P79374 (TNFA_TRIVU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

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

Organism

Trichosurus vulpecula (Brush-tailed possum)

Taxonomic identifier

9337 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Metatheria › Diprotodontia › Phalangeridae › Trichosurus

Protein attributes

Sequence length	233 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity. 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 component	Cell membrane Membrane Secreted
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Lipoprotein Myristate Phosphoprotein
Gene Ontology (GO)
Biological_process	immune response Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 233	233	Tumor necrosis factor, membrane form		PRO_0000034457
	Chain	1 – 39	39	Intracellular domain 1 By similarity		PRO_0000417299
	Chain	1 – 35	35	Intracellular domain 2 By similarity		PRO_0000417300
	Chain	50 – ?		C-domain 1 By similarity		PRO_0000417301
	Chain	52 – ?		C-domain 2 By similarity		PRO_0000417302
	Chain	?78 – 233	156	Tumor necrosis factor, soluble form		PRO_0000034458
Regions
	Topological domain	1 – 35	35	Cytoplasmic Potential
	Transmembrane	36 – 56	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	57 – 233	177	Extracellular Potential
Sites
	Site	34 – 35	2	Cleavage; by SPPL2A or SPPL2B By similarity
	Site	49 – 50	2	Cleavage; by SPPL2A or SPPL2B By similarity
	Site	51 – 52	2	Cleavage; by SPPL2A or SPPL2B By similarity
	Site	77 – 78	2	Cleavage; by ADAM17 Potential
Amino acid modifications
	Modified residue	2	1	Phosphoserine; by CK1 By similarity
	Lipidation	20	1	N6-myristoyl lysine By similarity
	Disulfide bond	145 ↔ 177		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P79374 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 56FDD9F46DC4406E	FASTA	233	25,705
	10 20 30 40 50 60 MSTESMIRDL ELAEEALKRK ARGPLGLGRC LCLTLISSFL LAGATVLFCL LHFGVIGPQK 70 80 90 100 110 120 EQESTDTFLD MKPLTQRVRS LQNESAKPVA HLIADQLAEG QLLWVGDVAN TLLMNGMELV 130 140 150 160 170 180 DNQLVLPSTG LYLVYSQLLY KGSQCGKESL VLTHKISRFT LSYQKKVTLL ANIRSSCRKA 190 200 210 220 230 AEDDGEPSAW YEPVYLAGVF QLTEGDKLVV DTNYPENLDF AEPGQLYFGA IAL

References

[1]

"Molecular cloning and characterization of tumor necrosis factor alpha (TNF-alpha) from the Australian common brushtail possum, Trichosurus vulpecula." Wedlock D.N., Aldwell F.E., Buddle B.M. Immunol. Cell Biol. 74:151-158(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	S83283 mRNA. Translation: AAB49506.1. AF016102 mRNA. Translation: AAC48766.1.
3D structure databases
ProteinModelPortal	P79374.
SMR	P79374. Positions 82-233.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG012516.
Family and domain databases
Gene3D	2.60.120.40. 1 hit.
InterPro	IPR006052. TNF. IPR006053. TNF_a/b/c. IPR002959. TNF_alpha. IPR021184. TNF_CS. IPR008983. Tumour_necrosis_fac-like_dom. [Graphical view]
Pfam	PF00229. TNF. 1 hit. [Graphical view]
PRINTS	PR01234. TNECROSISFCT. PR01235. TNFALPHA.
SMART	SM00207. TNF. 1 hit. [Graphical view]
SUPFAM	SSF49842. TNF_like. 1 hit.
PROSITE	PS00251. TNF_1. 1 hit. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

TNFA_TRIVU

Accession

Primary (citable) accession number: P79374

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program