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 13-FEB-2019, entry version 141. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RP 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., RA Malaspina A., Parolini S., Moretta L., Moretta A., Biassoni R.; RT "NKp44, a triggering receptor involved in tumor cell lysis by RT activated human natural killer cells, is a novel member of the RT immunoglobulin 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., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA 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., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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 RT receptor 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., RA Moretta A., Moretta L., Bolognesi M., Bordo D.; RT "The three-dimensional structure of the human NK cell receptor NKp44, RT a triggering partner in natural cytotoxicity."; RL Structure 11:725-734(2003). CC -!- FUNCTION: Cytotoxicity-activating receptor that may contribute to CC the increased efficiency of activated natural killer (NK) cells to CC mediate tumor cell lysis. {ECO:0000269|PubMed:10049942}. CC -!- SUBUNIT: Interacts with TYROBP/DAP12. Interacts with KMT2E isoform CC NKp44L. {ECO:0000269|PubMed:10049942, CC ECO:0000269|PubMed:23958951}. CC -!- INTERACTION: CC Q8IZD2-8:KMT2E; NbExp=4; IntAct=EBI-14058375, EBI-15014150; CC P12004:PCNA; NbExp=7; IntAct=EBI-14058375, EBI-358311; CC O43914:TYROBP; NbExp=2; IntAct=EBI-14058375, EBI-2214794; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass CC type I 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 Note=No experimental confirmation available.; CC Name=3; Synonyms=NKp44RG1; CC IsoId=O95944-3; Sequence=VSP_010410; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Selectively expressed by activated NK cells CC and by in vitro cultured (i.e. activated) TCRg/d lymphoid cells. CC {ECO:0000269|PubMed:10049942}. CC -!- SIMILARITY: Belongs to the natural cytotoxicity receptor (NCR) CC family. {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; 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 UniGene; Hs.194721; -. DR PDB; 1HKF; X-ray; 2.20 A; A=19-130. DR PDBsum; 1HKF; -. DR ProteinModelPortal; O95944; -. DR SMR; O95944; -. DR BioGrid; 114827; 1. DR IntAct; O95944; 4. DR STRING; 9606.ENSP00000362181; -. DR iPTMnet; O95944; -. DR PhosphoSitePlus; O95944; -. DR BioMuta; NCR2; -. DR PaxDb; O95944; -. DR PeptideAtlas; O95944; -. DR PRIDE; O95944; -. DR ProteomicsDB; 51137; -. DR ProteomicsDB; 51138; -. [O95944-2] DR ProteomicsDB; 51139; -. [O95944-3] DR DNASU; 9436; -. DR Ensembl; ENST00000373083; ENSP00000362175; ENSG00000096264. [O95944-3] DR Ensembl; ENST00000373086; ENSP00000362178; ENSG00000096264. [O95944-2] DR Ensembl; ENST00000373089; ENSP00000362181; ENSG00000096264. [O95944-1] DR GeneID; 9436; -. DR KEGG; hsa:9436; -. DR UCSC; uc003oqh.3; human. [O95944-1] DR CTD; 9436; -. DR DisGeNET; 9436; -. DR EuPathDB; HostDB:ENSG00000096264.13; -. DR GeneCards; NCR2; -. DR H-InvDB; HIX0165054; -. DR HGNC; HGNC:6732; NCR2. DR HPA; HPA067249; -. DR MIM; 604531; gene. DR neXtProt; NX_O95944; -. DR OpenTargets; ENSG00000096264; -. DR PharmGKB; PA30496; -. DR eggNOG; ENOG410JAGF; Eukaryota. DR eggNOG; ENOG41117WD; LUCA. DR GeneTree; ENSGT00940000153835; -. DR HOGENOM; HOG000293324; -. DR HOVERGEN; HBG052589; -. DR InParanoid; O95944; -. DR KO; K06742; -. DR OMA; YWCRIYH; -. DR OrthoDB; 1273737at2759; -. DR PhylomeDB; O95944; -. DR TreeFam; TF334441; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-2172127; DAP12 interactions. DR EvolutionaryTrace; O95944; -. DR GeneWiki; NCR2; -. DR GenomeRNAi; 9436; -. DR PRO; PR:O95944; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000096264; Expressed in 106 organ(s), highest expression level in pleura. DR Genevisible; O95944; HS. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR Gene3D; 2.60.40.10; -; 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 Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 1. DR SUPFAM; SSF48726; SSF48726; 1. DR PROSITE; PS50835; IG_LIKE; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; KW Polymorphism; Receptor; Reference proteome; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 276 Natural cytotoxicity triggering receptor FT 2. FT /FTId=PRO_0000015031. FT TOPO_DOM 22 192 Extracellular. {ECO:0000255}. FT TRANSMEM 193 213 Helical. {ECO:0000255}. FT TOPO_DOM 214 276 Cytoplasmic. {ECO:0000255}. FT DOMAIN 22 120 Ig-like. FT COMPBIAS 269 272 Poly-Asp. FT CARBOHYD 180 180 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 40 109 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 55 63 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 177 177 Q -> HPSSPLPVPLPSR (in isoform 2). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_010409. FT VAR_SEQ 216 276 GDIWWKTMMELRSLDTQKATCHLQQVTDLPWTSVSSPVERE FT ILYHTVARTKISDDDDEHTL -> VLRNRHMQHQGRSLLHP FT AQPRPQAHRHFPLSHRAPGGTYGGKP (in isoform 2 FT and isoform 3). {ECO:0000303|Ref.2}. FT /FTId=VSP_010410. FT VARIANT 75 75 M -> V (in dbSNP:rs9471577). FT /FTId=VAR_018634. FT VARIANT 139 139 S -> P (in dbSNP:rs2236369). FT {ECO:0000269|PubMed:10049942, FT ECO:0000269|Ref.2}. FT /FTId=VAR_018635. FT VARIANT 218 218 I -> K (in dbSNP:rs2273961). FT /FTId=VAR_018636. FT VARIANT 223 223 M -> V (in dbSNP:rs2273962). FT {ECO:0000269|PubMed:10049942}. FT /FTId=VAR_018637. FT STRAND 26 31 {ECO:0000244|PDB:1HKF}. FT STRAND 36 41 {ECO:0000244|PDB:1HKF}. FT STRAND 51 59 {ECO:0000244|PDB:1HKF}. FT STRAND 62 69 {ECO:0000244|PDB:1HKF}. FT STRAND 81 85 {ECO:0000244|PDB:1HKF}. FT TURN 87 89 {ECO:0000244|PDB:1HKF}. FT STRAND 90 96 {ECO:0000244|PDB:1HKF}. FT HELIX 101 103 {ECO:0000244|PDB:1HKF}. FT STRAND 105 112 {ECO:0000244|PDB:1HKF}. FT TURN 114 116 {ECO:0000244|PDB:1HKF}. FT STRAND 119 130 {ECO:0000244|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 //