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P23563 (TNFA_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Tumor necrosis factor, membrane form
    Alternative name(s):
    N-terminal fragment
    Short name=NTF
  2. Intracellular domain 1
    Short name=ICD1
  3. Intracellular domain 2
    Short name=ICD2
  4. C-domain 1
  5. C-domain 2
  6. Tumor necrosis factor, soluble form
Gene names
Name:TNF
Synonyms:TNFA, TNFSF2
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length232 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells By similarity.

Subunit structure

Homotrimer. Interacts with SPPL2B By similarity.

Subcellular location

Cell membrane; Single-pass type II membrane protein By similarity.

Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein By similarity.

Tumor necrosis factor, soluble form: Secreted By similarity.

C-domain 1: Secreted By similarity.

C-domain 2: Secreted By similarity.

Post-translational modification

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 By similarity.

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 By similarity.

O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid By similarity.

Sequence similarities

Belongs to the tumor necrosis factor family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Myristate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from electronic annotation. Source: Ensembl

activation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

activation of MAPKKK activity

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

cellular amino acid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

cellular response to amino acid stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to nicotine

Inferred from electronic annotation. Source: Ensembl

chronic inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

embryonic digestive tract development

Inferred from electronic annotation. Source: Ensembl

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

humoral immune response

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

leukocyte tethering or rolling

Inferred from electronic annotation. Source: Ensembl

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

necroptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of alkaline phosphatase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of branching involved in lung morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytokine secretion involved in immune response

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

negative regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of lipid catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein complex disassembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of viral genome replication

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of NFAT protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of calcidiol 1-monooxygenase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine (C-X-C motif) ligand 2 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chronic inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

positive regulation of fever generation

Inferred from electronic annotation. Source: Ensembl

positive regulation of hair follicle development

Inferred from electronic annotation. Source: Ensembl

positive regulation of heterotypic cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of humoral immune response mediated by circulating immunoglobulin

Inferred from electronic annotation. Source: Ensembl

positive regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-8 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of membrane protein ectodomain proteolysis

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of podosome assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein complex disassembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein localization to cell surface

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of translational initiation by iron

Inferred from electronic annotation. Source: Ensembl

positive regulation of vitamin D biosynthetic process

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

receptor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in salivary gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

regulation of immunoglobulin secretion

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to virus

Inferred from electronic annotation. Source: Ensembl

sequestering of triglyceride

Inferred from electronic annotation. Source: Ensembl

transformed cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

tumor necrosis factor-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from electronic annotation. Source: Ensembl

phagocytic cup

Inferred from electronic annotation. Source: Ensembl

recycling endosome

Inferred from electronic annotation. Source: Ensembl

   Molecular_functiontranscription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 232232Tumor necrosis factor, membrane form
PRO_0000034445
Chain1 – 3939Intracellular domain 1 By similarity
PRO_0000417275
Chain1 – 3535Intracellular domain 2 By similarity
PRO_0000417276
Chain50 – ?C-domain 1 By similarityPRO_0000417277
Chain52 – ?C-domain 2 By similarityPRO_0000417278
Chain77 – 232156Tumor necrosis factor, soluble form
PRO_0000034446

Regions

Topological domain1 – 3535Cytoplasmic Potential
Transmembrane36 – 5621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain57 – 232176Extracellular Potential

Sites

Site34 – 352Cleavage; by SPPL2A or SPPL2B By similarity
Site39 – 402Cleavage; by SPPL2A or SPPL2B By similarity
Site49 – 502Cleavage; by SPPL2A or SPPL2B By similarity
Site51 – 522Cleavage; by SPPL2A or SPPL2B By similarity
Site76 – 772Cleavage; by ADAM17 By similarity

Amino acid modifications

Modified residue21Phosphoserine; by CK1 By similarity
Lipidation191N6-myristoyl lysine By similarity
Lipidation201N6-myristoyl lysine By similarity
Glycosylation801O-linked (GalNAc...); in soluble form By similarity
Disulfide bond144 ↔ 176 By similarity

Sequences

Sequence LengthMass (Da)Tools
P23563 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: 65B28F702D99C8BE

FASTA23225,254
        10         20         30         40         50         60 
MSTESMIRDV ELAEEALAKK AGGPQGSRRC LCLSLFSFLL VAGATTLFCL LHFEVIGPQK 

        70         80         90        100        110        120 
EEFPAGPLSI NPLAQGLRSS SQTSDKPVAH VVANVKAEGQ LQWQSGYANA LLANGVKLKD 

       130        140        150        160        170        180 
NQLVVPTDGL YLIYSQVLFR GQGCPSTNVF LTHTISRIAV SYQTKVNLLS AIKSPCQRET 

       190        200        210        220        230 
PEGAEAKPWY EPIYLGGVFQ LEKDDRLSAE INLPDYLDFA ESGQVYFGII AL 

« Hide

References

« Hide 'large scale' references
[1]"Gene sequence of porcine tumor necrosis factor alpha."
Drews R.T., Coffee B.W., Prestwood A.K., McGraw R.A.
Nucleic Acids Res. 18:5564-5564(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The porcine tumor necrosis factor-encoding genes: sequence and comparative analysis."
Kuhnert P., Wuethrich C., Peterhans E., Pauli U.
Gene 102:171-178(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver.
[3]"Complete nucleotide sequence of a cDNA encoding porcine tumor necrosis factor-alpha."
Choi C.S., Molitor T.W., Lin G.F., Murtaugh M.P.
Anim. Biotechnol. 2:97-105(1991)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Macrophage.
[4]"Sequence of the swine major histocompatibility complex region containing all non-classical class I genes."
Chardon P., Rogel-Gaillard C., Cattolico L., Duprat S., Vaiman M., Renard C.
Tissue Antigens 57:55-65(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Large white.
Tissue: Fibroblast.
[5]Porcine genome sequencing project
Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Porcine tumor necrosis factor alpha: cloning with the polymerase chain reaction and determination of the nucleotide sequence."
Pauli U., Beutler B., Peterhans E.
Gene 81:185-191(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 44-232.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54001 Genomic DNA. Translation: CAA37949.1.
X54859 Genomic DNA. Translation: CAA38639.1.
X57321 mRNA. Translation: CAA40591.1.
AJ251914 Genomic DNA. Translation: CAB63852.1.
BX548169 Genomic DNA. Translation: CAN59689.1.
M29079 mRNA. Translation: AAA31128.1.
PIRS12606.
RefSeqNP_999187.1. NM_214022.1.
UniGeneSsc.100.

3D structure databases

ProteinModelPortalP23563.
SMRP23563. Positions 84-232.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9823.ENSSSCP00000001491.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSSSCT00000001533; ENSSSCP00000001491; ENSSSCG00000001404.
GeneID397086.
KEGGssc:397086.

Organism-specific databases

CTD7124.

Phylogenomic databases

eggNOGNOG40413.
GeneTreeENSGT00530000062992.
HOGENOMHOG000048729.
HOVERGENHBG012516.
KOK03156.
OMAPWYEPIY.
OrthoDBEOG7V4B0Q.
TreeFamTF332169.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008064. TNFalpha/TNFSF15.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PANTHERPTHR11471:SF7. PTHR11471:SF7. 1 hit.
PfamPF00229. TNF. 1 hit.
[Graphical view]
PRINTSPR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameTNFA_PIG
AccessionPrimary (citable) accession number: P23563
Secondary accession number(s): A5D9N8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: April 16, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families