TNFRSF1A

Protein identityUniProt · HPA

UniProt accession

P19438

Gene

TNFRSF1A

Ensembl

ENSG00000067182

Chromosome

12

Canonical length

455 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted to blood

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

Canonical amino-acid sequenceUniProt

455 residues, UniProt reviewed canonical sequence.

>P19438|TNFRSF1A
     1  MGLSTVPDLL LPLVLLELLV GIYPSGVIGL VPHLGDREKR DSVCPQGKYI HPQNNSICCT
    61  KCHKGTYLYN DCPGPGQDTD CRECESGSFT ASENHLRHCL SCSKCRKEMG QVEISSCTVD
   121  RDTVCGCRKN QYRHYWSENL FQCFNCSLCL NGTVHLSCQE KQNTVCTCHA GFFLRENECV
   181  SCSNCKKSLE CTKLCLPQIE NVKGTEDSGT TVLLPLVIFF GLCLLSLLFI GLMYRYQRWK
   241  SKLYSIVCGK STPEKEGELE GTTTKPLAPN PSFSPTPGFT PTLGFSPVPS STFTSSSTYT
   301  PGDCPNFAAP RREVAPPYQG ADPILATALA SDPIPNPLQK WEDSAHKPQS LDTDDPATLY
   361  AVVENVPPLR WKEFVRRLGL SDHEIDRLEL QNGRCLREAQ YSMLATWRRR TPRREATLEL
   421  LGRVLRDMDL LGCLEDIEEA LCGPAALPPA PSLLR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TNFRSF1A 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)

0.5

Highest tissue expression

154 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TNFRSF1A.

Disease | AllUniProt

Conditions TNFRSF1A is implicated in, by any mechanism.

• Periodic fever, familial, autosomal dominant (FPF) MIM:142680
• Multiple sclerosis 5 (MS5) MIM:614810

Disease | GeneticClinVar

35 pathogenic / likely-pathogenic of 649 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• TNF receptor-associated periodic fever syndrome (TRAPS)
• Inborn genetic diseases
• Autoinflammatory syndrome
• Multiple sclerosis
• TNFRSF1A-related disorder

ReferencesPubMed · IEDB

Publications for TNFRSF1A 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)

0.24

gnomAD pLI

0.99

gnomAD missense Z

2.1

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aortic valve development
• canonical NF-kappaB signal transduction
• cell surface receptor signaling pathway via JAK-STAT
• cellular response to mechanical stimulus
• cytokine-mediated signaling pathway
• defense response to bacterium
• extrinsic apoptotic signaling pathway via death domain receptors
• inflammatory response
• intrinsic apoptotic signaling pathway in response to DNA damage
• negative regulation of canonical NF-kappaB signal transduction
• negative regulation of cardiac muscle hypertrophy
• negative regulation of extracellular matrix constituent secretion
• negative regulation of inflammatory response
• positive regulation of amide metabolic process
• positive regulation of apoptotic process involved in morphogenesis
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of execution phase of apoptosis
• positive regulation of inflammatory response
• positive regulation of lipid metabolic process
• positive regulation of transcription by RNA polymerase II
• prostaglandin metabolic process
• protein localization to plasma membrane
• protein polyubiquitination
• pulmonary valve development
• regulation of establishment of endothelial barrier
• regulation of membrane lipid metabolic process
• regulation of tumor necrosis factor-mediated signaling pathway
• transcription by RNA polymerase II
• tumor necrosis factor-mediated signaling pathway

Molecular functions

• signaling receptor activity
• tumor necrosis factor binding
• tumor necrosis factor receptor activity

Cellular components

• cell surface
• extracellular region
• extracellular space
• Golgi membrane
• membrane
• membrane raft
• plasma membrane
• receptor complex
• tumor necrosis factor receptor superfamily complex

Protein domainsUniProt · Pfam · InterPro

• Death domain
• TNFR/NGFR cysteine-rich region
• Death-like domain superfamily
• TNFR/NGFR cysteine-rich region
• Death domain
• Tumour necrosis factor receptor 1A
• Tumor necrosis factor receptor 1A, N-terminal
• Tumor necrosis factor receptor 1A, death domain
• Tumor necrosis factor receptor superfamily member 1A

KeywordsUniProt

• Amyloidosis
• Apoptosis
• Cell membrane
• Cleavage on pair of basic residues
• Disulfide bond
• Glycoprotein
• Golgi apparatus
• Host-virus interaction
• Membrane
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of TNFRSF1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BABAM2
• BAG4
• FEM1B
• GRB2
• NOL3
• PGLYRP1
• RIPK1
• SH3RF2
• SQSTM1
• TRADD
• TRPC4AP
• CRADD
• ARFGEF2
• EGFR
• RFK
• TNF