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Protein

Tumor necrosis factor receptor superfamily member 12A

Gene

TNFRSF12A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins.1 Publication

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. extrinsic apoptotic signaling pathway Source: Ensembl
  3. positive regulation of apoptotic process Source: UniProtKB
  4. positive regulation of axon extension Source: Ensembl
  5. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  6. regulation of angiogenesis Source: Ensembl
  7. regulation of wound healing Source: UniProtKB
  8. substrate-dependent cell migration, cell attachment to substrate Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Angiogenesis, Apoptosis, Cell adhesion, Differentiation

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 12A
Alternative name(s):
Fibroblast growth factor-inducible immediate-early response protein 14
Short name:
FGF-inducible 14
Tweak-receptor
Short name:
TweakR
CD_antigen: CD266
Gene namesi
Name:TNFRSF12A
Synonyms:FN14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:18152. TNFRSF12A.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 8053ExtracellularSequence AnalysisAdd
BLAST
Transmembranei81 – 10121HelicalSequence AnalysisAdd
BLAST
Topological domaini102 – 12928CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: Ensembl
  4. ruffle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134976874.

Polymorphism and mutation databases

BioMutaiTNFRSF12A.
DMDMi21263626.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 129102Tumor necrosis factor receptor superfamily member 12APRO_0000034611Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi36 ↔ 491 Publication
Disulfide bondi52 ↔ 671 Publication
Disulfide bondi55 ↔ 641 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiQ9NP84.
PaxDbiQ9NP84.
PeptideAtlasiQ9NP84.
PRIDEiQ9NP84.

PTM databases

PhosphoSiteiQ9NP84.

Expressioni

Tissue specificityi

Highly expressed in heart, placenta and kidney. Intermediate expression in lung, skeletal muscle and pancreas.

Inductioni

By FGF1 and phorbol ester.

Gene expression databases

BgeeiQ9NP84.
CleanExiHS_TNFRSF12A.
ExpressionAtlasiQ9NP84. baseline and differential.
GenevestigatoriQ9NP84.

Organism-specific databases

HPAiCAB015941.
HPA007853.

Interactioni

Subunit structurei

Associates with TRAF1 and TRAF2, and probably also with TRAF3.

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC2Q134902EBI-2851995,EBI-514538
SLC30A2Q9BRI33EBI-2851995,EBI-8644112
TNFSF12O435082EBI-2851995,EBI-6932080
TRAF2Q129333EBI-2851995,EBI-355744

Protein-protein interaction databases

BioGridi119478. 7 interactions.
IntActiQ9NP84. 5 interactions.
MINTiMINT-8415044.
STRINGi9606.ENSP00000326737.

Structurei

Secondary structure

1
129
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi30 – 334Combined sources
Beta strandi41 – 433Combined sources
Turni44 – 474Combined sources
Beta strandi48 – 503Combined sources
Helixi52 – 576Combined sources
Helixi62 – 654Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EQPNMR-A28-70[»]
2KMZNMR-A28-80[»]
2RPJNMR-A28-70[»]
SMRiQ9NP84. Positions 28-80.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NP84.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati36 – 6732TNFR-Cys; atypicalAdd
BLAST

Sequence similaritiesi

Contains 1 TNFR-Cys repeat.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG39144.
GeneTreeiENSGT00390000001948.
HOGENOMiHOG000154660.
HOVERGENiHBG031553.
InParanoidiQ9NP84.
KOiK05149.
OMAiMDCASCP.
PhylomeDBiQ9NP84.
TreeFamiTF337901.

Family and domain databases

InterProiIPR022316. TNFR_12.
[Graphical view]
PfamiPF12191. stn_TNFRSF12A. 1 hit.
[Graphical view]
PRINTSiPR01962. TNFACTORR12.
ProDomiPD336131. TNFR_12. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NP84-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MARGSLRRLL RLLVLGLWLA LLRSVAGEQA PGTAPCSRGS SWSADLDKCM
60 70 80 90 100
DCASCRARPH SDFCLGCAAA PPAPFRLLWP ILGGALSLTF VLGLLSGFLV
110 120
WRRCRRREKF TTPIEETGGE GCPAVALIQ
Length:129
Mass (Da):13,911
Last modified:October 1, 2000 - v1
Checksum:iBF3FDFB9C1E1C448
GO
Isoform 2 (identifier: Q9NP84-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-67: Missing.

Show »
Length:94
Mass (Da):10,191
Checksum:iE3C52B1308DC768F
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei33 – 6735Missing in isoform 2. 1 PublicationVSP_006519Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF191148 mRNA. Translation: AAF69108.1.
AB035480 mRNA. Translation: BAA94792.1.
AB035481 mRNA. Translation: BAB17850.1.
CH471112 Genomic DNA. Translation: EAW85429.1.
CH471112 Genomic DNA. Translation: EAW85430.1.
BC002718 mRNA. Translation: AAH02718.1.
CCDSiCCDS10489.1. [Q9NP84-1]
RefSeqiNP_057723.1. NM_016639.2. [Q9NP84-1]
UniGeneiHs.355899.

Genome annotation databases

EnsembliENST00000326577; ENSP00000326737; ENSG00000006327. [Q9NP84-1]
ENST00000341627; ENSP00000343894; ENSG00000006327. [Q9NP84-2]
GeneIDi51330.
KEGGihsa:51330.
UCSCiuc002csv.4. human. [Q9NP84-1]
uc002csw.4. human. [Q9NP84-2]

Polymorphism and mutation databases

BioMutaiTNFRSF12A.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF191148 mRNA. Translation: AAF69108.1.
AB035480 mRNA. Translation: BAA94792.1.
AB035481 mRNA. Translation: BAB17850.1.
CH471112 Genomic DNA. Translation: EAW85429.1.
CH471112 Genomic DNA. Translation: EAW85430.1.
BC002718 mRNA. Translation: AAH02718.1.
CCDSiCCDS10489.1. [Q9NP84-1]
RefSeqiNP_057723.1. NM_016639.2. [Q9NP84-1]
UniGeneiHs.355899.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EQPNMR-A28-70[»]
2KMZNMR-A28-80[»]
2RPJNMR-A28-70[»]
SMRiQ9NP84. Positions 28-80.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119478. 7 interactions.
IntActiQ9NP84. 5 interactions.
MINTiMINT-8415044.
STRINGi9606.ENSP00000326737.

Chemistry

GuidetoPHARMACOLOGYi1884.

PTM databases

PhosphoSiteiQ9NP84.

Polymorphism and mutation databases

BioMutaiTNFRSF12A.
DMDMi21263626.

Proteomic databases

MaxQBiQ9NP84.
PaxDbiQ9NP84.
PeptideAtlasiQ9NP84.
PRIDEiQ9NP84.

Protocols and materials databases

DNASUi51330.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000326577; ENSP00000326737; ENSG00000006327. [Q9NP84-1]
ENST00000341627; ENSP00000343894; ENSG00000006327. [Q9NP84-2]
GeneIDi51330.
KEGGihsa:51330.
UCSCiuc002csv.4. human. [Q9NP84-1]
uc002csw.4. human. [Q9NP84-2]

Organism-specific databases

CTDi51330.
GeneCardsiGC16P003155.
HGNCiHGNC:18152. TNFRSF12A.
HPAiCAB015941.
HPA007853.
MIMi605914. gene.
neXtProtiNX_Q9NP84.
PharmGKBiPA134976874.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39144.
GeneTreeiENSGT00390000001948.
HOGENOMiHOG000154660.
HOVERGENiHBG031553.
InParanoidiQ9NP84.
KOiK05149.
OMAiMDCASCP.
PhylomeDBiQ9NP84.
TreeFamiTF337901.

Miscellaneous databases

ChiTaRSiTNFRSF12A. human.
EvolutionaryTraceiQ9NP84.
GeneWikiiTNFRSF12A.
GenomeRNAii51330.
NextBioi54743.
PROiQ9NP84.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NP84.
CleanExiHS_TNFRSF12A.
ExpressionAtlasiQ9NP84. baseline and differential.
GenevestigatoriQ9NP84.

Family and domain databases

InterProiIPR022316. TNFR_12.
[Graphical view]
PfamiPF12191. stn_TNFRSF12A. 1 hit.
[Graphical view]
PRINTSiPR01962. TNFACTORR12.
ProDomiPD336131. TNFR_12. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas."
    Feng S.-L.Y., Guo Y., Factor V.M., Thorgeirsson S.S., Bell D.W., Testa J.R., Peifley K.A., Winkles J.A.
    Am. J. Pathol. 156:1253-1261(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Placenta.
  2. "Human homologue of Fn14."
    Tanaka S., Sugimachi K.
    Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Uterus.
  5. "A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis."
    Wiley S.R., Cassiano L., Lofton T., Davis-Smith T., Winkles J.A., Lindner V., Liu H., Daniel T.O., Smith C.A., Fanslow W.C.
    Immunity 15:837-846(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Solution structure of the STN_TNFRSF12A_TNFR domain of tumor necrosis factor receptor superfamily member 12A precursor."
    RIKEN structural genomics initiative (RSGI)
    Submitted (APR-2008) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 26-70.
  7. "Solution structure of the cysteine-rich domain in Fn14, a member of the tumor necrosis factor receptor superfamily."
    He F., Dang W., Saito K., Watanabe S., Kobayashi N., Guntert P., Kigawa T., Tanaka A., Muto Y., Yokoyama S.
    Protein Sci. 18:650-656(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 26-70, DISULFIDE BONDS.

Entry informationi

Entry nameiTNR12_HUMAN
AccessioniPrimary (citable) accession number: Q9NP84
Secondary accession number(s): D3DUA6, Q9HCS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 27, 2002
Last sequence update: October 1, 2000
Last modified: April 29, 2015
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.