O95944 (NCTR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	NCR2
Synonyms:	LY95

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	276 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis. Ref.1
Subunit structure	Interacts with TYROBP/DAP12. Ref.1
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential.
Tissue specificity	Selectively expressed by activated NK cells and by in vitro cultured (i.e. activated) TCRg/d lymphoid cells. Ref.1
Sequence similarities	Belongs to the natural cytotoxicity receptor (NCR) family. Contains 1 Ig-like (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular defense response Traceable author statement Ref.1. Source: ProtInc innate immune response Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	transmembrane signaling receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95944-1)

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.

Isoform 2 (identifier: O95944-2)

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.

Isoform 3 (identifier: O95944-3)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 276

255

Natural cytotoxicity triggering receptor 2

PRO_0000015031

Regions

Topological domain

22 – 192

171

Extracellular Potential

Transmembrane

193 – 213

21

Helical; Potential

Topological domain

214 – 276

63

Cytoplasmic Potential

Domain

22 – 120

99

Ig-like

Compositional bias

269 – 272

4

Poly-Asp

Amino acid modifications

Glycosylation

180

1

N-linked (GlcNAc...) Potential

Disulfide bond

40 ↔ 109

Potential

Disulfide bond

55 ↔ 63

Potential

Natural variations

Alternative sequence

177

1

Q → HPSSPLPVPLPSR in isoform 2.

VSP_010409

Alternative sequence

216 – 276

61

GDIWW…DEHTL → VLRNRHMQHQGRSLLHPAQP RPQAHRHFPLSHRAPGGTYG GKP in isoform 2 and isoform 3.

VSP_010410

Natural variant

75

1

M → V.
Corresponds to variant rs9471577 [ dbSNP | Ensembl ].

VAR_018634

Natural variant

139

1

S → P. Ref.1 Ref.2
Corresponds to variant rs2236369 [ dbSNP | Ensembl ].

VAR_018635

Natural variant

218

1

I → K.
Corresponds to variant rs2273961 [ dbSNP | Ensembl ].

VAR_018636

Natural variant

223

1

M → V. Ref.1
Corresponds to variant rs2273962 [ dbSNP | Ensembl ].

VAR_018637

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

276

Helix Strand Turn

Details...

Beta strand

26 – 31

6

Beta strand

36 – 41

6

Beta strand

51 – 59

9

Beta strand

62 – 69

8

Beta strand

81 – 85

5

Turn

87 – 89

3

Beta strand

90 – 96

7

Helix

101 – 103

3

Beta strand

105 – 112

8

Turn

114 – 116

3

Beta strand

119 – 130

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 7, 2009. Version 2. Checksum: 4B7AF3F451CA9F9E	FASTA	276	30,677
	10 20 30 40 50 60 MAWRALHPLL LLLLLFPGSQ AQSKAQVLQS VAGQTLTVRC QYPPTGSLYE KKGWCKEASA 70 80 90 100 110 120 LVCIRLVTSS KPRTMAWTSR FTIWDDPDAG FFTVTMTDLR EEDSGHYWCR IYRPSDNSVS 130 140 150 160 170 180 KSVRFYLVVS PASASTQTSW TPRDLVSSQT QTQSCVPPTA GARQAPESPS TIPVPSQPQN 190 200 210 220 230 240 STLRPGPAAP IALVPVFCGL LVAKSLVLSA LLVWWGDIWW KTMMELRSLD TQKATCHLQQ 250 260 270 VTDLPWTSVS SPVEREILYH TVARTKISDD DDEHTL
	Isoform 2 (NKp44RG2) [UniParc]. Checksum: 32791A7B49367E46	FASTA	270	29,668
	10 20 30 40 50 60 MAWRALHPLL LLLLLFPGSQ AQSKAQVLQS VAGQTLTVRC QYPPTGSLYE KKGWCKEASA 70 80 90 100 110 120 LVCIRLVTSS KPRTMAWTSR FTIWDDPDAG FFTVTMTDLR EEDSGHYWCR IYRPSDNSVS 130 140 150 160 170 180 KSVRFYLVVS PASASTQTSW TPRDLVSSQT QTQSCVPPTA GARQAPESPS TIPVPSHPSS 190 200 210 220 230 240 PLPVPLPSRP QNSTLRPGPA APIALVPVFC GLLVAKSLVL SALLVWWVLR NRHMQHQGRS 250 260 270 LLHPAQPRPQ AHRHFPLSHR APGGTYGGKP
	Isoform 3 (NKp44RG1) [UniParc]. Checksum: F21D9055BCA5DF0F	FASTA	258	28,431
	10 20 30 40 50 60 MAWRALHPLL LLLLLFPGSQ AQSKAQVLQS VAGQTLTVRC QYPPTGSLYE KKGWCKEASA 70 80 90 100 110 120 LVCIRLVTSS KPRTMAWTSR FTIWDDPDAG FFTVTMTDLR EEDSGHYWCR IYRPSDNSVS 130 140 150 160 170 180 KSVRFYLVVS PASASTQTSW TPRDLVSSQT QTQSCVPPTA GARQAPESPS TIPVPSQPQN 190 200 210 220 230 240 STLRPGPAAP IALVPVFCGL LVAKSLVLSA LLVWWVLRNR HMQHQGRSLL HPAQPRPQAH 250 RHFPLSHRAP GGTYGGKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00034050.
IPI00414863.
IPI00420072.

RefSeq

NP_001186438.1. NM_001199509.1.
NP_001186439.1. NM_001199510.1.
NP_004819.2. NM_004828.3.

UniGene

Hs.194721.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HKF	X-ray	2.20	A	19-130	[»]

ProteinModelPortal

O95944.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000362181.

Proteomic databases

PaxDb

O95944.

PRIDE

O95944.

Protocols and materials databases

DNASU

9436.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373083; ENSP00000362175; ENSG00000096264.
ENST00000373086; ENSP00000362178; ENSG00000096264.
ENST00000373089; ENSP00000362181; ENSG00000096264.

GeneID

9436.

KEGG

hsa:9436.

UCSC

uc003oqh.2. human.
uc003oqi.2. human.
uc003oqj.2. human.

Organism-specific databases

CTD

9436.

GeneCards

GC06P041303.

H-InvDB

HIX0165054.

HGNC

HGNC:6732. NCR2.

MIM

604531. gene.

neXtProt

NX_O95944.

PharmGKB

PA30496.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG82068.

HOGENOM

HOG000293324.

HOVERGEN

HBG052589.

InParanoid

O95944.

KO

K06742.

OMA

VPSQPQN.

PhylomeDB

O95944.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

O95944.

CleanEx

HS_NCR2.

Genevestigator

O95944.

GermOnline

ENSG00000096264. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]

Pfam

PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95944.

GenomeRNAi

9436.

NextBio

35336.

SOURCE

Search...

Entry information

Entry name

NCTR2_HUMAN

Accession

Primary (citable) accession number: O95944
Secondary accession number(s): Q9H562 , Q9H563, Q9H564, Q9UMT1, Q9UMT2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	July 7, 2009
Last modified:	May 29, 2013
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.