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Protein

Tumor necrosis factor

Gene

TNF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity).By similarity3 Publications
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5626978 TNFR1-mediated ceramide production
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-75893 TNF signaling

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P01375

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Tumor necrosis factor
Alternative name(s):
Cachectin
TNF-alpha
Tumor necrosis factor ligand superfamily member 2
Short name:
TNF-a
Cleaved into the following 6 chains:
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TNF
Synonyms:TNFA, TNFSF2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...
EuPathDBi
HostDB:ENSG00000232810.3

Human Gene Nomenclature Database

More...
HGNCi
HGNC:11892 TNF

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
191160 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P01375

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 35CytoplasmicSequence analysisAdd BLAST35
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei36 – 56Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini57 – 233ExtracellularSequence analysisAdd BLAST177

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Psoriatic arthritis (PSORAS)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAn inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
See also OMIM:607507

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi105L → S: Low activity. 1 Publication1
Mutagenesisi108R → W: Biologically inactive. 1 Publication1
Mutagenesisi112L → F: Biologically inactive. 1 Publication1
Mutagenesisi160A → V: Biologically inactive. 1 Publication1
Mutagenesisi162S → F: Biologically inactive. 1 Publication1
Mutagenesisi167V → A or D: Biologically inactive. 1 Publication1
Mutagenesisi222E → K: Biologically inactive. 1 Publication1

Organism-specific databases

DisGeNET

More...
DisGeNETi
7124

MalaCards human disease database

More...
MalaCardsi
TNF
MIMi607507 phenotype
610424 phenotype
611162 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000232810

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
40050 NON RARE IN EUROPE: Psoriatic arthritis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA435

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1825

Drug and drug target database

More...
DrugBanki
DB05250 681323
DB00051 Adalimumab
DB04956 Afelimomab
DB05879 AME-527
DB01427 Amrinone
DB05676 Apremilast
DB05066 AV411
DB08904 Certolizumab pegol
DB00608 Chloroquine
DB01407 Clenbuterol
DB05744 CRx-139
DB05869 CTI-01
DB05758 CYT007-TNFQb
DB00668 Epinephrine
DB00005 Etanercept
DB01296 Glucosamine
DB06674 Golimumab
DB05767 HMPL-004
DB00065 Infliximab
DB02325 Isopropyl Alcohol
DB05303 OMS-103HP
DB05218 PN0621
DB08910 Pomalidomide
DB01411 Pranlukast
DB00852 Pseudoephedrine
DB05412 SCIO-469
DB05207 SD118
DB01041 Thalidomide
DB05470 VX-702
DB05017 YSIL6

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
TNF

Domain mapping of disease mutations (DMDM)

More...
DMDMi
135934

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000344231 – 233Tumor necrosis factor, membrane formAdd BLAST233
ChainiPRO_00004172311 – 39Intracellular domain 1Add BLAST39
ChainiPRO_00004172321 – 35Intracellular domain 2Add BLAST35
ChainiPRO_000041723350 – ?C-domain 1
ChainiPRO_000041723452 – ?C-domain 2
ChainiPRO_000003442477 – 233Tumor necrosis factor, soluble form1 PublicationAdd BLAST157

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2Phosphoserine; by CK1Curated1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi19N6-myristoyl lysine1 Publication1
Lipidationi20N6-myristoyl lysine1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi80O-linked (GalNAc...) serine; in soluble form1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi145 ↔ 177

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.3 Publications
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.2 Publications
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections (‘Function’, ‘PTM / Processing’, ‘Pathology and Biotech’) according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei35 – 36Cleavage; by SPPL2A or SPPL2B2
Sitei39 – 40Cleavage; by SPPL2A or SPPL2B2
Sitei49 – 50Cleavage; by SPPL2A or SPPL2B2
Sitei51 – 52Cleavage; by SPPL2A or SPPL2B2
Sitei76 – 77Cleavage; by ADAM172

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P01375

PeptideAtlas

More...
PeptideAtlasi
P01375

PRoteomics IDEntifications database

More...
PRIDEi
P01375

ProteomicsDB human proteome resource

More...
ProteomicsDBi
12707
51379

PTM databases

GlyConnect protein glycosylation platform

More...
GlyConnecti
609

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P01375

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P01375

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
P01375

UniCarbKB; an annotated and curated database of glycan structures

More...
UniCarbKBi
P01375

Miscellaneous databases

CutDB - Proteolytic event database

More...
PMAP-CutDBi
P01375

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000232810 Expressed in 89 organ(s), highest expression level in leukocyte

CleanEx database of gene expression profiles

More...
CleanExi
HS_TNF

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P01375 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P01375 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotrimer. Interacts with SPPL2B.1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
112979, 103 interactors

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
P01375

Database of interacting proteins

More...
DIPi
DIP-2895N

Protein interaction database and analysis system

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IntActi
P01375, 83 interactors

Molecular INTeraction database

More...
MINTi
P01375

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000398698

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P01375

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1233
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P01375

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P01375

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P01375

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
ENOG410ISAN Eukaryota
ENOG410YQC4 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000153265

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000048729

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG012516

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P01375

KEGG Orthology (KO)

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KOi
K03156

Identification of Orthologs from Complete Genome Data

More...
OMAi
QLQWLSR

Database of Orthologous Groups

More...
OrthoDBi
EOG091G0HIG

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P01375

TreeFam database of animal gene trees

More...
TreeFami
TF332169

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00184 TNF, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.60.120.40, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR006053 TNF
IPR002959 TNF_alpha
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom

The PANTHER Classification System

More...
PANTHERi
PTHR11471:SF23 PTHR11471:SF23, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00229 TNF, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR01234 TNECROSISFCT
PR01235 TNFALPHA

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00207 TNF, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF49842 SSF49842, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P01375-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
110 120 130 140 150
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV
160 170 180 190 200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL
Length:233
Mass (Da):25,644
Last modified:July 21, 1986 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3DF90F96C9031FFE
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140T922A0A140T922_HUMAN
Tumor necrosis factor
TNF
171Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAF71992 differs from that shown. Reason: Frameshift at positions 91 and 157.Curated
The sequence CAA75070 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti63F → S in AAA61198 (PubMed:3856324).Curated1
Sequence conflicti84 – 86PSD → VNR in AAF71992 (Ref. 17) Curated3
Sequence conflicti183E → R in AAC03542 (Ref. 16) Curated1

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIMi:610424].
Genetic variations in TNF are involved in susceptibility to malaria [MIMi:611162].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01937884P → L1 PublicationCorresponds to variant dbSNP:rs4645843Ensembl.1
Natural variantiVAR_01192794A → T. Corresponds to variant dbSNP:rs1800620Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
M16441 Genomic DNA Translation: AAA61200.1
X02910 Genomic DNA Translation: CAA26669.1
X01394 mRNA Translation: CAA25650.1
M10988 mRNA Translation: AAA61198.1
M26331 Genomic DNA Translation: AAA36758.1
Z15026 Genomic DNA Translation: CAA78745.1
Y14768 Genomic DNA Translation: CAA75070.1 Sequence problems.
AF129756 Genomic DNA Translation: AAD18091.1
BA000025 Genomic DNA Translation: BAB63396.1
AB088112 Genomic DNA Translation: BAC54944.1
AY066019 Genomic DNA Translation: AAL47581.1
AY214167 Genomic DNA Translation: AAO21132.1
BC028148 mRNA Translation: AAH28148.1
AF043342 mRNA Translation: AAC03542.1
AF098751 mRNA Translation: AAF71992.1 Frameshift.

The Consensus CDS (CCDS) project

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CCDSi
CCDS4702.1

Protein sequence database of the Protein Information Resource

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PIRi
A93585 QWHUN

NCBI Reference Sequences

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RefSeqi
NP_000585.2, NM_000594.3

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.241570

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000376122; ENSP00000365290; ENSG00000204490
ENST00000383496; ENSP00000372988; ENSG00000206439
ENST00000412275; ENSP00000392858; ENSG00000228321
ENST00000420425; ENSP00000410668; ENSG00000228849
ENST00000443707; ENSP00000389492; ENSG00000230108
ENST00000448781; ENSP00000389490; ENSG00000223952
ENST00000449264; ENSP00000398698; ENSG00000232810

Database of genes from NCBI RefSeq genomes

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GeneIDi
7124

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:7124

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Wikipedia

Tumor necrosis factor alpha entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16441 Genomic DNA Translation: AAA61200.1
X02910 Genomic DNA Translation: CAA26669.1
X01394 mRNA Translation: CAA25650.1
M10988 mRNA Translation: AAA61198.1
M26331 Genomic DNA Translation: AAA36758.1
Z15026 Genomic DNA Translation: CAA78745.1
Y14768 Genomic DNA Translation: CAA75070.1 Sequence problems.
AF129756 Genomic DNA Translation: AAD18091.1
BA000025 Genomic DNA Translation: BAB63396.1
AB088112 Genomic DNA Translation: BAC54944.1
AY066019 Genomic DNA Translation: AAL47581.1
AY214167 Genomic DNA Translation: AAO21132.1
BC028148 mRNA Translation: AAH28148.1
AF043342 mRNA Translation: AAC03542.1
AF098751 mRNA Translation: AAF71992.1 Frameshift.
CCDSiCCDS4702.1
PIRiA93585 QWHUN
RefSeqiNP_000585.2, NM_000594.3
UniGeneiHs.241570

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A8MX-ray2.30A/B/C77-233[»]
1TNFX-ray2.60A/B/C77-233[»]
2AZ5X-ray2.10A/B/C/D86-233[»]
2E7AX-ray1.80A/B/C77-233[»]
2TUNX-ray3.10A/B/C/D/E/F77-233[»]
2ZJCX-ray2.50A/B/C77-233[»]
2ZPXX-ray2.83A/B/C77-233[»]
3ALQX-ray3.00A/B/C/D/E/F77-233[»]
3IT8X-ray2.80A/B/C/G/H/I82-233[»]
3L9JX-ray2.10T85-233[»]
3WD5X-ray3.10A77-233[»]
4G3YX-ray2.60C77-233[»]
4TSVX-ray1.80A84-233[»]
4TWTX-ray2.85A/B/C/D77-233[»]
4Y6OX-ray1.60C/D17-23[»]
5M2IX-ray2.15A/B/C/D/E/F77-233[»]
5M2JX-ray1.90A77-233[»]
5M2MX-ray2.30A/B/C/G/I/M77-233[»]
5MU8X-ray3.00A/B/C/D/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d/e77-233[»]
5TSWX-ray2.50A/B/C/D/E/F84-233[»]
5UUIX-ray1.40A77-233[»]
5WUXX-ray2.90E/F/G77-233[»]
5YOYX-ray2.73A/B/C/J/K/L76-233[»]
ProteinModelPortaliP01375
SMRiP01375
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112979, 103 interactors
CORUMiP01375
DIPiDIP-2895N
IntActiP01375, 83 interactors
MINTiP01375
STRINGi9606.ENSP00000398698

Chemistry databases

BindingDBiP01375
ChEMBLiCHEMBL1825
DrugBankiDB05250 681323
DB00051 Adalimumab
DB04956 Afelimomab
DB05879 AME-527
DB01427 Amrinone
DB05676 Apremilast
DB05066 AV411
DB08904 Certolizumab pegol
DB00608 Chloroquine
DB01407 Clenbuterol
DB05744 CRx-139
DB05869 CTI-01
DB05758 CYT007-TNFQb
DB00668 Epinephrine
DB00005 Etanercept
DB01296 Glucosamine
DB06674 Golimumab
DB05767 HMPL-004
DB00065 Infliximab
DB02325 Isopropyl Alcohol
DB05303 OMS-103HP
DB05218 PN0621
DB08910 Pomalidomide
DB01411 Pranlukast
DB00852 Pseudoephedrine
DB05412 SCIO-469
DB05207 SD118
DB01041 Thalidomide
DB05470 VX-702
DB05017 YSIL6

PTM databases

GlyConnecti609
iPTMnetiP01375
PhosphoSitePlusiP01375
SwissPalmiP01375
UniCarbKBiP01375

Polymorphism and mutation databases

BioMutaiTNF
DMDMi135934

Proteomic databases

PaxDbiP01375
PeptideAtlasiP01375
PRIDEiP01375
ProteomicsDBi12707
51379

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
7124
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376122; ENSP00000365290; ENSG00000204490
ENST00000383496; ENSP00000372988; ENSG00000206439
ENST00000412275; ENSP00000392858; ENSG00000228321
ENST00000420425; ENSP00000410668; ENSG00000228849
ENST00000443707; ENSP00000389492; ENSG00000230108
ENST00000448781; ENSP00000389490; ENSG00000223952
ENST00000449264; ENSP00000398698; ENSG00000232810
GeneIDi7124
KEGGihsa:7124

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
7124
DisGeNETi7124
EuPathDBiHostDB:ENSG00000232810.3

GeneCards: human genes, protein and diseases

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GeneCardsi
TNF

H-Invitational Database, human transcriptome db

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H-InvDBi
HIX0165948
HGNCiHGNC:11892 TNF
MalaCardsiTNF
MIMi191160 gene
607507 phenotype
610424 phenotype
611162 phenotype
neXtProtiNX_P01375
OpenTargetsiENSG00000232810
Orphaneti40050 NON RARE IN EUROPE: Psoriatic arthritis
PharmGKBiPA435

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410ISAN Eukaryota
ENOG410YQC4 LUCA
GeneTreeiENSGT00940000153265
HOGENOMiHOG000048729
HOVERGENiHBG012516
InParanoidiP01375
KOiK03156
OMAiQLQWLSR
OrthoDBiEOG091G0HIG
PhylomeDBiP01375
TreeFamiTF332169

Enzyme and pathway databases

ReactomeiR-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5626978 TNFR1-mediated ceramide production
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-75893 TNF signaling
SIGNORiP01375

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
TNF human
EvolutionaryTraceiP01375

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
Tumor_necrosis_factor-alpha

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
7124
PMAP-CutDBiP01375

Protein Ontology

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PROi
PR:P01375

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000232810 Expressed in 89 organ(s), highest expression level in leukocyte
CleanExiHS_TNF
ExpressionAtlasiP01375 baseline and differential
GenevisibleiP01375 HS

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR002959 TNF_alpha
IPR021184 TNF_CS
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PANTHERiPTHR11471:SF23 PTHR11471:SF23, 1 hit
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
PR01235 TNFALPHA
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS00251 TNF_1, 1 hit
PS50049 TNF_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTNFA_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P01375
Secondary accession number(s): O43647, Q9P1Q2, Q9UIV3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: December 5, 2018
This is version 242 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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