HAVCR2

Protein identityUniProt · HPA

UniProt accession

Q8TDQ0

Gene

HAVCR2

Ensembl

ENSG00000135077

Chromosome

5

Canonical length

301 aa

Protein class

CD markers, Disease related genes, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

Canonical amino-acid sequenceUniProt

301 residues, UniProt reviewed canonical sequence.

>Q8TDQ0|HAVCR2
     1  MFSHLPFDCV LLLLLLLLTR SSEVEYRAEV GQNAYLPCFY TPAAPGNLVP VCWGKGACPV
    61  FECGNVVLRT DERDVNYWTS RYWLNGDFRK GDVSLTIENV TLADSGIYCC RIQIPGIMND
   121  EKFNLKLVIK PAKVTPAPTR QRDFTAAFPR MLTTRGHGPA ETQTLGSLPD INLTQISTLA
   181  NELRDSRLAN DLRDSGATIR IGIYIGAGIC AGLALALIFG ALIFKWYSHS KEKIQNLSLI
   241  SLANLPPSGL ANAVAEGIRS EENIYTIEEN VYEVEEPNEY YCYVSSRQQP SQPLGCRFAM
   301  P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HAVCR2 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)

0.51

Highest tissue expression

27 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HAVCR2.

Disease | AllUniProt

Conditions HAVCR2 is implicated in, by any mechanism.

• T-cell lymphoma, subcutaneous panniculitis-like (SPTCL) MIM:618398

ReferencesPubMed · IEDB

Publications for HAVCR2 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)

0.86

gnomAD pLI

0.04

gnomAD missense Z

0.64

DepMap mean gene effect

0.06

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

• adaptive immune response
• cellular response to lipopolysaccharide
• defense response to Gram-positive bacterium
• inflammatory response
• innate immune response
• macrophage activation involved in immune response
• maternal process involved in female pregnancy
• natural killer cell tolerance induction
• negative regulation of defense response to bacterium
• negative regulation of gene expression
• negative regulation of immunological synapse formation
• negative regulation of interferon-alpha production
• negative regulation of interleukin-2 production
• negative regulation of interleukin-6 production
• negative regulation of myeloid dendritic cell activation
• negative regulation of natural killer cell activation
• negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
• negative regulation of NF-kappaB transcription factor activity
• negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
• negative regulation of T cell proliferation
• negative regulation of T-helper 1 type immune response
• negative regulation of tumor necrosis factor production
• negative regulation of type II interferon production
• positive regulation of chemokine production
• positive regulation of defense response to bacterium
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of interleukin-1 production
• positive regulation of interleukin-4 production
• positive regulation of macrophage activation
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of T cell proliferation
• positive regulation of tumor necrosis factor production
• positive regulation of type II interferon production
• regulation of transcription by RNA polymerase II
• toll-like receptor 3 signaling pathway
• toll-like receptor 7 signaling pathway
• toll-like receptor 9 signaling pathway
• negative regulation of granulocyte colony-stimulating factor production
• negative regulation of interleukin-3 production
• regulation of tolerance induction dependent upon immune response

Molecular functions

• metal ion binding
• transmembrane signaling receptor activity

Cellular components

• anchoring junction
• cell surface
• early endosome
• immunological synapse
• mediator complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin V-set domain
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• Immune Modulating & Transcription Coactivator
• Immunoglobulin V-set domain

KeywordsUniProt

• Adaptive immunity
• Cell junction
• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunity
• Immunoglobulin domain
• Inflammatory response
• Innate immunity
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Phosphoprotein
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of HAVCR2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BAG6
• HMGB1
• ILF3