TNFB_MOUSE
ID TNFB_MOUSE Reviewed; 202 AA.
AC P09225;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Lymphotoxin-alpha;
DE Short=LT-alpha;
DE AltName: Full=TNF-beta;
DE AltName: Full=Tumor necrosis factor ligand superfamily member 1;
DE Flags: Precursor;
GN Name=Lta; Synonyms=Tnfb, Tnfsf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3684584; DOI=10.1093/nar/15.21.9083;
RA Semon D., Kawashima E., Jongeneel C.V., Shakhov A.N., Nedospasov S.A.;
RT "Nucleotide sequence of the murine TNF locus, including the TNF-alpha
RT (tumor necrosis factor) and TNF-beta (lymphotoxin) genes.";
RL Nucleic Acids Res. 15:9083-9084(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3490653; DOI=10.1093/nar/14.19.7713;
RA Nedospasov S.A., Hirt B., Shakhov A.N., Dobrynin V.N., Kawashima E.,
RA Accolla R.S., Jongeneel C.V.;
RT "The genes for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta)
RT are tandemly arranged on chromosome 17 of the mouse.";
RL Nucleic Acids Res. 14:7713-7725(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3588316; DOI=10.1093/nar/15.9.3937;
RA Gray P.W., Chen E., Tang W.-L., Ruddle N.H.;
RT "The murine tumor necrosis factor-beta (lymphotoxin) gene sequence.";
RL Nucleic Acids Res. 15:3937-3937(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2884262;
RA Li C.B., Gray P.W., Lin P.F., McGrath K.M., Ruddle F.H., Ruddle N.H.;
RT "Cloning and expression of murine lymphotoxin cDNA.";
RL J. Immunol. 138:4496-4501(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2885372;
RA Gardner S.M., Mock B.A., Hilgers J., Huppi K.E., Roeder W.D.;
RT "Mouse lymphotoxin and tumor necrosis factor: structural analysis of the
RT cloned genes, physical linkage, and chromosomal position.";
RL J. Immunol. 139:476-483(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 6-202.
RX PubMed=3147435;
RA Weil D., Dautry F.;
RT "Induction of tumor necrosis factor-alpha and -beta and interferon-gamma
RT mRNA by interleukin 2 in murine lymphocytic cell lines.";
RL Oncogene Res. 3:409-414(1988).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-76.
RX PubMed=1700275; DOI=10.1128/mcb.10.11.5865-5875.1990;
RA Weil D., Brosset S., Dautry F.;
RT "RNA processing is a limiting step for murine tumor necrosis factor beta
RT expression in response to interleukin-2.";
RL Mol. Cell. Biol. 10:5865-5875(1990).
CC -!- FUNCTION: Cytokine that in its homotrimeric form binds to
CC TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (By similarity). In
CC its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is
CC produced by lymphocytes and is cytotoxic for a wide range of tumor
CC cells in vitro and in vivo. {ECO:0000250|UniProtKB:P01374}.
CC -!- SUBUNIT: Homotrimer, and heterotrimer of either two LTB and one LTA
CC subunits or (less prevalent) two LTA and one LTB subunits. Interacts
CC with TNFRSF14. {ECO:0000250|UniProtKB:P01374}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Membrane {ECO:0000250}.
CC Note=The homotrimer is secreted. The heterotrimer is membrane-
CC associated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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DR EMBL; U06950; AAA18593.1; -; Unassigned_DNA.
DR EMBL; Y00467; CAA68529.1; -; Genomic_DNA.
DR EMBL; X06217; CAA29566.1; -; Genomic_DNA.
DR EMBL; X06218; CAA29567.1; -; Genomic_DNA.
DR EMBL; Y00137; CAA68330.1; -; Genomic_DNA.
DR EMBL; M16819; AAA40460.1; -; mRNA.
DR EMBL; M17015; AAA39450.1; -; Genomic_DNA.
DR EMBL; AF109719; AAC82485.1; -; Genomic_DNA.
DR EMBL; X14800; CAA32906.1; -; mRNA.
DR EMBL; M60586; AAA40461.1; -; Genomic_DNA.
DR CCDS; CCDS28692.1; -.
DR PIR; B27303; B27303.
DR RefSeq; NP_034865.1; NM_010735.2.
DR RefSeq; XP_006523794.1; XM_006523731.3.
DR AlphaFoldDB; P09225; -.
DR SMR; P09225; -.
DR BioGRID; 201216; 1.
DR STRING; 10090.ENSMUSP00000025266; -.
DR GlyGen; P09225; 1 site.
DR EPD; P09225; -.
DR PaxDb; P09225; -.
DR PRIDE; P09225; -.
DR Antibodypedia; 27173; 822 antibodies from 42 providers.
DR DNASU; 16992; -.
DR Ensembl; ENSMUST00000025266; ENSMUSP00000025266; ENSMUSG00000024402.
DR GeneID; 16992; -.
DR KEGG; mmu:16992; -.
DR UCSC; uc008cgu.2; mouse.
DR CTD; 4049; -.
DR MGI; MGI:104797; Lta.
DR VEuPathDB; HostDB:ENSMUSG00000024402; -.
DR eggNOG; ENOG502S956; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_070352_4_0_1; -.
DR InParanoid; P09225; -.
DR OMA; MEGECKV; -.
DR OrthoDB; 1124938at2759; -.
DR PhylomeDB; P09225; -.
DR TreeFam; TF332169; -.
DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR BioGRID-ORCS; 16992; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Lta; mouse.
DR PRO; PR:P09225; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P09225; protein.
DR Bgee; ENSMUSG00000024402; Expressed in spleen and 30 other tissues.
DR ExpressionAtlas; P09225; baseline and differential.
DR Genevisible; P09225; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; TAS:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IGI:MGI.
DR GO; GO:0006959; P:humoral immune response; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; TAS:MGI.
DR GO; GO:0048535; P:lymph node development; IMP:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:MGI.
DR GO; GO:0002876; P:positive regulation of chronic inflammatory response to antigenic stimulus; IGI:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IGI:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IGI:MGI.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR CDD; cd00184; TNF; 1.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR006053; TNF.
DR InterPro; IPR002960; TNF_beta.
DR InterPro; IPR021184; TNF_CS.
DR InterPro; IPR006052; TNF_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01234; TNECROSISFCT.
DR PRINTS; PR01236; TNFBETA.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_2; 1.
PE 2: Evidence at transcript level;
KW Cytokine; Glycoprotein; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..33
FT CHAIN 34..202
FT /note="Lymphotoxin-alpha"
FT /id="PRO_0000034467"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 26
FT /note="A -> P (in Ref. 5; AAA39450)"
FT /evidence="ECO:0000305"
FT CONFLICT 161..162
FT /note="VR -> CG (in Ref. 2; CAA29567)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 202 AA; 21999 MW; F496F83C685950D3 CRC64;
MTLLGRLHLL RVLGTPPVFL LGLLLALPLG AQGLSGVRFS AARTAHPLPQ KHLTHGILKP
AAHLVGYPSK QNSLLWRAST DRAFLRHGFS LSNNSLLIPT SGLYFVYSQV VFSGESCSPR
AIPTPIYLAH EVQLFSSQYP FHVPLLSAQK SVYPGLQGPW VRSMYQGAVF LLSKGDQLST
HTDGISHLHF SPSSVFFGAF AL
