TNR12_HUMAN
ID TNR12_HUMAN Reviewed; 129 AA.
AC Q9NP84; D3DUA6; Q9HCS0;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 12A;
DE AltName: Full=Fibroblast growth factor-inducible immediate-early response protein 14;
DE Short=FGF-inducible 14;
DE AltName: Full=Tweak-receptor;
DE Short=TweakR;
DE AltName: CD_antigen=CD266;
DE Flags: Precursor;
GN Name=TNFRSF12A; Synonyms=FN14;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=10751351; DOI=10.1016/s0002-9440(10)64996-6;
RA Feng S.-L.Y., Guo Y., Factor V.M., Thorgeirsson S.S., Bell D.W.,
RA Testa J.R., Peifley K.A., Winkles J.A.;
RT "The Fn14 immediate-early response gene is induced during liver
RT regeneration and highly expressed in both human and murine hepatocellular
RT carcinomas.";
RL Am. J. Pathol. 156:1253-1261(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Tanaka S., Sugimachi K.;
RT "Human homologue of Fn14.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [5]
RP FUNCTION.
RX PubMed=11728344; DOI=10.1016/s1074-7613(01)00232-1;
RA Wiley S.R., Cassiano L., Lofton T., Davis-Smith T., Winkles J.A.,
RA Lindner V., Liu H., Daniel T.O., Smith C.A., Fanslow W.C.;
RT "A novel TNF receptor family member binds TWEAK and is implicated in
RT angiogenesis.";
RL Immunity 15:837-846(2001).
RN [6]
RP STRUCTURE BY NMR OF 26-70.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the STN_TNFRSF12A_TNFR domain of tumor necrosis
RT factor receptor superfamily member 12A precursor.";
RL Submitted (APR-2008) to the PDB data bank.
RN [7]
RP STRUCTURE BY NMR OF 26-70, AND DISULFIDE BONDS.
RX PubMed=19241374; DOI=10.1002/pro.49;
RA He F., Dang W., Saito K., Watanabe S., Kobayashi N., Guntert P., Kigawa T.,
RA Tanaka A., Muto Y., Yokoyama S.;
RT "Solution structure of the cysteine-rich domain in Fn14, a member of the
RT tumor necrosis factor receptor superfamily.";
RL Protein Sci. 18:650-656(2009).
CC -!- FUNCTION: Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some
CC cell types. Promotes angiogenesis and the proliferation of endothelial
CC cells. May modulate cellular adhesion to matrix proteins.
CC {ECO:0000269|PubMed:11728344}.
CC -!- SUBUNIT: Associates with TRAF1 and TRAF2, and probably also with TRAF3.
CC -!- INTERACTION:
CC Q9NP84; Q13490: BIRC2; NbExp=2; IntAct=EBI-2851995, EBI-514538;
CC Q9NP84; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-2851995, EBI-3957694;
CC Q9NP84; Q9BRI3: SLC30A2; NbExp=9; IntAct=EBI-2851995, EBI-8644112;
CC Q9NP84; O43508: TNFSF12; NbExp=2; IntAct=EBI-2851995, EBI-6932080;
CC Q9NP84; Q12933: TRAF2; NbExp=3; IntAct=EBI-2851995, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NP84-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NP84-2; Sequence=VSP_006519;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta and kidney.
CC Intermediate expression in lung, skeletal muscle and pancreas.
CC -!- INDUCTION: By FGF1 and phorbol ester.
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DR EMBL; AF191148; AAF69108.1; -; mRNA.
DR EMBL; AB035480; BAA94792.1; -; mRNA.
DR EMBL; AB035481; BAB17850.1; -; mRNA.
DR EMBL; CH471112; EAW85429.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85430.1; -; Genomic_DNA.
DR EMBL; BC002718; AAH02718.1; -; mRNA.
DR CCDS; CCDS10489.1; -. [Q9NP84-1]
DR RefSeq; NP_057723.1; NM_016639.2. [Q9NP84-1]
DR PDB; 2EQP; NMR; -; A=28-70.
DR PDB; 2KMZ; NMR; -; A=28-80.
DR PDB; 2RPJ; NMR; -; A=28-70.
DR PDBsum; 2EQP; -.
DR PDBsum; 2KMZ; -.
DR PDBsum; 2RPJ; -.
DR AlphaFoldDB; Q9NP84; -.
DR BMRB; Q9NP84; -.
DR SMR; Q9NP84; -.
DR BioGRID; 119478; 7.
DR IntAct; Q9NP84; 7.
DR MINT; Q9NP84; -.
DR STRING; 9606.ENSP00000326737; -.
DR ChEMBL; CHEMBL3712850; -.
DR PhosphoSitePlus; Q9NP84; -.
DR SwissPalm; Q9NP84; -.
DR BioMuta; TNFRSF12A; -.
DR DMDM; 21263626; -.
DR EPD; Q9NP84; -.
DR jPOST; Q9NP84; -.
DR MassIVE; Q9NP84; -.
DR MaxQB; Q9NP84; -.
DR PaxDb; Q9NP84; -.
DR PeptideAtlas; Q9NP84; -.
DR PRIDE; Q9NP84; -.
DR ProteomicsDB; 81927; -. [Q9NP84-1]
DR ProteomicsDB; 81928; -. [Q9NP84-2]
DR ABCD; Q9NP84; 1 sequenced antibody.
DR Antibodypedia; 2115; 506 antibodies from 43 providers.
DR DNASU; 51330; -.
DR Ensembl; ENST00000326577.9; ENSP00000326737.5; ENSG00000006327.14. [Q9NP84-1]
DR Ensembl; ENST00000341627.5; ENSP00000343894.5; ENSG00000006327.14. [Q9NP84-2]
DR GeneID; 51330; -.
DR KEGG; hsa:51330; -.
DR MANE-Select; ENST00000326577.9; ENSP00000326737.5; NM_016639.3; NP_057723.1.
DR UCSC; uc002csv.5; human. [Q9NP84-1]
DR CTD; 51330; -.
DR DisGeNET; 51330; -.
DR GeneCards; TNFRSF12A; -.
DR HGNC; HGNC:18152; TNFRSF12A.
DR HPA; ENSG00000006327; Low tissue specificity.
DR MIM; 605914; gene.
DR neXtProt; NX_Q9NP84; -.
DR OpenTargets; ENSG00000006327; -.
DR PharmGKB; PA134976874; -.
DR VEuPathDB; HostDB:ENSG00000006327; -.
DR eggNOG; ENOG502SFZC; Eukaryota.
DR GeneTree; ENSGT00390000001948; -.
DR InParanoid; Q9NP84; -.
DR OMA; HSDFCRG; -.
DR OrthoDB; 1502512at2759; -.
DR PhylomeDB; Q9NP84; -.
DR TreeFam; TF337901; -.
DR PathwayCommons; Q9NP84; -.
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; Q9NP84; -.
DR SIGNOR; Q9NP84; -.
DR BioGRID-ORCS; 51330; 22 hits in 1080 CRISPR screens.
DR ChiTaRS; TNFRSF12A; human.
DR EvolutionaryTrace; Q9NP84; -.
DR GeneWiki; TNFRSF12A; -.
DR GenomeRNAi; 51330; -.
DR Pharos; Q9NP84; Tbio.
DR PRO; PR:Q9NP84; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NP84; protein.
DR Bgee; ENSG00000006327; Expressed in apex of heart and 178 other tissues.
DR ExpressionAtlas; Q9NP84; baseline and differential.
DR Genevisible; Q9NP84; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0061041; P:regulation of wound healing; IDA:UniProtKB.
DR CDD; cd13413; TNFRSF12A; 1.
DR InterPro; IPR022316; TNFR_12.
DR PANTHER; PTHR32037; PTHR32037; 1.
DR Pfam; PF12191; stn_TNFRSF12A; 1.
DR PRINTS; PR01962; TNFACTORR12.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Apoptosis; Cell adhesion;
KW Developmental protein; Differentiation; Disulfide bond; Membrane; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..129
FT /note="Tumor necrosis factor receptor superfamily member
FT 12A"
FT /id="PRO_0000034611"
FT TOPO_DOM 28..80
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 36..67
FT /note="TNFR-Cys; atypical"
FT DISULFID 36..49
FT /evidence="ECO:0000269|PubMed:19241374"
FT DISULFID 52..67
FT /evidence="ECO:0000269|PubMed:19241374"
FT DISULFID 55..64
FT /evidence="ECO:0000269|PubMed:19241374"
FT VAR_SEQ 33..67
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_006519"
FT HELIX 30..33
FT /evidence="ECO:0007829|PDB:2EQP"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:2EQP"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:2EQP"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2EQP"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:2EQP"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:2EQP"
SQ SEQUENCE 129 AA; 13911 MW; BF3FDFB9C1E1C448 CRC64;
MARGSLRRLL RLLVLGLWLA LLRSVAGEQA PGTAPCSRGS SWSADLDKCM DCASCRARPH
SDFCLGCAAA PPAPFRLLWP ILGGALSLTF VLGLLSGFLV WRRCRRREKF TTPIEETGGE
GCPAVALIQ
