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   13-FEB-2019, entry version 138.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAC80267.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP   VARIANT ARG-321.
RX   PubMed=10811014;
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
RT   restricted 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
RP   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
RT   project: 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
RT   and 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.,
RA   Lechner S.M., Ortiz-Navarrete V., Zlotnik A.;
RT   "Human class-I restricted T cell associated molecule is highly
RT   expressed in the cerebellum and is a marker for activated NKT and CD8+
RT   T lymphocytes.";
RL   J. Neuroimmunol. 171:145-155(2006).
RN   [7] {ECO:0000305, ECO:0000312|EMBL:BAD93067.1}
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 18-117, AND DISULFIDE BOND.
RG   New York structural genomics research consortium (NYSGRC);
RT   "Structure analysis of human class-I MHC restricted T-cell associated
RT   molecule.";
RL   Submitted (MAY-2011) to the PDB data bank.
CC   -!- FUNCTION: Interaction with CADM1 promotes natural killer (NK) cell
CC       cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+
CC       cells in vitro as well as NK cell-mediated rejection of tumors
CC       expressing CADM3 in vivo. {ECO:0000250|UniProtKB:Q149L7,
CC       ECO:0000269|PubMed:15811952}.
CC   -!- SUBUNIT: Interacts with CADM1. {ECO:0000269|PubMed:15781451,
CC       ECO:0000269|PubMed:15811952}.
CC   -!- INTERACTION:
CC       Q9BY67:CADM1; NbExp=4; IntAct=EBI-16044697, EBI-5652260;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC       membrane protein {ECO:0000255}.
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         Note=No experimental confirmation available. {ECO:0000305};
CC   -!- TISSUE SPECIFICITY: In the immune system, expression is restricted
CC       to activated class-I MHC-restricted cells, including NKT and CD8
CC       cells. Strongly expressed in spleen, thymus, small intestine,
CC       peripheral blood leukocyte, and in Purkinje neurons in cerebellum.
CC       Expressed at much lower levels in testis, ovary, colon, lung and
CC       lymphoid tissues. {ECO:0000269|PubMed:10811014,
CC       ECO:0000269|PubMed:15811952, ECO:0000269|PubMed:16300832}.
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   UniGene; Hs.159523; -.
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   ProteinModelPortal; O95727; -.
DR   SMR; O95727; -.
DR   DIP; DIP-60155N; -.
DR   IntAct; O95727; 1.
DR   STRING; 9606.ENSP00000227348; -.
DR   iPTMnet; O95727; -.
DR   PhosphoSitePlus; O95727; -.
DR   BioMuta; CRTAM; -.
DR   EPD; O95727; -.
DR   PaxDb; O95727; -.
DR   PeptideAtlas; O95727; -.
DR   PRIDE; O95727; -.
DR   ProteomicsDB; 51015; -.
DR   ProteomicsDB; 51016; -. [O95727-2]
DR   DNASU; 56253; -.
DR   Ensembl; ENST00000227348; ENSP00000227348; ENSG00000109943. [O95727-1]
DR   Ensembl; ENST00000533709; ENSP00000433728; ENSG00000109943. [O95727-2]
DR   GeneID; 56253; -.
DR   KEGG; hsa:56253; -.
DR   UCSC; uc001pyj.4; human. [O95727-1]
DR   CTD; 56253; -.
DR   DisGeNET; 56253; -.
DR   EuPathDB; HostDB:ENSG00000109943.8; -.
DR   GeneCards; CRTAM; -.
DR   H-InvDB; HIX0035844; -.
DR   HGNC; HGNC:24313; CRTAM.
DR   MIM; 612597; gene.
DR   neXtProt; NX_O95727; -.
DR   OpenTargets; ENSG00000109943; -.
DR   PharmGKB; PA145149072; -.
DR   eggNOG; ENOG410IESB; Eukaryota.
DR   eggNOG; ENOG4111KGD; LUCA.
DR   GeneTree; ENSGT00940000159804; -.
DR   HOGENOM; HOG000008690; -.
DR   HOVERGEN; HBG053014; -.
DR   InParanoid; O95727; -.
DR   KO; K16361; -.
DR   OMA; CIIRHKG; -.
DR   OrthoDB; 753787at2759; -.
DR   PhylomeDB; O95727; -.
DR   TreeFam; TF326804; -.
DR   Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR   ChiTaRS; CRTAM; human.
DR   EvolutionaryTrace; O95727; -.
DR   GenomeRNAi; 56253; -.
DR   PRO; PR:O95727; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000109943; Expressed in 107 organ(s), highest expression level in cerebellar vermis.
DR   Genevisible; O95727; HS.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:HGNC.
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.
DR   GO; GO:0051606; P:detection of stimulus; IDA:HGNC.
DR   GO; GO:0002355; P:detection of tumor cell; IDA:HGNC.
DR   GO; GO:0050715; P:positive regulation of cytokine secretion; IDA:HGNC.
DR   GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:HGNC.
DR   GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IDA:HGNC.
DR   GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
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;
KW   Complete proteome; Disulfide bond; Glycoprotein; Immunity;
KW   Immunoglobulin domain; Membrane; Polymorphism; Reference proteome;
KW   Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     17       {ECO:0000255}.
FT   CHAIN        18    393       Cytotoxic and regulatory T-cell molecule.
FT                                /FTId=PRO_0000292602.
FT   TOPO_DOM     18    287       Extracellular. {ECO:0000255}.
FT   TRANSMEM    288    308       Helical. {ECO:0000255}.
FT   TOPO_DOM    309    393       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       18    114       Ig-like V-type. {ECO:0000255}.
FT   DOMAIN      118    210       Ig-like C2-type. {ECO:0000255}.
FT   CARBOHYD     21     21       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     87     87       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    178    178       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     38     98       {ECO:0000255|PROSITE-ProRule:PRU00114,
FT                                ECO:0000269|Ref.7}.
FT   DISULFID    141    196       {ECO:0000255|PROSITE-ProRule:PRU00114}.
FT   VAR_SEQ       1    199       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.2}.
FT                                /FTId=VSP_052471.
FT   VAR_SEQ     200    216       HRGLQGRKLVAPFRFED -> MWVKLLSIVAEFCFSPF
FT                                (in isoform 2). {ECO:0000303|Ref.2}.
FT                                /FTId=VSP_052472.
FT   VARIANT      16     16       E -> A (in dbSNP:rs35411582).
FT                                /FTId=VAR_049868.
FT   VARIANT      78     78       A -> D (in dbSNP:rs34397316).
FT                                /FTId=VAR_049869.
FT   VARIANT     173    173       D -> G (in dbSNP:rs35136295).
FT                                /FTId=VAR_049870.
FT   VARIANT     321    321       K -> R (in dbSNP:rs2272094).
FT                                {ECO:0000269|PubMed:10811014}.
FT                                /FTId=VAR_032999.
FT   VARIANT     368    368       A -> G (in dbSNP:rs1916036).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_033000.
FT   CONFLICT     65     65       A -> V (in Ref. 3; AAH70266).
FT                                {ECO:0000305}.
FT   CONFLICT    315    315       A -> T (in Ref. 3; AAH70266).
FT                                {ECO:0000305}.
FT   STRAND       24     29       {ECO:0000244|PDB:4H5S}.
FT   STRAND       34     39       {ECO:0000244|PDB:4H5S}.
FT   STRAND       47     51       {ECO:0000244|PDB:4H5S}.
FT   STRAND       57     60       {ECO:0000244|PDB:4H5S}.
FT   STRAND       72     77       {ECO:0000244|PDB:4H5S}.
FT   STRAND       80     85       {ECO:0000244|PDB:4H5S}.
FT   HELIX        90     92       {ECO:0000244|PDB:4H5S}.
FT   STRAND       94    115       {ECO:0000244|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
//