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Protein

Natural cytotoxicity triggering receptor 2

Gene

NCR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.1 Publication

GO - Molecular functioni

  1. transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  1. cellular defense response Source: ProtInc
  2. innate immune response Source: Reactome
  3. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_147694. DAP12 interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Natural cytotoxicity triggering receptor 2
Alternative name(s):
Lymphocyte antigen 95 homolog
NK cell-activating receptor
Natural killer cell p44-related protein
Short name:
NK-p44
Short name:
NKp44
CD_antigen: CD336
Gene namesi
Name:NCR2
Synonyms:LY95
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:6732. NCR2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 192171ExtracellularSequence AnalysisAdd
BLAST
Transmembranei193 – 21321HelicalSequence AnalysisAdd
BLAST
Topological domaini214 – 27663CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30496.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 276255Natural cytotoxicity triggering receptor 2PRO_0000015031Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi40 ↔ 109PROSITE-ProRule annotation
Disulfide bondi55 ↔ 63PROSITE-ProRule annotation
Glycosylationi180 – 1801N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO95944.
PRIDEiO95944.

Expressioni

Tissue specificityi

Selectively expressed by activated NK cells and by in vitro cultured (i.e. activated) TCRg/d lymphoid cells.1 Publication

Gene expression databases

BgeeiO95944.
CleanExiHS_NCR2.
GenevestigatoriO95944.

Organism-specific databases

HPAiHPA067249.

Interactioni

Subunit structurei

Interacts with TYROBP/DAP12. Interacts with KMT2E isoform NKp44L.2 Publications

Protein-protein interaction databases

BioGridi114827. 1 interaction.
STRINGi9606.ENSP00000362181.

Structurei

Secondary structure

1
276
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi26 – 316Combined sources
Beta strandi36 – 416Combined sources
Beta strandi51 – 599Combined sources
Beta strandi62 – 698Combined sources
Beta strandi81 – 855Combined sources
Turni87 – 893Combined sources
Beta strandi90 – 967Combined sources
Helixi101 – 1033Combined sources
Beta strandi105 – 1128Combined sources
Turni114 – 1163Combined sources
Beta strandi119 – 13012Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HKFX-ray2.20A19-130[»]
ProteinModelPortaliO95944.
SMRiO95944. Positions 23-130.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95944.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 12099Ig-likeAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi269 – 2724Poly-Asp

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG82068.
GeneTreeiENSGT00530000064177.
HOGENOMiHOG000293324.
HOVERGENiHBG052589.
InParanoidiO95944.
KOiK06742.
OMAiYWCRIYH.
OrthoDBiEOG7ZPNKZ.
PhylomeDBiO95944.
TreeFamiTF334441.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95944-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAWRALHPLL LLLLLFPGSQ AQSKAQVLQS VAGQTLTVRC QYPPTGSLYE
60 70 80 90 100
KKGWCKEASA LVCIRLVTSS KPRTMAWTSR FTIWDDPDAG FFTVTMTDLR
110 120 130 140 150
EEDSGHYWCR IYRPSDNSVS KSVRFYLVVS PASASTQTSW TPRDLVSSQT
160 170 180 190 200
QTQSCVPPTA GARQAPESPS TIPVPSQPQN STLRPGPAAP IALVPVFCGL
210 220 230 240 250
LVAKSLVLSA LLVWWGDIWW KTMMELRSLD TQKATCHLQQ VTDLPWTSVS
260 270
SPVEREILYH TVARTKISDD DDEHTL
Length:276
Mass (Da):30,677
Last modified:July 7, 2009 - v2
Checksum:i4B7AF3F451CA9F9E
GO
Isoform 2 (identifier: O95944-2) [UniParc]FASTAAdd to basket

Also known as: NKp44RG2

The sequence of this isoform differs from the canonical sequence as follows:
     177-177: Q → HPSSPLPVPLPSR
     216-276: GDIWWKTMME...ISDDDDEHTL → VLRNRHMQHQ...APGGTYGGKP

Note: No experimental confirmation available.

Show »
Length:270
Mass (Da):29,668
Checksum:i32791A7B49367E46
GO
Isoform 3 (identifier: O95944-3) [UniParc]FASTAAdd to basket

Also known as: NKp44RG1

The sequence of this isoform differs from the canonical sequence as follows:
     216-276: GDIWWKTMME...ISDDDDEHTL → VLRNRHMQHQ...APGGTYGGKP

Note: No experimental confirmation available.

Show »
Length:258
Mass (Da):28,431
Checksum:iF21D9055BCA5DF0F
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti75 – 751M → V.
Corresponds to variant rs9471577 [ dbSNP | Ensembl ].
VAR_018634
Natural varianti139 – 1391S → P.2 Publications
Corresponds to variant rs2236369 [ dbSNP | Ensembl ].
VAR_018635
Natural varianti218 – 2181I → K.
Corresponds to variant rs2273961 [ dbSNP | Ensembl ].
VAR_018636
Natural varianti223 – 2231M → V.1 Publication
Corresponds to variant rs2273962 [ dbSNP | Ensembl ].
VAR_018637

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei177 – 1771Q → HPSSPLPVPLPSR in isoform 2. 1 PublicationVSP_010409
Alternative sequencei216 – 27661GDIWW…DEHTL → VLRNRHMQHQGRSLLHPAQP RPQAHRHFPLSHRAPGGTYG GKP in isoform 2 and isoform 3. 1 PublicationVSP_010410Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225109 mRNA. Translation: CAB39168.1.
AJ010099 mRNA. Translation: CAB52289.1.
AJ010100 mRNA. Translation: CAB52290.1.
AL136967 Genomic DNA. Translation: CAC09452.3.
AL136967 Genomic DNA. Translation: CAC09453.3.
AL136967 Genomic DNA. Translation: CAC09454.3.
CCDSiCCDS4855.1. [O95944-1]
CCDS56428.1. [O95944-2]
CCDS56429.1. [O95944-3]
RefSeqiNP_001186438.1. NM_001199509.1. [O95944-2]
NP_001186439.1. NM_001199510.1. [O95944-3]
NP_004819.2. NM_004828.3. [O95944-1]
UniGeneiHs.194721.

Genome annotation databases

EnsembliENST00000373083; ENSP00000362175; ENSG00000096264. [O95944-3]
ENST00000373086; ENSP00000362178; ENSG00000096264. [O95944-2]
ENST00000373089; ENSP00000362181; ENSG00000096264. [O95944-1]
GeneIDi9436.
KEGGihsa:9436.
UCSCiuc003oqh.2. human. [O95944-1]
uc003oqi.2. human. [O95944-2]
uc003oqj.2. human. [O95944-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225109 mRNA. Translation: CAB39168.1.
AJ010099 mRNA. Translation: CAB52289.1.
AJ010100 mRNA. Translation: CAB52290.1.
AL136967 Genomic DNA. Translation: CAC09452.3.
AL136967 Genomic DNA. Translation: CAC09453.3.
AL136967 Genomic DNA. Translation: CAC09454.3.
CCDSiCCDS4855.1. [O95944-1]
CCDS56428.1. [O95944-2]
CCDS56429.1. [O95944-3]
RefSeqiNP_001186438.1. NM_001199509.1. [O95944-2]
NP_001186439.1. NM_001199510.1. [O95944-3]
NP_004819.2. NM_004828.3. [O95944-1]
UniGeneiHs.194721.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HKFX-ray2.20A19-130[»]
ProteinModelPortaliO95944.
SMRiO95944. Positions 23-130.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114827. 1 interaction.
STRINGi9606.ENSP00000362181.

Proteomic databases

PaxDbiO95944.
PRIDEiO95944.

Protocols and materials databases

DNASUi9436.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373083; ENSP00000362175; ENSG00000096264. [O95944-3]
ENST00000373086; ENSP00000362178; ENSG00000096264. [O95944-2]
ENST00000373089; ENSP00000362181; ENSG00000096264. [O95944-1]
GeneIDi9436.
KEGGihsa:9436.
UCSCiuc003oqh.2. human. [O95944-1]
uc003oqi.2. human. [O95944-2]
uc003oqj.2. human. [O95944-3]

Organism-specific databases

CTDi9436.
GeneCardsiGC06P041303.
H-InvDBHIX0165054.
HGNCiHGNC:6732. NCR2.
HPAiHPA067249.
MIMi604531. gene.
neXtProtiNX_O95944.
PharmGKBiPA30496.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG82068.
GeneTreeiENSGT00530000064177.
HOGENOMiHOG000293324.
HOVERGENiHBG052589.
InParanoidiO95944.
KOiK06742.
OMAiYWCRIYH.
OrthoDBiEOG7ZPNKZ.
PhylomeDBiO95944.
TreeFamiTF334441.

Enzyme and pathway databases

ReactomeiREACT_147694. DAP12 interactions.

Miscellaneous databases

EvolutionaryTraceiO95944.
GeneWikiiNCR2.
GenomeRNAii9436.
NextBioi35336.
PROiO95944.
SOURCEiSearch...

Gene expression databases

BgeeiO95944.
CleanExiHS_NCR2.
GenevestigatoriO95944.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily."
    Cantoni C., Bottino C., Vitale M., Pessino A., Augugliaro R., Malaspina A., Parolini S., Moretta L., Moretta A., Biassoni R.
    J. Exp. Med. 189:787-796(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DISULFIDE BONDS, FUNCTION, INTERACTION WITH TYROBP, VARIANTS PRO-139 AND VAL-223.
    Tissue: Lymphoid tissue.
  2. "NKp44 related genes."
    Cantoni C., Biassoni R.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), VARIANT PRO-139.
    Tissue: Natural killer cell.
  3. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Identification of a cellular ligand for the natural cytotoxicity receptor NKp44."
    Baychelier F., Sennepin A., Ermonval M., Dorgham K., Debre P., Vieillard V.
    Blood 122:2935-2942(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KMT2E, SUBUNIT.
  5. "The three-dimensional structure of the human NK cell receptor NKp44, a triggering partner in natural cytotoxicity."
    Cantoni C., Ponassi M., Biassoni R., Conte R., Spallarossa A., Moretta A., Moretta L., Bolognesi M., Bordo D.
    Structure 11:725-734(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 29-130.

Entry informationi

Entry nameiNCTR2_HUMAN
AccessioniPrimary (citable) accession number: O95944
Secondary accession number(s): Q9H562
, Q9H563, Q9H564, Q9UMT1, Q9UMT2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: July 7, 2009
Last modified: March 4, 2015
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.