IL4R

Protein identityUniProt · HPA

UniProt accession

P24394

Gene

IL4R

Ensembl

ENSG00000077238

Chromosome

16

Canonical length

825 aa

Protein class

Cancer-related genes, CD markers, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Subcellular location

Nucleoplasm,Plasma membrane,Centriolar satellite

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

Canonical amino-acid sequenceUniProt

825 residues, UniProt reviewed canonical sequence.

>P24394|IL4R
     1  MGWLCSGLLF PVSCLVLLQV ASSGNMKVLQ EPTCVSDYMS ISTCEWKMNG PTNCSTELRL
    61  LYQLVFLLSE AHTCIPENNG GAGCVCHLLM DDVVSADNYT LDLWAGQQLL WKGSFKPSEH
   121  VKPRAPGNLT VHTNVSDTLL LTWSNPYPPD NYLYNHLTYA VNIWSENDPA DFRIYNVTYL
   181  EPSLRIAAST LKSGISYRAR VRAWAQCYNT TWSEWSPSTK WHNSYREPFE QHLLLGVSVS
   241  CIVILAVCLL CYVSITKIKK EWWDQIPNPA RSRLVAIIIQ DAQGSQWEKR SRGQEPAKCP
   301  HWKNCLTKLL PCFLEHNMKR DEDPHKAAKE MPFQGSGKSA WCPVEISKTV LWPESISVVR
   361  CVELFEAPVE CEEEEEVEEE KGSFCASPES SRDDFQEGRE GIVARLTESL FLDLLGEENG
   421  GFCQQDMGES CLLPPSGSTS AHMPWDEFPS AGPKEAPPWG KEQPLHLEPS PPASPTQSPD
   481  NLTCTETPLV IAGNPAYRSF SNSLSQSPCP RELGPDPLLA RHLEEVEPEM PCVPQLSEPT
   541  TVPQPEPETW EQILRRNVLQ HGAAAAPVSA PTSGYQEFVH AVEQGGTQAS AVVGLGPPGE
   601  AGYKAFSSLL ASSAVSPEKC GFGASSGEEG YKPFQDLIPG CPGDPAPVPV PLFTFGLDRE
   661  PPRSPQSSHL PSSSPEHLGL EPGEKVEDMP KPPLPQEQAT DPLVDSLGSG IVYSALTCHL
   721  CGHLKQCHGQ EDGGQTPVMA SPCCGCCCGD RSSPPTTPLR APDPSPGGVP LEASLCPASL
   781  APSGISEKSK SSSSFHPAPG NAQSSSQTPK IVNFVSVGPT YMRVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL4R 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)

0.59

Highest tissue expression

114 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL4R.

Disease | ImmuneIEDB

Conditions an epitope on IL4R was assayed in.

• chronic lymphocytic leukemia T cell

ReferencesPubMed · IEDB

Publications for IL4R from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.83

gnomAD pLI

0

gnomAD missense Z

0.77

DepMap mean gene effect

-0.01

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

• defense response to protozoan
• immune response
• immunoglobulin mediated immune response
• interleukin-4-mediated signaling pathway
• negative regulation of T-helper 1 cell differentiation
• positive regulation of chemokine production
• positive regulation of cold-induced thermogenesis
• positive regulation of immunoglobulin production
• positive regulation of macrophage activation
• positive regulation of mast cell degranulation
• positive regulation of myoblast fusion
• positive regulation of T-helper 2 cell differentiation
• production of molecular mediator involved in inflammatory response
• signal transduction
• T-helper 1 cell differentiation
• T-helper 2 cell differentiation

Molecular functions

• interleukin-4 receptor activity

Cellular components

• centriolar satellite
• external side of plasma membrane
• extracellular region
• nucleoplasm
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Short hematopoietin receptor, family 1, conserved site
• Fibronectin type III
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Interleukin-4 receptor alpha, N-terminal
• Interleukin-4 receptor alpha chain, N-terminal

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunity
• Membrane
• Phosphoprotein
• Receptor
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of IL4R in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLM1
• IL13RA2
• JAK3
• PIK3C3
• SOCS5
• IL4
• CD300LF
• PIBF1
• IL13