Q99706 (KI2L4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Killer cell immunoglobulin-like receptor 2DL4

Alternative name(s):
CD158 antigen-like family member D
G9P
Killer cell inhibitory receptor 103AS
Short name=KIR-103AS
MHC class I NK cell receptor KIR103AS
CD_antigen=CD158d

Gene names

Name:	KIR2DL4
Synonyms:	CD158D, KIR103AS

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	377 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	Receptor on natural killer (NK) cells for HLA-C alleles. Inhibits the activity of NK cells thus preventing cell lysis.
Subunit structure	Interacts with ARRB2. Ref.9
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the immunoglobulin superfamily. Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular defense response Traceable author statement Ref.1. Source: ProtInc regulation of 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 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99706-1)

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: Q99706-2)

Also known as: AST;

The sequence of this isoform differs from the canonical sequence as follows:
     219-235: Missing.

Isoform 3 (identifier: Q99706-3)

Also known as: AS;

The sequence of this isoform differs from the canonical sequence as follows:
     236-270: Missing.

Isoform 4 (identifier: Q99706-4)

Also known as: ASD1;

The sequence of this isoform differs from the canonical sequence as follows:
     219-235: Missing.
     236-270: Missing.

Isoform 5 (identifier: Q99706-5)

Also known as: ASD2;

The sequence of this isoform differs from the canonical sequence as follows:
     219-235: Missing.
     236-270: Missing.
     271-288: Missing.

Isoform 6 (identifier: Q99706-6)

The sequence of this isoform differs from the canonical sequence as follows:
     27-121: Missing.
     219-235: Missing.
     236-270: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	By similarity
	Chain	22 – 377	356	Killer cell immunoglobulin-like receptor 2DL4		PRO_0000015081
Regions
	Topological domain	22 – 242	221	Extracellular Potential
	Transmembrane	243 – 263	21	Helical; Potential
	Topological domain	264 – 377	114	Cytoplasmic Potential
	Domain	44 – 104	61	Ig-like C2-type 1
	Domain	139 – 202	64	Ig-like C2-type 2
Amino acid modifications
	Glycosylation	141	1	N-linked (GlcNAc...) Potential
	Glycosylation	175	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 97		By similarity
	Disulfide bond	146 ↔ 195		By similarity
Natural variations
	Alternative sequence	27 – 121	95	Missing in isoform 6.		VSP_002608
	Alternative sequence	219 – 235	17	Missing in isoform 2, isoform 4, isoform 5 and isoform 6.		VSP_002609
	Alternative sequence	236 – 270	35	Missing in isoform 3, isoform 4, isoform 5 and isoform 6.		VSP_002610
	Alternative sequence	271 – 288	18	Missing in isoform 5.		VSP_002611
	Natural variant	53	1	Y → C. Ref.2 Ref.5 Ref.7 Corresponds to variant rs618835 [ dbSNP | Ensembl ].		VAR_010307
	Natural variant	87	1	V → L. Ref.1 Ref.3 Ref.4 Corresponds to variant rs1057767 [ dbSNP | Ensembl ].		VAR_010308
	Natural variant	138	1	A → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs1051454 [ dbSNP | Ensembl ].		VAR_010309
	Natural variant	209	1	P → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs1051456 [ dbSNP | Ensembl ].		VAR_010310
	Natural variant	271 – 273	3	DAA → MLL in allele KIR2DL4*0501.		VAR_064649
	Natural variant	271	1	D → N. Ref.2 Ref.4 Ref.6 Ref.7		VAR_010311
	Natural variant	274 – 377	104	Missing in allele KIR2DL4*0501.		VAR_065101
	Natural variant	371	1	N → H. Ref.1 Ref.2 Ref.3 Ref.4 Corresponds to variant rs1051460 [ dbSNP | Ensembl ].		VAR_010312
Experimental info
	Sequence conflict	47	1	V → A in ABW73961. Ref.5
	Sequence conflict	229	1	T → P in AAD24763. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 8, 2011. Version 3. Checksum: 888B3297332D6C59	FASTA	377	41,487
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF 70 80 90 100 110 120 TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT 130 140 150 160 170 180 GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA 190 200 210 220 230 240 DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTGN PSSSWPSPTE PSFKTGIARH 250 260 270 280 290 300 LHAVIRYSVA IILFTILPFF LLHRWCSKKK DAAVMNQEPA GHRTVNREDS DEQDPQEVTY 310 320 330 340 350 360 AQLDHCIFTQ RKITGPSQRS KRPSTDTSVC IELPNAEPRA LSPAHEHHSQ ALMGSSRETT 370 ALSQTQLASS NVPAAGI
	Isoform 2 (AST) [UniParc]. Checksum: A7E18C6F0DDBD526	FASTA	360	39,699
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF 70 80 90 100 110 120 TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT 130 140 150 160 170 180 GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA 190 200 210 220 230 240 DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTGI ARHLHAVIRY SVAIILFTIL 250 260 270 280 290 300 PFFLLHRWCS KKKDAAVMNQ EPAGHRTVNR EDSDEQDPQE VTYAQLDHCI FTQRKITGPS 310 320 330 340 350 360 QRSKRPSTDT SVCIELPNAE PRALSPAHEH HSQALMGSSR ETTALSQTQL ASSNVPAAGI
	Isoform 3 (AS) [UniParc]. Checksum: 963B74BC0E5C7B64	FASTA	342	37,356
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF 70 80 90 100 110 120 TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT 130 140 150 160 170 180 GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA 190 200 210 220 230 240 DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTGN PSSSWPSPTE PSFKTDAAVM 250 260 270 280 290 300 NQEPAGHRTV NREDSDEQDP QEVTYAQLDH CIFTQRKITG PSQRSKRPST DTSVCIELPN 310 320 330 340 AEPRALSPAH EHHSQALMGS SRETTALSQT QLASSNVPAA GI
	Isoform 4 (ASD1) [UniParc]. Checksum: A07C525E18C55C79	FASTA	325	35,568
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF 70 80 90 100 110 120 TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT 130 140 150 160 170 180 GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA 190 200 210 220 230 240 DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTDA AVMNQEPAGH RTVNREDSDE 250 260 270 280 290 300 QDPQEVTYAQ LDHCIFTQRK ITGPSQRSKR PSTDTSVCIE LPNAEPRALS PAHEHHSQAL 310 320 MGSSRETTAL SQTQLASSNV PAAGI
	Isoform 5 (ASD2) [UniParc]. Checksum: 360E7C2058E1788E	FASTA	307	33,591
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF 70 80 90 100 110 120 TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT 130 140 150 160 170 180 GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA 190 200 210 220 230 240 DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTDS DEQDPQEVTY AQLDHCIFTQ 250 260 270 280 290 300 RKITGPSQRS KRPSTDTSVC IELPNAEPRA LSPAHEHHSQ ALMGSSRETT ALSQTQLASS NVPAAGI
	Isoform 6 [UniParc]. Checksum: 0FCFE3EE13BACBB7	FASTA	230	24,917
	10 20 30 40 50 60 MSMSPTVIIL ACLGFFLDQS VWAHVGLYEK PSLTARPGPT VRAGENVTLS CSSQSSFDIY 70 80 90 100 110 120 HLSREGEAHE LRLPAVPSIN GTFQADFPLG PATHGETYRC FGSFHGSPYE WSDPSDPLPV 130 140 150 160 170 180 SVTDAAVMNQ EPAGHRTVNR EDSDEQDPQE VTYAQLDHCI FTQRKITGPS QRSKRPSTDT 190 200 210 220 230 SVCIELPNAE PRALSPAHEH HSQALMGSSR ETTALSQTQL ASSNVPAAGI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NK cell receptor gene of the KIR family with two IG domains but highest homology to KIR receptors with three IG domains." Selvakumar A., Steffens U., Dupont B. Tissue Antigens 48:285-294(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-87; THR-138; ALA-209 AND HIS-371.
[2]	"Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors." Valiante N.M., Uhrberg M., Shilling H.G., Lienert-Weidenbach K., Arnett K.L., D'Andrea A., Phillips J.H., Lanier L.L., Parham P. Immunity 7:739-751(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS CYS-53; THR-138; ALA-209; ASN-271 AND HIS-371.
[3]	"Polymorphism and domain variability of human killer cell inhibitory receptors." Selvakumar A., Steffens U., Dupont B. Immunol. Rev. 155:183-196(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS LEU-87; THR-138; ALA-209 AND HIS-371.
[4]	"Genomic organization and allelic polymorphism of the human killer cell inhibitory receptor gene KIR103." Selvakumar A., Steffens U., Palanisamy N., Chaganti R.S.K., Dupont B. Tissue Antigens 49:564-573(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 3; 4 AND 5), VARIANTS LEU-87; THR-138; ALA-209; ASN-271 AND HIS-371.
[5]	"The elucidation of KIR2DL4 gene polymorphism." Schellekens J., Tilanus M.G., Rozemuller E.H. Mol. Immunol. 45:1900-1906(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE KIR2DL4*0501), VARIANT CYS-53.
[6]	Biassoni R. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 6), VARIANTS THR-138; ALA-209 AND ASN-271. Tissue: Lymphoid tissue.
[7]	"Exon deletion contributes to structural diversity of 2DL4 killer inhibitory receptors." Chan H.W., Salter R.D. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-53 AND ASN-271.
[8]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells." Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X. Nat. Immunol. 9:898-907(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARRB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U71199 mRNA. Translation: AAB49756.1. AF034771 mRNA. Translation: AAB95164.1. AF034772 mRNA. Translation: AAB95165.1. AF034773 mRNA. Translation: AAB95166.1. U73394 mRNA. Translation: AAC51146.1. AF003123 , AF003116, AF003117, AF003118, AF003119, AF003121, AF003122, AF003120 Genomic DNA. Translation: AAB61926.1. AF002979 mRNA. Translation: AAB71387.1. AF002980 mRNA. Translation: AAB71388.1. AF002981 mRNA. Translation: AAB71389.1. AF002982 mRNA. Translation: AAB71390.1. EU194342 mRNA. Translation: ABW73961.1. X97229 mRNA. Translation: CAA65868.1. X99479 mRNA. Translation: CAA67842.1. X99480 mRNA. Translation: CAA67843.1. X99481 mRNA. Translation: CAA67844.1. AF110035 , AF110032, AF110033, AF110034 Genomic DNA. Translation: AAD24763.1. AC011501 Genomic DNA. No translation available. AL133414 Genomic DNA. Translation: CAC40708.1.
IPI	IPI00218705. IPI00218706. IPI00218708. IPI00871946. IPI00872526. IPI01025846.
RefSeq	NP_001074239.1. NM_001080770.1. NP_002246.5. NM_002255.5.
UniGene	Hs.512572. Hs.661219.
3D structure databases
ProteinModelPortal	Q99706.
SMR	Q99706. Positions 30-218.
ModBase	Search...
PTM databases
PhosphoSite	Q99706.
Polymorphism databases
DMDM	13124325.
Proteomic databases
PaxDb	Q99706.
PRIDE	Q99706.
Protocols and materials databases
DNASU	3805.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000345540; ENSP00000339634; ENSG00000189013. ENST00000357494; ENSP00000350088; ENSG00000189013. ENST00000396293; ENSP00000379588; ENSG00000189013.
GeneID	3805.
KEGG	hsa:3805.
UCSC	uc002qhg.3. human. uc002qhi.3. human. uc002qhj.3. human. uc002quc.4. human.
Organism-specific databases
CTD	3805.
GeneCards	GC19P055260.
HGNC	HGNC:6332. KIR2DL4.
MIM	604945. gene.
neXtProt	NX_Q99706.
PharmGKB	PA30117.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG25862.
HOVERGEN	HBG074353.
KO	K07981.
OrthoDB	EOG4NS3C8.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q99706.
Bgee	Q99706.
Genevestigator	Q99706.
GermOnline	ENSG00000189013. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 2 hits.
InterPro	IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013151. Immunoglobulin. [Graphical view]
Pfam	PF00047. ig. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3805.
NextBio	14949.
SOURCE	Search...

Entry information

Entry name

KI2L4_HUMAN

Accession

Primary (citable) accession number: Q99706
Secondary accession number(s): A8W795 , O14621, O14622, O14623, O14624, O43534, P78400, P78401, Q8N738, Q99559, Q99560, Q99561, Q99562, Q9UQJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	March 8, 2011
Last modified:	May 1, 2013
This is version 131 of the entry and version 3 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.