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P48094

- TNFA_MACMU

UniProt

P48094 - TNFA_MACMU

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Protein

Tumor necrosis factor

Gene

TNF

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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.
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei34 – 352Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei39 – 402Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei49 – 502Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei51 – 522Cleavage; by SPPL2A or SPPL2BBy similarity
Sitei76 – 772Cleavage; by ADAM17By similarity

GO - Molecular functioni

  1. transcription regulatory region DNA binding Source: Ensembl

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  2. activation of MAPK activity Source: Ensembl
  3. activation of MAPKKK activity Source: Ensembl
  4. cellular response to amino acid stimulus Source: Ensembl
  5. cellular response to nicotine Source: Ensembl
  6. chronic inflammatory response to antigenic stimulus Source: Ensembl
  7. defense response to Gram-positive bacterium Source: Ensembl
  8. embryonic digestive tract development Source: Ensembl
  9. epithelial cell proliferation involved in salivary gland morphogenesis Source: Ensembl
  10. extracellular matrix organization Source: Ensembl
  11. extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  12. glucose metabolic process Source: Ensembl
  13. humoral immune response Source: Ensembl
  14. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  15. JNK cascade Source: Ensembl
  16. leukocyte tethering or rolling Source: Ensembl
  17. lipopolysaccharide-mediated signaling pathway Source: Ensembl
  18. necroptotic signaling pathway Source: UniProtKB
  19. negative regulation of alkaline phosphatase activity Source: Ensembl
  20. negative regulation of branching involved in lung morphogenesis Source: Ensembl
  21. negative regulation of cytokine secretion involved in immune response Source: Ensembl
  22. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  23. negative regulation of glucose import Source: Ensembl
  24. negative regulation of growth of symbiont in host Source: Ensembl
  25. negative regulation of interleukin-6 production Source: Ensembl
  26. negative regulation of lipid catabolic process Source: Ensembl
  27. negative regulation of osteoblast differentiation Source: Ensembl
  28. negative regulation of protein complex disassembly Source: UniProtKB
  29. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  30. negative regulation of viral genome replication Source: Ensembl
  31. organ morphogenesis Source: Ensembl
  32. osteoclast differentiation Source: Ensembl
  33. positive regulation of apoptotic process Source: UniProtKB
  34. positive regulation of calcidiol 1-monooxygenase activity Source: Ensembl
  35. positive regulation of chemokine (C-X-C motif) ligand 2 production Source: Ensembl
  36. positive regulation of chemokine biosynthetic process Source: Ensembl
  37. positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
  38. positive regulation of cytokine secretion Source: Ensembl
  39. positive regulation of fever generation Source: Ensembl
  40. positive regulation of hair follicle development Source: Ensembl
  41. positive regulation of heterotypic cell-cell adhesion Source: Ensembl
  42. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
  43. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  44. positive regulation of interferon-gamma production Source: Ensembl
  45. positive regulation of interleukin-6 production Source: Ensembl
  46. positive regulation of interleukin-8 biosynthetic process Source: Ensembl
  47. positive regulation of JNK cascade Source: Ensembl
  48. positive regulation of JUN kinase activity Source: UniProtKB
  49. positive regulation of MAP kinase activity Source: UniProtKB
  50. positive regulation of membrane protein ectodomain proteolysis Source: Ensembl
  51. positive regulation of NFAT protein import into nucleus Source: Ensembl
  52. positive regulation of NF-kappaB import into nucleus Source: Ensembl
  53. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  54. positive regulation of nitric oxide biosynthetic process Source: Ensembl
  55. positive regulation of osteoclast differentiation Source: Ensembl
  56. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  57. positive regulation of podosome assembly Source: Ensembl
  58. positive regulation of protein complex disassembly Source: UniProtKB
  59. positive regulation of protein kinase B signaling Source: Ensembl
  60. positive regulation of protein localization to cell surface Source: Ensembl
  61. positive regulation of protein phosphorylation Source: UniProtKB
  62. positive regulation of smooth muscle cell proliferation Source: Ensembl
  63. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  64. positive regulation of translational initiation by iron Source: Ensembl
  65. positive regulation of vitamin D biosynthetic process Source: Ensembl
  66. protein import into nucleus, translocation Source: Ensembl
  67. protein kinase B signaling Source: Ensembl
  68. receptor biosynthetic process Source: Ensembl
  69. regulation of branching involved in salivary gland morphogenesis Source: Ensembl
  70. regulation of immunoglobulin secretion Source: Ensembl
  71. regulation of insulin secretion Source: Ensembl
  72. regulation of reactive oxygen species metabolic process Source: Ensembl
  73. response to glucocorticoid Source: Ensembl
  74. response to virus Source: Ensembl
  75. sequestering of triglyceride Source: Ensembl
  76. transformed cell apoptotic process Source: Ensembl
  77. tumor necrosis factor-mediated signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

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
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
ProteomesiUP000006718: Chromosome 4

Subcellular locationi

Chain C-domain 1 : Secreted By similarity
Chain C-domain 2 : Secreted By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei36 – 5621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini57 – 233177ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. extracellular space Source: UniProtKB-KW
  3. integral component of plasma membrane Source: Ensembl
  4. membrane raft Source: Ensembl
  5. phagocytic cup Source: Ensembl
  6. recycling endosome Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 233233Tumor necrosis factor, membrane formPRO_0000034431Add
BLAST
Chaini1 – 3939Intracellular domain 1By similarityPRO_0000417247Add
BLAST
Chaini1 – 3535Intracellular domain 2By similarityPRO_0000417248Add
BLAST
Chaini50 – ?C-domain 1By similarityPRO_0000417249
Chaini52 – ?C-domain 2By similarityPRO_0000417250
Chaini77 – 233157Tumor necrosis factor, soluble formPRO_0000034432Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21Phosphoserine; by CK1By similarity
Lipidationi20 – 201N6-myristoyl lysineBy similarity
Glycosylationi80 – 801O-linked (GalNAc...); in soluble formBy similarity
Disulfide bondi145 ↔ 177By similarity

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 (By similarity).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).By similarity
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Myristate, Phosphoprotein

Interactioni

Subunit structurei

Homotrimer. Interacts with SPPL2B (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP48094.
SMRiP48094. Positions 82-233.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG40413.
GeneTreeiENSGT00530000062992.
HOGENOMiHOG000048729.
HOVERGENiHBG012516.
InParanoidiP48094.
KOiK03156.
OMAiPWYEPIY.
OrthoDBiEOG7V4B0Q.
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.

P48094-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSTESMIRDV ELAEEALPRK TAGPQGSRRC WFLSLFSFLL VAGATTLFCL
60 70 80 90 100
LHFGVIGPQR EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
110 120 130 140 150
QLQWLNRRAN ALLANGVELT DNQLVVPSEG LYLIYSQVLF KGQGCPSNHV
160 170 180 190 200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
210 220 230
QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL
Length:233
Mass (Da):25,630
Last modified:February 1, 1996 - v1
Checksum:i9F6F85050595FD59
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19850 mRNA. Translation: AAA86712.1.
AB128049 Genomic DNA. Translation: BAD69724.1.
AY091967 Genomic DNA. Translation: AAM76585.1.
RefSeqiNP_001040614.1. NM_001047149.1.
UniGeneiMmu.3364.

Genome annotation databases

EnsembliENSMMUT00000012362; ENSMMUP00000011594; ENSMMUG00000008845.
GeneIDi715467.
KEGGimcc:715467.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19850 mRNA. Translation: AAA86712.1 .
AB128049 Genomic DNA. Translation: BAD69724.1 .
AY091967 Genomic DNA. Translation: AAM76585.1 .
RefSeqi NP_001040614.1. NM_001047149.1.
UniGenei Mmu.3364.

3D structure databases

ProteinModelPortali P48094.
SMRi P48094. Positions 82-233.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMMUT00000012362 ; ENSMMUP00000011594 ; ENSMMUG00000008845 .
GeneIDi 715467.
KEGGi mcc:715467.

Organism-specific databases

CTDi 7124.

Phylogenomic databases

eggNOGi NOG40413.
GeneTreei ENSGT00530000062992.
HOGENOMi HOG000048729.
HOVERGENi HBG012516.
InParanoidi P48094.
KOi K03156.
OMAi PWYEPIY.
OrthoDBi EOG7V4B0Q.
TreeFami TF332169.

Miscellaneous databases

NextBioi 19970636.

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. "Comparative sequence analysis of cytokine genes from human and nonhuman primates."
    Villinger F.J., Brar S.S., Mayne A.E., Chikkala N., Ansari A.A.
    J. Immunol. 155:3946-3954(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Rhesus macaque class I duplicon structures, organization, and evolution within the alpha block of the major histocompatibility complex."
    Kulski J.K., Anzai T., Shiina T., Inoko H.
    Mol. Biol. Evol. 21:2079-2091(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Molecular evolution in higher primates; gene specific and organism specific characteristics."
    O'Huigin C., Tichy H., Klein J.
    Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 33-187.

Entry informationi

Entry nameiTNFA_MACMU
AccessioniPrimary (citable) accession number: P48094
Secondary accession number(s): Q5TM21, Q8HZD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: October 29, 2014
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3