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Protein

Killer cell immunoglobulin-like receptor 2DS5

Gene

KIR2DS5

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

Functioni

Activating natural killer (NK) receptor that recognizes C2 epitopes of HLA-C alleles. Bridging the innate and adaptive immune systems, NK cells express a number of cell surface receptors which either inhibit or stimulate their cytotoxicity (PubMed:28685972, PubMed:18624290, PubMed:18682925). Able to activate NK cells citotoxicity and cytokine production such as IFNG (PubMed:18624290, PubMed:24269691). Receptor functions are attenuated even lost in some alleles, such as KIR2DS5*002 reprensented in this entry (PubMed:28685972).4 Publications

GO - Molecular functioni

  • HLA-C specific inhibitory MHC class I receptor activity Source: UniProtKB

GO - Biological processi

  • immune response Source: UniProtKB
  • innate immune response Source: Reactome

Keywordsi

Molecular functionReceptor

Enzyme and pathway databases

ReactomeiR-HSA-2172127 DAP12 interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Killer cell immunoglobulin-like receptor 2DS5
Alternative name(s):
CD158 antigen-like family member G
MHC class I NK cell receptor
Natural killer-associated transcript 9
Short name:
NKAT-9
CD_antigen: CD158g
Gene namesi
Name:KIR2DS5
Synonyms:CD158G, NKAT9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6337 KIR2DS5
MIMi604956 gene
neXtProtiNX_Q14953

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 245ExtracellularSequence analysisAdd BLAST224
Transmembranei246 – 264HelicalSequence analysisAdd BLAST19
Topological domaini265 – 304CytoplasmicSequence analysisAdd BLAST40

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68H → D: Increases expression at the cell surface. 1 Publication1
Mutagenesisi68H → L: Reduces expression at the cell surface. 1 Publication1

Organism-specific databases

DisGeNETi3810

Polymorphism and mutation databases

DMDMi2833260

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000001508622 – 304Killer cell immunoglobulin-like receptor 2DS5Add BLAST283

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 100By similarity
Glycosylationi67N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi84N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi149 ↔ 198By similarity
Glycosylationi178N-linked (GlcNAc...) asparagineSequence analysis1 Publication1
Glycosylationi223N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated, glycosylation varies depending on the allele which alters cell surface expression levels.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiQ14953
PRIDEiQ14953

Expressioni

Tissue specificityi

Expressed on a discrete subset of peripheral blood NK cells.1 Publication

Gene expression databases

CleanExiHS_KIR2DS5

Interactioni

Subunit structurei

Interacts with TYROBP.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

IntActiQ14953, 6 interactors

Structurei

3D structure databases

ProteinModelPortaliQ14953
SMRiQ14953
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 107Ig-like C2-type 1Add BLAST66
Domaini142 – 205Ig-like C2-type 2Add BLAST64

Sequence similaritiesi

Belongs to the immunoglobulin superfamily.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG074353
InParanoidiQ14953
KOiK07982
PhylomeDBiQ14953

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013151 Immunoglobulin
PfamiView protein in Pfam
PF00047 ig, 2 hits
SMARTiView protein in SMART
SM00409 IG, 2 hits
SUPFAMiSSF48726 SSF48726, 2 hits

Sequencei

Sequence statusi: Complete.

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

Q14953-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLMVISMAC VAFFLLQGAW PHEGFRRKPS LLAHPGPLVK SEETVILQCW
60 70 80 90 100
SDVMFEHFLL HREGTFNHTL RLIGEHIDGV SKGNFSIGRM TQDLAGTYRC
110 120 130 140 150
YGSVTHSPYQ LSAPSDPLDI VITGLYEKPS LSAQPGPTVL AGESVTLSCS
160 170 180 190 200
SRSSYDMYHL SREGEAHERR LPAGPKVNRT FQADFPLDPA THGGTYRCFG
210 220 230 240 250
SFRDSPYEWS KSSDPLLVSV TGNSSNSWPS PTEPSSETGN PRHLHVLIGT
260 270 280 290 300
SVVKLPFTIL LFFLLHRWCS NKKNASVMDQ GPAGNRTVNR EDSDEQDHQE

VSYA
Length:304
Mass (Da):33,698
Last modified:February 28, 2018 - v2
Checksum:i83AFBB6A08D8DC9B
GO

Polymorphismi

The following alleles are known: KIR2DS5*001, KIR2DS5*002, KIR2DS5*003, KIR2DS5*004, KIR2DS5*005, KIR2DS5*006, KIR2DS5*007, KIR2DS5*008, KIR2DS5*009, KIR2DS5*010 and KIR2DS5*011. Allele KIR2DS5*002 is represented in this entry. Allele KIR2DS5*001 product is not expressed at the surface (PubMed:24269691, PubMed:18682925). In Europeans, KIR2DS5 is essentially monomorphic, with allele KIR2DS5*002 being predominant (PubMed:28685972). However, KIR2DS5 is highly polymorphic in Africans (PubMed:28685972). Alleles KIR2DS5*003, KIR2DS5*004, KIR2DS5*005, KIR2DS5*006, KIR2DS5*007 and KIR2DS5*008 have activating potential and recocognize C2 epitopes of HLA-C alleles (PubMed:28685972). Alleles KIR2DS5*002, KIR2DS5*009, KIR2DS5*010 and KIR2DS5*011 have activating potential but do not recocognize (or with very slight avidity) C2 epitopes of HLA-C alleles (PubMed:28685972). Allele KIR2DS5*006 protects pregnant women from pre-eclampsia (PubMed:28685972). Allele KIR2DS5*003 has increased glycosylation levels due to the variant Asn-144 instead of Ser-144, it also has increased cell surface expression. Alleles with variant Gly-179 instead of Arg-179 show lower levels of glycosylation (PubMed:24269691).3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0801262S → L in allele KIR2DS5*001; not expressed at the cell surface when associated with P-132, S-185 and A-195 in allele KIR2DS5*001; no effect cell surface expression. 1 Publication1
Natural variantiVAR_08012722H → R in allele KIR2DS5*008; increases binding to C2 epitopes of HLA-C alleles when associated with G-179 in allele KIR2DS5*008. 1 Publication1
Natural variantiVAR_080128132S → P in allele KIR2DS5*001; not expressed at the cell surface when associated with R-22, S-185 and A-195 in allele KIR2DS5*001; abolishes cell surface expression. 1 Publication1
Natural variantiVAR_080129144S → N in allele KIR2DS5*003; increases cell surface expression, glycosylation levels and binding to C2 epitopes of HLA-C alleles when associated with G-179 in allele KIR2DS5*003. 2 Publications1
Natural variantiVAR_080130148S → F in allele KIR2DS5*010; decreases binding to C2 epitopes of HLA-C alleles when associated with G-179 and H-203 in allele KIR2DS5*010. 1 Publication1
Natural variantiVAR_080131175P → T in alleles KIR2DS5*006 and KIR2DS5*011; increases binding to C2 epitopes of HLA-C alleles when associated with G-179 in allele KIR2DS5*006; decreases binding to C2 epitopes of HLA-C alleles when associated with T-197 in allele KIR2DS5*011. 1 Publication1
Natural variantiVAR_080132179R → G in alleles KIR2DS5*003, KIR2DS5*004, KIR2DS5*005, KIR2DS5*006, KIR2DS5*007, KIR2DS5*008 and KIR2DS5*010; increases binding to C2 epitopes of HLA-C alleles in allele KIR2DS5*005; increases binding to C2 epitopes of HLA-C alleles but no effect on cell suface expression when associated with R-22 in allele KIR2DS5*008; increases cell surface expression, glycosylation levels and binding to C2 epitopes of HLA-C alleles when associated with N-144 in allele KIR2DS5*003; decreases binding to C2 epitopes of HLA-C alleles when associated with F-148 and H-203 in allele KIR2DS5*010; increases binding to C2 epitopes of HLA-C alleles when associated with T-175 in allele KIR2DS5*006; increases binding to C2 epitopes of HLA-C alleles when associated with H-203 in allele KIR2DS5*004; increases binding to C2 epitopes of HLA-C alleles when associated with K-237 in allele KIR2DS5*007. 2 Publications1
Natural variantiVAR_080133185F → S in allele KIR2DS5*001; not expressed at the cell surface when associated with R-22, P-132 and A-195 in allele KIR2DS5*001; abolishes cell surface expression. 1 Publication1
Natural variantiVAR_080134195T → A in allele KIR2DS5*001; not expressed at the cell surface when associated with R-22, P-132 and S-185 in allele KIR2DS5*001; decreases cell surface expression. 1 Publication1
Natural variantiVAR_080135197R → T in alleles KIR2DS5*009 and KIR2DS5*011; decreases binding to C2 epitopes of HLA-C alleles but no effect on cell suface expression in allele KIR2DS5*009; decreases binding to C2 epitopes of HLA-C alleles when associated with T-175 in allele KIR2DS5*011. 2 Publications1
Natural variantiVAR_080136203R → H in alleles KIR2DS5*004 and KIR2DS5*010; increases binding to C2 epitopes of HLA-C alleles when associated with G-179 in allele KIR2DS5*004; decreases binding to C2 epitopes of HLA-C alleles when associated with F-148 and G-179 in allele KIR2DS5*010. 1 Publication1
Natural variantiVAR_080137237E → K in allele KIR2DS5*007; increases binding to C2 epitopes of HLA-C alleles when associated with G-179 in allele KIR2DS5*007. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76672 mRNA Translation: AAB36600.1
KU645197 Genomic DNA Translation: ANJ04806.1
KU645196 Genomic DNA Translation: ANJ04799.1
KP420441 Genomic DNA Translation: AJI81015.1
AL133414 Genomic DNA No translation available.
GU182355 Genomic DNA No translation available.
CU459006 Genomic DNA No translation available.
RefSeqiNP_055328.2, NM_014513.2
UniGeneiHs.744266

Genome annotation databases

EnsembliENST00000618443; ENSP00000484843; ENSG00000274739
GeneIDi3810
KEGGihsa:3810

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKI2S5_HUMAN
AccessioniPrimary (citable) accession number: Q14953
Secondary accession number(s): A0A0C4ZMZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 28, 2018
Last modified: May 23, 2018
This is version 133 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome

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