Tumor necrosis factor ligand superfamily member 12

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Reviewed, UniProtKB/Swiss-Prot O43508 (TNF12_HUMAN)

Last modified November 25, 2008. Version 78. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Tumor necrosis factor ligand superfamily member 12
Alternative name(s):
    TNF-related weak inducer of apoptosis
      Short name=TWEAK
    APO3 ligand
Cleaved into the following 2 chains:
    1- Recommended name:
            Tumor necrosis factor ligand superfamily member 12, membrane form
    2- Recommended name:
            Tumor necrosis factor ligand superfamily member 12, secreted form

Gene names

Name:	TNFSF12
Synonyms:	APO3L, DR3LG
ORF Names:	UNQ181/PRO207

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	249 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines.
Subunit structure	Homotrimer Potential. Interacts with the angiogenic factor AGGF1/VG5Q.
Subcellular location	Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor ligand superfamily member 12, secreted form: Secreted.
Tissue specificity	Highly expressed in adult heart, pancreas, skeletal muscle, brain, colon, small intestine, lung, ovary, prostate, spleen, lymph node, appendix and peripheral blood lymphocytes. Low expression in kidney, testis, liver, placenta, thymus and bone marrow. Also detected in fetal kidney, liver, lung and brain.
Post-translational modification	The soluble form derives from the membrane form by proteolytic processing.
Sequence similarities	Belongs to the tumor necrosis factor family.
Sequence caution	The sequence AAH19047.1 differs from that shown. Reason: Frameshift at position 125.

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Ontologies

Keywords
Biological process	Angiogenesis Apoptosis Differentiation
Cellular component	Cell membrane Membrane Secreted
Domain	Signal-anchor Transmembrane
Molecular function	Cytokine Developmental protein
PTM	Cleavage on pair of basic residues Glycoprotein
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW endothelial cell migration Ref.6 Traceable author statement. Source: UniProtKB immune response Inferred from electronic annotation. Source: InterPro induction of apoptosis Ref.2 Traceable author statement. Source: ProtInc positive regulation of angiogenesis Ref.6 Traceable author statement. Source: UniProtKB positive regulation of endothelial cell proliferation Ref.6 Traceable author statement. Source: UniProtKB signal transduction Ref.2 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc perinuclear region of cytoplasm Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 249

249

Tumor necrosis factor ligand superfamily member 12, membrane form

PRO_0000034520

Chain

94 – 249

156

Tumor necrosis factor ligand superfamily member 12, secreted form

PRO_0000034521

Regions

Topological domain

1 – 21

Cytoplasmic Potential

Transmembrane

22 – 42

Signal-anchor for type II membrane protein Potential

Topological domain

43 – 249

207

Extracellular Potential

Sites

Site

93 – 94

Cleavage

Amino acid modifications

Glycosylation

139

N-linked (GlcNAc...)

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Sequences

Sequence

Length

Mass (Da)

Tools

O43508-1 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: E660843361C28EBA
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FASTA

249

27,216

        10         20         30         40         50         60 
MAARRSQRRR GRRGEPGTAL LVPLALGLGL ALACLGLLLA VVSLGSRASL SAQEPAQEEL 

        70         80         90        100        110        120 
VAEEDQDPSE LNPQTEESQD PAPFLNRLVR PRRSAPKGRK TRARRAIAAH YEVHPRPGQD 

       130        140        150        160        170        180 
GAQAGVDGTV SGWEEARINS SSPLRYNRQI GEFIVTRAGL YYLYCQVHFD EGKAVYLKLD 

       190        200        210        220        230        240 
LLVDGVLALR CLEEFSATAA SSLGPQLRLC QVSGLLALRP GSSLRIRTLP WAHLKAAPFL 


TYFGLFQVH

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis." Chicheportiche Y., Bourdon P.R., Xu H., Hsu Y.-M., Scott H., Hession C., Garcia I., Browning J.L. J. Biol. Chem. 272:32401-32410(1997) [PubMed: 9405449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], N-TERMINUS OF SOLUBLE FORM. Tissue: Fetal liver and Tonsil.
[2]	"Identification of a ligand for the death-domain-containing receptor Apo3." Marsters S.A., Sheridan J.P., Pitti R.M., Brush J., Goddard A., Ashkenazi A. Curr. Biol. 8:525-528(1998) [PubMed: 9560343] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal kidney.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tonsil.
[5]	"TWEAK induces angiogenesis and proliferation of endothelial cells." Lynch C.N., Wang Y.C., Lund J.K., Chen Y.-W., Leal J.A., Wiley S.R. J. Biol. Chem. 274:8455-8459(1999) [PubMed: 10085077] [Abstract] Cited for: FUNCTION.
[6]	"Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome." Tian X.-L., Kadaba R., You S.-A., Liu M., Timur A.A., Yang L., Chen Q., Szafranski P., Rao S., Wu L., Housman D.E., DiCorleto P.E., Driscoll D.J., Borrow J., Wang Q. Nature 427:640-645(2004) [PubMed: 14961121] [Abstract] Cited for: INTERACTION WITH AGGF1/VG5Q.
[7]	"TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor." Wiley S.R., Winkles J.A. Cytokine Growth Factor Rev. 14:241-249(2003) [PubMed: 12787562] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF030099 mRNA. Translation: AAC51923.1. AF055872 mRNA. Translation: AAC39724.1. AY358870 mRNA. Translation: AAQ89229.1. BC019047 mRNA. Translation: AAH19047.1. Frameshift.
RefSeq	NP_003800.1.
UniGene	Hs.54673
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000161955. Homo sapiens. [Contig view]
GeneID	8742.
KEGG	hsa:8742.
Organism-specific databases
HGNC	HGNC:11927. TNFSF12.
MIM	602695. gene.
PharmGKB	PA36620.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	O43508.
Gene expression databases
ArrayExpress	O43508.
GermOnline	ENSG00000161955. Homo sapiens.
Family and domain databases
InterPro	IPR006052. TNF_family. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
SMART	SM00207. TNF. 1 hit. [Graphical view]
PROSITE	PS00251. TNF_1. False negative. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32801.
SOURCE	Search...

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Entry information

Entry name

TNF12_HUMAN

Accession

Primary (citable) accession number: O43508
Secondary accession number(s): Q8WUZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	June 1, 1998
Last modified:	November 25, 2008
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents