CD4

Protein identityUniProt · HPA

UniProt accession

P01730

Gene

CD4

Ensembl

ENSG00000010610

Chromosome

12

Canonical length

458 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the CD4 membrane glycoprotein of T lymphocytes. The CD4 antigen acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class II MHC molecules. The CD4 antigen is also a primary receptor for entry of the human immunodeficiency virus through interactions with the HIV Env gp120 subunit. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, granulocytes, as well as in various regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, May 2020]

Canonical amino-acid sequenceUniProt

458 residues, UniProt reviewed canonical sequence.

>P01730|CD4
     1  MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQIK
    61  ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK IEDSDTYICE VEDQKEEVQL
   121  LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG
   181  TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW
   241  QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA
   301  LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV
   361  LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV
   421  RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD4 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)

0.35

Highest tissue expression

204 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD4.

Disease | AllUniProt

Conditions CD4 is implicated in, by any mechanism.

• Immunodeficiency 79 (IMD79) MIM:619238

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 63 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency 79

Disease | AutoantibodyPubMed

Conditions in which antibodies against CD4 are reported. Each links to that disease's full target list.

• HIV Infections 32
• Lupus Erythematosus, Systemic 11
• Acquired Immunodeficiency Syndrome 7
• Arthritis, Rheumatoid 7
• Diabetes Mellitus, Type 1 7
• Proteinuria 6
• Vasculitis 5
• Glomerulonephritis 4
• Antiphospholipid Syndrome 3
• Encephalomyelitis, Autoimmune, Experimental 3
• Thyroiditis, Autoimmune 3

Showing 11 of 15 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CD4 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. 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)

0.71

gnomAD pLI

0

gnomAD missense Z

1.06

DepMap mean gene effect

0.03

DepMap dependency class

none

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

• adaptive immune response
• calcium-mediated signaling
• cell adhesion
• cell surface receptor protein tyrosine kinase signaling pathway
• cell surface receptor signaling pathway
• cellular response to granulocyte macrophage colony-stimulating factor stimulus
• cellular response to ionomycin
• defense response to Gram-negative bacterium
• enzyme-linked receptor protein signaling pathway
• immune response
• interleukin-15-mediated signaling pathway
• macrophage differentiation
• maintenance of protein location in cell
• positive regulation of calcium ion transport into cytosol
• positive regulation of calcium-mediated signaling
• positive regulation of interleukin-2 production
• positive regulation of monocyte differentiation
• positive regulation of T cell proliferation
• regulation of T cell activation
• response to estradiol
• response to ethanol
• response to methamphetamine hydrochloride
• response to vitamin D
• signal transduction
• symbiont entry into host cell
• T cell differentiation
• T cell receptor signaling pathway
• T cell selection
• helper T cell enhancement of adaptive immune response

Molecular functions

• coreceptor activity
• enzyme binding
• extracellular matrix structural constituent
• identical protein binding
• immunoglobulin binding
• lipid binding
• MHC class II protein binding
• MHC class II protein complex binding
• protein homodimerization activity
• protein kinase binding
• protein tyrosine kinase binding
• signaling receptor activity
• transmembrane signaling receptor activity
• virus receptor activity
• zinc ion binding
• interleukin-16 binding
• interleukin-16 receptor activity

Cellular components

• clathrin-coated endocytic vesicle membrane
• early endosome
• endoplasmic reticulum lumen
• endoplasmic reticulum membrane
• external side of plasma membrane
• membrane raft
• plasma membrane
• T cell receptor complex

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin C2-set
• Immunoglobulin V-set domain
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Immunoglobulin domain
• Immunoglobulin C2-set domain
• T-cell surface antigen CD4
• CD4, extracellular
• T cell CD4 receptor C-terminal region
• CD4, extracellular
• T cell CD4 receptor C terminal region

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Immunity
• Immunoglobulin domain
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CD4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IL16
• LCK
• SPG21
• PTK2
• DEFA4
• LGALS1