NCTR1_HUMAN
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 03-AUG-2022, entry version 177.
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}.
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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 GlyGen; O76036; 1 site.
DR iPTMnet; O76036; -.
DR PhosphoSitePlus; O76036; -.
DR BioMuta; NCR1; -.
DR MassIVE; O76036; -.
DR PaxDb; O76036; -.
DR PeptideAtlas; O76036; -.
DR PRIDE; O76036; -.
DR ABCD; O76036; 2 sequenced antibodies.
DR Antibodypedia; 19469; 784 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 CTD; 9437; -.
DR DisGeNET; 9437; -.
DR GeneCards; NCR1; -.
DR HGNC; HGNC:6731; NCR1.
DR HPA; ENSG00000189430; Tissue enhanced (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; ENSGT01000000214458; -.
DR HOGENOM; CLU_021100_1_1_1; -.
DR InParanoid; O76036; -.
DR OrthoDB; 1327293at2759; -.
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 1069 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 76 other tissues.
DR ExpressionAtlas; O76036; baseline and differential.
DR Genevisible; O76036; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
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 Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
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