KI2S5_HUMAN
ID KI2S5_HUMAN Reviewed; 304 AA.
AC Q14953; A0A0C4ZMZ1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 2.
DT 25-MAY-2022, entry version 153.
DE RecName: Full=Killer cell immunoglobulin-like receptor 2DS5 {ECO:0000305};
DE AltName: Full=CD158 antigen-like family member G;
DE AltName: Full=Natural killer-associated transcript 9;
DE Short=NKAT-9;
DE AltName: CD_antigen=CD158g;
DE Flags: Precursor;
GN Name=KIR2DS5 {ECO:0000303|PubMed:18624290, ECO:0000312|HGNC:HGNC:6337};
GN Synonyms=CD158G, NKAT9;
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].
RX PubMed=8662091; DOI=10.1007/bf02602590;
RA Doehring C., Samaridis J., Colonna M.;
RT "Alternatively spliced forms of human killer inhibitory receptors.";
RL Immunogenetics 44:227-230(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=28569259; DOI=10.1038/gene.2017.10;
RA Roe D., Vierra-Green C., Pyo C.W., Eng K., Hall R., Kuang R., Spellman S.,
RA Ranade S., Geraghty D.E., Maiers M.;
RT "Revealing complete complex KIR haplotypes phased by long-read sequencing
RT technology.";
RL Genes Immun. 18:127-134(2017).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP TYROBP.
RX PubMed=18624290; DOI=10.1002/eji.200838434;
RA Della Chiesa M., Romeo E., Falco M., Balsamo M., Augugliaro R., Moretta L.,
RA Bottino C., Moretta A., Vitale M.;
RT "Evidence that the KIR2DS5 gene codes for a surface receptor triggering
RT natural killer cell function.";
RL Eur. J. Immunol. 38:2284-2289(2008).
RN [5]
RP POLYMORPHISM, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-68, GLYCOSYLATION,
RP AND CHARACTERIZATION OF VARIANTS LEU-2; PRO-132; SER-185 AND ALA-195.
RX PubMed=18682925; DOI=10.1007/s00251-008-0322-2;
RA Steiner N.K., Dakshanamurthy S., VandenBussche C.J., Hurley C.K.;
RT "Extracellular domain alterations impact surface expression of stimulatory
RT natural killer cell receptor KIR2DS5.";
RL Immunogenetics 60:655-667(2008).
RN [6]
RP FUNCTION, POLYMORPHISM, GLYCOSYLATION AT ASN-178, SUBCELLULAR LOCATION, AND
RP CHARACTERIZATION OF VARIANTS ASN-144; GLY-179 AND THR-197.
RX PubMed=24269691; DOI=10.1016/j.humimm.2013.11.012;
RA Steiner N.K., Dakshanamurthy S., Nguyen N., Hurley C.K.;
RT "Allelic variation of killer cell immunoglobulin-like receptor 2DS5 impacts
RT glycosylation altering cell surface expression levels.";
RL Hum. Immunol. 75:124-128(2014).
RN [7]
RP POLYMORPHISM, FUNCTION, VARIANTS ARG-22; ASN-144; PHE-148; THR-175;
RP GLY-179; THR-197; HIS-203 AND LYS-237, AND CHARACTERIZATION OF VARIANTS
RP ARG-22; ASN-144; PHE-148; THR-175; GLY-179; THR-197; HIS-203 AND LYS-237.
RX PubMed=28685972; DOI=10.1002/iid3.178;
RA Blokhuis J.H., Hilton H.G., Guethlein L.A., Norman P.J., Nemat-Gorgani N.,
RA Nakimuli A., Chazara O., Moffett A., Parham P.;
RT "KIR2DS5 allotypes that recognize the C2 epitope of HLA-C are common among
RT Africans and absent from Europeans.";
RL Immun. Inflammation. Dis. 5:461-468(2017).
CC -!- FUNCTION: Activating natural killer (NK) receptor that recognizes C2
CC epitopes of HLA-C alleles. Bridging the innate and adaptive immune
CC systems, NK cells express a number of cell surface receptors which
CC either inhibit or stimulate their cytotoxicity (PubMed:28685972,
CC PubMed:18624290, PubMed:18682925). Able to activate NK cells
CC citotoxicity and cytokine production such as IFNG (PubMed:18624290,
CC PubMed:24269691). Receptor functions are attenuated even lost in some
CC alleles, such as KIR2DS5*002 reprensented in this entry
CC (PubMed:28685972). {ECO:0000269|PubMed:18624290,
CC ECO:0000269|PubMed:18682925, ECO:0000269|PubMed:24269691,
CC ECO:0000269|PubMed:28685972}.
CC -!- SUBUNIT: Interacts with TYROBP. {ECO:0000269|PubMed:18624290}.
CC -!- INTERACTION:
CC Q14953; A0A583ZBW8: HLA-C; NbExp=6; IntAct=EBI-16823921, EBI-9978392;
CC Q14953; P10321: HLA-C; NbExp=30; IntAct=EBI-16823921, EBI-1051396;
CC Q14953; O43914: TYROBP; NbExp=3; IntAct=EBI-16823921, EBI-2214794;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18624290,
CC ECO:0000269|PubMed:18682925, ECO:0000269|PubMed:24269691}; Single-pass
CC type I membrane protein {ECO:0000305}; Extracellular side
CC {ECO:0000269|PubMed:18682925, ECO:0000269|PubMed:24269691}.
CC -!- TISSUE SPECIFICITY: Expressed on a discrete subset of peripheral blood
CC NK cells. {ECO:0000269|PubMed:18624290}.
CC -!- PTM: N-glycosylated, glycosylation varies depending on the allele which
CC alters cell surface expression levels. {ECO:0000269|PubMed:18682925,
CC ECO:0000269|PubMed:24269691}.
CC -!- POLYMORPHISM: The following alleles are known: KIR2DS5*001,
CC KIR2DS5*002, KIR2DS5*003, KIR2DS5*004, KIR2DS5*005, KIR2DS5*006,
CC KIR2DS5*007, KIR2DS5*008, KIR2DS5*009, KIR2DS5*010 and KIR2DS5*011.
CC Allele KIR2DS5*002 is represented in this entry. Allele KIR2DS5*001
CC product is not expressed at the surface (PubMed:24269691,
CC PubMed:18682925). In Europeans, KIR2DS5 is essentially monomorphic,
CC with allele KIR2DS5*002 being predominant (PubMed:28685972). However,
CC KIR2DS5 is highly polymorphic in Africans (PubMed:28685972). Alleles
CC KIR2DS5*003, KIR2DS5*004, KIR2DS5*005, KIR2DS5*006, KIR2DS5*007 and
CC KIR2DS5*008 have activating potential and recocognize C2 epitopes of
CC HLA-C alleles (PubMed:28685972). Alleles KIR2DS5*002, KIR2DS5*009,
CC KIR2DS5*010 and KIR2DS5*011 have activating potential but do not
CC recocognize (or with very slight avidity) C2 epitopes of HLA-C alleles
CC (PubMed:28685972). Allele KIR2DS5*006 protects pregnant women from pre-
CC eclampsia (PubMed:28685972). Allele KIR2DS5*003 has increased
CC glycosylation levels due to the variant Asn-144 instead of Ser-144, it
CC also has increased cell surface expression. Alleles with variant Gly-
CC 179 instead of Arg-179 show lower levels of glycosylation
CC (PubMed:24269691). {ECO:0000269|PubMed:18682925,
CC ECO:0000269|PubMed:24269691, ECO:0000269|PubMed:28685972}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
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DR EMBL; L76672; AAB36600.1; -; mRNA.
DR EMBL; KU645197; ANJ04806.1; -; Genomic_DNA.
DR EMBL; KU645196; ANJ04799.1; -; Genomic_DNA.
DR EMBL; KP420441; AJI81015.1; -; Genomic_DNA.
DR EMBL; AL133414; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; GU182355; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU459006; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_055328.2; NM_014513.2.
DR AlphaFoldDB; Q14953; -.
DR SMR; Q14953; -.
DR IntAct; Q14953; 4.
DR GlyGen; Q14953; 4 sites.
DR iPTMnet; Q14953; -.
DR BioMuta; KIR2DS5; -.
DR DMDM; 2833260; -.
DR jPOST; Q14953; -.
DR MassIVE; Q14953; -.
DR PeptideAtlas; Q14953; -.
DR PRIDE; Q14953; -.
DR ProteomicsDB; 60256; -.
DR DNASU; 3810; -.
DR Ensembl; ENST00000614053.1; ENSP00000482547.1; ENSG00000275047.1.
DR Ensembl; ENST00000618443.1; ENSP00000484843.1; ENSG00000274739.1.
DR Ensembl; ENST00000619698.1; ENSP00000483733.1; ENSG00000277650.1.
DR Ensembl; ENST00000638690.1; ENSP00000492235.1; ENSG00000284217.3.
DR Ensembl; ENST00000639440.1; ENSP00000492394.1; ENSG00000288206.1.
DR Ensembl; ENST00000639571.1; ENSP00000492015.1; ENSG00000288357.1.
DR Ensembl; ENST00000643495.1; ENSP00000496607.1; ENSG00000284217.3.
DR Ensembl; ENST00000644792.1; ENSP00000496107.1; ENSG00000288206.1.
DR Ensembl; ENST00000645738.1; ENSP00000493745.1; ENSG00000288357.1.
DR GeneID; 3810; -.
DR KEGG; hsa:3810; -.
DR CTD; 3810; -.
DR DisGeNET; 3810; -.
DR GeneCards; KIR2DS5; -.
DR HGNC; HGNC:6337; KIR2DS5.
DR MIM; 604956; gene.
DR neXtProt; NX_Q14953; -.
DR InParanoid; Q14953; -.
DR OrthoDB; 1055520at2759; -.
DR PhylomeDB; Q14953; -.
DR PathwayCommons; Q14953; -.
DR Reactome; R-HSA-2172127; DAP12 interactions.
DR SignaLink; Q14953; -.
DR BioGRID-ORCS; 3810; 2 hits in 36 CRISPR screens.
DR GenomeRNAi; 3810; -.
DR Pharos; Q14953; Tdark.
DR PRO; PR:Q14953; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14953; protein.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030110; F:HLA-C specific inhibitory MHC class I receptor activity; NAS:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 2.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Membrane; Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000250"
FT CHAIN 22..304
FT /note="Killer cell immunoglobulin-like receptor 2DS5"
FT /id="PRO_0000015086"
FT TOPO_DOM 22..245
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 42..107
FT /note="Ig-like C2-type 1"
FT DOMAIN 142..205
FT /note="Ig-like C2-type 2"
FT REGION 275..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..304
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:24269691"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..100
FT /evidence="ECO:0000250|UniProtKB:P43626"
FT DISULFID 149..198
FT /evidence="ECO:0000250|UniProtKB:P43626"
FT VARIANT 2
FT /note="S -> L (in allele KIR2DS5*001; not expressed at the
FT cell surface when associated with P-132, S-185 and A-195 in
FT allele KIR2DS5*001; no effect cell surface expression)"
FT /evidence="ECO:0000269|PubMed:18682925"
FT /id="VAR_080126"
FT VARIANT 22
FT /note="H -> R (in allele KIR2DS5*008; increases binding to
FT C2 epitopes of HLA-C alleles when associated with G-179 in
FT allele KIR2DS5*008)"
FT /evidence="ECO:0000269|PubMed:28685972"
FT /id="VAR_080127"
FT VARIANT 132
FT /note="S -> P (in allele KIR2DS5*001; not expressed at the
FT cell surface when associated with R-22, S-185 and A-195 in
FT allele KIR2DS5*001; abolishes cell surface expression)"
FT /evidence="ECO:0000269|PubMed:18682925"
FT /id="VAR_080128"
FT VARIANT 144
FT /note="S -> N (in allele KIR2DS5*003; increases cell
FT surface expression, glycosylation levels and binding to C2
FT epitopes of HLA-C alleles when associated with G-179 in
FT allele KIR2DS5*003)"
FT /evidence="ECO:0000269|PubMed:24269691,
FT ECO:0000269|PubMed:28685972"
FT /id="VAR_080129"
FT VARIANT 148
FT /note="S -> F (in allele KIR2DS5*010; decreases binding to
FT C2 epitopes of HLA-C alleles when associated with G-179 and
FT H-203 in allele KIR2DS5*010)"
FT /evidence="ECO:0000269|PubMed:28685972"
FT /id="VAR_080130"
FT VARIANT 175
FT /note="P -> T (in alleles KIR2DS5*006 and KIR2DS5*011;
FT increases binding to C2 epitopes of HLA-C alleles when
FT associated with G-179 in allele KIR2DS5*006; decreases
FT binding to C2 epitopes of HLA-C alleles when associated
FT with T-197 in allele KIR2DS5*011)"
FT /evidence="ECO:0000269|PubMed:28685972"
FT /id="VAR_080131"
FT VARIANT 179
FT /note="R -> G (in alleles KIR2DS5*003, KIR2DS5*004,
FT KIR2DS5*005, KIR2DS5*006, KIR2DS5*007, KIR2DS5*008 and
FT KIR2DS5*010; increases binding to C2 epitopes of HLA-C
FT alleles in allele KIR2DS5*005; increases binding to C2
FT epitopes of HLA-C alleles but no effect on cell surface
FT expression when associated with R-22 in allele KIR2DS5*008;
FT increases cell surface expression, glycosylation levels and
FT binding to C2 epitopes of HLA-C alleles when associated
FT with N-144 in allele KIR2DS5*003; decreases binding to C2
FT epitopes of HLA-C alleles when associated with F-148 and H-
FT 203 in allele KIR2DS5*010; increases binding to C2 epitopes
FT of HLA-C alleles when associated with T-175 in allele
FT KIR2DS5*006; increases binding to C2 epitopes of HLA-C
FT alleles when associated with H-203 in allele KIR2DS5*004;
FT increases binding to C2 epitopes of HLA-C alleles when
FT associated with K-237 in allele KIR2DS5*007)"
FT /evidence="ECO:0000269|PubMed:24269691,
FT ECO:0000269|PubMed:28685972"
FT /id="VAR_080132"
FT VARIANT 185
FT /note="F -> S (in allele KIR2DS5*001; not expressed at the
FT cell surface when associated with R-22, P-132 and A-195 in
FT allele KIR2DS5*001; abolishes cell surface expression)"
FT /evidence="ECO:0000269|PubMed:18682925"
FT /id="VAR_080133"
FT VARIANT 195
FT /note="T -> A (in allele KIR2DS5*001; not expressed at the
FT cell surface when associated with R-22, P-132 and S-185 in
FT allele KIR2DS5*001; decreases cell surface expression)"
FT /evidence="ECO:0000269|PubMed:18682925"
FT /id="VAR_080134"
FT VARIANT 197
FT /note="R -> T (in alleles KIR2DS5*009 and KIR2DS5*011;
FT decreases binding to C2 epitopes of HLA-C alleles but no
FT effect on cell surface expression in allele KIR2DS5*009;
FT decreases binding to C2 epitopes of HLA-C alleles when
FT associated with T-175 in allele KIR2DS5*011)"
FT /evidence="ECO:0000269|PubMed:24269691,
FT ECO:0000269|PubMed:28685972"
FT /id="VAR_080135"
FT VARIANT 203
FT /note="R -> H (in alleles KIR2DS5*004 and KIR2DS5*010;
FT increases binding to C2 epitopes of HLA-C alleles when
FT associated with G-179 in allele KIR2DS5*004; decreases
FT binding to C2 epitopes of HLA-C alleles when associated
FT with F-148 and G-179 in allele KIR2DS5*010)"
FT /evidence="ECO:0000269|PubMed:28685972"
FT /id="VAR_080136"
FT VARIANT 237
FT /note="E -> K (in allele KIR2DS5*007; increases binding to
FT C2 epitopes of HLA-C alleles when associated with G-179 in
FT allele KIR2DS5*007)"
FT /evidence="ECO:0000269|PubMed:28685972"
FT /id="VAR_080137"
FT MUTAGEN 68
FT /note="H->D: Increases expression at the cell surface."
FT /evidence="ECO:0000269|PubMed:18682925"
FT MUTAGEN 68
FT /note="H->L: Reduces expression at the cell surface."
FT /evidence="ECO:0000269|PubMed:18682925"
SQ SEQUENCE 304 AA; 33698 MW; 83AFBB6A08D8DC9B CRC64;
MSLMVISMAC VAFFLLQGAW PHEGFRRKPS LLAHPGPLVK SEETVILQCW SDVMFEHFLL
HREGTFNHTL RLIGEHIDGV SKGNFSIGRM TQDLAGTYRC YGSVTHSPYQ LSAPSDPLDI
VITGLYEKPS LSAQPGPTVL AGESVTLSCS SRSSYDMYHL SREGEAHERR LPAGPKVNRT
FQADFPLDPA THGGTYRCFG SFRDSPYEWS KSSDPLLVSV TGNSSNSWPS PTEPSSETGN
PRHLHVLIGT SVVKLPFTIL LFFLLHRWCS NKKNASVMDQ GPAGNRTVNR EDSDEQDHQE
VSYA
