Q9NP84 (TNR12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	TNFRSF12A
Synonyms:	FN14

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	129 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5
Subunit structure	Associates with TRAF1 and TRAF2, and probably also with TRAF3.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Highly expressed in heart, placenta and kidney. Intermediate expression in lung, skeletal muscle and pancreas.
Induction	By FGF1 and phorbol ester.
Sequence similarities	Contains 1 TNFR-Cys repeat.

Ontologies

Keywords
Biological process	Angiogenesis Apoptosis Cell adhesion Differentiation
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cellular component movement Traceable author statement PubMed 10551889. Source: ProtInc induction of apoptosis Inferred from direct assay PubMed 21525013. Source: UniProtKB multicellular organismal development Traceable author statement PubMed 10551889. Source: ProtInc positive regulation of axon extension Inferred from electronic annotation. Source: Compara positive regulation of extrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 21525013. Source: UniProtKB substrate-dependent cell migration, cell attachment to substrate Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: Compara ruffle Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC2	Q13490	2	EBI-2851995,EBI-514538
TRAF2	Q12933	3	EBI-2851995,EBI-355744

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NP84-1)

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.

Isoform 2 (identifier: Q9NP84-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 129

102

Tumor necrosis factor receptor superfamily member 12A

PRO_0000034611

Regions

Topological domain

28 – 80

53

Extracellular Potential

Transmembrane

81 – 101

21

Helical; Potential

Topological domain

102 – 129

28

Cytoplasmic Potential

Repeat

36 – 67

32

TNFR-Cys; atypical

Amino acid modifications

Disulfide bond

36 ↔ 49

Ref.7

Disulfide bond

52 ↔ 67

Ref.7

Disulfide bond

55 ↔ 64

Ref.7

Natural variations

Alternative sequence

33 – 67

35

Missing in isoform 2.

VSP_006519

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

129

Helix Strand Turn

Details...

Helix

30 – 33

4

Beta strand

41 – 43

3

Turn

44 – 47

4

Beta strand

48 – 50

3

Helix

52 – 57

6

Helix

62 – 65

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: BF3FDFB9C1E1C448	FASTA	129	13,911
	10 20 30 40 50 60 MARGSLRRLL RLLVLGLWLA LLRSVAGEQA PGTAPCSRGS SWSADLDKCM DCASCRARPH 70 80 90 100 110 120 SDFCLGCAAA PPAPFRLLWP ILGGALSLTF VLGLLSGFLV WRRCRRREKF TTPIEETGGE GCPAVALIQ
	Isoform 2 [UniParc]. Checksum: E3C52B1308DC768F	FASTA	94	10,191
	10 20 30 40 50 60 MARGSLRRLL RLLVLGLWLA LLRSVAGEQA PGAAAPPAPF RLLWPILGGA LSLTFVLGLL 70 80 90 SGFLVWRRCR RREKFTTPIE ETGGEGCPAV ALIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00010277.
IPI00219878.

RefSeq

NP_057723.1. NM_016639.2.

UniGene

Hs.355899.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EQP	NMR	-	A	27-70	[»]
2KMZ	NMR	-	A	28-80	[»]
2RPJ	NMR	-	A	27-70	[»]

ProteinModelPortal

Q9NP84.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NP84. 3 interactions.

STRING

9606.ENSP00000326737.

PTM databases

PhosphoSite

Q9NP84.

Polymorphism databases

DMDM

21263626.

Proteomic databases

PaxDb

Q9NP84.

PeptideAtlas

Q9NP84.

PRIDE

Q9NP84.

Protocols and materials databases

DNASU

51330.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000326577; ENSP00000326737; ENSG00000006327.
ENST00000341627; ENSP00000343894; ENSG00000006327.

GeneID

51330.

KEGG

hsa:51330.

UCSC

uc002csv.4. human.
uc002csw.4. human.

Organism-specific databases

CTD

51330.

GeneCards

GC16P003091.

HGNC

HGNC:18152. TNFRSF12A.

HPA

CAB015941.
HPA007853.

MIM

605914. gene.

neXtProt

NX_Q9NP84.

PharmGKB

PA134976874.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39144.

HOGENOM

HOG000154660.

HOVERGEN

HBG031553.

KO

K05149.

OMA

MDCASCP.

OrthoDB

EOG4RR6JT.

PhylomeDB

Q9NP84.

Gene expression databases

ArrayExpress

Q9NP84.

Bgee

Q9NP84.

CleanEx

HS_TNFRSF12A.

Genevestigator

Q9NP84.

GermOnline

ENSG00000006327. Homo sapiens.

Family and domain databases

InterPro

IPR022316. TNFR_12.
[Graphical view]

Pfam

PF12191. stn_TNFRSF12A. 1 hit.
[Graphical view]

PRINTS

PR01962. TNFACTORR12.

ProDom

PD336131. TNFR_12. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00652. TNFR_NGFR_1. False negative.
PS50050. TNFR_NGFR_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TNFRSF12A. human.

EvolutionaryTrace

Q9NP84.

GenomeRNAi

51330.

NextBio

54743.

SOURCE

Search...

Entry information

Entry name

TNR12_HUMAN

Accession

Primary (citable) accession number: Q9NP84
Secondary accession number(s): D3DUA6, Q9HCS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.