ID   NCTR1_HUMAN             Reviewed;         304 AA.
AC   O76036; B0V3L2; B0V3L3; B0V3L4; B0V3L5; B8JL03; O76016; O76017; O76018;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   24-JAN-2024, entry version 185.
DE   RecName: Full=Natural cytotoxicity triggering receptor 1;
DE   AltName: Full=Lymphocyte antigen 94 homolog;
DE   AltName: Full=NK cell-activating receptor;
DE   AltName: Full=Natural killer cell p46-related protein;
DE            Short=NK-p46;
DE            Short=NKp46;
DE            Short=hNKp46;
DE   AltName: CD_antigen=CD335;
DE   Flags: Precursor;
GN   Name=NCR1; Synonyms=LY94;
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]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, TISSUE
RP   SPECIFICITY, GLYCOSYLATION, AND INTERACTION WITH CD247.
RC   TISSUE=Lymphoid tissue;
RX   PubMed=9730896; DOI=10.1084/jem.188.5.953;
RA   Pessino A., Sivori S., Bottino C., Malaspina A., Morelli L., Moretta L.,
RA   Biassoni R., Moretta A.;
RT   "Molecular cloning of NKp46: a novel member of the immunoglobulin
RT   superfamily involved in triggering of natural cytotoxicity.";
RL   J. Exp. Med. 188:953-960(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA   Lin L., Yu R., Zhong J., Li H., Zhou G., Shen C., Ke R., Zheng G., Yang S.;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC   TISSUE=Blood;
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   [6]
RP   REVIEW.
RX   PubMed=14754506; DOI=10.1111/j.1582-4934.2003.tb00240.x;
RA   Biassoni R., Cantoni C., Marras D., Giron-Michel J., Falco M., Moretta L.,
RA   Dimasi N.;
RT   "Human natural killer cell receptors: insights into their molecular
RT   function and structure.";
RL   J. Cell. Mol. Med. 7:376-387(2003).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 25-212, AND DISULFIDE BONDS.
RX   PubMed=12951052; DOI=10.1016/j.bbrc.2003.08.007;
RA   Ponassi M., Cantoni C., Biassoni R., Conte R., Spallarossa A., Pesce A.,
RA   Moretta A., Moretta L., Bolognesi M., Bordo D.;
RT   "Structure of the human NK cell triggering receptor NKp46 ectodomain.";
RL   Biochem. Biophys. Res. Commun. 309:317-323(2003).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-212, AND DISULFIDE BONDS.
RX   PubMed=12960161; DOI=10.1074/jbc.m308491200;
RA   Foster C.E., Colonna M., Sun P.D.;
RT   "Crystal structure of the human natural killer (NK) cell activating
RT   receptor NKp46 reveals structural relationship to other leukocyte receptor
RT   complex immunoreceptors.";
RL   J. Biol. Chem. 278:46081-46086(2003).
RN   [9]
RP   VARIANT [LARGE SCALE ANALYSIS] TYR-87.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Cytotoxicity-activating receptor that may contribute to the
CC       increased efficiency of activated natural killer (NK) cells to mediate
CC       tumor cell lysis. {ECO:0000269|PubMed:9730896}.
CC   -!- SUBUNIT: Interacts with CD247 and FCER1G. {ECO:0000269|PubMed:9730896}.
CC   -!- INTERACTION:
CC       O76036; PRO_0000035863 [P27918]: CFP; NbExp=5; IntAct=EBI-13915737, EBI-15183949;
CC       O76036; P08670: VIM; NbExp=3; IntAct=EBI-13915737, EBI-353844;
CC       O76036-6; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-19157577, EBI-10225815;
CC       O76036-6; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-19157577, EBI-12195227;
CC       O76036-6; P56557: TMEM50B; NbExp=3; IntAct=EBI-19157577, EBI-12366453;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=1;
CC         IsoId=O76036-1; Sequence=Displayed;
CC       Name=2; Synonyms=b;
CC         IsoId=O76036-2; Sequence=VSP_010408;
CC       Name=3; Synonyms=c;
CC         IsoId=O76036-3; Sequence=VSP_010407;
CC       Name=4; Synonyms=d;
CC         IsoId=O76036-4; Sequence=VSP_010407, VSP_010408;
CC       Name=5;
CC         IsoId=O76036-5; Sequence=VSP_010406;
CC       Name=6;
CC         IsoId=O76036-6; Sequence=VSP_038384;
CC   -!- TISSUE SPECIFICITY: Selectively expressed by both resting and activated
CC       NK cells. {ECO:0000269|PubMed:9730896}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9730896}.
CC   -!- PTM: O-glycosylated. {ECO:0000269|PubMed:9730896}.
CC   -!- SIMILARITY: Belongs to the natural cytotoxicity receptor (NCR) family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AJ006121; CAA06872.1; -; mRNA.
DR   EMBL; AJ006122; CAA06873.1; -; mRNA.
DR   EMBL; AJ006123; CAA06874.1; -; mRNA.
DR   EMBL; AJ001383; CAA04714.1; -; mRNA.
DR   EMBL; AY346373; AAQ54328.1; -; mRNA.
DR   EMBL; CU151839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CU459006; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471135; EAW72308.1; -; Genomic_DNA.
DR   EMBL; CH471135; EAW72310.1; -; Genomic_DNA.
DR   EMBL; CH471135; EAW72311.1; -; Genomic_DNA.
DR   EMBL; BC064806; AAH64806.1; -; mRNA.
DR   CCDS; CCDS12911.1; -. [O76036-1]
DR   CCDS; CCDS46181.1; -. [O76036-6]
DR   CCDS; CCDS46182.1; -. [O76036-2]
DR   CCDS; CCDS56103.1; -. [O76036-3]
DR   RefSeq; NP_001138929.2; NM_001145457.2.
DR   RefSeq; NP_001138930.2; NM_001145458.2.
DR   RefSeq; NP_001229285.1; NM_001242356.2. [O76036-3]
DR   RefSeq; NP_001229286.1; NM_001242357.2. [O76036-4]
DR   RefSeq; NP_004820.2; NM_004829.6.
DR   PDB; 1OLL; X-ray; 1.93 A; A=25-212.
DR   PDB; 1P6F; X-ray; 2.20 A; A=22-263.
DR   PDB; 6IAP; X-ray; 2.90 A; A=25-206.
DR   PDBsum; 1OLL; -.
DR   PDBsum; 1P6F; -.
DR   PDBsum; 6IAP; -.
DR   AlphaFoldDB; O76036; -.
DR   SMR; O76036; -.
DR   BioGRID; 114828; 22.
DR   IntAct; O76036; 9.
DR   STRING; 9606.ENSP00000291890; -.
DR   GlyCosmos; O76036; 1 site, No reported glycans.
DR   GlyGen; O76036; 1 site.
DR   iPTMnet; O76036; -.
DR   PhosphoSitePlus; O76036; -.
DR   BioMuta; NCR1; -.
DR   MassIVE; O76036; -.
DR   PaxDb; 9606-ENSP00000291890; -.
DR   PeptideAtlas; O76036; -.
DR   ABCD; O76036; 2 sequenced antibodies.
DR   Antibodypedia; 19469; 864 antibodies from 35 providers.
DR   DNASU; 9437; -.
DR   Ensembl; ENST00000350790.9; ENSP00000344358.4; ENSG00000189430.13. [O76036-3]
DR   Ensembl; ENST00000357397.5; ENSP00000349972.4; ENSG00000189430.13. [O76036-5]
DR   Ensembl; ENST00000610621.4; ENSP00000483452.1; ENSG00000273535.4. [O76036-1]
DR   Ensembl; ENST00000610753.4; ENSP00000484377.1; ENSG00000273535.4. [O76036-3]
DR   Ensembl; ENST00000611098.1; ENSP00000479222.1; ENSG00000275156.4. [O76036-5]
DR   Ensembl; ENST00000611105.4; ENSP00000483028.1; ENSG00000278362.4. [O76036-3]
DR   Ensembl; ENST00000611942.4; ENSP00000483723.1; ENSG00000275156.4. [O76036-2]
DR   Ensembl; ENST00000612239.4; ENSP00000481692.1; ENSG00000275156.4. [O76036-6]
DR   Ensembl; ENST00000612645.4; ENSP00000481540.1; ENSG00000275156.4. [O76036-3]
DR   Ensembl; ENST00000612896.4; ENSP00000484520.1; ENSG00000278362.4. [O76036-1]
DR   Ensembl; ENST00000613135.4; ENSP00000480145.1; ENSG00000278362.4. [O76036-5]
DR   Ensembl; ENST00000613556.1; ENSP00000482092.1; ENSG00000273535.4. [O76036-5]
DR   Ensembl; ENST00000615622.4; ENSP00000478507.1; ENSG00000273535.4. [O76036-1]
DR   Ensembl; ENST00000617154.4; ENSP00000481971.1; ENSG00000275156.4. [O76036-1]
DR   Ensembl; ENST00000617784.4; ENSP00000482423.1; ENSG00000278362.4. [O76036-1]
DR   Ensembl; ENST00000618973.4; ENSP00000483611.1; ENSG00000273535.4. [O76036-2]
DR   Ensembl; ENST00000619077.4; ENSP00000484221.1; ENSG00000273535.4. [O76036-1]
DR   Ensembl; ENST00000619451.1; ENSP00000482536.1; ENSG00000278362.4. [O76036-6]
DR   Ensembl; ENST00000620296.4; ENSP00000484067.1; ENSG00000278362.4. [O76036-2]
DR   Ensembl; ENST00000621059.4; ENSP00000484831.1; ENSG00000278362.4. [O76036-4]
DR   Ensembl; ENST00000621652.4; ENSP00000477625.1; ENSG00000273535.4. [O76036-4]
DR   GeneID; 9437; -.
DR   KEGG; hsa:9437; -.
DR   UCSC; uc002qid.3; human. [O76036-1]
DR   AGR; HGNC:6731; -.
DR   CTD; 9437; -.
DR   DisGeNET; 9437; -.
DR   GeneCards; NCR1; -.
DR   HGNC; HGNC:6731; NCR1.
DR   HPA; ENSG00000189430; Tissue enriched (lymphoid).
DR   MalaCards; NCR1; -.
DR   MIM; 604530; gene.
DR   neXtProt; NX_O76036; -.
DR   OpenTargets; ENSG00000189430; -.
DR   PharmGKB; PA30495; -.
DR   VEuPathDB; HostDB:ENSG00000189430; -.
DR   eggNOG; ENOG502RWVC; Eukaryota.
DR   GeneTree; ENSGT01100000263478; -.
DR   HOGENOM; CLU_021100_1_1_1; -.
DR   InParanoid; O76036; -.
DR   OrthoDB; 5263025at2759; -.
DR   PhylomeDB; O76036; -.
DR   TreeFam; TF336644; -.
DR   PathwayCommons; O76036; -.
DR   Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR   SignaLink; O76036; -.
DR   BioGRID-ORCS; 9437; 5 hits in 1147 CRISPR screens.
DR   ChiTaRS; NCR1; human.
DR   EvolutionaryTrace; O76036; -.
DR   GeneWiki; NCR1; -.
DR   GenomeRNAi; 9437; -.
DR   Pharos; O76036; Tbio.
DR   PRO; PR:O76036; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O76036; Protein.
DR   Bgee; ENSG00000189430; Expressed in granulocyte and 77 other cell types or tissues.
DR   ExpressionAtlas; O76036; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0016514; C:SWI/SNF complex; ISS:UniProtKB.
DR   GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR   GO; GO:0030101; P:natural killer cell activation; NAS:UniProtKB.
DR   GO; GO:0042269; P:regulation of natural killer cell mediated cytotoxicity; TAS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd05751; IgC2_D1_LILR_KIR_like; 1.
DR   CDD; cd05711; IgC2_D2_LILR_KIR_like; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR013151; Immunoglobulin.
DR   PANTHER; PTHR11738; MHC CLASS I NK CELL RECEPTOR; 1.
DR   PANTHER; PTHR11738:SF14; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 1; 1.
DR   Pfam; PF00047; ig; 1.
DR   SMART; SM00409; IG; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 2.
DR   Genevisible; O76036; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW   Glycoprotein; Immunoglobulin domain; Membrane; Receptor;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..304
FT                   /note="Natural cytotoxicity triggering receptor 1"
FT                   /id="PRO_0000015027"
FT   TOPO_DOM        22..258
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        259..279
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        280..304
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          34..118
FT                   /note="Ig-like 1"
FT   DOMAIN          129..211
FT                   /note="Ig-like 2"
FT   CARBOHYD        216
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        49..98
FT                   /evidence="ECO:0000269|PubMed:12960161,
FT                   ECO:0000269|PubMed:16959974, ECO:0007744|PDB:1OLL,
FT                   ECO:0007744|PDB:1P6F"
FT   DISULFID        144..190
FT                   /evidence="ECO:0000269|PubMed:12960161,
FT                   ECO:0000269|PubMed:16959974, ECO:0007744|PDB:1OLL,
FT                   ECO:0007744|PDB:1P6F"
FT   VAR_SEQ         12..118
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_010406"
FT   VAR_SEQ         25..119
FT                   /note="Missing (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:9730896"
FT                   /id="VSP_010407"
FT   VAR_SEQ         228..244
FT                   /note="Missing (in isoform 2 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:9730896"
FT                   /id="VSP_010408"
FT   VAR_SEQ         228
FT                   /note="Missing (in isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_038384"
FT   VARIANT         82
FT                   /note="K -> Q (in dbSNP:rs2278428)"
FT                   /id="VAR_018633"
FT   VARIANT         87
FT                   /note="D -> Y (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035527"
FT   STRAND          30..35
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          37..40
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          45..50
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          57..62
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          65..70
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:6IAP"
FT   STRAND          80..87
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   HELIX           90..92
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          94..102
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          113..119
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          125..130
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          132..135
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          139..145
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          147..149
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          151..161
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          163..168
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          170..179
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   HELIX           182..184
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          186..191
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          193..195
FT                   /evidence="ECO:0007829|PDB:1OLL"
FT   STRAND          206..211
FT                   /evidence="ECO:0007829|PDB:1OLL"
SQ   SEQUENCE   304 AA;  34481 MW;  FBCBDE50D2F34CD3 CRC64;
     MSSTLPALLC VGLCLSQRIS AQQQTLPKPF IWAEPHFMVP KEKQVTICCQ GNYGAVEYQL
     HFEGSLFAVD RPKPPERINK VKFYIPDMNS RMAGQYSCIY RVGELWSEPS NLLDLVVTEM
     YDTPTLSVHP GPEVISGEKV TFYCRLDTAT SMFLLLKEGR SSHVQRGYGK VQAEFPLGPV
     TTAHRGTYRC FGSYNNHAWS FPSEPVKLLV TGDIENTSLA PEDPTFPADT WGTYLLTTET
     GLQKDHALWD HTAQNLLRMG LAFLVLVALV WFLVEDWLSR KRTRERASRA STWEGRRRLN
     TQTL
//