[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1016/1074-7613(95)90057-8; PubMed=8777713 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Identification and characterization of a new member of the TNF family that induces apoptosis."; Immunity 3:673-682(1995).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Placenta; DOI=10.1074/jbc.271.22.12687; PubMed=8663110 [NCBI, ExPASy, EBI, Israel, Japan] Pitti R.M., Marsters S.A., Ruppert S., Donahue C.J., Moore A., Ashkenazi A.; "Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family."; J. Biol. Chem. 271:12687-12690(1996).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Lymph; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 114-281. DOI=10.1016/S1097-2765(00)80207-5; PubMed=10549288 [NCBI, ExPASy, EBI, Israel, Japan] Hymowitz S.G., Christinger H.W., Fuh G., Ultsch M., O'Connell M., Kelley R.F., Ashkenazi A., de Vos A.M.; "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5."; Mol. Cell 4:563-571(1999).
[5]	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 119-281. DOI=10.1038/14935; PubMed=10542098 [NCBI, ExPASy, EBI, Israel, Japan] Mongkolsapaya J., Grimes J.M., Chen N., Xu X.-N., Stuart D.I., Jones E.Y., Screaton G.R.; "Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation."; Nat. Struct. Biol. 6:1048-1053(1999).
[6]	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 114-281. DOI=10.1016/S1074-7613(00)80100-4; PubMed=10485660 [NCBI, ExPASy, EBI, Israel, Japan] Cha S.-S., Kim M.S., Choi Y.H., Sung B.J., Shin N.K., Shin H.C., Sung Y.C., Oh B.-H.; "2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity."; Immunity 11:253-261(1999).

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: Homotrimer.
SUBCELLULAR LOCATION: Membrane; Single-pass type II membrane protein (Potential).
TISSUE SPECIFICITY: Widespread; most predominant in spleen, lung and prostate.
SIMILARITY: Belongs to the tumor necrosis factor family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TNFSF10ID42632ch3q26.html";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U37518; AAC50332.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U57059; AAB01233.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC032722; AAH32722.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00747054; -.

NP_003801.1; -.

3D structure databases

PDB

1D0G; X-ray; 2.40 A; A/B/D=114-281.	[ExPASy / RCSB / EBI]
1D2Q; X-ray; 2.80 A; A/B=114-281.	[ExPASy / RCSB / EBI]
1D4V; X-ray; 2.20 A; B=119-281.	[ExPASy / RCSB / EBI]
1DG6; X-ray; 1.30 A; A=91-281.	[ExPASy / RCSB / EBI]
1DU3; X-ray; 2.20 A; D/E/F/J/K/L=114-281.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1D0G; -.
1D2Q; -.
1D4V; -.
1DG6; -.
1DU3; -.

ModBase

P50591.

Protein-protein interaction databases

DIP

DIP:6230N; -.

IntAct

P50591; 10.

Enzyme and pathway databases

Pathway_Interaction_DB

trail_pathway; TRAIL signaling pathway.

Reactome

REACT_578; Apoptosis.

Organism-specific databases

GC03M173706; -.

HIX0003863; -.

HGNC:11925; TNFSF10.

CAB002446; -.

603598; gene. [NCBI / EBI]

PharmGKB

PA36618; -.

Gene expression databases

P50591; -.

P50591; -.

HS_TNFSF10; -.

ENSG00000121858; Homo sapiens.

Ontologies

GO:0005615;	Cellular component: extracellular space (inferred from electronic annotation from UniProtKB-KW).
GO:0005887;	Cellular component: integral to plasma membrane (traceable author statement from ProtInc).
GO:0005625;	Cellular component: soluble fraction (traceable author statement from ProtInc).
GO:0005125;	Molecular function: cytokine activity (inferred from electronic annotation from UniProtKB-KW).
GO:0005164;	Molecular function: tumor necrosis factor receptor binding (inferred from electronic annotation from InterPro).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0008633;	Biological process: activation of pro-apoptotic gene products (inferred from experiment from Reactome).
GO:0007267;	Biological process: cell-cell signaling (traceable author statement from ProtInc).
GO:0006955;	Biological process: immune response (inferred from electronic annotation from InterPro).
GO:0006917;	Biological process: induction of apoptosis (traceable author statement from ProtInc).
GO:0043123;	Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
GO:0007165;	Biological process: signal transduction (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR017355; TNF10_TNF11.
IPR006052; TNF_family.
IPR008983; Tumour_necrosis_fac-like.
Graphical view of domain structure.

Gene3D

G3DSA:2.60.120.40; Tumour_necrosis_fac-like; 1.

Pfam

PF00229; TNF; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF038013; TNF10_TNF11; 1.

ProDom

PD002012; TNF_subf; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00207; TNF; 1.
SMART graphical view of domain structure.

PROSITE

PS00251; TNF_1; 1.
PS50049; TNF_2; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSG00000121858; Homo sapiens. [Contig view]

GeneID

8743; -.

KEGG

hsa:8743; -.

Phylogenomic databases

HOVERGEN

P50591; -.

Other

NextBio

32805; -.

SOURCE

TNFSF10; Homo sapiens.

ProtoNet

P50591.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Apoptosis; Cytokine; Membrane; Metal-binding; Polymorphism; Signal-anchor; Transmembrane; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 281`	`281`	`Tumor necrosis factor ligand superfamily member 10.`	`PRO_0000185503`
`TOPO_DOM`	`1 17`	`17`	`Cytoplasmic (Potential).`
`TRANSMEM`	`18 38`	`21`	`Signal-anchor for type II membrane protein (Potential).`
`TOPO_DOM`	`39 281`	`243`	`Extracellular (Potential).`
`METAL`	`230 230`		`Zinc.`
`VARIANT`	`33 33`	`1`	`V -> I (in dbSNP:rs6763816 [NCBI]).`	`VAR_052584`
`VARIANT`	`47 47`	`1`	`D -> E (in dbSNP:rs16845759 [NCBI]).`	`VAR_052585`
`STRAND`	`123 127`	`5`
`STRAND`	`148 150`	`3`
`STRAND`	`163 170`	`8`
`STRAND`	`173 178`	`6`
`STRAND`	`180 193`	`14`
`STRAND`	`205 213`	`9`
`STRAND`	`215 218`	`4`
`STRAND`	`220 228`	`9`
`STRAND`	`237 250`	`14`
`STRAND`	`255 262`	`8`
`HELIX`	`263 265`	`3`
`TURN`	`270 272`	`3`
`STRAND`	`273 279`	`7`

Sequence information

Length: 281 AA [This is the length of the unprocessed precursor]

Molecular weight: 32509 Da [This is the MW of the unprocessed precursor]

CRC64: DDAAAF78DAAB2F6D [This is a checksum on the sequence]

        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

P50591 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools