntAct=EBI-16044697, EBI-5652260;
CC O95727-1; O95727-1: CRTAM; NbExp=5; IntAct=EBI-16044697, EBI-16044697;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q149L7};
CC Single-pass type I membrane protein {ECO:0000255}. Note=In a subset of
CC CD4+ T-cells, colocalizes with SCRIB at the immunological synapse
CC during the late phase of T-cell activation.
CC {ECO:0000250|UniProtKB:Q149L7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:10811014};
CC IsoId=O95727-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95727-2; Sequence=VSP_052471, VSP_052472;
CC -!- TISSUE SPECIFICITY: In the immune system, expression is restricted to
CC activated class-I MHC-restricted cells, including NKT and CD8 T-cells
CC (PubMed:10811014, PubMed:15811952, PubMed:16300832). Strongly expressed
CC in spleen, thymus, small intestine, peripheral blood leukocyte, and in
CC Purkinje neurons in cerebellum. Expressed at much lower levels in
CC testis, ovary, colon, lung and lymphoid tissues (PubMed:16300832).
CC {ECO:0000269|PubMed:10811014, ECO:0000269|PubMed:15811952,
CC ECO:0000269|PubMed:16300832}.
CC -!- DOMAIN: The extracellular domain is required for the regulation of IFNG
CC and IL22 production, but is dispensable for late T-cell polarization.
CC {ECO:0000250|UniProtKB:Q149L7}.
CC -!- SIMILARITY: Belongs to the nectin family.
CC {ECO:0000269|PubMed:16300832}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93067.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF001622; AAC80267.1; -; mRNA.
DR EMBL; AB209830; BAD93067.1; ALT_INIT; mRNA.
DR EMBL; BC070266; AAH70266.1; -; mRNA.
DR CCDS; CCDS76489.1; -. [O95727-2]
DR CCDS; CCDS8437.1; -. [O95727-1]
DR RefSeq; NP_001291711.1; NM_001304782.1. [O95727-2]
DR RefSeq; NP_062550.2; NM_019604.3. [O95727-1]
DR PDB; 3RBG; X-ray; 2.30 A; A/B/C/D=18-117.
DR PDB; 4H5S; X-ray; 1.70 A; A=18-117.
DR PDBsum; 3RBG; -.
DR PDBsum; 4H5S; -.
DR AlphaFoldDB; O95727; -.
DR SMR; O95727; -.
DR DIP; DIP-60155N; -.
DR IntAct; O95727; 1.
DR STRING; 9606.ENSP00000227348; -.
DR GlyGen; O95727; 5 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; O95727; -.
DR PhosphoSitePlus; O95727; -.
DR BioMuta; CRTAM; -.
DR MassIVE; O95727; -.
DR PaxDb; O95727; -.
DR PeptideAtlas; O95727; -.
DR PRIDE; O95727; -.
DR ProteomicsDB; 51015; -. [O95727-1]
DR ProteomicsDB; 51016; -. [O95727-2]
DR Antibodypedia; 32807; 264 antibodies from 25 providers.
DR DNASU; 56253; -.
DR Ensembl; ENST00000227348.9; ENSP00000227348.4; ENSG00000109943.9. [O95727-1]
DR Ensembl; ENST00000533709.1; ENSP00000433728.1; ENSG00000109943.9. [O95727-2]
DR GeneID; 56253; -.
DR KEGG; hsa:56253; -.
DR MANE-Select; ENST00000227348.9; ENSP00000227348.4; NM_019604.4; NP_062550.2.
DR UCSC; uc001pyj.4; human. [O95727-1]
DR CTD; 56253; -.
DR DisGeNET; 56253; -.
DR GeneCards; CRTAM; -.
DR HGNC; HGNC:24313; CRTAM.
DR HPA; ENSG00000109943; Tissue enriched (brain).
DR MIM; 612597; gene.
DR neXtProt; NX_O95727; -.
DR OpenTargets; ENSG00000109943; -.
DR PharmGKB; PA145149072; -.
DR VEuPathDB; HostDB:ENSG00000109943; -.
DR eggNOG; ENOG502RYH2; Eukaryota.
DR GeneTree; ENSGT00940000159804; -.
DR HOGENOM; CLU_061397_0_0_1; -.
DR InParanoid; O95727; -.
DR OMA; AFLTNHT; -.
DR OrthoDB; 753787at2759; -.
DR PhylomeDB; O95727; -.
DR TreeFam; TF326804; -.
DR PathwayCommons; O95727; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; O95727; -.
DR BioGRID-ORCS; 56253; 10 hits in 1058 CRISPR screens.
DR ChiTaRS; CRTAM; human.
DR EvolutionaryTrace; O95727; -.
DR GenomeRNAi; 56253; -.
DR Pharos; O95727; Tbio.
DR PRO; PR:O95727; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O95727; protein.
DR Bgee; ENSG00000109943; Expressed in cerebellar vermis and 113 other tissues.
DR Genevisible; O95727; HS.
DR GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0008037; P:cell recognition; IDA:HGNC-UCL.
DR GO; GO:0051606; P:detection of stimulus; IDA:HGNC-UCL.
DR GO; GO:0002355; P:detection of tumor cell; IDA:HGNC-UCL.
DR GO; GO:0001768; P:establishment of T cell polarity; ISS:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISS:UniProtKB.
DR GO; GO:0097021; P:lymphocyte migration into lymphoid organs; ISS:UniProtKB.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:HGNC-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:HGNC-UCL.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IDA:HGNC-UCL.
DR GO; GO:2001185; P:regulation of CD8-positive, alpha-beta T cell activation; ISS:UniProtKB.
DR GO; GO:0050863; P:regulation of T cell activation; ISS:UniProtKB.
DR GO; GO:0045580; P:regulation of T cell differentiation; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell adhesion;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..393
FT /note="Cytotoxic and regulatory T-cell molecule"
FT /id="PRO_0000292602"
FT TOPO_DOM 18..287
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..393
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 18..114
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255"
FT DOMAIN 118..210
FT /note="Ig-like C2-type"
FT /evidence="ECO:0000255"
FT REGION 225..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 374..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 390..393
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q149L7"
FT COMPBIAS 228..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..267
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..347
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 38..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:23583034, ECO:0000269|PubMed:23871486,
FT ECO:0007744|PDB:3RBG, ECO:0007744|PDB:4H5S"
FT DISULFID 141..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..199
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_052471"
FT VAR_SEQ 200..216
FT /note="HRGLQGRKLVAPFRFED -> MWVKLLSIVAEFCFSPF (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_052472"
FT VARIANT 16
FT /note="E -> A (in dbSNP:rs35411582)"
FT /id="VAR_049868"
FT VARIANT 78
FT /note="A -> D (in dbSNP:rs34397316)"
FT /id="VAR_049869"
FT VARIANT 173
FT /note="D -> G (in dbSNP:rs35136295)"
FT /id="VAR_049870"
FT VARIANT 321
FT /note="K -> R (in dbSNP:rs2272094)"
FT /evidence="ECO:0000269|PubMed:10811014"
FT /id="VAR_032999"
FT VARIANT 368
FT /note="A -> G (in dbSNP:rs1916036)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_033000"
FT MUTAGEN 56
FT /note="F->A: Reduced binding to CADM1. Severely impairs
FT interaction with CADM1; when associated with A-57, A-67 and
FT A-101."
FT /evidence="ECO:0000269|PubMed:23871486"
FT MUTAGEN 57
FT /note="T->A: Reduced binding to CADM1. Severely impairs
FT interaction with CADM1; when associated with A-56, A-67 and
FT A-101."
FT /evidence="ECO:0000269|PubMed:23871486"
FT MUTAGEN 67
FT /note="K->A: Reduced binding to CADM1. Severely impairs
FT interaction with CADM1; when associated with A-56, A-57 and
FT A-101."
FT /evidence="ECO:0000269|PubMed:23871486"
FT MUTAGEN 101
FT /note="Y->A: Reduced binding to CADM1. Severely impairs
FT interaction with CADM1; when associated with A-56, A-57 and
FT A-67."
FT /evidence="ECO:0000269|PubMed:23871486"
FT CONFLICT 65
FT /note="A -> V (in Ref. 3; AAH70266)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="A -> T (in Ref. 3; AAH70266)"
FT /evidence="ECO:0000305"
FT STRAND 24..29
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:4H5S"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:4H5S"
FT STRAND 94..115
FT /evidence="ECO:0007829|PDB:4H5S"
SQ SEQUENCE 393 AA; 44641 MW; CB8173032EE45F03 CRC64;
MWWRVLSLLA WFPLQEASLT NHTETITVEE GQTLTLKCVT SLRKNSSLQW LTPSGFTIFL
NEYPALKNSK YQLLHHSANQ LSITVPNVTL QDEGVYKCLH YSDSVSTKEV KVIVLATPFK
PILEASVIRK QNGEEHVVLM CSTMRSKPPP QITWLLGNSM EVSGGTLHEF ETDGKKCNTT
STLIIHTYGK NSTVDCIIRH RGLQGRKLVA PFRFEDLVTD EETASDALER NSLSSQDPQQ
PTSTVSVTED SSTSEIDKEE KEQTTQDPDL TTEANPQYLG LARKKSGILL LTLVSFLIFI
LFIIVQLFIM KLRKAHVIWK KENEVSEHTL ESYRSRSNNE ETSSEEKNGQ SSHPMRCMNY
ITKLYSEAKT KRKENVQHSK LEEKHIQVPE SIV
