ID   TNFL9_HUMAN             Reviewed;         254 AA.
AC   P41273; Q2M3S2;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   04-NOV-2026, entry version 177.
DE   RecName: Full=Tumor necrosis factor ligand superfamily member 9;
DE   AltName: Full=4-1BB ligand;
DE            Short=4-1BBL;
GN   Name=TNFSF9;
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 [MRNA].
RX   PubMed=8088337; DOI=10.1002/eji.1830240943;
RA   Alderson M.R., Smith C.A., Tough T.W., Davis-Smith T., Armitage R.J.,
RA   Falk B., Roux E., Baker E., Sutherland G.R., Din W.S., Goodwin R.G.;
RT   "Molecular and biological characterization of human 4-1BB and its ligand.";
RL   Eur. J. Immunol. 24:2219-2227(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY, FUNCTION, AND SUBUNIT.
RX   PubMed=20032458; DOI=10.1074/jbc.m109.084442;
RA   Won E.Y., Cha K., Byun J.S., Kim D.U., Shin S., Ahn B., Kim Y.H.,
RA   Rice A.J., Walz T., Kwon B.S., Cho H.S.;
RT   "The structure of the trimer of human 4-1BB ligand is unique among members
RT   of the tumor necrosis factor superfamily.";
RL   J. Biol. Chem. 285:9202-9210(2010).
CC   -!- FUNCTION: Cytokine that binds to TNFRSF9. Induces the proliferation of
CC       activated peripheral blood T-cells. May have a role in activation-
CC       induced cell death (AICD). May play a role in cognate interactions
CC       between T-cells and B-cells/macrophages. {ECO:0000269|PubMed:20032458}.
CC   -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:20032458}.
CC   -!- INTERACTION:
CC       P41273; Q99969: RARRES2; NbExp=2; IntAct=EBI-21507346, EBI-28951773;
CC       P41273; Q07011: TNFRSF9; NbExp=6; IntAct=EBI-21507346, EBI-12945620;
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, placenta, lung, skeletal muscle
CC       and kidney.
CC   -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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DR   EMBL; U03398; AAA53134.1; -; mRNA.
DR   EMBL; BC104805; AAI04806.1; -; mRNA.
DR   EMBL; BC104807; AAI04808.1; -; mRNA.
DR   CCDS; CCDS12169.1; -.
DR   PIR; I38427; I38427.
DR   RefSeq; NP_003802.1; NM_003811.4.
DR   PDB; 2X29; X-ray; 2.30 A; A=80-246.
DR   PDB; 6A3V; X-ray; 3.39 A; A/C/E/G/I/K/M/O/Q/S/U/W=58-254.
DR   PDB; 6BWV; X-ray; 2.40 A; A/B=89-242.
DR   PDB; 6CPR; X-ray; 2.70 A; A/B/C=80-244.
DR   PDB; 6CU0; X-ray; 3.20 A; A/B/C/D/E/F=80-244.
DR   PDB; 6D3N; X-ray; 2.70 A; A=80-244.
DR   PDB; 6FIB; X-ray; 2.70 A; A/B/C=71-248.
DR   PDB; 6MGE; X-ray; 2.95 A; A/B/C=58-254.
DR   PDB; 6MGP; X-ray; 2.13 A; A/B/C=58-254.
DR   SMR; P41273; -.
DR   BioGRID; 114281; 148.
DR   DIP; DIP-3020N; -.
DR   IntAct; P41273; 86.
DR   STRING; 9606.ENSP00000245817; -.
DR   NDEx; IQUERY-CP-TNFSF9; 4 NDEx IQuery Curated Pathways.
DR   iPTMnet; P41273; -.
DR   PhosphoSitePlus; P41273; -.
DR   SwissPalm; P41273; -.
DR   BioMuta; TNFSF9; -.
DR   DMDM; 728739; -.
DR   CPTAC; CPTAC-5963; -.
DR   PaxDb; 9606-ENSP00000245817; -.
DR   PeptideAtlas; P41273; -.
DR   ProteomicsDB; 55457; -.
DR   Pumba; P41273; -.
DR   jPOST; P41273; -.
DR   MassIVE; P41273; -.
DR   DNASU; 8744; -.
DR   Ensembl; ENST00000245817.5; ENSP00000245817.2; ENSG00000125657.5.
DR   GeneID; 8744; -.
DR   KEGG; hsa:8744; -.
DR   MANE-Select; ENST00000245817.5; ENSP00000245817.2; NM_003811.4; NP_003802.1.
DR   UCSC; uc002mfh.2; human.
DR   CTD; 8744; -.
DR   DisGeNET; 8744; -.
DR   VEuPathDB; HostDB:ENSG00000125657; -.
DR   GeneCards; TNFSF9; -.
DR   HGNC; HGNC:11939; TNFSF9.
DR   AGR; HGNC:11939; -.
DR   HPA; ENSG00000125657; Tissue enhanced (esophagus, vagina).
DR   MIM; 606182; gene.
DR   OpenTargets; ENSG00000125657; -.
DR   ClinPGx; PA36629; -.
DR   eggNOG; ENOG502SSK0; Eukaryota.
DR   GeneTree; ENSGT00390000006244; -.
DR   HOGENOM; CLU_095541_0_0_1; -.
DR   InParanoid; P41273; -.
DR   OMA; AACAFRW; -.
DR   OrthoDB; 9450706at2759; -.
DR   PhylomeDB; P41273; -.
DR   Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR   SignaLink; P41273; -.
DR   ChiTaRS; TNFSF9; human.
DR   EvolutionaryTrace; P41273; -.
DR   Agora; ENSG00000125657; -.
DR   GenomeRNAi; 8744; -.
DR   PRO; PR:P41273; -.
DR   Bgee; ENSG00000125657; Expressed in buccal mucosa cell and 113 other cell types or tissues.
DR   ExpressionAtlas; P41273; baseline and differential.
DR   CDD; cd00184; TNF; 1.
DR   FunFam; 2.60.120.40:FF:000032; Tumor necrosis factor ligand superfamily member 9; 1.
DR   Gene3D; 2.60.120.40; -; 1.
DR   InterPro; IPR021184; TNF_CS.
DR   InterPro; IPR006052; TNF_dom.
DR   InterPro; IPR042373; TNFSF9.
DR   InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR   PANTHER; PTHR15153; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 9; 1.
DR   PANTHER; PTHR15153:SF0; TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 9; 1.
DR   Pfam; PF00229; TNF; 1.
DR   SMART; SM00207; TNF; 1.
DR   SUPFAM; SSF49842; TNF-like; 1.
DR   PROSITE; PS00251; THD_1; 1.
DR   PROSITE; PS50049; THD_2; 1.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0032813; F:tumor necrosis factor receptor superfamily binding; IBA:GO_Central.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0042104; P:positive regulation of activated T cell proliferation; IBA:GO_Central.
DR   GO; GO:0045585; P:positive regulation of cytotoxic T cell differentiation; IBA:GO_Central.
DR   GO; GO:0042981; P:regulation of apoptotic process; TAS:GO_Central.
DR   GO; GO:0042129; P:regulation of T cell proliferation; TAS:GO_Central.
DR   Proteomes; UP000005640; Chromosome 19.
DR   PathwayCommons; P41273; -.
DR   Pharos; P41273; Tbio.
DR   Antibodypedia; 24211; 782 antibodies from 45 providers.
DR   CPTC; P41273; 2 antibodies.
DR   RNAct; P41273; protein.
DR   BioGRID-ORCS; 8744; 12 hits in 1160 CRISPR screens.
DR   AlphaFoldDB; P41273; -.
DR   FunCoup; P41273; 548.
DR   PAN-GO; P41273; 4 GO annotations based on evolutionary models.
PE   1: Evidence at protein level;
KW   3D-structure; Cytokine; Membrane; Proteomics identification;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..254
FT                   /note="Tumor necrosis factor ligand superfamily member 9"
FT                   /id="PRO_0000185501"
FT   TOPO_DOM        1..28
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        29..49
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        50..254
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          91..240
FT                   /note="THD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01387"
FT   VARIANT         17
FT                   /note="P -> A (in dbSNP:rs442511)"
FT                   /id="VAR_011928"
FT   STRAND          83..85
FT                   /evidence="ECO:0007829|PDB:2X29"
FT   STRAND          92..97
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          104..106
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          109..111
FT                   /evidence="ECO:0007829|PDB:6D3N"
FT   STRAND          115..117
FT                   /evidence="ECO:0007829|PDB:2X29"
FT   STRAND          121..123
FT                   /evidence="ECO:0007829|PDB:2X29"
FT   STRAND          124..127
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   TURN            128..131
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          132..135
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          139..151
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          158..169
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          171..175
FT                   /evidence="ECO:0007829|PDB:6CPR"
FT   STRAND          178..185
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          189..191
FT                   /evidence="ECO:0007829|PDB:6FIB"
FT   STRAND          195..206
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          211..222
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   HELIX           223..225
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   STRAND          226..228
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   TURN            230..232
FT                   /evidence="ECO:0007829|PDB:6CPR"
FT   STRAND          234..241
FT                   /evidence="ECO:0007829|PDB:6MGP"
FT   HELIX           242..245
FT                   /evidence="ECO:0007829|PDB:2X29"
SQ   SEQUENCE   254 AA;  26625 MW;  827551F34563E508 CRC64;
     MEYASDASLD PEAPWPPAPR ARACRVLPWA LVAGLLLLLL LAAACAVFLA CPWAVSGARA
     SPGSAASPRL REGPELSPDD PAGLLDLRQG MFAQLVAQNV LLIDGPLSWY SDPGLAGVSL
     TGGLSYKEDT KELVVAKAGV YYVFFQLELR RVVAGEGSGS VSLALHLQPL RSAAGAAALA
     LTVDLPPASS EARNSAFGFQ GRLLHLSAGQ RLGVHLHTEA RARHAWQLTQ GATVLGLFRV
     TPEIPAGLPS PRSE
//