TNFC_HUMAN
ID TNFC_HUMAN Reviewed; 244 AA.
AC Q06643; P78370; Q52LU8; Q99761;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Lymphotoxin-beta;
DE Short=LT-beta;
DE AltName: Full=Tumor necrosis factor C;
DE Short=TNF-C;
DE AltName: Full=Tumor necrosis factor ligand superfamily member 3;
GN Name=LTB; Synonyms=TNFC, TNFSF3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=T-cell;
RX PubMed=7916655; DOI=10.1016/0092-8674(93)90574-a;
RA Browning J.L., Ngam-Ek A., Lawton P., Demarinis J., Tizard R., Chow E.P.,
RA Hession C., O'Brine-Greco B., Foley S.F., Ware C.F.;
RT "Lymphotoxin beta, a novel member of the TNF family that forms a
RT heteromeric complex with lymphotoxin on the cell surface.";
RL Cell 72:847-856(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9299492; DOI=10.1006/bbrc.1997.7277;
RA Warzocha K., Renard N., Charlot C., Bienvenu J., Coiffier B., Salles G.;
RT "Identification of two lymphotoxin beta isoforms expressed in human
RT lymphoid cell lines and non-Hodgkin's lymphomas.";
RL Biochem. Biophys. Res. Commun. 238:273-276(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX PubMed=10202016;
RA Neville M.J., Campbell R.D.;
RT "A new member of the Ig superfamily and a V-ATPase G subunit are among the
RT predicted products of novel genes close to the TNF locus in the human
RT MHC.";
RL J. Immunol. 162:4745-4754(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-70 AND PRO-111.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-84 AND PHE-87.
RG NIEHS SNPs program;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Cytokine that binds to LTBR/TNFRSF3. May play a specific role
CC in immune response regulation. Provides the membrane anchor for the
CC attachment of the heterotrimeric complex to the cell surface. Isoform 2
CC is probably non-functional.
CC -!- SUBUNIT: Heterotrimer of either two LTB and one LTA subunits or (less
CC prevalent) one LTB and two LTA subunits.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q06643-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06643-2; Sequence=VSP_006441, VSP_006442;
CC -!- TISSUE SPECIFICITY: Spleen and thymus.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ltb/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ltb/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L11016; AAA99888.1; -; Genomic_DNA.
DR EMBL; U89922; AAC51769.1; -; mRNA.
DR EMBL; U79029; AAB37342.1; -; mRNA.
DR EMBL; L11015; AAA36191.1; -; mRNA.
DR EMBL; Y14768; CAA75069.1; -; Genomic_DNA.
DR EMBL; AF129756; AAD18089.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63395.1; -; Genomic_DNA.
DR EMBL; AY070219; AAL49954.1; -; Genomic_DNA.
DR EMBL; AY070219; AAL49955.1; -; Genomic_DNA.
DR EMBL; AY216497; AAO21134.1; -; Genomic_DNA.
DR EMBL; AK312210; BAG35143.1; -; mRNA.
DR EMBL; CH471081; EAX03425.1; -; Genomic_DNA.
DR EMBL; BC069330; AAH69330.1; -; mRNA.
DR EMBL; BC093783; AAH93783.1; -; mRNA.
DR CCDS; CCDS4703.1; -. [Q06643-1]
DR CCDS; CCDS4704.1; -. [Q06643-2]
DR PIR; A46066; A46066.
DR PIR; JC5645; JC5645.
DR RefSeq; NP_002332.1; NM_002341.1. [Q06643-1]
DR RefSeq; NP_033666.1; NM_009588.1. [Q06643-2]
DR PDB; 4MXW; X-ray; 3.60 A; B/D/Y/Z=86-244.
DR PDBsum; 4MXW; -.
DR AlphaFoldDB; Q06643; -.
DR SMR; Q06643; -.
DR BioGRID; 110228; 2.
DR CORUM; Q06643; -.
DR DIP; DIP-2996N; -.
DR IntAct; Q06643; 6.
DR STRING; 9606.ENSP00000410481; -.
DR BindingDB; Q06643; -.
DR ChEMBL; CHEMBL3713022; -.
DR GlyGen; Q06643; 1 site.
DR PhosphoSitePlus; Q06643; -.
DR BioMuta; LTB; -.
DR DMDM; 549088; -.
DR MassIVE; Q06643; -.
DR PaxDb; Q06643; -.
DR PeptideAtlas; Q06643; -.
DR PRIDE; Q06643; -.
DR ProteomicsDB; 58468; -. [Q06643-1]
DR ProteomicsDB; 58469; -. [Q06643-2]
DR ABCD; Q06643; 8 sequenced antibodies.
DR Antibodypedia; 27204; 205 antibodies from 25 providers.
DR DNASU; 4050; -.
DR Ensembl; ENST00000376117.3; ENSP00000365285.3; ENSG00000204487.8. [Q06643-1]
DR Ensembl; ENST00000383493.2; ENSP00000372985.2; ENSG00000206437.10. [Q06643-1]
DR Ensembl; ENST00000420402.2; ENSP00000398741.2; ENSG00000223448.7. [Q06643-1]
DR Ensembl; ENST00000421268.2; ENSP00000393693.2; ENSG00000238114.7. [Q06643-1]
DR Ensembl; ENST00000429299.3; ENSP00000410481.3; ENSG00000227507.3. [Q06643-1]
DR Ensembl; ENST00000444479.2; ENSP00000395102.2; ENSG00000236925.7. [Q06643-1]
DR Ensembl; ENST00000446745.2; ENSP00000416113.2; ENSG00000227507.3. [Q06643-2]
DR Ensembl; ENST00000456113.2; ENSP00000404014.2; ENSG00000236237.7. [Q06643-1]
DR Ensembl; ENST00000457552.2; ENSP00000404450.2; ENSG00000231314.7. [Q06643-1]
DR GeneID; 4050; -.
DR KEGG; hsa:4050; -.
DR MANE-Select; ENST00000429299.3; ENSP00000410481.3; NM_002341.2; NP_002332.1.
DR UCSC; uc003nul.4; human. [Q06643-1]
DR CTD; 4050; -.
DR DisGeNET; 4050; -.
DR GeneCards; LTB; -.
DR HGNC; HGNC:6711; LTB.
DR HPA; ENSG00000227507; Group enriched (intestine, lymphoid tissue).
DR MIM; 600978; gene.
DR neXtProt; NX_Q06643; -.
DR OpenTargets; ENSG00000227507; -.
DR PharmGKB; PA30475; -.
DR VEuPathDB; HostDB:ENSG00000227507; -.
DR eggNOG; ENOG502SMSQ; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_096531_0_0_1; -.
DR InParanoid; Q06643; -.
DR OMA; IGAWTTG; -.
DR PhylomeDB; Q06643; -.
DR TreeFam; TF337780; -.
DR PathwayCommons; Q06643; -.
DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR SignaLink; Q06643; -.
DR SIGNOR; Q06643; -.
DR BioGRID-ORCS; 4050; 11 hits in 1065 CRISPR screens.
DR ChiTaRS; LTB; human.
DR GeneWiki; Lymphotoxin_beta; -.
DR GenomeRNAi; 4050; -.
DR Pharos; Q06643; Tbio.
DR PRO; PR:Q06643; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q06643; protein.
DR Bgee; ENSG00000227507; Expressed in granulocyte and 100 other tissues.
DR ExpressionAtlas; Q06643; baseline and differential.
DR Genevisible; Q06643; HS.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0048535; P:lymph node development; IEA:Ensembl.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR CDD; cd00184; TNF; 1.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR006053; TNF.
DR InterPro; IPR002961; TNF_C.
DR InterPro; IPR021184; TNF_CS.
DR InterPro; IPR006052; TNF_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR PANTHER; PTHR11471:SF29; PTHR11471:SF29; 1.
DR Pfam; PF00229; TNF; 1.
DR PRINTS; PR01234; TNECROSISFCT.
DR PRINTS; PR01237; TNFC.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytokine; Direct protein sequencing;
KW Glycoprotein; Membrane; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..244
FT /note="Lymphotoxin-beta"
FT /id="PRO_0000185486"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 19..48
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 53..77
FT /note="GLVTETADPGAQAQQGLGFQKLPEE -> GLGFRSCQRRSQKQISAPGSQLP
FT TS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9299492"
FT /id="VSP_006441"
FT VAR_SEQ 78..244
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9299492"
FT /id="VSP_006442"
FT VARIANT 70
FT /note="G -> E (in dbSNP:rs3093554)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_013025"
FT VARIANT 84
FT /note="S -> R (in dbSNP:rs4647186)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_016331"
FT VARIANT 87
FT /note="L -> F (in dbSNP:rs4647187)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_016332"
FT VARIANT 111
FT /note="A -> P (in dbSNP:rs3093555)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_013026"
FT VARIANT 122
FT /note="A -> D (in dbSNP:rs2229699)"
FT /id="VAR_029145"
FT CONFLICT 60..69
FT /note="DPGAQAQQGL -> GLSAPGSGRT (in Ref. 2; AAB37342)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 244 AA; 25390 MW; F41569459830ED4C CRC64;
MGALGLEGRG GRLQGRGSLL LAVAGATSLV TLLLAVPITV LAVLALVPQD QGGLVTETAD
PGAQAQQGLG FQKLPEEEPE TDLSPGLPAA HLIGAPLKGQ GLGWETTKEQ AFLTSGTQFS
DAEGLALPQD GLYYLYCLVG YRGRAPPGGG DPQGRSVTLR SSLYRAGGAY GPGTPELLLE
GAETVTPVLD PARRQGYGPL WYTSVGFGGL VQLRRGERVY VNISHPDMVD FARGKTFFGA
VMVG
