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Protein

Leukocyte immunoglobulin-like receptor subfamily A member 4

Gene

LILRA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G (PubMed:16735691, PubMed:19564354). Down-regulates the production of IFNA1, IFNA2, IFNA4, IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to influenza virus or cytidine-phosphate-guanosine (CpG) dinucleotides, indicating it functions as negative regulator of TLR7 and TLR9 signaling cascades (PubMed:16735691, PubMed:19564354, PubMed:24586760). Down-regulates interferon production in response to interaction with BST2 on HIV-1 infected cells (PubMed:26172439). Activates a signaling cascade in complex with FCER1G that results in phosphorylation of Src family and Syk kinases and thereby triggers mobilization of intracellular Ca2+ (PubMed:16735691, PubMed:19564354). Does not interfere with the differentiation of plasmacytoid dendritic cells into antigen-presenting cells (PubMed:24586760).4 Publications

GO - Molecular functioni

  • coreceptor activity Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • Fc-epsilon receptor signaling pathway Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • negative regulation of interferon-alpha production Source: UniProtKB
  • negative regulation of toll-like receptor 7 signaling pathway Source: UniProtKB
  • negative regulation of toll-like receptor 9 signaling pathway Source: UniProtKB
  • negative regulation of tumor necrosis factor production Source: UniProtKB

Keywordsi

Molecular functionReceptor
Biological processImmunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukocyte immunoglobulin-like receptor subfamily A member 4
Alternative name(s):
CD85 antigen-like family member G
Immunoglobulin-like transcript 72 Publications
Short name:
ILT-72 Publications
CD_antigen: CD85g
Gene namesi
Name:LILRA4
Synonyms:ILT73 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000239961.2.
HGNCiHGNC:15503. LILRA4.

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 domaini24 – 446ExtracellularSequence analysisAdd BLAST423
Transmembranei447 – 467HelicalSequence analysisAdd BLAST21
Topological domaini468 – 499CytoplasmicSequence analysisAdd BLAST32

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi23547.
PharmGKBiPA142671546.

Polymorphism and mutation databases

BioMutaiLILRA4.
DMDMi288558815.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001481924 – 499Leukocyte immunoglobulin-like receptor subfamily A member 4Add BLAST476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 98PROSITE-ProRule annotation
Glycosylationi138N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi143 ↔ 195PROSITE-ProRule annotation
Glycosylationi239N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi244 ↔ 295PROSITE-ProRule annotation
Glycosylationi279N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi300N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi344 ↔ 395PROSITE-ProRule annotation
Modified residuei404Nitrated tyrosineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Nitration

Proteomic databases

PaxDbiP59901.
PeptideAtlasiP59901.
PRIDEiP59901.
TopDownProteomicsiP59901-1. [P59901-1]

PTM databases

iPTMnetiP59901.
PhosphoSitePlusiP59901.

Expressioni

Tissue specificityi

Detected on plasmacytoid dendritic cells (at protein level). Detected on plasmacytoid dendritic cells, but not on monocytes or B cells.1 Publication

Gene expression databases

BgeeiENSG00000239961.
CleanExiHS_LILRA4.
ExpressionAtlasiP59901. baseline and differential.
GenevisibleiP59901. HS.

Organism-specific databases

HPAiHPA049418.

Interactioni

Subunit structurei

Interacts with FCER1G; this stabilizes the expression of both proteins at the cell membrane (PubMed:16735691). Interacts with BST2; leads to activation of LILRA4-mediated signaling and down-regulation of the innate immune response to viral pathogens (PubMed:19564354, PubMed:26172439).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BST2Q105892EBI-2841591,EBI-2476339

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

IntActiP59901. 2 interactors.
STRINGi9606.ENSP00000291759.

Structurei

3D structure databases

ProteinModelPortaliP59901.
SMRiP59901.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 118Ig-like C2-type 1Add BLAST95
Domaini123 – 213Ig-like C2-type 2Add BLAST91
Domaini224 – 313Ig-like C2-type 3Add BLAST90
Domaini324 – 413Ig-like C2-type 4Add BLAST90

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKJD. Eukaryota.
ENOG41116BR. LUCA.
HOGENOMiHOG000234395.
HOVERGENiHBG074353.
InParanoidiP59901.
KOiK06512.
OrthoDBiEOG091G0D6W.
PhylomeDBiP59901.
TreeFamiTF336644.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiView protein in InterPro
IPR016332. A1B_glyco/leuk_Ig-like_rcpt.
IPR007110. Ig-like_dom.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
PfamiView protein in Pfam
PF00047. ig. 1 hit.
PF13895. Ig_2. 2 hits.
PIRSFiPIRSF001979. Alpha_1B_glycoprot_prd. 1 hit.
SMARTiView protein in SMART
SM00409. IG. 4 hits.
SM00408. IGc2. 3 hits.
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 3 hits.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P59901-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTLILTSLLF FGLSLGPRTR VQAENLPKPI LWAEPGPVIT WHNPVTIWCQ
60 70 80 90 100
GTLEAQGYRL DKEGNSMSRH ILKTLESENK VKLSIPSMMW EHAGRYHCYY
110 120 130 140 150
QSPAGWSEPS DPLELVVTAY SRPTLSALPS PVVTSGVNVT LRCASRLGLG
160 170 180 190 200
RFTLIEEGDH RLSWTLNSHQ HNHGKFQALF PMGPLTFSNR GTFRCYGYEN
210 220 230 240 250
NTPYVWSEPS DPLQLLVSGV SRKPSLLTLQ GPVVTPGENL TLQCGSDVGY
260 270 280 290 300
IRYTLYKEGA DGLPQRPGRQ PQAGLSQANF TLSPVSRSYG GQYRCYGAHN
310 320 330 340 350
VSSEWSAPSD PLDILIAGQI SDRPSLSVQP GPTVTSGEKV TLLCQSWDPM
360 370 380 390 400
FTFLLTKEGA AHPPLRLRSM YGAHKYQAEF PMSPVTSAHA GTYRCYGSRS
410 420 430 440 450
SNPYLLSHPS EPLELVVSGA TETLNPAQKK SDSKTAPHLQ DYTVENLIRM
460 470 480 490
GVAGLVLLFL GILLFEAQHS QRSPPRCSQE ANSRKDNAPF RVVEPWEQI
Length:499
Mass (Da):55,165
Last modified:February 9, 2010 - v2
Checksum:i16FDB2A6C458F53B
GO
Isoform 2 (identifier: P59901-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Show »
Length:433
Mass (Da):47,806
Checksum:i52A2EF57AA9CA775
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3L → P in AAD02203 (Ref. 1) Curated1
Sequence conflicti7S → V in AAD02203 (Ref. 1) Curated1
Sequence conflicti9 – 11LFF → ICL in AAD02203 (Ref. 1) Curated3
Sequence conflicti235T → N in BI834924 (Ref. 4) Curated1
Sequence conflicti398S → T in AAD02203 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05605427P → L. Corresponds to variant dbSNP:rs2241384Ensembl.1
Natural variantiVAR_056055155I → V. Corresponds to variant dbSNP:rs10419832Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0386941 – 66Missing in isoform 2. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041261 mRNA. Translation: AAD02203.1.
AC008746 Genomic DNA. No translation available.
AC008984 Genomic DNA. No translation available.
BC109198 mRNA. Translation: AAI09199.1.
BI834924 mRNA. No translation available.
AF283989 mRNA. Translation: AAL36993.1.
CCDSiCCDS12890.1. [P59901-1]
RefSeqiNP_036408.4. NM_012276.4.
UniGeneiHs.406708.

Genome annotation databases

EnsembliENST00000291759; ENSP00000291759; ENSG00000239961.
ENST00000613813; ENSP00000479979; ENSG00000277092. [P59901-1]
ENST00000616790; ENSP00000483846; ENSG00000274185. [P59901-1]
ENST00000619832; ENSP00000481073; ENSG00000276798. [P59901-1]
GeneIDi23547.
KEGGihsa:23547.
UCSCiuc002qfj.4. human. [P59901-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLIRA4_HUMAN
AccessioniPrimary (citable) accession number: P59901
Secondary accession number(s): Q32MC4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: February 9, 2010
Last modified: November 22, 2017
This is version 130 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

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot