P50591 (TNF10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	281 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Cytokine
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of cysteine-type endopeptidase activity involved in apoptotic process Traceable author statement. Source: Reactome activation of pro-apoptotic gene products Traceable author statement. Source: Reactome cell-cell signaling Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro induction of apoptosis by extracellular signals Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB signal transduction Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement. Source: ProtInc soluble fraction Traceable author statement. Source: ProtInc
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CUL3	Q13618	2	EBI-495373,EBI-456129
TNFRSF10B	O14763	5	EBI-495373,EBI-518882

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 281

281

Tumor necrosis factor ligand superfamily member 10

PRO_0000185503

Regions

Topological domain

1 – 17

17

Cytoplasmic Potential

Transmembrane

18 – 38

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

39 – 281

243

Extracellular Potential

Sites

Metal binding

230

1

Zinc

Natural variations

Natural variant

33

1

V → I.
Corresponds to variant rs6763816 [ dbSNP | Ensembl ].

VAR_052584

Natural variant

47

1

D → E.
Corresponds to variant rs16845759 [ dbSNP | Ensembl ].

VAR_052585

Secondary structure

1

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281

Helix Strand Turn

Details...

Beta strand

123 – 127

5

Beta strand

148 – 150

3

Beta strand

163 – 170

8

Beta strand

173 – 178

6

Beta strand

180 – 193

14

Beta strand

205 – 213

9

Beta strand

215 – 218

4

Beta strand

220 – 228

9

Beta strand

237 – 250

14

Beta strand

255 – 262

8

Helix

263 – 265

3

Turn

270 – 272

3

Beta strand

273 – 279

7

Sequences

	Sequence		Length	Mass (Da)
	P50591 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: DDAAAF78DAAB2F6D	FASTA	281	32,509
	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

References

	« Hide 'large scale' referencesShow '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: 8777713] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 8663110] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"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: Lymph.
[4]	"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: 10549288] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 114-281.
[5]	"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: 10542098] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 119-281.
[6]	"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: 10485660] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 114-281.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U37518 mRNA. Translation: AAC50332.1.
U57059 mRNA. Translation: AAB01233.1.
BC032722 mRNA. Translation: AAH32722.1.

IPI

IPI00000049.

RefSeq

NP_003801.1. NM_003810.3.

UniGene

Hs.478275.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D0G	X-ray	2.40	A/B/D	114-281	[»]
1D2Q	X-ray	2.80	A/B	114-281	[»]
1D4V	X-ray	2.20	B	119-281	[»]
1DG6	X-ray	1.30	A	91-281	[»]
1DU3	X-ray	2.20	D/E/F/J/K/L	114-281	[»]

ProteinModelPortal

P50591.

SMR

P50591. Positions 119-281.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6230N.

IntAct

P50591. 13 interactions.

MINT

MINT-109168.

STRING

P50591.

PTM databases

PhosphoSite

P50591.

Polymorphism databases

DMDM

1730015.

Proteomic databases

PRIDE

P50591.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000241261; ENSP00000241261; ENSG00000121858.

GeneID

8743.

KEGG

hsa:8743.

UCSC

uc003fid.1. human.

Organism-specific databases

CTD

8743.

GeneCards

GC03M172223.

H-InvDB

HIX0003863.

HGNC

HGNC:11925. TNFSF10.

HPA

CAB002446.

MIM

603598. gene.

neXtProt

NX_P50591.

PharmGKB

PA36618.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11281.

HOVERGEN

HBG059007.

OrthoDB

EOG4PVP0J.

PhylomeDB

P50591.

Enzyme and pathway databases

Pathway_Interaction_DB

trail_pathway. TRAIL signaling pathway.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P50591.

Bgee

P50591.

CleanEx

HS_TNFSF10.

Genevestigator

P50591.

GermOnline

ENSG00000121858. Homo sapiens.

Family and domain databases

InterPro

IPR006052. TNF.
IPR021184. TNF_CS.
IPR017355. TNF_ligand_10/11.
IPR008983. Tumour_necrosis_fac-like.
[Graphical view]

Gene3D

G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.

KO

K04721.

Pfam

PF00229. TNF. 1 hit.
[Graphical view]

PIRSF

PIRSF038013. TNF10_TNF11. 1 hit.

SMART

SM00207. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32805.

SOURCE

Search...

Entry information

Entry name

TNF10_HUMAN

Accession

Primary (citable) accession number: P50591

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 119 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.