Reviewed, UniProtKB/Swiss-Prot P50591 (TNF10_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor ligand superfamily member 10
Alternative name(s):
    TNF-related apoptosis-inducing ligand
      Short name=Protein TRAIL
    Apo-2 ligand
      Short name=Apo-2L
    CD_antigen=CD253

Gene names

Name:	TNFSF10
Synonyms:	APO2L, TRAIL

Organism

Homo sapiens (Human) [Complete proteome]

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.
Sequence processing	The displayed sequence is not processed.
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
Ligand	Metal-binding Zinc
Molecular function	Cytokine
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro induction of apoptosis Ref.2 Traceable author statement. Source: ProtInc positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB signal transduction Ref.1 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 soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CUL3	Q13618	2	EBI-495373,EBI-456129

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

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: dbSNP rs6763816.

VAR_052584

Natural variant

47

1

D → E: dbSNP rs16845759.

VAR_052585

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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)
	P50591-1 [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

EMBLGenBankDDBJ

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

IPI

IPI00747054.

RefSeq

NP_003801.1.

UniGene

Hs.478275

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6230N.

IntAct

P50591. 11 interactions.

STRING

P50591.

PTM databases

PhosphoSite

P50591.

Genome annotation databases

Ensembl

ENST00000241261; ENSP00000241261; ENSG00000121858; Homo sapiens. [Genome view]
ENST00000382750; ENSP00000372198; ENSG00000121858; Homo sapiens. [Genome view]
ENST00000419945; ENSP00000394836; ENSG00000121858; Homo sapiens. [Genome view]
ENST00000420541; ENSP00000389931; ENSG00000121858; Homo sapiens. [Genome view]
ENST00000430881; ENSP00000404008; ENSG00000121858; Homo sapiens. [Genome view]

GeneID

8743.

KEGG

hsa:8743.

UCSC

uc003fid.1. human.

Organism-specific databases

CTD

8743.

GeneCards

GC03M173706.

H-InvDB

HIX0003863.

HGNC

HGNC:11925. TNFSF10.

HPA

CAB002446.

MIM

603598. gene.

PharmGKB

PA36618.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

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

IPR017355. TNF10_TNF11.
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]

PIRSF

PIRSF038013. TNF10_TNF11. 1 hit.

ProDom

PD002012. TNF_subf. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00207. TNF. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	November 3, 2009
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.