ID   NCTR2_HUMAN             Reviewed;         276 AA.
AC   O95944; Q9H562; Q9H563; Q9H564; Q9UMT1; Q9UMT2;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   07-JUL-2009, sequence version 2.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Natural cytotoxicity triggering receptor 2;
DE   AltName: Full=Lymphocyte antigen 95 homolog;
DE   AltName: Full=NK cell-activating receptor;
DE   AltName: Full=Natural killer cell p44-related protein;
DE            Short=NK-p44;
DE            Short=NKp44;
DE   AltName: CD_antigen=CD336;
DE   Flags: Precursor;
GN   Name=NCR2; Synonyms=LY95;
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] (ISOFORM 1), TISSUE SPECIFICITY, DISULFIDE
RP   BONDS, FUNCTION, INTERACTION WITH TYROBP, AND VARIANTS PRO-139 AND VAL-223.
RC   TISSUE=Lymphoid tissue;
RX   PubMed=10049942; DOI=10.1084/jem.189.5.787;
RA   Cantoni C., Bottino C., Vitale M., Pessino A., Augugliaro R., Malaspina A.,
RA   Parolini S., Moretta L., Moretta A., Biassoni R.;
RT   "NKp44, a triggering receptor involved in tumor cell lysis by activated
RT   human natural killer cells, is a novel member of the immunoglobulin
RT   superfamily.";
RL   J. Exp. Med. 189:787-796(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANT PRO-139.
RC   TISSUE=Natural killer cell;
RA   Cantoni C., Biassoni R.;
RT   "NKp44 related genes.";
RL   Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [4]
RP   INTERACTION WITH KMT2E, AND SUBUNIT.
RX   PubMed=23958951; DOI=10.1182/blood-2013-03-489054;
RA   Baychelier F., Sennepin A., Ermonval M., Dorgham K., Debre P.,
RA   Vieillard V.;
RT   "Identification of a cellular ligand for the natural cytotoxicity receptor
RT   NKp44.";
RL   Blood 122:2935-2942(2013).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 29-130.
RX   PubMed=12791260; DOI=10.1016/s0969-2126(03)00095-9;
RA   Cantoni C., Ponassi M., Biassoni R., Conte R., Spallarossa A., Moretta A.,
RA   Moretta L., Bolognesi M., Bordo D.;
RT   "The three-dimensional structure of the human NK cell receptor NKp44, a
RT   triggering partner in natural cytotoxicity.";
RL   Structure 11:725-734(2003).
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:10049942}.
CC   -!- SUBUNIT: Interacts with TYROBP/DAP12. Interacts with KMT2E isoform
CC       NKp44L. {ECO:0000269|PubMed:10049942, ECO:0000269|PubMed:23958951}.
CC   -!- INTERACTION:
CC       O95944; Q8IZD2-8: KMT2E; NbExp=4; IntAct=EBI-14058375, EBI-15014150;
CC       O95944; P12004: PCNA; NbExp=7; IntAct=EBI-14058375, EBI-358311;
CC       O95944; O43914: TYROBP; NbExp=2; IntAct=EBI-14058375, EBI-2214794;
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=3;
CC       Name=1;
CC         IsoId=O95944-1; Sequence=Displayed;
CC       Name=2; Synonyms=NKp44RG2;
CC         IsoId=O95944-2; Sequence=VSP_010409, VSP_010410;
CC       Name=3; Synonyms=NKp44RG1;
CC         IsoId=O95944-3; Sequence=VSP_010410;
CC   -!- TISSUE SPECIFICITY: Selectively expressed by activated NK cells and by
CC       in vitro cultured (i.e. activated) TCRg/d lymphoid cells.
CC       {ECO:0000269|PubMed:10049942}.
CC   -!- SIMILARITY: Belongs to the natural cytotoxicity receptor (NCR) family.
CC       {ECO:0000305}.
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DR   EMBL; AJ225109; CAB39168.1; -; mRNA.
DR   EMBL; AJ010099; CAB52289.1; -; mRNA.
DR   EMBL; AJ010100; CAB52290.1; -; mRNA.
DR   EMBL; AL136967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS4855.1; -. [O95944-1]
DR   CCDS; CCDS56428.1; -. [O95944-2]
DR   CCDS; CCDS56429.1; -. [O95944-3]
DR   RefSeq; NP_001186438.1; NM_001199509.1. [O95944-2]
DR   RefSeq; NP_001186439.1; NM_001199510.1. [O95944-3]
DR   RefSeq; NP_004819.2; NM_004828.3. [O95944-1]
DR   PDB; 1HKF; X-ray; 2.20 A; A=19-130.
DR   PDBsum; 1HKF; -.
DR   AlphaFoldDB; O95944; -.
DR   SMR; O95944; -.
DR   BioGRID; 114827; 3.
DR   IntAct; O95944; 4.
DR   STRING; 9606.ENSP00000362181; -.
DR   GlyCosmos; O95944; 1 site, No reported glycans.
DR   GlyGen; O95944; 1 site.
DR   iPTMnet; O95944; -.
DR   PhosphoSitePlus; O95944; -.
DR   BioMuta; NCR2; -.
DR   PaxDb; 9606-ENSP00000362181; -.
DR   PeptideAtlas; O95944; -.
DR   Antibodypedia; 30041; 416 antibodies from 29 providers.
DR   DNASU; 9436; -.
DR   Ensembl; ENST00000373083.8; ENSP00000362175.4; ENSG00000096264.14. [O95944-3]
DR   Ensembl; ENST00000373086.3; ENSP00000362178.3; ENSG00000096264.14. [O95944-2]
DR   Ensembl; ENST00000373089.10; ENSP00000362181.5; ENSG00000096264.14. [O95944-1]
DR   GeneID; 9436; -.
DR   KEGG; hsa:9436; -.
DR   MANE-Select; ENST00000373089.10; ENSP00000362181.5; NM_004828.4; NP_004819.2.
DR   UCSC; uc003oqh.3; human. [O95944-1]
DR   AGR; HGNC:6732; -.
DR   CTD; 9436; -.
DR   DisGeNET; 9436; -.
DR   GeneCards; NCR2; -.
DR   HGNC; HGNC:6732; NCR2.
DR   HPA; ENSG00000096264; Not detected.
DR   MIM; 604531; gene.
DR   neXtProt; NX_O95944; -.
DR   OpenTargets; ENSG00000096264; -.
DR   PharmGKB; PA30496; -.
DR   VEuPathDB; HostDB:ENSG00000096264; -.
DR   eggNOG; ENOG502TG0M; Eukaryota.
DR   GeneTree; ENSGT00940000153835; -.
DR   HOGENOM; CLU_051023_2_0_1; -.
DR   InParanoid; O95944; -.
DR   OMA; IWDNPST; -.
DR   OrthoDB; 3800959at2759; -.
DR   PhylomeDB; O95944; -.
DR   TreeFam; TF334441; -.
DR   PathwayCommons; O95944; -.
DR   Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR   Reactome; R-HSA-2172127; DAP12 interactions.
DR   SignaLink; O95944; -.
DR   SIGNOR; O95944; -.
DR   BioGRID-ORCS; 9436; 12 hits in 1138 CRISPR screens.
DR   EvolutionaryTrace; O95944; -.
DR   GeneWiki; NCR2; -.
DR   GenomeRNAi; 9436; -.
DR   Pharos; O95944; Tbio.
DR   PRO; PR:O95944; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; O95944; Protein.
DR   Bgee; ENSG00000096264; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 29 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd05716; IgV_pIgR_like; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
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   PANTHER; PTHR16423:SF7; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 2; 1.
DR   PANTHER; PTHR16423; TREM-LIKE TRANSCRIPT PROTEIN; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   Genevisible; O95944; 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; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..276
FT                   /note="Natural cytotoxicity triggering receptor 2"
FT                   /id="PRO_0000015031"
FT   TOPO_DOM        22..192
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        193..213
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        214..276
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          22..120
FT                   /note="Ig-like"
FT   REGION          138..184
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        180
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        40..109
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        55..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VAR_SEQ         177
FT                   /note="Q -> HPSSPLPVPLPSR (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_010409"
FT   VAR_SEQ         216..276
FT                   /note="GDIWWKTMMELRSLDTQKATCHLQQVTDLPWTSVSSPVEREILYHTVARTKI
FT                   SDDDDEHTL -> VLRNRHMQHQGRSLLHPAQPRPQAHRHFPLSHRAPGGTYGGKP
FT                   (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_010410"
FT   VARIANT         75
FT                   /note="M -> V (in dbSNP:rs9471577)"
FT                   /id="VAR_018634"
FT   VARIANT         139
FT                   /note="S -> P (in dbSNP:rs2236369)"
FT                   /evidence="ECO:0000269|PubMed:10049942, ECO:0000269|Ref.2"
FT                   /id="VAR_018635"
FT   VARIANT         218
FT                   /note="I -> K (in dbSNP:rs2273961)"
FT                   /id="VAR_018636"
FT   VARIANT         223
FT                   /note="M -> V (in dbSNP:rs2273962)"
FT                   /evidence="ECO:0000269|PubMed:10049942"
FT                   /id="VAR_018637"
FT   STRAND          26..31
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          36..41
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          51..59
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          62..69
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          81..85
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   TURN            87..89
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          90..96
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   HELIX           101..103
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          105..112
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   TURN            114..116
FT                   /evidence="ECO:0007829|PDB:1HKF"
FT   STRAND          119..130
FT                   /evidence="ECO:0007829|PDB:1HKF"
SQ   SEQUENCE   276 AA;  30677 MW;  4B7AF3F451CA9F9E CRC64;
     MAWRALHPLL LLLLLFPGSQ AQSKAQVLQS VAGQTLTVRC QYPPTGSLYE KKGWCKEASA
     LVCIRLVTSS KPRTMAWTSR FTIWDDPDAG FFTVTMTDLR EEDSGHYWCR IYRPSDNSVS
     KSVRFYLVVS PASASTQTSW TPRDLVSSQT QTQSCVPPTA GARQAPESPS TIPVPSQPQN
     STLRPGPAAP IALVPVFCGL LVAKSLVLSA LLVWWGDIWW KTMMELRSLD TQKATCHLQQ
     VTDLPWTSVS SPVEREILYH TVARTKISDD DDEHTL
//