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P50591 (TNF10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tumor necrosis factor ligand superfamily member 10
Alternative name(s):
Apo-2 ligand
Short name=Apo-2L
TNF-related apoptosis-inducing ligand
Short name=Protein TRAIL
CD_antigen=CD253
Gene names
Name:TNFSF10
Synonyms:APO2L, TRAIL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length281 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.

Cofactor

Binds 1 zinc ion per trimer.

Subunit structure

Homotrimer.

Subcellular location

Membrane; Single-pass type II membrane protein Potential.

Tissue specificity

Widespread; most predominant in spleen, lung and prostate.

Sequence similarities

Belongs to the tumor necrosis factor family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionCytokine
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

immune response

Inferred from electronic annotation. Source: InterPro

male gonad development

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern PubMed 12761501. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 21525171. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 21459798PubMed 21525171PubMed 22266862. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 20097879PubMed 21525171PubMed 22266862. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from direct assay PubMed 22266862. Source: UniProtKB

regulation of extrinsic apoptotic signaling pathway in absence of ligand

Traceable author statement. Source: Reactome

response to insulin

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.2Ref.1. Source: ProtInc

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of plasma membrane

Traceable author statement Ref.2. Source: ProtInc

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

receptor binding

Traceable author statement Ref.2Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P50591-1)

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: P50591-2)

Also known as: TRAIL-short; TRAIL-s;

The sequence of this isoform differs from the canonical sequence as follows:
     91-101: MILRTSEETIS → TPRMKRLWAAK
     102-281: Missing.
Note: Induced upon HIV infection, antagonizes signaling via TRAIL receptor R2 (TNFRSF10B).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 281281Tumor necrosis factor ligand superfamily member 10
PRO_0000185503

Regions

Topological domain1 – 1717Cytoplasmic Potential
Transmembrane18 – 3821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain39 – 281243Extracellular Potential

Sites

Metal binding2301Zinc

Natural variations

Alternative sequence91 – 10111MILRTSEETIS → TPRMKRLWAAK in isoform 2.
VSP_043507
Alternative sequence102 – 281180Missing in isoform 2.
VSP_043508
Natural variant331V → I.
Corresponds to variant rs6763816 [ dbSNP | Ensembl ].
VAR_052584
Natural variant471D → E.
Corresponds to variant rs16845759 [ dbSNP | Ensembl ].
VAR_052585

Secondary structure

............................... 281
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: DDAAAF78DAAB2F6D

FASTA28132,509
        10         20         30         40         50         60 
MAMMEVQGGP SLGQTCVLIV IFTVLLQSLC VAVTYVYFTN ELKQMQDKYS KSGIACFLKE 

        70         80         90        100        110        120 
DDSYWDPNDE ESMNSPCWQV KWQLRQLVRK MILRTSEETI STVQEKQQNI SPLVRERGPQ 

       130        140        150        160        170        180 
RVAAHITGTR GRSNTLSSPN SKNEKALGRK INSWESSRSG HSFLSNLHLR NGELVIHEKG 

       190        200        210        220        230        240 
FYYIYSQTYF RFQEEIKENT KNDKQMVQYI YKYTSYPDPI LLMKSARNSC WSKDAEYGLY 

       250        260        270        280 
SIYQGGIFEL KENDRIFVSV TNEHLIDMDH EASFFGAFLV G 

« Hide

Isoform 2 (TRAIL-short) (TRAIL-s) [UniParc].

Checksum: 205B6BA004A7C104
Show »

FASTA10111,746

References

« Hide 'large scale' references
[1]"Identification and characterization of a new member of the TNF family that induces apoptosis."
Wiley S.R., Schooley K., Smolak P.J., Din W.S., Huang C.-P., Nicholl J.K., Sutherland G.R., Davis-Smith T., Rauch C., Smith C.A., Goodwin R.G.
Immunity 3:673-682(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family."
Pitti R.M., Marsters S.A., Ruppert S., Donahue C.J., Moore A., Ashkenazi A.
J. Biol. Chem. 271:12687-12690(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[3]"Isolation of a TRAIL antagonist from the serum of HIV-infected patients."
Schnepple D.J., Shepard B., Bren G.D., Cummins N.W., Natesampillai S., Trushin S., Algeciras-Schimnich A., Meng X.W., Sainski A.M., Rizza S.A., Kaufmann S.H., Badley A.D.
J. Biol. Chem. 286:35742-35754(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[4]"Novel TRAIL splice variant TRAIL-delta."
Woods D.C., Haugen M.J., Johnson A.L.
Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Thalamus.
[6]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Lymph.
[8]"Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5."
Hymowitz S.G., Christinger H.W., Fuh G., Ultsch M., O'Connell M., Kelley R.F., Ashkenazi A., de Vos A.M.
Mol. Cell 4:563-571(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 114-281.
[9]"Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation."
Mongkolsapaya J., Grimes J.M., Chen N., Xu X.-N., Stuart D.I., Jones E.Y., Screaton G.R.
Nat. Struct. Biol. 6:1048-1053(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 119-281.
[10]"2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity."
Cha S.-S., Kim M.S., Choi Y.H., Sung B.J., Shin N.K., Shin H.C., Sung Y.C., Oh B.-H.
Immunity 11:253-261(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 114-281.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U37518 mRNA. Translation: AAC50332.1.
U57059 mRNA. Translation: AAB01233.1.
DQ848564 mRNA. Translation: ABI24016.1.
EU183231 mRNA. Translation: ABW24658.1.
AK296085 mRNA. Translation: BAG58840.1.
AC007919 Genomic DNA. No translation available.
AC016938 Genomic DNA. No translation available.
BC032722 mRNA. Translation: AAH32722.1.
RefSeqNP_001177871.1. NM_001190942.1.
NP_003801.1. NM_003810.3.
UniGeneHs.478275.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1D0GX-ray2.40A/B/D114-281[»]
1D2QX-ray2.80A/B114-281[»]
1D4VX-ray2.20B119-281[»]
1DG6X-ray1.30A91-281[»]
1DU3X-ray2.20D/E/F/J/K/L114-281[»]
ProteinModelPortalP50591.
SMRP50591. Positions 119-281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114280. 14 interactions.
DIPDIP-6230N.
IntActP50591. 16 interactions.
MINTMINT-109168.
STRING9606.ENSP00000241261.

Chemistry

BindingDBP50591.
ChEMBLCHEMBL5813.

PTM databases

PhosphoSiteP50591.

Polymorphism databases

DMDM1730015.

Proteomic databases

PaxDbP50591.
PRIDEP50591.

Protocols and materials databases

DNASU8743.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000241261; ENSP00000241261; ENSG00000121858. [P50591-1]
ENST00000420541; ENSP00000389931; ENSG00000121858. [P50591-2]
GeneID8743.
KEGGhsa:8743.
UCSCuc003fid.3. human. [P50591-1]
uc003fie.3. human. [P50591-2]

Organism-specific databases

CTD8743.
GeneCardsGC03M172223.
HGNCHGNC:11925. TNFSF10.
HPACAB002446.
MIM603598. gene.
neXtProtNX_P50591.
PharmGKBPA36618.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46547.
HOGENOMHOG000230484.
HOVERGENHBG059007.
KOK04721.
OMAQTCVLIL.
PhylomeDBP50591.
TreeFamTF332169.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP50591.
BgeeP50591.
CleanExHS_TNFSF10.
GenevestigatorP50591.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR017355. TNF_ligand_10/11.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
PIRSFPIRSF038013. TNF10_TNF11. 1 hit.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNFSF10. human.
EvolutionaryTraceP50591.
GeneWikiTRAIL.
GenomeRNAi8743.
NextBio32805.
PROP50591.
SOURCESearch...

Entry information

Entry nameTNF10_HUMAN
AccessionPrimary (citable) accession number: P50591
Secondary accession number(s): A1Y9B3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries