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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

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Angiogenesis, Apoptosis, Cell adhesion, Differentiation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006327-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:18152. TNFRSF12A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 80ExtracellularSequence analysisAdd BLAST53
Transmembranei81 – 101HelicalSequence analysisAdd BLAST21
Topological domaini102 – 129CytoplasmicSequence analysisAdd BLAST28

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi51330.
OpenTargetsiENSG00000006327.
PharmGKBiPA134976874.

Polymorphism and mutation databases

BioMutaiTNFRSF12A.
DMDMi21263626.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000003461128 – 129Tumor necrosis factor receptor superfamily member 12AAdd BLAST102

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 491 Publication
Disulfide bondi52 ↔ 671 Publication
Disulfide bondi55 ↔ 641 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ9NP84.
MaxQBiQ9NP84.
PaxDbiQ9NP84.
PeptideAtlasiQ9NP84.
PRIDEiQ9NP84.

PTM databases

PhosphoSitePlusiQ9NP84.
SwissPalmiQ9NP84.

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

BgeeiENSG00000006327.
CleanExiHS_TNFRSF12A.
ExpressionAtlasiQ9NP84. baseline and differential.
GenevisibleiQ9NP84. HS.

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
SLC30A2Q9BRI35EBI-2851995,EBI-8644112
TNFSF12O435082EBI-2851995,EBI-6932080
TRAF2Q129333EBI-2851995,EBI-355744

Protein-protein interaction databases

BioGridi119478. 4 interactors.
IntActiQ9NP84. 5 interactors.
MINTiMINT-8415044.
STRINGi9606.ENSP00000326737.

Structurei

Secondary structure

1129
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 33Combined sources4
Beta strandi41 – 43Combined sources3
Turni44 – 47Combined sources4
Beta strandi48 – 50Combined sources3
Helixi52 – 57Combined sources6
Helixi62 – 65Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EQPNMR-A28-70[»]
2KMZNMR-A28-80[»]
2RPJNMR-A28-70[»]
ProteinModelPortaliQ9NP84.
SMRiQ9NP84.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NP84.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati36 – 67TNFR-Cys; atypicalAdd BLAST32

Sequence similaritiesi

Contains 1 TNFR-Cys repeat.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IYHX. Eukaryota.
ENOG41116AK. LUCA.
GeneTreeiENSGT00390000001948.
HOGENOMiHOG000154660.
HOVERGENiHBG031553.
InParanoidiQ9NP84.
KOiK05149.
OMAiMDCASCP.
PhylomeDBiQ9NP84.
TreeFamiTF337901.

Family and domain databases

CDDicd13413. TNFRSF12A. 1 hit.
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00651933 – 67Missing in isoform 2. 1 PublicationAdd BLAST35

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.5. human. [Q9NP84-1]

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EQPNMR-A28-70[»]
2KMZNMR-A28-80[»]
2RPJNMR-A28-70[»]
ProteinModelPortaliQ9NP84.
SMRiQ9NP84.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119478. 4 interactors.
IntActiQ9NP84. 5 interactors.
MINTiMINT-8415044.
STRINGi9606.ENSP00000326737.

PTM databases

PhosphoSitePlusiQ9NP84.
SwissPalmiQ9NP84.

Polymorphism and mutation databases

BioMutaiTNFRSF12A.
DMDMi21263626.

Proteomic databases

EPDiQ9NP84.
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.5. human. [Q9NP84-1]

Organism-specific databases

CTDi51330.
DisGeNETi51330.
GeneCardsiTNFRSF12A.
HGNCiHGNC:18152. TNFRSF12A.
HPAiCAB015941.
HPA007853.
MIMi605914. gene.
neXtProtiNX_Q9NP84.
OpenTargetsiENSG00000006327.
PharmGKBiPA134976874.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYHX. Eukaryota.
ENOG41116AK. LUCA.
GeneTreeiENSGT00390000001948.
HOGENOMiHOG000154660.
HOVERGENiHBG031553.
InParanoidiQ9NP84.
KOiK05149.
OMAiMDCASCP.
PhylomeDBiQ9NP84.
TreeFamiTF337901.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006327-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000006327.
CleanExiHS_TNFRSF12A.
ExpressionAtlasiQ9NP84. baseline and differential.
GenevisibleiQ9NP84. HS.

Family and domain databases

CDDicd13413. TNFRSF12A. 1 hit.
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...

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: November 30, 2016
This is version 137 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

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 one 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.