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O43508

- TNF12_HUMAN

UniProt

O43508 - TNF12_HUMAN

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Protein

Tumor necrosis factor ligand superfamily member 12

Gene

TNFSF12

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

Functioni

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. Promotes IL8 secretion.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei93 – 942Cleavage

GO - Molecular functioni

  1. cytokine activity Source: UniProtKB
  2. receptor binding Source: ProtInc

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. apoptotic process Source: ProtInc
  3. apoptotic signaling pathway Source: UniProtKB
  4. cell differentiation Source: UniProtKB-KW
  5. endothelial cell migration Source: UniProtKB
  6. immune response Source: InterPro
  7. positive regulation of angiogenesis Source: UniProtKB
  8. positive regulation of endothelial cell proliferation Source: UniProtKB
  9. positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  10. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Developmental protein

Keywords - Biological processi

Angiogenesis, Apoptosis, Differentiation

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 12
Alternative name(s):
APO3 ligand
TNF-related weak inducer of apoptosis
Short name:
TWEAK
Cleaved into the following 2 chains:
Gene namesi
Name:TNFSF12
Synonyms:APO3L, DR3LG
ORF Names:UNQ181/PRO207
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:11927. TNFSF12.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2121CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei22 – 4221Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini43 – 249207ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
  2. integral component of plasma membrane Source: ProtInc
  3. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA162406662.
PA36620.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 249249Tumor necrosis factor ligand superfamily member 12, membrane formPRO_0000034520Add
BLAST
Chaini94 – 249156Tumor necrosis factor ligand superfamily member 12, secreted formPRO_0000034521Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi139 – 1391N-linked (GlcNAc...)
Disulfide bondi191 ↔ 2101 Publication

Post-translational modificationi

The soluble form derives from the membrane form by proteolytic processing.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43508.
PRIDEiO43508.

PTM databases

PhosphoSiteiO43508.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO43508.
ExpressionAtlasiO43508. baseline.
GenevestigatoriO43508.

Interactioni

Subunit structurei

Homotrimer (Probable). Interacts with the angiogenic factor AGGF1/VG5Q.2 PublicationsCurated

Binary interactionsi

WithEntry#Exp.IntActNotes
TNFRSF12AQ9NP842EBI-6932080,EBI-2851995
tnfrsf12aQ6SIX72EBI-6932080,EBI-8445678From a different organism.

Protein-protein interaction databases

BioGridi114279. 5 interactions.
IntActiO43508. 5 interactions.
MINTiMINT-8415042.
STRINGi9606.ENSP00000293826.

Structurei

Secondary structure

1
249
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi108 – 1136Combined sources
Beta strandi133 – 1353Combined sources
Beta strandi143 – 1464Combined sources
Turni148 – 1503Combined sources
Beta strandi153 – 1553Combined sources
Beta strandi159 – 17315Combined sources
Beta strandi175 – 1839Combined sources
Beta strandi186 – 1938Combined sources
Beta strandi205 – 21814Combined sources
Beta strandi223 – 2275Combined sources
Turni238 – 2403Combined sources
Beta strandi241 – 2477Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4HT1X-ray2.50T97-249[»]
ProteinModelPortaliO43508.
SMRiO43508. Positions 105-249.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45253.
GeneTreeiENSGT00530000063837.
HOGENOMiHOG000134435.
HOVERGENiHBG055510.
InParanoidiO43508.
KOiK05474.
OMAiRIMSFIE.
OrthoDBiEOG79KPGF.
PhylomeDBiO43508.
TreeFamiTF332331.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS50049. TNF_2. 1 hit.
[Graphical view]

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. Align

Isoform 1 (identifier: O43508-1) [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
MAARRSQRRR GRRGEPGTAL LVPLALGLGL ALACLGLLLA VVSLGSRASL
60 70 80 90 100
SAQEPAQEEL VAEEDQDPSE LNPQTEESQD PAPFLNRLVR PRRSAPKGRK
110 120 130 140 150
TRARRAIAAH YEVHPRPGQD GAQAGVDGTV SGWEEARINS SSPLRYNRQI
160 170 180 190 200
GEFIVTRAGL YYLYCQVHFD EGKAVYLKLD LLVDGVLALR CLEEFSATAA
210 220 230 240
SSLGPQLRLC QVSGLLALRP GSSLRIRTLP WAHLKAAPFL TYFGLFQVH
Length:249
Mass (Da):27,216
Last modified:June 1, 1998 - v1
Checksum:iE660843361C28EBA
GO
Isoform TWE-PRIL (identifier: O43508-2) [UniParc]FASTAAdd to Basket

Also known as: TNFSF12-TNFSF13

The sequence of this isoform differs from the canonical sequence as follows:
     167-249: VHFDEGKAVY...LTYFGLFQVH → SSDALEAWEN...HGTFLGFVKL

Note: Based on a readthrough transcript which may produce a TWE-PRIL (TNFSF12-TNFSF13) fusion protein. Expressed at protein level in primary T-lymphocytes and monocytic cell lines.

Show »
Length:330
Mass (Da):36,589
Checksum:iFC6F3BCA29C029AE
GO

Sequence cautioni

The sequence AAH19047.1 differs from that shown. Reason: Frameshift at position 125. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei167 – 24983VHFDE…LFQVH → SSDALEAWENGERSRKRRAV LTQKQKKQHSVLHLVPINAT SKDDSDVTEVMWQPALRRGR GLQAQGYGVRIQDAGVYLLY SQVLFQDVTFTMGQVVSREG QGRQETLFRCIRSMPSHPDR AYNSCYSAGVFHLHQGDILS VIIPRARAKLNLSPHGTFLG FVKL in isoform TWE-PRIL. 1 PublicationVSP_045245Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030099 mRNA. Translation: AAC51923.1.
AF055872 mRNA. Translation: AAC39724.1.
AY081051 mRNA. Translation: AAL90443.1.
AY358870 mRNA. Translation: AAQ89229.1.
AC016876 Genomic DNA. No translation available.
BC019047 mRNA. Translation: AAH19047.1. Frameshift.
CCDSiCCDS11109.1. [O43508-1]
RefSeqiNP_003800.1. NM_003809.2. [O43508-1]
NP_742086.1. NM_172089.3. [O43508-2]
UniGeneiHs.54673.

Genome annotation databases

EnsembliENST00000293825; ENSP00000293825; ENSG00000239697. [O43508-1]
GeneIDi407977.
8742.
KEGGihsa:407977.
hsa:8742.
UCSCiuc002ghg.3. human. [O43508-1]
uc002ghi.1. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030099 mRNA. Translation: AAC51923.1 .
AF055872 mRNA. Translation: AAC39724.1 .
AY081051 mRNA. Translation: AAL90443.1 .
AY358870 mRNA. Translation: AAQ89229.1 .
AC016876 Genomic DNA. No translation available.
BC019047 mRNA. Translation: AAH19047.1 . Frameshift.
CCDSi CCDS11109.1. [O43508-1 ]
RefSeqi NP_003800.1. NM_003809.2. [O43508-1 ]
NP_742086.1. NM_172089.3. [O43508-2 ]
UniGenei Hs.54673.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4HT1 X-ray 2.50 T 97-249 [» ]
ProteinModelPortali O43508.
SMRi O43508. Positions 105-249.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114279. 5 interactions.
IntActi O43508. 5 interactions.
MINTi MINT-8415042.
STRINGi 9606.ENSP00000293826.

PTM databases

PhosphoSitei O43508.

Proteomic databases

PaxDbi O43508.
PRIDEi O43508.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000293825 ; ENSP00000293825 ; ENSG00000239697 . [O43508-1 ]
GeneIDi 407977.
8742.
KEGGi hsa:407977.
hsa:8742.
UCSCi uc002ghg.3. human. [O43508-1 ]
uc002ghi.1. human.

Organism-specific databases

CTDi 407977.
8742.
GeneCardsi GC17P007452.
HGNCi HGNC:11927. TNFSF12.
MIMi 602695. gene.
neXtProti NX_O43508.
Orphaneti 1572. Common variable immunodeficiency.
PharmGKBi PA162406662.
PA36620.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45253.
GeneTreei ENSGT00530000063837.
HOGENOMi HOG000134435.
HOVERGENi HBG055510.
InParanoidi O43508.
KOi K05474.
OMAi RIMSFIE.
OrthoDBi EOG79KPGF.
PhylomeDBi O43508.
TreeFami TF332331.

Miscellaneous databases

GeneWikii TNFSF12.
TNFSF12-TNFSF13.
NextBioi 108346.
PROi O43508.
SOURCEi Search...

Gene expression databases

Bgeei O43508.
ExpressionAtlasi O43508. baseline.
Genevestigatori O43508.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Fetal kidney.
  3. "An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein."
    Pradet-Balade B., Medema J.P., Lopez-Fraga M., Lozano J.C., Kolfschoten G.M., Picard A., Martinez-A C., Garcia-Sanz J.A., Hahne M.
    EMBO J. 21:5711-5720(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TWE-PRIL), SUBCELLULAR LOCATION.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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: Tonsil.
  7. "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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AGGF1/VG5Q.
  9. "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] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. "Crystal structure of human TWEAK in complex with the Fab fragment of a neutralizing antibody reveals insights into receptor binding."
    Lammens A., Baehner M., Kohnert U., Niewoehner J., von Proff L., Schraeml M., Lammens K., Hopfner K.P.
    PLoS ONE 8:E62697-E62697(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 97-249 IN COMPLEX WITH THE FAB FRAGMENT OF A NEUTRALIZING ANTIBODY, FUNCTION, SUBUNIT, DISULFIDE BOND.

Entry informationi

Entry nameiTNF12_HUMAN
AccessioniPrimary (citable) accession number: O43508
Secondary accession number(s): Q8IZK7, Q8WUZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: June 1, 1998
Last modified: November 26, 2014
This is version 132 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 chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3