P01375 (TNFA_HUMAN) 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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 protein 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.
Subcellular location	Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted.
Post-translational modification	The soluble form derives from the membrane form by proteolytic processing. 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. Ref.18 Ref.19 O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid. Ref.15
Polymorphism	Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]. Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162].
Involvement in disease	Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an 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 rheumatoidlike 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).
Sequence similarities	Belongs to the tumor necrosis factor family.
Sequence caution	The sequence AAF71992.1 differs from that shown. Reason: Frameshift at positions 91 and 157. The sequence CAA75070.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of MAPK activity Inferred from direct assay. Source: BHF-UCL activation of MAPKKK activity Inferred from direct assay. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay. Source: BHF-UCL anti-apoptosis Inferred from direct assay. Source: BHF-UCL cellular response to nicotine Inferred from direct assay. Source: UniProtKB chronic inflammatory response to antigenic stimulus Inferred from mutant phenotype. Source: BHF-UCL embryonic digestive tract development Inferred from expression pattern. Source: DFLAT induction of apoptosis via death domain receptors Inferred from direct assay. Source: UniProtKB induction of necroptosis by extracellular signals Inferred from direct assay. Source: BHF-UCL leukocyte tethering or rolling Inferred from direct assay. Source: BHF-UCL necrotic cell death Inferred from direct assay. Source: BHF-UCL negative regulation of branching involved in lung morphogenesis Inferred from direct assay. Source: UniProtKB negative regulation of cytokine secretion involved in immune response Inferred from direct assay. Source: BHF-UCL negative regulation of fat cell differentiation Non-traceable author statement. Source: BHF-UCL negative regulation of interleukin-6 production Inferred from direct assay. Source: BHF-UCL negative regulation of lipid catabolic process Inferred from direct assay. Source: BHF-UCL negative regulation of lipid storage Non-traceable author statement. Source: BHF-UCL negative regulation of viral genome replication Inferred from direct assay. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Non-traceable author statement. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay. Source: BHF-UCL positive regulation of NF-kappaB import into nucleus Inferred from direct assay. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: UniProtKB positive regulation of NFAT protein import into nucleus Inferred from direct assay. Source: MGI positive regulation of calcidiol 1-monooxygenase activity Inferred from direct assay. Source: BHF-UCL positive regulation of chemokine biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of chemokine production Inferred from direct assay. Source: BHF-UCL positive regulation of cytokine secretion Inferred from direct assay. Source: BHF-UCL positive regulation of fever generation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of heterotypic cell-cell adhesion Inferred from direct assay. Source: BHF-UCL positive regulation of membrane protein ectodomain proteolysis Inferred from direct assay. Source: BHF-UCL positive regulation of nitric oxide biosynthetic process Inferred from direct assay. Source: BHF-UCL positive regulation of osteoclast differentiation Inferred from direct assay. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: BHF-UCL positive regulation of podosome assembly Inferred from direct assay. Source: BHF-UCL positive regulation of protein complex disassembly Inferred from direct assay. Source: BHF-UCL positive regulation of smooth muscle cell proliferation Inferred from direct assay. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI positive regulation of vitamin D biosynthetic process Inferred from direct assay. Source: BHF-UCL protein import into nucleus, translocation Inferred from direct assay. Source: UniProtKB receptor biosynthetic process Inferred from direct assay. Source: BHF-UCL regulation of insulin secretion Inferred from direct assay. Source: BHF-UCL response to glucocorticoid stimulus Inferred from direct assay. Source: BHF-UCL response to salt stress Traceable author statement. Source: BHF-UCL response to virus Inferred from direct assay. Source: BHF-UCL sequestering of triglyceride Inferred from direct assay. Source: BHF-UCL transformed cell apoptosis Inferred from direct assay Ref.3. Source: BHF-UCL tumor necrosis factor-mediated signaling pathway Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	external side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL extracellular space Inferred from direct assay Ref.6. Source: BHF-UCL integral to plasma membrane Inferred from direct assay. Source: BHF-UCL membrane raft Inferred from direct assay. Source: BHF-UCL phagocytic cup Inferred from sequence or structural similarity. Source: BHF-UCL recycling endosome Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	cytokine activity Inferred from direct assay. Source: BHF-UCL identical protein binding Inferred from direct assay. Source: BHF-UCL protease binding Inferred from physical interaction. Source: BHF-UCL transcription regulatory region DNA binding Inferred from direct assay. Source: UniProtKB tumor necrosis factor receptor binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF1A	P19438	4	EBI-359977,EBI-299451

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_0000034423

Chain

77 – 233

157

Tumor necrosis factor, soluble form Ref.5

PRO_0000034424

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

76 – 77

2

Cleavage; by ADAM17

Amino acid modifications

Modified residue

2

1

Phosphoserine; by CK1 Probable

Lipidation

19

1

N6-myristoyl lysine Ref.21

Lipidation

20

1

N6-myristoyl lysine Ref.21

Glycosylation

80

1

O-linked (GalNAc...); in soluble form Ref.15

Disulfide bond

145 ↔ 177

Natural variations

Natural variant

84

1

P → L. Ref.13
Corresponds to variant rs4645843 [ dbSNP | Ensembl ].

VAR_019378

Natural variant

94

1

A → T.
Corresponds to variant rs1800620 [ dbSNP | Ensembl ].

VAR_011927

Experimental info

Mutagenesis

105

1

L → S: Low activity.

Mutagenesis

108

1

R → W: Biologically inactive.

Mutagenesis

112

1

L → F: Biologically inactive.

Mutagenesis

160

1

A → V: Biologically inactive.

Mutagenesis

162

1

S → F: Biologically inactive.

Mutagenesis

167

1

V → A or D: Biologically inactive.

Mutagenesis

222

1

E → K: Biologically inactive.

Sequence conflict

63

1

F → S in AAA61198. Ref.5

Sequence conflict

84 – 86

3

PSD → VNR Ref.17

Sequence conflict

183

1

E → R in AAC03542. Ref.16

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

233

Helix Strand Turn

Details...

Beta strand

106 – 108

3

Beta strand

121 – 125

5

Beta strand

130 – 144

15

Beta strand

152 – 159

8

Beta strand

161 – 163

3

Beta strand

167 – 174

8

Beta strand

177 – 179

3

Beta strand

183 – 185

3

Beta strand

189 – 202

14

Beta strand

207 – 213

7

Helix

215 – 217

3

Beta strand

223 – 229

7

Sequences

	Sequence		Length	Mass (Da)
	P01375 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 3DF90F96C9031FFE	FASTA	233	25,644
	10 20 30 40 50 60 MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL LHFGVIGPQR 70 80 90 100 110 120 EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG QLQWLNRRAN ALLANGVELR 130 140 150 160 170 180 DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV LLTHTISRIA VSYQTKVNLL SAIKSPCQRE 190 200 210 220 230 TPEGAEAKPW YEPIYLGGVF QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome." Nedospasov S.A., Shakhov A.N., Turetskaya R.L., Mett V.A., Azizov M.M., Georgiev G.P., Korobko V.G., Dobrynin V.N., Filippov S.A., Bystrov N.S., Boldyreva E.F., Chuvpilo S.A., Chumakov A.M., Shingarova L.N., Ovchinnikov Y.A. Cold Spring Harb. Symp. Quant. Biol. 51:611-624(1986) [PubMed: 3555974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin." Pennica D., Nedwin G.E., Hayflick J.S., Seeburg P.H., Derynck R., Palladino M.A., Kohr W.J., Aggarwal B.B., Goeddel D.V. Nature 312:724-729(1984) [PubMed: 6392892] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor." Shirai T., Yamaguchi H., Ito H., Todd C.W., Wallace R.B. Nature 313:803-806(1985) [PubMed: 3883195] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization." Nedwin G.E., Naylor S.L., Sakaguchi A.Y., Smith D.H., Jarrett-Nedwin J., Pennica D., Goeddel D.V., Gray P.W. Nucleic Acids Res. 13:6361-6373(1985) [PubMed: 2995927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[5]	"Molecular cloning of the complementary DNA for human tumor necrosis factor." Wang A.M., Creasey A.A., Ladner M.B., Lin L.S., Strickler J., van Arsdell J.N., Yamamoto R., Mark D.F. Science 228:149-154(1985) [PubMed: 3856324] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Molecular cloning and expression of human tumor necrosis factor and comparison with mouse tumor necrosis factor." Marmenout A., Fransen L., Tavernier J., van der Heyden J., Tizard R., Kawashima E., Shaw A., Johnson M.J., Semon D., Mueller R., Ruysschaert M.-R., van Vliet A., Fiers W. Eur. J. Biochem. 152:515-522(1985) [PubMed: 3932069] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment." Iris F.J.M., Bougueleret L., Prieur S., Caterina D., Primas G., Perrot V., Jurka J., Rodriguez-Tome P., Claverie J.-M., Dausset J., Cohen D. Nat. Genet. 3:137-145(1993) [PubMed: 8499947] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC." Neville M.J., Campbell R.D. J. Immunol. 162:4745-4754(1999) [PubMed: 10202016] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed: 14656967] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"Genome diversity in HLA: a new strategy for detection of genetic polymorphisms in expressed genes within the HLA class III and class I regions." Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	SeattleSNPs variation discovery resource Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[13]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-84.
[14]	"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: Blood.
[15]	"O-glycosylated species of natural human tumor-necrosis factor-alpha." Takakura-Yamamoto R., Yamamoto S., Fukuda S., Kurimoto M. Eur. J. Biochem. 235:431-437(1996) [PubMed: 8631363] [Abstract] Cited for: PROTEIN SEQUENCE OF 77-99, GLYCOSYLATION AT SER-80.
[16]	Jang J.S., Kim B.E. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 77-233.
[17]	Shao C., Yan W., Zhu F., Yue W., Chai Y., Zhao Z., Wang C. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 84-214. Tissue: Prostatic carcinoma.
[18]	"Phosphorylation of the 26 kDa TNF precursor in monocytic cells and in transfected HeLa cells." Pocsik E., Duda E., Wallach D. J. Inflamm. 45:152-160(1995) [PubMed: 8597870] [Abstract] Cited for: PHOSPHORYLATION (MEMBRANE FORM).
[19]	"A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'." Watts A.D., Hunt N.H., Wanigasekara Y., Bloomfield G., Wallach D., Roufogalis B.D., Chaudhri G. EMBO J. 18:2119-2126(1999) [PubMed: 10205166] [Abstract] Cited for: PHOSPHORYLATION BY CK1, DEPHOSPHORYLATION.
[20]	"Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis." Ostade X.V., Tavernier J., Prange T., Fiers W. EMBO J. 10:827-836(1991) [PubMed: 2009860] [Abstract] Cited for: MUTAGENESIS.
[21]	"Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues." Stevenson F.T., Bursten S.L., Locksley R.M., Lovett D.H. J. Exp. Med. 176:1053-1062(1992) [PubMed: 1402651] [Abstract] Cited for: MYRISTOYLATION AT LYS-19 AND LYS-20.
[22]	"Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha." Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L., Chen W.-J., Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R., Kost T.A., Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G., Mitchell J., Moyer M., Pahel G. , Rocque W., Overton L.K., Schoenen F., Seaton T., Su J.-L., Warner J., Willard D., Becherer J.D. Nature 385:733-736(1997) [PubMed: 9034191] [Abstract] Cited for: CLEAVAGE BY ADAM17.
[23]	"A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria." Knight J.C., Udalova I., Hill A.V., Greenwood B.M., Peshu N., Marsh K., Kwiatkowski D. Nat. Genet. 22:145-150(1999) [PubMed: 10369255] [Abstract] Cited for: POLYMORPHISM, INVOLVEMENT IN SUSCEPTIBILITY TO MALARIA.
[24]	"Structure of tumour necrosis factor." Jones E.Y., Stuart D.I., Walker N.P. Nature 338:225-228(1989) [PubMed: 2922050] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[25]	"The structure of tumour necrosis factor -- implications for biological function." Jones E.Y., Stuart D.I., Walker N.P. J. Cell Sci. Suppl. 13:11-18(1990) [PubMed: 1964681] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[26]	"The structure of tumor necrosis factor-alpha at 2.6-A resolution. Implications for receptor binding." Eck M.J., Sprang S.R. J. Biol. Chem. 264:17595-17605(1989) [PubMed: 2551905] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[27]	"Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2." Reed C., Fu Z.Q., Wu J., Xue Y.N., Harrison R.W., Chen M.J., Weber I.T. Protein Eng. 10:1101-1107(1997) [PubMed: 9488135] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-107.
[28]	"High resolution crystal structure of a human tumor necrosis factor-alpha mutant with low systemic toxicity." Cha S.S., Kim J.S., Cho H.S., Shin N.K., Jeong W., Shin H.C., Kim Y.J., Hahn J.H., Oh B.H. J. Biol. Chem. 273:2153-2160(1998) [PubMed: 9442056] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-3.
[29]	"Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity." Balding J., Kane D., Livingstone W., Mynett-Johnson L., Bresnihan B., Smith O., FitzGerald O. Arthritis Rheum. 48:1408-1413(2003) [PubMed: 12746914] [Abstract] Cited for: INVOLVEMENT IN PSORIATIC ARTHRITIS SUSCEPTIBILITY.
[30]	"Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection." Kim Y.J., Lee H.-S., Yoon J.-H., Kim C.Y., Park M.H., Kim L.H., Park B.L., Shin H.D. Hum. Mol. Genet. 12:2541-2546(2003) [PubMed: 12915457] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION.
+	Additional computationally mapped references.

Web resources

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00001671.

PIR

QWHUN. A93585.

RefSeq

NP_000585.2. NM_000594.2.

UniGene

Hs.241570.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A8M	X-ray	2.30	A/B/C	77-233	[»]
1TNF	X-ray	2.60	A/B/C	77-233	[»]
2AZ5	X-ray	2.10	A/B/C/D	86-233	[»]
2E7A	X-ray	1.80	A/B/C	77-233	[»]
2TUN	X-ray	3.10	A/B/C/D/E/F	77-233	[»]
2ZJC	X-ray	2.50	A/B/C	77-233	[»]
2ZPX	X-ray	2.83	A/B/C	77-233	[»]
3ALQ	X-ray	3.00	A/B/C/D/E/F	77-233	[»]
3IT8	X-ray	2.80	A/B/C/G/H/I	82-233	[»]
3L9J	X-ray	2.10	T	85-233	[»]
4TSV	X-ray	1.80	A	84-233	[»]
5TSW	X-ray	2.50	A/B/C/D/E/F	84-233	[»]

ProteinModelPortal

P01375.

SMR

P01375. Positions 85-233.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2895N.

IntAct

P01375. 24 interactions.

MINT

MINT-1131842.

STRING

P01375.

PTM databases

GlycoSuiteDB

P01375.

PhosphoSite

P01375.

Polymorphism databases

DMDM

135934.

Proteomic databases

PRIDE

P01375.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

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

GeneID

7124.

KEGG

hsa:7124.

UCSC

uc003nui.1. human.

Organism-specific databases

CTD

7124.

GeneCards

GC06P031543.

HGNC

HGNC:11892. TNF.

MIM

191160. gene.
607507. phenotype.
610424. phenotype.
611162. phenotype.

neXtProt

NX_P01375.

Orphanet

40050. Adult psoriatic arthritis.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05738.

HOGENOM

HBG125617.

HOVERGEN

HBG012516.

InParanoid

P01375.

OMA

KAGGPQG.

OrthoDB

EOG4JWVFT.

PhylomeDB

P01375.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
caspase_pathway. Caspase cascade in apoptosis.
anthraxpathway. Cellular roles of Anthrax toxin.
ceramidepathway. Ceramide signaling pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_578. Apoptosis.

Gene expression databases

CleanEx

HS_TNF.

Genevestigator

P01375.

GermOnline

ENSG00000204490. Homo sapiens.

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

DrugBank

DB00051. Adalimumab.
DB00640. Adenosine.
DB01427. Amrinone.
DB01076. Atorvastatin.
DB00608. Chloroquine.
DB01407. Clenbuterol.
DB00005. Etanercept.
DB01296. Glucosamine.
DB00065. Infliximab.
DB00704. Naltrexone.
DB01411. Pranlukast.
DB01366. Procaterol.
DB01232. Saquinavir.
DB00641. Simvastatin.
DB01041. Thalidomide.

NextBio

27879.

PMAP-CutDB

P01375.

SOURCE

Search...

Entry information

Entry name

TNFA_HUMAN

Accession

Primary (citable) accession number: P01375
Secondary accession number(s): O43647, Q9P1Q2, Q9UIV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 25, 2012
This is version 168 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.