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P01375

- TNFA_HUMAN

UniProt

P01375 - TNFA_HUMAN

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Protein
Tumor necrosis factor
Gene
TNF, TNFA, TNFSF2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei35 – 362Cleavage; by SPPL2A or SPPL2B
Sitei39 – 402Cleavage; by SPPL2A or SPPL2B
Sitei49 – 502Cleavage; by SPPL2A or SPPL2B
Sitei51 – 522Cleavage; by SPPL2A or SPPL2B
Sitei76 – 772Cleavage; by ADAM17

GO - Molecular functioni

  1. cytokine activity Source: BHF-UCL
  2. identical protein binding Source: BHF-UCL
  3. protease binding Source: BHF-UCL
  4. protein binding Source: UniProtKB
  5. transcription regulatory region DNA binding Source: UniProtKB
  6. tumor necrosis factor receptor binding Source: BHF-UCL

GO - Biological processi

  1. JNK cascade Source: Ensembl
  2. MAPK cascade Source: UniProtKB
  3. activation of MAPK activity Source: BHF-UCL
  4. activation of MAPKKK activity Source: BHF-UCL
  5. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  6. apoptotic process Source: Reactome
  7. apoptotic signaling pathway Source: Reactome
  8. calcium-mediated signaling Source: Ensembl
  9. cell activation Source: Ensembl
  10. cellular amino acid biosynthetic process Source: Ensembl
  11. cellular response to amino acid stimulus Source: Ensembl
  12. cellular response to nicotine Source: UniProtKB
  13. cellular response to organic cyclic compound Source: UniProtKB
  14. chronic inflammatory response to antigenic stimulus Source: BHF-UCL
  15. defense response to Gram-positive bacterium Source: Ensembl
  16. embryonic digestive tract development Source: DFLAT
  17. epithelial cell proliferation involved in salivary gland morphogenesis Source: Ensembl
  18. extracellular matrix organization Source: Ensembl
  19. extrinsic apoptotic signaling pathway Source: UniProtKB
  20. extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
  21. glucose metabolic process Source: Ensembl
  22. humoral immune response Source: Ensembl
  23. inflammatory response Source: UniProtKB
  24. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  25. leukocyte tethering or rolling Source: BHF-UCL
  26. lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  27. necroptotic signaling pathway Source: UniProtKB
  28. negative regulation of L-glutamate transport Source: Ensembl
  29. negative regulation of alkaline phosphatase activity Source: Ensembl
  30. negative regulation of branching involved in lung morphogenesis Source: UniProtKB
  31. negative regulation of cell proliferation Source: Ensembl
  32. negative regulation of cytokine secretion involved in immune response Source: BHF-UCL
  33. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  34. negative regulation of fat cell differentiation Source: BHF-UCL
  35. negative regulation of gene expression Source: UniProtKB
  36. negative regulation of glucose import Source: Ensembl
  37. negative regulation of growth of symbiont in host Source: Ensembl
  38. negative regulation of interleukin-6 production Source: BHF-UCL
  39. negative regulation of lipid catabolic process Source: BHF-UCL
  40. negative regulation of lipid storage Source: BHF-UCL
  41. negative regulation of osteoblast differentiation Source: Ensembl
  42. negative regulation of protein complex disassembly Source: UniProtKB
  43. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  44. negative regulation of transcription, DNA-templated Source: UniProtKB
  45. negative regulation of viral genome replication Source: BHF-UCL
  46. organ morphogenesis Source: Ensembl
  47. osteoclast differentiation Source: Ensembl
  48. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  49. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
  50. positive regulation of JNK cascade Source: Ensembl
  51. positive regulation of JUN kinase activity Source: UniProtKB
  52. positive regulation of MAP kinase activity Source: UniProtKB
  53. positive regulation of NF-kappaB import into nucleus Source: BHF-UCL
  54. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  55. positive regulation of NFAT protein import into nucleus Source: MGI
  56. positive regulation of apoptotic process Source: UniProtKB
  57. positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
  58. positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  59. positive regulation of chemokine biosynthetic process Source: BHF-UCL
  60. positive regulation of chemokine production Source: BHF-UCL
  61. positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
  62. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  63. positive regulation of cytokine production Source: BHF-UCL
  64. positive regulation of cytokine secretion Source: BHF-UCL
  65. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  66. positive regulation of fever generation Source: BHF-UCL
  67. positive regulation of gene expression Source: AgBase
  68. positive regulation of hair follicle development Source: Ensembl
  69. positive regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  70. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
  71. positive regulation of interferon-gamma production Source: Ensembl
  72. positive regulation of interleukin-18 production Source: Ensembl
  73. positive regulation of interleukin-6 production Source: Ensembl
  74. positive regulation of interleukin-8 biosynthetic process Source: BHF-UCL
  75. positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  76. positive regulation of mitosis Source: Ensembl
  77. positive regulation of mononuclear cell migration Source: BHF-UCL
  78. positive regulation of neuron apoptotic process Source: Ensembl
  79. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  80. positive regulation of osteoclast differentiation Source: BHF-UCL
  81. positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  82. positive regulation of podosome assembly Source: BHF-UCL
  83. positive regulation of programmed cell death Source: UniProtKB
  84. positive regulation of protein complex assembly Source: BHF-UCL
  85. positive regulation of protein complex disassembly Source: UniProtKB
  86. positive regulation of protein kinase B signaling Source: Ensembl
  87. positive regulation of protein localization to cell surface Source: BHF-UCL
  88. positive regulation of protein phosphorylation Source: UniProtKB
  89. positive regulation of protein transport Source: BHF-UCL
  90. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  91. positive regulation of smooth muscle cell proliferation Source: BHF-UCL
  92. positive regulation of synaptic transmission Source: Ensembl
  93. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  94. positive regulation of transcription, DNA-templated Source: UniProtKB
  95. positive regulation of translational initiation by iron Source: Ensembl
  96. positive regulation of vitamin D biosynthetic process Source: BHF-UCL
  97. protein import into nucleus, translocation Source: UniProtKB
  98. protein kinase B signaling Source: UniProtKB
  99. receptor biosynthetic process Source: BHF-UCL
  100. regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
  101. regulation of branching involved in salivary gland morphogenesis Source: Ensembl
  102. regulation of immunoglobulin secretion Source: Ensembl
  103. regulation of insulin secretion Source: BHF-UCL
  104. response to activity Source: Ensembl
  105. response to drug Source: Ensembl
  106. response to glucocorticoid Source: BHF-UCL
  107. response to hypoxia Source: Ensembl
  108. response to mechanical stimulus Source: Ensembl
  109. response to salt stress Source: BHF-UCL
  110. response to virus Source: BHF-UCL
  111. sequestering of triglyceride Source: BHF-UCL
  112. skeletal muscle contraction Source: Ensembl
  113. transformed cell apoptotic process Source: BHF-UCL
  114. tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

ReactomeiREACT_1432. TNF signaling.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.

Names & Taxonomyi

Protein namesi
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:
Gene namesi
Name:TNF
Synonyms:TNFA, TNFSF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:11892. TNF.

Subcellular locationi

Cell membrane; Single-pass type II membrane protein 1 Publication
Chain Tumor necrosis factor, membrane form : Membrane; Single-pass type II membrane protein 1 Publication
Chain Tumor necrosis factor, soluble form : Secreted 1 Publication
Chain C-domain 1 : Secreted 1 Publication
Chain C-domain 2 : Secreted 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei36 – 5621Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini57 – 233177Extracellular Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. external side of plasma membrane Source: BHF-UCL
  3. extracellular region Source: Reactome
  4. extracellular space Source: BHF-UCL
  5. integral component of plasma membrane Source: BHF-UCL
  6. membrane raft Source: BHF-UCL
  7. phagocytic cup Source: BHF-UCL
  8. plasma membrane Source: Reactome
  9. recycling endosome Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Psoriatic arthritis (PSORAS) [MIM:607507]: 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 rheumatoid like 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).
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi105 – 1051L → S: Low activity.
Mutagenesisi108 – 1081R → W: Biologically inactive.
Mutagenesisi112 – 1121L → F: Biologically inactive.
Mutagenesisi160 – 1601A → V: Biologically inactive.
Mutagenesisi162 – 1621S → F: Biologically inactive.
Mutagenesisi167 – 1671V → A or D: Biologically inactive.
Mutagenesisi222 – 2221E → K: Biologically inactive.

Organism-specific databases

MIMi607507. phenotype.
610424. phenotype.
611162. phenotype.
Orphaneti40050. Adult psoriatic arthritis.
PharmGKBiPA435.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 233233Tumor necrosis factor, membrane form
PRO_0000034423Add
BLAST
Chaini1 – 3939Intracellular domain 1
PRO_0000417231Add
BLAST
Chaini1 – 3535Intracellular domain 2
PRO_0000417232Add
BLAST
Chaini50 – ?C-domain 1PRO_0000417233
Chaini52 – ?C-domain 2PRO_0000417234
Chaini77 – 233157Tumor necrosis factor, soluble form1 Publication
PRO_0000034424Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1 Inferred
Lipidationi19 – 191N6-myristoyl lysine1 Publication
Lipidationi20 – 201N6-myristoyl lysine1 Publication
Glycosylationi80 – 801O-linked (GalNAc...); in soluble form1 Publication
Disulfide bondi145 ↔ 177

Post-translational modificationi

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.
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.2 Publications
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP01375.
PRIDEiP01375.

PTM databases

PhosphoSiteiP01375.
UniCarbKBiP01375.

Miscellaneous databases

PMAP-CutDBP01375.

Expressioni

Gene expression databases

ArrayExpressiP01375.
BgeeiP01375.
CleanExiHS_TNF.
GenevestigatoriP01375.

Interactioni

Subunit structurei

Homotrimer. Interacts with SPPL2B.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
crmEQ8UYL33EBI-359977,EBI-7539950From a different organism.
IKBKGQ9Y6K92EBI-359977,EBI-81279
TNFRSF1AP194388EBI-359977,EBI-299451
TNFRSF1BP203332EBI-359977,EBI-358983

Protein-protein interaction databases

BioGridi112979. 47 interactions.
DIPiDIP-2895N.
IntActiP01375. 30 interactions.
MINTiMINT-1131842.
STRINGi9606.ENSP00000392858.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi89 – 946
Beta strandi96 – 983
Beta strandi99 – 1013
Beta strandi106 – 1083
Beta strandi112 – 1143
Beta strandi118 – 1203
Beta strandi123 – 1253
Beta strandi130 – 14415
Beta strandi146 – 1483
Beta strandi152 – 1598
Helixi161 – 1633
Beta strandi167 – 1748
Beta strandi177 – 1793
Beta strandi182 – 1854
Beta strandi189 – 20214
Beta strandi207 – 2137
Helixi215 – 2173
Beta strandi221 – 2233
Beta strandi225 – 2328

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1A8MX-ray2.30A/B/C77-233[»]
1TNFX-ray2.60A/B/C77-233[»]
2AZ5X-ray2.10A/B/C/D86-233[»]
2E7AX-ray1.80A/B/C77-233[»]
2TUNX-ray3.10A/B/C/D/E/F77-233[»]
2ZJCX-ray2.50A/B/C77-233[»]
2ZPXX-ray2.83A/B/C77-233[»]
3ALQX-ray3.00A/B/C/D/E/F77-233[»]
3IT8X-ray2.80A/B/C/G/H/I82-233[»]
3L9JX-ray2.10T85-233[»]
3WD5X-ray3.10A77-233[»]
4G3YX-ray2.60C77-233[»]
4TSVX-ray1.80A84-233[»]
5TSWX-ray2.50A/B/C/D/E/F84-233[»]
ProteinModelPortaliP01375.
SMRiP01375. Positions 85-233.

Miscellaneous databases

EvolutionaryTraceiP01375.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG40413.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP01375.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG7V4B0Q.
PhylomeDBiP01375.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01375-1 [UniParc]FASTAAdd to Basket

« Hide

MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL    50
LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG 100
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV 150
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF 200
QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL 233
Length:233
Mass (Da):25,644
Last modified:July 21, 1986 - v1
Checksum:i3DF90F96C9031FFE
GO

Sequence cautioni

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.

Polymorphismi

Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIMi:610424].
Genetic variations in TNF are involved in susceptibility to malaria [MIMi:611162].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti84 – 841P → L.1 Publication
Corresponds to variant rs4645843 [ dbSNP | Ensembl ].
VAR_019378
Natural varianti94 – 941A → T.
Corresponds to variant rs1800620 [ dbSNP | Ensembl ].
VAR_011927

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti63 – 631F → S in AAA61198. 1 Publication
Sequence conflicti84 – 863PSD → VNR in AAF71992. 1 Publication
Sequence conflicti183 – 1831E → R in AAC03542. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4702.1.
PIRiA93585. QWHUN.
RefSeqiNP_000585.2. NM_000594.3.
UniGeneiHs.241570.

Genome annotation databases

EnsembliENST00000376122; ENSP00000365290; ENSG00000204490.
ENST00000383496; ENSP00000372988; ENSG00000206439.
ENST00000412275; ENSP00000392858; ENSG00000228321.
ENST00000420425; ENSP00000410668; ENSG00000228849.
ENST00000443707; ENSP00000389492; ENSG00000230108.
ENST00000448781; ENSP00000389490; ENSG00000223952.
ENST00000449264; ENSP00000398698; ENSG00000232810.
GeneIDi7124.
KEGGihsa:7124.
UCSCiuc003nui.4. human.

Polymorphism databases

DMDMi135934.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS4702.1.
PIRi A93585. QWHUN.
RefSeqi NP_000585.2. NM_000594.3.
UniGenei Hs.241570.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
3WD5 X-ray 3.10 A 77-233 [» ]
4G3Y X-ray 2.60 C 77-233 [» ]
4TSV X-ray 1.80 A 84-233 [» ]
5TSW X-ray 2.50 A/B/C/D/E/F 84-233 [» ]
ProteinModelPortali P01375.
SMRi P01375. Positions 85-233.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112979. 47 interactions.
DIPi DIP-2895N.
IntActi P01375. 30 interactions.
MINTi MINT-1131842.
STRINGi 9606.ENSP00000392858.

Chemistry

BindingDBi P01375.
ChEMBLi CHEMBL1825.
DrugBanki 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.
GuidetoPHARMACOLOGYi 2635.

PTM databases

PhosphoSitei P01375.
UniCarbKBi P01375.

Polymorphism databases

DMDMi 135934.

Proteomic databases

PaxDbi P01375.
PRIDEi P01375.

Protocols and materials databases

DNASUi 7124.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000376122 ; ENSP00000365290 ; ENSG00000204490 .
ENST00000383496 ; ENSP00000372988 ; ENSG00000206439 .
ENST00000412275 ; ENSP00000392858 ; ENSG00000228321 .
ENST00000420425 ; ENSP00000410668 ; ENSG00000228849 .
ENST00000443707 ; ENSP00000389492 ; ENSG00000230108 .
ENST00000448781 ; ENSP00000389490 ; ENSG00000223952 .
ENST00000449264 ; ENSP00000398698 ; ENSG00000232810 .
GeneIDi 7124.
KEGGi hsa:7124.
UCSCi uc003nui.4. human.

Organism-specific databases

CTDi 7124.
GeneCardsi GC06P031543.
GC06Pj31530.
GC06Pk31525.
GC06Pl31582.
GC06Pm31619.
GC06Pn31533.
GC06Po31533.
H-InvDB HIX0165948.
HGNCi HGNC:11892. TNF.
MIMi 191160. gene.
607507. phenotype.
610424. phenotype.
611162. phenotype.
neXtProti NX_P01375.
Orphaneti 40050. Adult psoriatic arthritis.
PharmGKBi PA435.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40413.
HOGENOMi HOG000048729.
HOVERGENi HBG012516.
InParanoidi P01375.
KOi K03156.
OMAi PWYEPIY.
OrthoDBi EOG7V4B0Q.
PhylomeDBi P01375.
TreeFami TF332169.

Enzyme and pathway databases

Reactomei REACT_1432. TNF signaling.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.

Miscellaneous databases

ChiTaRSi TNF. human.
EvolutionaryTracei P01375.
GeneWikii Tumor_necrosis_factor-alpha.
GenomeRNAii 7124.
NextBioi 27879.
PMAP-CutDB P01375.
PROi P01375.
SOURCEi Search...

Gene expression databases

ArrayExpressi P01375.
Bgeei P01375.
CleanExi HS_TNF.
Genevestigatori P01375.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR006053. TNF.
IPR002959. TNF_alpha.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
PRINTSi PR01234. TNECROSISFCT.
PR01235. TNFALPHA.
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: MYRISTOYLATION AT LYS-19 AND LYS-20.
  22. 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] [Europe PMC] [Abstract]
    Cited for: POLYMORPHISM, INVOLVEMENT IN SUSCEPTIBILITY TO MALARIA.
  24. "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production."
    Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S., Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B.
    Nat. Cell Biol. 8:843-848(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF TNF INTRACELLULAR DOMAIN, CLEAVAGE BY SPPL2A AND SPPL2B, SUBCELLULAR LOCATION.
  25. "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b."
    Fluhrer R., Grammer G., Israel L., Condron M.M., Haffner C., Friedmann E., Bohland C., Imhof A., Martoglio B., Teplow D.B., Haass C.
    Nat. Cell Biol. 8:894-896(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY SPPL2A AND SPPL2B, CLEAVAGE SITE, INTERACTION WITH SPPL2B, IDENTIFICATION BY MASS SPECTROMETRY.
  26. Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
  27. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
  28. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
  29. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ARG-107.
  30. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-3.
  31. "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] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN PSORIATIC ARTHRITIS SUSCEPTIBILITY.
  32. "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] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION.

Entry informationi

Entry nameiTNFA_HUMAN
AccessioniPrimary (citable) accession number: P01375
Secondary accession number(s): O43647, Q9P1Q2, Q9UIV3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 3, 2014
This is version 196 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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