KIR2DL4

Protein identityUniProt · HPA

UniProt accession

Q99706

Gene

KIR2DL4

Ensembl

ENSG00000189013

Chromosome

19

Canonical length

377 aa

Protein class

CD markers, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several """"""""""""""""""""""""""""""""framework"""""""""""""""""""""""""""""""" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the """"""""""""""""""""""""""""""""framework"""""""""""""""""""""""""""""""" loci that is present on all haplotypes. Alternate alleles of this gene are represented on multiple alternate reference loci (ALT_REF_LOCs). Alternative splicing results in multiple transcript variants, some of which may not be annotated on the primary reference assembly. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

377 residues, UniProt reviewed canonical sequence.

>Q99706|KIR2DL4
     1  MSMSPTVIIL ACLGFFLDQS VWAHVGGQDK PFCSAWPSAV VPQGGHVTLR CHYRRGFNIF
    61  TLYKKDGVPV PELYNRIFWN SFLISPVTPA HAGTYRCRGF HPHSPTEWSA PSNPLVIMVT
   121  GLYEKPSLTA RPGPTVRAGE NVTLSCSSQS SFDIYHLSRE GEAHELRLPA VPSINGTFQA
   181  DFPLGPATHG ETYRCFGSFH GSPYEWSDPS DPLPVSVTGN PSSSWPSPTE PSFKTGIARH
   241  LHAVIRYSVA IILFTILPFF LLHRWCSKKK DAAVMNQEPA GHRTVNREDS DEQDPQEVTY
   301  AQLDHCIFTQ RKITGPSQRS KRPSTDTSVC IELPNAEPRA LSPAHEHHSQ ALMGSSRETT
   361  ALSQTQLASS NVPAAGI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KIR2DL4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

4.3 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.15

gnomAD pLI

0.04

gnomAD missense Z

0.28

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular defense response
• immune response-regulating signaling pathway
• negative regulation of natural killer cell mediated cytotoxicity
• positive regulation of cellular senescence
• positive regulation of natural killer cell cytokine production
• signal transduction

Molecular functions

• MHC class Ib receptor activity
• transmembrane signaling receptor activity

Cellular components

• early endosome membrane
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Immunoglobulin-like Receptors in Immune Regulation
• Immunoglobulin domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Endosome
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of KIR2DL4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRB2
• HLA-G