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P48094

- TNFA_MACMU

UniProt

P48094 - TNFA_MACMU

Protein

Tumor necrosis factor

Gene

TNF

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    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 amino acid biosynthetic process Source: Ensembl
    5. cellular response to amino acid stimulus Source: Ensembl
    6. cellular response to nicotine Source: Ensembl
    7. chronic inflammatory response to antigenic stimulus Source: Ensembl
    8. defense response to Gram-positive bacterium Source: Ensembl
    9. embryonic digestive tract development Source: Ensembl
    10. epithelial cell proliferation involved in salivary gland morphogenesis Source: Ensembl
    11. extracellular matrix organization Source: Ensembl
    12. extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
    13. glucose metabolic process Source: Ensembl
    14. humoral immune response Source: Ensembl
    15. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
    16. JNK cascade Source: Ensembl
    17. leukocyte tethering or rolling Source: Ensembl
    18. lipopolysaccharide-mediated signaling pathway Source: Ensembl
    19. necroptotic signaling pathway Source: UniProtKB
    20. negative regulation of alkaline phosphatase activity Source: Ensembl
    21. negative regulation of branching involved in lung morphogenesis Source: Ensembl
    22. negative regulation of cytokine secretion involved in immune response Source: Ensembl
    23. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    24. negative regulation of glucose import Source: Ensembl
    25. negative regulation of growth of symbiont in host Source: Ensembl
    26. negative regulation of interleukin-6 production Source: Ensembl
    27. negative regulation of lipid catabolic process Source: Ensembl
    28. negative regulation of osteoblast differentiation Source: Ensembl
    29. negative regulation of protein complex disassembly Source: UniProtKB
    30. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    31. negative regulation of viral genome replication Source: Ensembl
    32. organ morphogenesis Source: Ensembl
    33. osteoclast differentiation Source: Ensembl
    34. positive regulation of apoptotic process Source: UniProtKB
    35. positive regulation of calcidiol 1-monooxygenase activity Source: Ensembl
    36. positive regulation of chemokine (C-X-C motif) ligand 2 production Source: Ensembl
    37. positive regulation of chemokine biosynthetic process Source: Ensembl
    38. positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
    39. positive regulation of cytokine secretion Source: Ensembl
    40. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
    41. positive regulation of fever generation Source: Ensembl
    42. positive regulation of hair follicle development Source: Ensembl
    43. positive regulation of heterotypic cell-cell adhesion Source: Ensembl
    44. positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
    45. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
    46. positive regulation of interferon-gamma production Source: Ensembl
    47. positive regulation of interleukin-6 production Source: Ensembl
    48. positive regulation of interleukin-8 biosynthetic process Source: Ensembl
    49. positive regulation of JNK cascade Source: Ensembl
    50. positive regulation of JUN kinase activity Source: UniProtKB
    51. positive regulation of MAP kinase activity Source: UniProtKB
    52. positive regulation of membrane protein ectodomain proteolysis Source: Ensembl
    53. positive regulation of NFAT protein import into nucleus Source: Ensembl
    54. positive regulation of NF-kappaB import into nucleus Source: Ensembl
    55. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
    56. positive regulation of nitric oxide biosynthetic process Source: Ensembl
    57. positive regulation of osteoclast differentiation Source: Ensembl
    58. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    59. positive regulation of podosome assembly Source: Ensembl
    60. positive regulation of protein complex disassembly Source: UniProtKB
    61. positive regulation of protein kinase B signaling Source: Ensembl
    62. positive regulation of protein localization to cell surface Source: Ensembl
    63. positive regulation of protein phosphorylation Source: UniProtKB
    64. positive regulation of smooth muscle cell proliferation Source: Ensembl
    65. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    66. positive regulation of translational initiation by iron Source: Ensembl
    67. positive regulation of vitamin D biosynthetic process Source: Ensembl
    68. protein import into nucleus, translocation Source: Ensembl
    69. protein kinase B signaling Source: Ensembl
    70. receptor biosynthetic process Source: Ensembl
    71. regulation of branching involved in salivary gland morphogenesis Source: Ensembl
    72. regulation of immunoglobulin secretion Source: Ensembl
    73. regulation of insulin secretion Source: Ensembl
    74. response to glucocorticoid Source: Ensembl
    75. response to virus Source: Ensembl
    76. sequestering of triglyceride Source: Ensembl
    77. transformed cell apoptotic process Source: Ensembl
    78. tumor necrosis factor-mediated signaling pathway Source: Ensembl

    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

    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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3535CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini57 – 233177ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei36 – 5621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    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

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    MSTESMIRDV ELAEEALPRK TAGPQGSRRC WFLSLFSFLL VAGATTLFCL    50
    LHFGVIGPQR EEFPKDPSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG 100
    QLQWLNRRAN ALLANGVELT DNQLVVPSEG LYLIYSQVLF KGQGCPSNHV 150
    LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF 200
    QLEKGDRLSA EINLPDYLDF AESGQVYFGI IAL 233
    Length:233
    Mass (Da):25,630
    Last modified:February 1, 1996 - v1
    Checksum:i9F6F85050595FD59
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    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 1, 2014
    This is version 104 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