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P23510 (TNFL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length183 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentMembrane
   DiseaseSystemic lupus erythematosus
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCD4-positive, alpha-beta T cell costimulation

Inferred from electronic annotation. Source: Ensembl

T cell proliferation

Inferred from electronic annotation. Source: Ensembl

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 nitrogen dioxide

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

defense response to nematode

Inferred from sequence or structural similarity. Source: BHF-UCL

immune response

Inferred from electronic annotation. Source: InterPro

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: Ensembl

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-templated

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 CD4-positive, alpha-beta T cell differentiation

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 activation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of alpha-beta T cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cell proliferation

Traceable author statement Ref.2. Source: ProtInc

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: Ensembl

positive regulation of interleukin-4 production

Inferred from direct assay PubMed 18501882. Source: BHF-UCL

positive regulation of interleukin-4-dependent isotype switching to IgE isotypes

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 20844189. Source: BHF-UCL

positive regulation of memory T cell activation

Inferred from electronic annotation. Source: Ensembl

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

regulation of adaptive immune response

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of inflammatory response

Inferred from sequence or structural similarity. Source: BHF-UCL

response to nitrogen dioxide

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_componentcell surface

Inferred from direct assay PubMed 18397322. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 17166734. Source: BHF-UCL

integral component of plasma membrane

Non-traceable author statement PubMed 18397322. Source: BHF-UCL

   Molecular_functionreceptor binding

Traceable author statement Ref.2. Source: ProtInc

tumor necrosis factor receptor superfamily binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 183183Tumor necrosis factor ligand superfamily member 4
PRO_0000185493

Regions

Topological domain1 – 2323Cytoplasmic Potential
Transmembrane24 – 5027Helical; Signal-anchor for type II membrane protein; Potential
Topological domain51 – 183133Extracellular Potential

Amino acid modifications

Glycosylation901N-linked (GlcNAc...) Potential
Glycosylation1141N-linked (GlcNAc...) Potential
Glycosylation1521N-linked (GlcNAc...) Ref.8
Glycosylation1571N-linked (GlcNAc...) Potential
Disulfide bond97 ↔ 181 Ref.8

Secondary structure

............... 183
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23510 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: 0D5604AD29D529CF

FASTA18321,050
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS1306.1.
PIRA39680.
RefSeqNP_003317.1. NM_003326.3.
UniGeneHs.181097.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HEVX-ray2.41F51-183[»]
ProteinModelPortalP23510.
SMRP23510. Positions 58-183.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-3023N.
STRING9606.ENSP00000281834.

PTM databases

PhosphoSiteP23510.

Polymorphism databases

DMDM121540.

Proteomic databases

PaxDbP23510.
PRIDEP23510.

Protocols and materials databases

DNASU7292.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281834; ENSP00000281834; ENSG00000117586.
GeneID7292.
KEGGhsa:7292.
UCSCuc001giw.3. human.

Organism-specific databases

CTD7292.
GeneCardsGC01M173152.
HGNCHGNC:11934. TNFSF4.
HPAHPA059579.
MIM152700. phenotype.
603594. gene.
neXtProtNX_P23510.
Orphanet2073. Narcolepsy-cataplexy.
536. Systemic lupus erythematosus.
PharmGKBPA36625.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47572.
HOGENOMHOG000076309.
HOVERGENHBG056457.
InParanoidP23510.
KOK05469.
OMAMEGVQPL.
PhylomeDBP23510.
TreeFamTF336384.

Gene expression databases

ArrayExpressP23510.
BgeeP23510.
CleanExHS_TNFSF4.
GenevestigatorP23510.

Family and domain databases

InterProIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS00251. TNF_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNFSF4. human.
EvolutionaryTraceP23510.
GenomeRNAi7292.
NextBio28511.
PROP23510.
SOURCESearch...

Entry information

Entry nameTNFL4_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 124 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 chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

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