CCR5

Protein identityUniProt · HPA

UniProt accession

P51681

Gene

CCR5

Ensembl

ENSG00000160791

Chromosome

3

Canonical length

352 aa

Protein class

CD markers, Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

Canonical amino-acid sequenceUniProt

352 residues, UniProt reviewed canonical sequence.

>P51681|CCR5
     1  MDYQVSSPIY DINYYTSEPC QKINVKQIAA RLLPPLYSLV FIFGFVGNML VILILINCKR
    61  LKSMTDIYLL NLAISDLFFL LTVPFWAHYA AAQWDFGNTM CQLLTGLYFI GFFSGIFFII
   121  LLTIDRYLAV VHAVFALKAR TVTFGVVTSV ITWVVAVFAS LPGIIFTRSQ KEGLHYTCSS
   181  HFPYSQYQFW KNFQTLKIVI LGLVLPLLVM VICYSGILKT LLRCRNEKKR HRAVRLIFTI
   241  MIVYFLFWAP YNIVLLLNTF QEFFGLNNCS SSNRLDQAMQ VTETLGMTHC CINPIIYAFV
   301  GEKFRNYLLV FFQKHIAKRF CKCCSIFQQE APERASSVYT RSTGEQEISV GL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CCR5 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

7

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CCR5.

Disease | AllUniProt

Conditions CCR5 is implicated in, by any mechanism.

• Type 1 diabetes mellitus 22 (T1D22) MIM:612522

Disease | AutoantibodyPubMed

Conditions in which antibodies against CCR5 are reported. Each links to that disease's full target list.

• HIV Infections 3

ReferencesPubMed · IEDB

Publications for CCR5 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)

1.93

gnomAD pLI

0

gnomAD missense Z

-1.45

DepMap mean gene effect

0.02

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

• apoptotic process
• calcium ion transport
• calcium-mediated signaling
• cell chemotaxis
• cell surface receptor signaling pathway
• cell-cell signaling
• cellular defense response
• cellular response to lipopolysaccharide
• chemotaxis
• dendritic cell chemotaxis
• G protein-coupled receptor signaling pathway
• immune response
• inflammatory response
• MAPK cascade
• negative regulation of macrophage apoptotic process
• positive regulation of cytosolic calcium ion concentration
• release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• response to cholesterol
• signaling

Molecular functions

• actin binding
• C-C chemokine binding
• C-C chemokine receptor activity
• chemokine (C-C motif) ligand 5 binding
• chemokine receptor activity
• coreceptor activity
• identical protein binding
• phosphatidylinositol-4,5-bisphosphate phospholipase C activity
• virus receptor activity

Cellular components

• cell surface
• cytoplasm
• endosome
• external side of plasma membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Chemokine receptor family
• GPCR, rhodopsin-like, 7TM
• C-C chemokine receptor type 1-9-like
• 7 transmembrane receptor (rhodopsin family)
• CC chemokine receptor 5

KeywordsUniProt

• Cell membrane
• Diabetes mellitus
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Receptor
• Sulfation
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CCR5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRB1
• ARRB2
• CNIH4
• GRK2
• PRAF2
• S100A4
• CCL4L1
• CCL5