NCTR2_HUMAN
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 03-AUG-2022, entry version 159.
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 GlyGen; O95944; 1 site.
DR iPTMnet; O95944; -.
DR PhosphoSitePlus; O95944; -.
DR BioMuta; NCR2; -.
DR PaxDb; O95944; -.
DR PeptideAtlas; O95944; -.
DR PRIDE; O95944; -.
DR Antibodypedia; 30041; 378 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 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; FIVTMTG; -.
DR OrthoDB; 1273737at2759; -.
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 1060 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 tibialis anterior and 30 other tissues.
DR Genevisible; O95944; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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 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; 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
