P16599 (TNFA_RAT) 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 2 chains:

1. Tumor necrosis factor, membrane form
2. Tumor necrosis factor, soluble form

Gene names

Name:	Tnf
Synonyms:	Tnfa, Tnfsf2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	235 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.
Subunit structure	Homotrimer By similarity.
Subcellular location	Cell membrane; Single-pass type II membrane protein By similarity. Tumor necrosis factor, soluble form: Secreted By similarity.
Post-translational modification	The soluble form derives from the membrane form by proteolytic processing 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.
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 Glycoprotein Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	calcium-mediated signaling Inferred from direct assay. Source: RGD cell activation Inferred from direct assay. Source: RGD negative regulation of L-glutamate transport Inferred from direct assay. Source: RGD negative regulation of cell proliferation Inferred from direct assay. Source: RGD negative regulation of glucose import Inferred from direct assay. Source: RGD positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from genetic interaction. Source: RGD positive regulation of mitosis Inferred from mutant phenotype. Source: RGD positive regulation of neuron apoptosis Inferred from mutant phenotype. Source: RGD positive regulation of synaptic transmission Inferred from mutant phenotype. Source: RGD response to activity Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to mechanical stimulus Inferred from expression pattern. Source: RGD skeletal muscle contraction Inferred from expression pattern. Source: RGD
Cellular component	extracellular space Traceable author statement. Source: RGD
Molecular function	cytokine activity Traceable author statement. Source: RGD tumor necrosis factor receptor binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 235	235	Tumor necrosis factor, membrane form		PRO_0000034451
	Chain	80 – 235	156	Tumor necrosis factor, soluble form		PRO_0000034452
Regions
	Topological domain	1 – 35	35	Cytoplasmic Potential
	Transmembrane	36 – 56	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	57 – 235	179	Extracellular Potential
Sites
	Site	79 – 80	2	Cleavage; by ADAM17 By similarity
Amino acid modifications
	Modified residue	2	1	Phosphoserine; by CK1 By similarity
	Lipidation	19	1	N6-myristoyl lysine By similarity
	Lipidation	20	1	N6-myristoyl lysine By similarity
	Glycosylation	83	1	O-linked (GalNAc...); in soluble form By similarity
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Disulfide bond	148 ↔ 179		By similarity
Natural variations
	Natural variant	122	1	L → P. Ref.5
	Natural variant	190	1	K → E. Ref.5
Experimental info
	Sequence conflict	39	1	L → P in CAA05290. Ref.2
	Sequence conflict	39	1	L → P in CAA47146. Ref.2
	Sequence conflict	163	1	I → T in CAA05290. Ref.2
	Sequence conflict	163	1	I → T in CAA47146. Ref.2
	Sequence conflict	202	1	F → S in CAA05290. Ref.2
	Sequence conflict	202	1	F → S in CAA47146. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P16599 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: B808EC6D049C2F3B	FASTA	235	25,806
	10 20 30 40 50 60 MSTESMIRDV ELAEEALPKK MGGLQNSRRC LCLSLFSFLL VAGATTLFCL LNFGVIGPNK 70 80 90 100 110 120 EEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ AEEQLEWLSQ RANALLANGM 130 140 150 160 170 180 DLKDNQLVVP ADGLYLIYSQ VLFKGQGCPD YVLLTHTVSR FAISYQEKVS LLSAIKSPCP 190 200 210 220 230 KDTPEGAELK PWYEPMYLGG VFQLEKGDLL SAEVNLPKYL DITESGQVYF GVIAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression in Escherichia coli of the gene for rat tumor necrosis factor." Shirai T., Shimizu N., Horiguchi S., Ito H. Agric. Biol. Chem. 53:1733-1736(1989) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Rat tumor necrosis factor-alpha. Transcription in rat Kupffer cells and in vitro posttranslational processing based on a PCR-derived cDNA." Estler H.C., Grewe M., Gaussling R., Pavlovic M., Decker K.F. Biol. Chem. Hoppe-Seyler 373:271-281(1992) [PubMed: 1627266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and sequence analysis of the rat tumor necrosis factor-encoding genes." Kwon J., Chung I.Y., Benveniste E.N. Gene 132:227-236(1993) [PubMed: 8224868] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley. Tissue: Testis.
[4]	"Polymorphisms of the tumor necrosis factor alpha locus among autoimmune disease susceptible and resistant inbred rat strains." Furuya T., Joe B., Salstrom J.L., Hashiramoto A., Dobbins D.E., Wilder R.L., Remmers E.F. Genes Immun. 2:229-232(2001) [PubMed: 11477479] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ACI/SegHsd, BB(DR)/Wor, Brown Norway/SsNHsd, DA/Bkl, F344/NHsd and LEW/NHsd.
[5]	"TNF-alpha polymorphism in rats with collagen-induced arthritis." Seidel M.F., Junier M.-P., Vetter H. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-122 AND GLU-190. Strain: Dark agouti.
[6]	"No association between tumor necrosis factor-alpha production and gene polymorphisms among inbred rat strains." Warle M.C., van der Laan L.J., Kusters J.G., Pot R.G., Hop W.C., Segeren K.C., Ijzermans J.N., Metselaar H.J., Tilanus H.W. Transpl. Immunol. 14:77-82(2005) [PubMed: 15935297] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: AUG/OlaHsd, PVG/OlaHsd and WF/HanHsd.
[7]	"The genomic sequence and comparative analysis of the rat major histocompatibility complex." Hurt P., Walter L., Sudbrak R., Klages S., Mueller I., Shiina T., Inoko H., Lehrach H., Guenther E., Reinhardt R., Himmelbauer H. Genome Res. 14:631-639(2004) [PubMed: 15060004] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[9]	"Mapping of the TNF-alpha locus in the rat." Kirisits M.J., Vardimon D., Kunz H.W., Gill T.J. III Submitted (JUN-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-231. Tissue: Tail.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D00475 Genomic DNA. Translation: BAA00367.1. X66539 mRNA. Translation: CAA47146.1. AJ002278 mRNA. Translation: CAA05290.1. L00981 Genomic DNA. Translation: AAA16275.1. AF329982 Genomic DNA. Translation: AAK53568.1. AF329983 Genomic DNA. Translation: AAK53569.1. AF329984 Genomic DNA. Translation: AAK53570.1. AF329985 Genomic DNA. Translation: AAK53571.1. AF329986 Genomic DNA. Translation: AAK53572.1. AF329987 Genomic DNA. Translation: AAK53573.1. AF269159 mRNA. Translation: AAF82567.1. AF269160 mRNA. Translation: AAF82568.1. AY427673 Genomic DNA. Translation: AAR91624.1. AY427674 Genomic DNA. Translation: AAR91625.1. AY427675 Genomic DNA. Translation: AAR91626.1. BX883046 Genomic DNA. Translation: CAE84003.1. BC107671 mRNA. Translation: AAI07672.1. L19123 Genomic DNA. Translation: AAA42255.1.
IPI	IPI00213948.
PIR	JU0029.
RefSeq	NP_036807.1. NM_012675.3.
UniGene	Rn.2275.
3D structure databases
ProteinModelPortal	P16599.
SMR	P16599. Positions 88-235.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16599. 70 interactions.
STRING	P16599.
Proteomic databases
PRIDE	P16599.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000001110; ENSRNOP00000001110; ENSRNOG00000000837.
GeneID	24835.
KEGG	rno:24835.
NMPDR	fig|10116.3.peg.17422.
UCSC	NM_012675. rat.
Organism-specific databases
CTD	7124.
RGD	3876. Tnf.
Phylogenomic databases
eggNOG	roNOG07642.
GeneTree	ENSGT00530000062992.
HOVERGEN	HBG012516.
InParanoid	P16599.
OMA	KAGGPQG.
OrthoDB	EOG4JWVFT.
PhylomeDB	P16599.
Gene expression databases
ArrayExpress	P16599.
Genevestigator	P16599.
GermOnline	ENSRNOG00000000837. Rattus norvegicus.
Family and domain databases
InterPro	IPR006052. TNF. IPR006053. TNF_a/b/c. IPR002959. TNF_alpha. IPR021184. TNF_CS. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
KO	K03156.
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...
Other
NextBio	604572.

Entry information

Entry name

TNFA_RAT

Accession

Primary (citable) accession number: P16599
Secondary accession number(s): Q6EE11, Q9JI26, Q9JI27

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program