P23510 (TNFL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 4

Alternative name(s):
Glycoprotein Gp34
OX40 ligand
Short name=OX40L
TAX transcriptionally-activated glycoprotein 1
CD_antigen=CD252

Gene names

Name:	TNFSF4
Synonyms:	TXGP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	183 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.
Subunit structure	Homotrimer. Ref.8
Subcellular location	Membrane; Single-pass type II membrane protein.
Induction	By HTLV-1 transactivator p40-Tax.
Involvement in disease	Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. The upstream region of TNFSF4 contains a single risk haplotype for SLE, which is correlated with increased expression of both cell-surface TNFSF4 and TNFSF4 transcripts. Increased levels of TNFSF4 are thought to augment T-cell-APC interaction and the functional consequences of T-cell activation, thereby destabilizing peripheral tolerance. Ref.7
Sequence similarities	Belongs to the tumor necrosis factor family.
Sequence caution	The sequence CAA18438.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Membrane
Disease	Systemic lupus erythematosus
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell proliferation Inferred from electronic annotation. Source: Compara T-helper 2 cell activation Inferred from sequence or structural similarity. Source: BHF-UCL acute inflammatory response Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to lipopolysaccharide Inferred from direct assay PubMed 20844189. Source: BHF-UCL cellular response to prostaglandin E stimulus Inferred from direct assay PubMed 19029446. Source: BHF-UCL chemokine (C-C motif) ligand 11 production Inferred from sequence or structural similarity. Source: BHF-UCL cholesterol metabolic process Inferred from electronic annotation. Source: Compara defense response to nematode Inferred from sequence or structural similarity. Source: BHF-UCL interleukin-4-dependent isotype switching to IgE isotypes Inferred from sequence or structural similarity. Source: BHF-UCL memory T cell activation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of T-helper 1 cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cytokine secretion Inferred from electronic annotation. Source: Compara negative regulation of interferon-gamma production Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of interleukin-17 production Inferred from direct assay PubMed 18501882. Source: BHF-UCL negative regulation of regulatory T cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of B cell activation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of CD4-positive, alpha beta T cell costimulation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of T cell cytokine production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of T-helper 2 cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of activated T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of alpha-beta T cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of immunoglobulin mediated immune response Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of immunoglobulin secretion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of inflammatory response Inferred from direct assay PubMed 20844189. Source: BHF-UCL positive regulation of interferon-gamma production Inferred from direct assay PubMed 18501882. Source: BHF-UCL positive regulation of interleukin-10 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-13 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-2 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-4 production Inferred from direct assay PubMed 18501882. Source: BHF-UCL positive regulation of interleukin-6 production Inferred from direct assay PubMed 20844189. Source: BHF-UCL positive regulation of memory T cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of type 2 immune response Inferred from sequence or structural similarity. Source: BHF-UCL response to virus Inferred from sequence or structural similarity. Source: BHF-UCL signal transduction Traceable author statement Ref.2. Source: ProtInc
Cellular_component	cell surface Inferred from direct assay PubMed 18397322. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 17166734. Source: BHF-UCL integral to plasma membrane Non-traceable author statement PubMed 18397322. Source: BHF-UCL
Molecular_function	tumor necrosis factor receptor superfamily binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 183

183

Tumor necrosis factor ligand superfamily member 4

PRO_0000185493

Regions

Topological domain

1 – 23

23

Cytoplasmic Potential

Transmembrane

24 – 50

27

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

Topological domain

51 – 183

133

Extracellular Potential

Amino acid modifications

Glycosylation

90

1

N-linked (GlcNAc...) Potential

Glycosylation

114

1

N-linked (GlcNAc...) Potential

Glycosylation

152

1

N-linked (GlcNAc...) Ref.8

Glycosylation

157

1

N-linked (GlcNAc...) Potential

Disulfide bond

97 ↔ 181

Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

183

Helix Strand Turn

Details...

Beta strand

61 – 70

10

Turn

71 – 73

3

Beta strand

74 – 78

5

Beta strand

92 – 94

3

Beta strand

99 – 120

22

Beta strand

126 – 143

18

Beta strand

148 – 155

8

Beta strand

165 – 174

10

Sequences

	Sequence		Length	Mass (Da)
	P23510 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: 0D5604AD29D529CF	FASTA	183	21,050
	10 20 30 40 50 60 MERVQPLEEN VGNAARPRFE RNKLLLVASV IQGLGLLLCF TYICLHFSAL QVSHRYPRIQ 70 80 90 100 110 120 SIKVQFTEYK KEKGFILTSQ KEDEIMKVQN NSVIINCDGF YLISLKGYFS QEVNISLHYQ 130 140 150 160 170 180 KDEEPLFQLK KVRSVNSLMV ASLTYKDKVY LNVTTDNTSL DDFHVNGGEL ILIHQNPGEF CVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax." Miura S., Ohtani K., Numata N., Niki M., Ohbo K., Ina Y., Gojobori T., Tanaka Y., Tozawa H., Nakamura M., Sugamura K. Mol. Cell. Biol. 11:1313-1325(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor." Godfrey W.R., Fagnoni F.F., Harara M.A., Buck D., Engleman E.G. J. Exp. Med. 180:757-762(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"New variations in human OX40 ligand (CD134L) gene." Hikami K., Tsuchiya N., Tokunaga K. Genes Immun. 1:521-522(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
[6]	"Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34." Baum P.R., Gayle R.B. III, Ramsdell F., Srinivasan S., Sorensen R.A., Watson M.L., Seldin M.F., Baker E., Sutherland G.R., Clifford K.N., Alderson M.R., Goodwin R.G., Fanslow W.C. EMBO J. 13:3992-4001(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus." Cunninghame Graham D.S., Graham R.R., Manku H., Wong A.K., Whittaker J.C., Gaffney P.M., Moser K.L., Rioux J.D., Altshuler D., Behrens T.W., Vyse T.J. Nat. Genet. 40:83-89(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SLE.
[8]	"The crystal structure of the costimulatory OX40-OX40L complex." Compaan D.M., Hymowitz S.G. Structure 14:1321-1330(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 48-183 IN COMPLEX WITH TNFRSF4, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-152.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D90224 mRNA. Translation: BAA14259.1.
X79929 mRNA. Translation: CAA56284.1.
AL022310 Genomic DNA. Translation: CAA18438.2. Sequence problems.
AL022310 Genomic DNA. Translation: CAI20416.1.
CH471067 Genomic DNA. Translation: EAW90938.1.
AB042988 Genomic DNA. Translation: BAB18304.1.

IPI

IPI00011974.

PIR

A39680.

RefSeq

NP_003317.1. NM_003326.3.

UniGene

Hs.181097.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HEV	X-ray	2.41	F	51-183	[»]

ProteinModelPortal

P23510.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3023N.

STRING

9606.ENSP00000281834.

PTM databases

PhosphoSite

P23510.

Polymorphism databases

DMDM

121540.

Proteomic databases

PaxDb

P23510.

PRIDE

P23510.

Protocols and materials databases

DNASU

7292.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000281834; ENSP00000281834; ENSG00000117586.

GeneID

7292.

KEGG

hsa:7292.

UCSC

uc001giw.3. human.

Organism-specific databases

CTD

7292.

GeneCards

GC01M173152.

HGNC

HGNC:11934. TNFSF4.

MIM

152700. phenotype.
603594. gene.

neXtProt

NX_P23510.

PharmGKB

PA36625.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47572.

HOGENOM

HOG000076309.

HOVERGEN

HBG056457.

InParanoid

P23510.

KO

K05469.

OMA

MEGVQPL.

OrthoDB

EOG4K3KXF.

PhylomeDB

P23510.

Gene expression databases

ArrayExpress

P23510.

Bgee

P23510.

CleanEx

HS_TNFSF4.

Genevestigator

P23510.

GermOnline

ENSG00000117586. Homo sapiens.

Family and domain databases

InterPro

IPR006052. TNF.
IPR021184. TNF_CS.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]

Pfam

PF00229. TNF. 1 hit.
[Graphical view]

SMART

SM00207. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

ChiTaRS

TNFSF4. human.

EvolutionaryTrace

P23510.

GenomeRNAi

7292.

NextBio

28511.

SOURCE

Search...

Entry information

Entry name

TNFL4_HUMAN

Accession

Primary (citable) accession number: P23510
Secondary accession number(s): Q5JZA5, Q9HCN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	November 1, 1991
Last modified:	May 1, 2013
This is version 115 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.