TNF (Homo sapiens)

Description [+]

Synonyms: TNF, TNFSF2, DIF, TNF-ALPHA
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Tumor necrosis factor Precursor (TNF-alpha)(Tumor necrosis factor ligand superfamily member 2)(TNF-a)(Cachectin) [Contains Tumor necrosis factor, membrane form;Tumor necrosis factor, soluble form] [Source:UniProtKB/Swiss-Prot;Acc:P01375]
Family: death ligand
Process: apoptosis, immunity,
Pathways: extrinsic pathway, TNF/NF-kappaB signaling,
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Tnf
WIKI: TNF-H_sapiens

References [+]

Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin.
Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV
Human tumour necrosis factor has about 30% homology in its amino acid sequence with lymphotoxin, a lymphokine that has similar biological properties. Recombinant tumour necrosis factor can be obtained by expression of its complementary DNA in Escherichia coli and induces the haemorrhagic necrosis of transplanted methylcholanthrene-induced sarcomas in syngeneic mice. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.

References from Mouse ortholog(s):

Identity of tumour necrosis factor and the macrophage-secreted factor cachectin.
Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YC, Mathison J, Ulevitch R, Cerami A
In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system. Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL). We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells). When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF). Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the 'cachectin' and 'TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors. Nature. 1985 Aug 8-14;316(6028):552-4.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	TNF	102	233

Evolution [+]

Name	Relationship	Species
TNFA_PANTR	orthology	Chimpanzee
TNFA_BOVIN	orthology	Cow
TNFA_CANFA	orthology	Dog
NP_001033074.1	orthology	Fugu
G_aculeatus_ENSGACP00000017676	orthology	Gasterosteus
G_aculeatus_ENSGACP00000000611	orthology	Gasterosteus
Q8HZD8_9PRIM	orthology	Gorilla
TNFA_HORSE	orthology	Horse
TNFA_MACMU	orthology	Macaca
O_latipes_ENSORLP00000020071	orthology	Medaka
O_latipes_ENSORLP00000013121	orthology	Medaka
TNF	orthology	Monodelphis
Tnf	orthology	Mouse
Q8HZD7_PONPY	orthology	Orangutan
TNFA_RABIT	orthology	Rabbit
Tnf	orthology	Rat
TNF	orthology	Tetraodon
X_tropicalis_ENSXETP00000005341	orthology	Xenopus
tnfb	orthology	Zebrafish
tnfa	orthology	Zebrafish
NP_001019749.1	paralogy	Chicken
G_gallus_ENSGALP00000034816	paralogy	Chicken
NP_989710.1	paralogy	Chicken
NP_989922.1	paralogy	Chicken
NP_001026730.1	paralogy	Chicken
TNFC_PANTR	paralogy	Chimpanzee
FASLG	paralogy	Chimpanzee
TNFB_PANTR	paralogy	Chimpanzee
TNFSF11	paralogy	Chimpanzee
TNFSF14	paralogy	Chimpanzee
TNFSF15	paralogy	Chimpanzee
IPI00690656.3	paralogy	Cow
IPI00694513.2	paralogy	Cow
TNFB_BOVIN	paralogy	Cow
A6QQA4_BOVIN	paralogy	Cow
Q9TTJ2_BOVIN	paralogy	Cow
NP_001095325.1	paralogy	Cow
NP_001092329.1	paralogy	Cow
NP_001092329.1	paralogy	Cow
TNFSF14	paralogy	Dog
TNFSF11	paralogy	Dog
FASLG	paralogy	Dog
TNFSF15	paralogy	Dog
TNFB_CANFA	paralogy	Dog
T_rubripes_ENSTRUP00000014307	paralogy	Fugu
FASLG	paralogy	Fugu
G_aculeatus_ENSGACP00000004738	paralogy	Gasterosteus
LTB	paralogy	Gorilla
TNFSF11	paralogy	Gorilla
TNFSF15	paralogy	Gorilla
LTA	paralogy	Gorilla
TNFSF14	paralogy	Gorilla
TNFSF15	paralogy	Horse
TNFSF14	paralogy	Horse
FASLG	paralogy	Horse
LTA	paralogy	Horse
TNFSF11	paralogy	Horse
LTB	paralogy	Horse
LTB	paralogy	Human
LTA	paralogy	Human
TNFSF15	paralogy	Human
TNFSF14	paralogy	Human
FASL	paralogy	Human
LTA	paralogy	Human
TNFSF11	paralogy	Human
LTB	paralogy	Human
LTB	paralogy	Human
LTA	paralogy	Human
TNFSF14	paralogy	Lyzard
TNFSF10	paralogy	Lyzard
TNFSF15	paralogy	Lyzard
TNFSF13	paralogy	Lyzard
TNFSF15	paralogy	Macaca
TNFSF11	paralogy	Macaca
TNFB_MACMU	paralogy	Macaca
TNFL6_MACMU	paralogy	Macaca
TNFSF14	paralogy	Macaca
TNFC_MACMU	paralogy	Macaca
O_latipes_ENSORLP00000010677	paralogy	Medaka
TNFSF15	paralogy	Monodelphis
TNFSF14	paralogy	Monodelphis
LTB	paralogy	Monodelphis
LTA	paralogy	Monodelphis
Fasl	paralogy	Mouse
Ltb	paralogy	Mouse
Tnfsf15	paralogy	Mouse
Lta	paralogy	Mouse
TRAIL	paralogy	Mouse
Tnfsf14	paralogy	Mouse
Tnfsf11	paralogy	Mouse
TNFSF11	paralogy	Orangutan
LTA	paralogy	Orangutan
TNFSF15	paralogy	Orangutan
FASLG	paralogy	Orangutan
LTB	paralogy	Orangutan
FASLG	paralogy	Ornithorhynchus
O_anatinus_ENSOANP00000022049	paralogy	Ornithorhynchus
TNFSF15	paralogy	Ornithorhynchus
O_cuniculus_ENSOCUP00000012761	paralogy	Rabbit
LTB	paralogy	Rabbit
TNFB_RABIT	paralogy	Rabbit
O_cuniculus_ENSOCUP00000004879	paralogy	Rabbit
TNFSF14	paralogy	Rabbit
TNFSF15	paralogy	Rabbit
Tnfsf15	paralogy	Rat
Ltb	paralogy	Rat
Tnfsf10	paralogy	Rat
Tnfsf11	paralogy	Rat
Lta	paralogy	Rat
Faslg	paralogy	Rat
FASLG	paralogy	Tetraodon
TNFSF15	paralogy	Xenopus
LTB	paralogy	Xenopus
FASLG	paralogy	Zebra finch
TNFSF10	paralogy	Zebra finch
TNFSF15	paralogy	Zebra finch
tnfsf10l	paralogy	Zebrafish
faslg	paralogy	Zebrafish
tnfsf10l2	paralogy	Zebrafish
tnfsf10l4	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological_proccess	IEA
GO:0002037	negative regulation of L-glutamate transport	biological_proccess	IEA
GO:0006006	glucose metabolic process	biological_proccess	IEA
GO:0006959	humoral immune response	biological_proccess	IEA
GO:0007275	multicellular organismal development	biological_proccess	IEA
GO:0008625	induction of apoptosis via death domain receptors	biological_proccess	IEA
GO:0009612	response to mechanical stimulus	biological_proccess	IEA
GO:0009887	organ morphogenesis	biological_proccess	IEA
GO:0019722	calcium-mediated signaling	biological_proccess	IEA
GO:0042742	defense response to bacterium	biological_proccess	IEA
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB cascade	biological_proccess	IEA
GO:0045670	regulation of osteoclast differentiation	biological_proccess	IEA
GO:0045840	positive regulation of mitosis	biological_proccess	IEA
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological_proccess	IEA
GO:0046325	negative regulation of glucose import	biological_proccess	IEA
GO:0046330	positive regulation of JNK cascade	biological_proccess	IEA
GO:0051222	positive regulation of protein transport	biological_proccess	IEA
GO:0051798	positive regulation of hair follicle development	biological_proccess	IEA
GO:0050901	leukocyte tethering or rolling	biological_proccess	IDA
GO:0000187	activation of MAPK activity	biological_proccess	IDA
GO:0001934	positive regulation of protein amino acid phosphorylation	biological_proccess	IDA
GO:0006916	anti-apoptosis	biological_proccess	IDA
GO:0006954	inflammatory response	biological_proccess	IDA
GO:0033209	tumor necrosis factor-mediated signaling pathway	biological_proccess	IMP
GO:0006927	transformed cell apoptosis	biological_proccess	IDA
GO:0048661	positive regulation of smooth muscle cell proliferation	biological_proccess	IDA
GO:0032722	positive regulation of chemokine production	biological_proccess	IDA
GO:0045071	negative regulation of viral genome replication	biological_proccess	IDA
GO:0045080	positive regulation of chemokine biosynthetic process	biological_proccess	IDA
GO:0009615	response to virus	biological_proccess	IDA
GO:0042346	positive regulation of NF-kappaB import into nucleus	biological_proccess	IDA
GO:0032715	negative regulation of interleukin-6 production	biological_proccess	IDA
GO:0050715	positive regulation of cytokine secretion	biological_proccess	IDA
GO:0051384	response to glucocorticoid stimulus	biological_proccess	IDA
GO:0002439	chronic inflammatory response to antigenic stimulus	biological_proccess	IMP
GO:0006919	activation of caspase activity	biological_proccess	IDA
GO:0043193	positive regulation of gene-specific transcription	biological_proccess	IDA
GO:0032800	receptor biosynthetic process	biological_proccess	IDA
GO:0034116	positive regulation of heterotypic cell-cell adhesion	biological_proccess	IDA
GO:0010940	positive regulation of necrotic cell death	biological_proccess	TAS
GO:0060557		biological_proccess	IDA
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	biological_proccess	IDA
GO:0060555		biological_proccess	IDA
GO:0008285	negative regulation of cell proliferation	biological_proccess	IEA
GO:0045994	positive regulation of translational initiation by iron	biological_proccess	IEA
GO:0009651	response to salt stress	biological_proccess	TAS
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological_proccess	IDA
GO:0050796	regulation of insulin secretion	biological_proccess	IDA
GO:0030730	sequestering of triglyceride	biological_proccess	IDA
GO:0050995	negative regulation of lipid catabolic process	biological_proccess	IDA
GO:0001775	cell activation	biological_proccess	IEA
GO:0007165	signal transduction	biological_proccess	IEA
GO:0043525	positive regulation of neuron apoptosis	biological_proccess	IEA
GO:0045941	positive regulation of transcription	biological_proccess	IEA
GO:0050806	positive regulation of synaptic transmission	biological_proccess	IEA
GO:0051023	regulation of immunoglobulin secretion	biological_proccess	IEA
GO:0002740	negative regulation of cytokine secretion during immune response	biological_proccess	IDA
GO:0060559		biological_proccess	IDA
GO:0000060	protein import into nucleus, translocation	biological_proccess	IDA
GO:0016481	negative regulation of transcription	biological_proccess	IDA
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological_proccess	IDA
GO:0006955	immune response	biological_proccess	IEA
GO:0042802	identical protein binding	mollecular_function	IDA
GO:0005125	cytokine activity	mollecular_function	IEA
GO:0005164	tumor necrosis factor receptor binding	mollecular_function	IEA
GO:0001891	phagocytic cup	cell_component	IEA
GO:0045121	membrane raft	cell_component	IEA
GO:0055037	recycling endosome	cell_component	IEA
GO:0005887	integral to plasma membrane	cell_component	IDA
GO:0009897	external side of plasma membrane	cell_component	IEA
GO:0005886	plasma membrane	cell_component	EXP
GO:0005576	extracellular region	cell_component	IEA
GO:0005615	extracellular space	cell_component	IEA
GO:0016020	membrane	cell_component	IEA

Check GO Evidence Codes here

KEGG Pathways [+]

KEGG report for TNF: 7124

KEGG pathways for TNF:

hsa04010: MAPK signaling pathway (entry, map)

hsa04060: Cytokine-cytokine receptor interaction (entry, map)

hsa04210: Apoptosis (entry, map)

hsa04350: TGF-beta signaling pathway (entry, map)

hsa04620: Toll-like receptor signaling pathway (entry, map)

hsa04640: Hematopoietic cell lineage (entry, map)

hsa04650: Natural killer cell mediated cytotoxicity (entry, map)

hsa04660: T cell receptor signaling pathway (entry, map)

hsa04664: Fc epsilon RI signaling pathway (entry, map)

hsa04920: Adipocytokine signaling pathway (entry, map)

hsa04930: Type II diabetes mellitus (entry, map)

hsa04940: Type I diabetes mellitus (entry, map)

hsa05010: Alzheimer's disease (entry, map)

hsa05060: Prion disease (entry, map)

hsa05310: Asthma (entry, map)

hsa05322: Systemic lupus erythematosus (entry, map)

hsa05330: Allograft rejection (entry, map)

hsa05332: Graft-versus-host disease (entry, map)

Curated Isoforms [+]

Transcript	Translation
OTTHUMT00000076390 *	OTTHUMP00000029281 *
OTTHUMT00000309318 *	OTTHUMP00000194885 *
OTTHUMT00000077129 *	OTTHUMP00000029720 *
OTTHUMT00000310016 *	OTTHUMP00000193290 *
OTTHUMT00000311172 *	OTTHUMP00000193749 *
OTTHUMT00000312060 *	OTTHUMP00000194120 *
OTTHUMT00000035237 *	OTTHUMP00000014621 *
OTTHUMT00000095764 *	OTTHUMP00000037669 *

Information from other databases [+]

Gene related links:

Ensembl genome browser [?] : ENSG00000204490
Expression info from Arrayexpress [?] : ENSG00000204490
Protein expression from Protein Atlas: [?] ENSG00000204490
Community gene edition from Wikigenes: [?] 7124

Protein related links:

Uniprot protein info: P01375
PIR protein info: P01375
Protein interactions from IntAct: P01375

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 191160
OMIM disease information: 610424 607507

Other links

entrezgene: 7124
refseq_dna: NM_000594
refseq_peptide: NP_000585

Click on [?] for more information.