P26718 (NKG2D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NKG2-D type II integral membrane protein

Alternative name(s):
Killer cell lectin-like receptor subfamily K member 1
NK cell receptor D
NKG2-D-activating NK receptor
CD_antigen=CD314

Gene names

Name:	KLRK1
Synonyms:	D12S2489E, NKG2D

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for MICA, MICB, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells. Involved in the immune surveillance exerted by T- and B-lymphocytes.
Subunit structure	Homodimer. Interacts with DAP10. The interaction with DAP10 is required for NKG2D cell surface expression.
Subcellular location	Membrane; Single-pass type II membrane protein.
Tissue specificity	Natural killer cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Also detected in gamma-delta cells and CD8+ alpha-beta T-cells. Expressed in interferon-producing killer dendritic cells (IKDCs). Ref.10
Miscellaneous	Structurally distinct families of ligands for mouse and human NKG2D receptors have been characterized. They might be orthologs.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Lectin
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell costimulation Traceable author statement. Source: BHF-UCL natural killer cell activation Traceable author statement. Source: BHF-UCL
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	sugar binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Note: A number of isoforms are produced.

Isoform 1 (identifier: P26718-1)

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 216

216

NKG2-D type II integral membrane protein

PRO_0000046665

Regions

Topological domain

1 – 51

51

Cytoplasmic Potential

Transmembrane

52 – 72

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

73 – 216

144

Extracellular Potential

Domain

98 – 213

116

C-type lectin

Amino acid modifications

Glycosylation

131

1

N-linked (GlcNAc...) Potential

Glycosylation

163

1

N-linked (GlcNAc...) Potential

Glycosylation

202

1

N-linked (GlcNAc...) Potential

Disulfide bond

96 ↔ 105

Disulfide bond

99 ↔ 110

Disulfide bond

127 ↔ 211

Disulfide bond

189 ↔ 203

Natural variations

Natural variant

72

1

A → T in allele NKG2-D*02. Ref.4 Ref.5 Ref.6 Ref.7
Corresponds to variant rs2255336 [ dbSNP | Ensembl ].

VAR_013295

Natural variant

177

1

N → S.
Corresponds to variant rs2306182 [ dbSNP | Ensembl ].

VAR_030738

Experimental info

Sequence conflict

186

1

K → R in BAF84709. Ref.5

Secondary structure

1

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216

Helix Strand Turn

Details...

Beta strand

95 – 100

6

Beta strand

104 – 106

3

Beta strand

109 – 118

10

Helix

120 – 128

9

Turn

140 – 143

4

Helix

144 – 148

5

Beta strand

151 – 160

10

Turn

161 – 164

4

Beta strand

165 – 171

7

Beta strand

176 – 178

3

Beta strand

180 – 183

4

Beta strand

185 – 193

9

Turn

194 – 196

3

Beta strand

197 – 201

5

Beta strand

207 – 213

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: C22F6BD533D7800E	FASTA	216	25,274
	10 20 30 40 50 60 MGWIRGRRSR HSWEMSEFHN YNLDLKKSDF STRWQKQRCP VVKSKCRENA SPFFFCCFIA 70 80 90 100 110 120 VAMGIRFIIM VAIWSAVFLN SLFNQEVQIP LTESYCGPCP KNWICYKNNC YQFFDESKNW 130 140 150 160 170 180 YESQASCMSQ NASLLKVYSK EDQDLLKLVK SYHWMGLVHI PTNGSWQWED GSILSPNLLT 190 200 210 IIEMQKGDCA LYASSFKGYI ENCSTPNTYI CMQRTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells." Houchins J.P., Yabe T., McSherry C., Bach F.H. J. Exp. Med. 173:1017-1020(1991) [PubMed: 2007850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex." Glienke J., Sobanov Y., Brostjan C., Steffens C., Nguyen C., Lehrach H., Hofer E., Francis F. Immunogenetics 48:163-173(1998) [PubMed: 9683661] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Identification and characterization of the NKG2D gene from large granular lymphocytic leukemia (LGL) cells." Kothapalli R., Kusmartseva I., Loughran T.P. Jr. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Conservation and variation in human and common chimpanzee CD94 and NKG2 genes." Shum B.P., Flodin L.R., Muir D.G., Rajalingam R., Khakoo S.I., Cleland S., Guethlein L.A., Uhrberg M., Parham P. J. Immunol. 168:240-252(2002) [PubMed: 11751968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-72.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-72. Tissue: Spleen and Stomach.
[6]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-72.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-72.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[9]	"Lymphocyte activation via NKG2D: towards a new paradigm in immune recognition?" Vivier E., Tomasello E., Paul P. Curr. Opin. Immunol. 14:306-311(2002) [PubMed: 11973127] [Abstract] Cited for: REVIEW, ALTERNATIVE SPLICING.
[10]	"Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity." Chan C.W., Crafton E., Fan H.-N., Flook J., Yoshimura K., Skarica M., Brockstedt D., Dubensky T.W., Stins M.F., Lanier L.L., Pardoll D.M., Housseau F. Nat. Med. 12:207-213(2006) [PubMed: 16444266] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA." Bauer S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., Spies T. Science 285:727-729(1999) [PubMed: 10426993] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 89-216 IN COMPLEX WITH MICA.
[12]	"Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3." Radaev S., Rostro B., Brooks A.G., Colonna M., Sun P.D. Immunity 15:1039-1049(2001) [PubMed: 11754823] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 93-216 IN COMPLEX WITH ULBP3.
[13]	"Symmetry recognizing asymmetry: analysis of the interactions between the C-type lectin-like immunoreceptor NKG2D and MHC class I-like ligands." McFarland B.J., Kortemme T., Yu S.F., Baker D., Strong R.K. Structure 11:411-422(2003) [PubMed: 12679019] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 88-215.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Functional Glycomics Gateway - Glycan Binding

NKG-2D

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54870 mRNA. Translation: CAA38652.1.
AJ001687, AJ001688, AJ001689 Genomic DNA. Translation: CAA04925.1.
AF461811 mRNA. Translation: AAL65233.1.
AF260135 mRNA. Translation: AAF86973.1.
AF260136 mRNA. Translation: AAF86974.1.
AK292059 mRNA. Translation: BAF84748.1.
AK292020 mRNA. Translation: BAF84709.1.
AC022075 Genomic DNA. No translation available.
CH471094 Genomic DNA. Translation: EAW96178.1.
BC039836 mRNA. Translation: AAH39836.1.

IPI

IPI00473104.

PIR

PT0375.

RefSeq

NP_001186734.1. NM_001199805.1.
NP_031386.2. NM_007360.3.

UniGene

Hs.387787.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HYR	X-ray	2.70	A/B	80-216	[»]
1KCG	X-ray	2.60	A/B	93-216	[»]
1MPU	X-ray	2.50	A	80-216	[»]

ProteinModelPortal

P26718.

SMR

P26718. Positions 88-215.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31100N.

IntAct

P26718. 4 interactions.

STRING

P26718.

Polymorphism databases

DMDM

128370.

Proteomic databases

PRIDE

P26718.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000240618; ENSP00000240618; ENSG00000213809.

GeneID

100528032.
22914.

KEGG

hsa:100528032.
hsa:22914.

Organism-specific databases

CTD

100528032.
22914.

GeneCards

GC12M010524.

H-InvDB

HIX0020427.

HGNC

HGNC:18788. KLRK1.

HPA

CAB021896.

MIM

611817. gene.

neXtProt

NX_P26718.

PharmGKB

PA128394594.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10803.

HOGENOM

HBG126635.

HOVERGEN

HBG052629.

InParanoid

P26718.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P26718.

Bgee

P26718.

CleanEx

HS_KLRK1.

Genevestigator

P26718.

GermOnline

ENSG00000183542. Homo sapiens.

Family and domain databases

InterPro

IPR002353. AntifreezeII.
IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]

Gene3D

G3DSA:3.10.100.10. C-type_lectin-like. 1 hit.

KO

K06728.

Pfam

PF00059. Lectin_C. 1 hit.
[Graphical view]

PRINTS

PR00356. ANTIFREEZEII.

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. False negative.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

NKG2D_HUMAN

Accession

Primary (citable) accession number: P26718
Secondary accession number(s): A8K7K5, A8K7P4, Q9NR41

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	January 25, 2012
This is version 118 of the entry and version 1 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.