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P23510

- TNFL4_HUMAN

UniProt

P23510 - TNFL4_HUMAN

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Protein
Tumor necrosis factor ligand superfamily member 4
Gene
TNFSF4, TXGP1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.

GO - Molecular functioni

  1. receptor binding Source: ProtInc
  2. tumor necrosis factor receptor superfamily binding Source: BHF-UCL

GO - Biological processi

  1. CD4-positive, alpha-beta T cell costimulation Source: Ensembl
  2. T cell proliferation Source: Ensembl
  3. T-helper 2 cell activation Source: BHF-UCL
  4. acute inflammatory response Source: BHF-UCL
  5. cellular response to lipopolysaccharide Source: BHF-UCL
  6. cellular response to nitrogen dioxide Source: Ensembl
  7. cellular response to prostaglandin E stimulus Source: BHF-UCL
  8. chemokine (C-C motif) ligand 11 production Source: BHF-UCL
  9. cholesterol metabolic process Source: Ensembl
  10. defense response to nematode Source: BHF-UCL
  11. immune response Source: InterPro
  12. memory T cell activation Source: BHF-UCL
  13. negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
  14. negative regulation of cytokine secretion Source: Ensembl
  15. negative regulation of interferon-gamma production Source: BHF-UCL
  16. negative regulation of interleukin-17 production Source: BHF-UCL
  17. negative regulation of regulatory T cell differentiation Source: BHF-UCL
  18. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  19. negative regulation of transcription, DNA-templated Source: BHF-UCL
  20. positive regulation of B cell activation Source: BHF-UCL
  21. positive regulation of CD4-positive, alpha-beta T cell costimulation Source: BHF-UCL
  22. positive regulation of CD4-positive, alpha-beta T cell differentiation Source: BHF-UCL
  23. positive regulation of T cell cytokine production Source: BHF-UCL
  24. positive regulation of T-helper 2 cell activation Source: Ensembl
  25. positive regulation of T-helper 2 cell differentiation Source: BHF-UCL
  26. positive regulation of activated T cell proliferation Source: Ensembl
  27. positive regulation of alpha-beta T cell proliferation Source: BHF-UCL
  28. positive regulation of cell proliferation Source: ProtInc
  29. positive regulation of immunoglobulin mediated immune response Source: BHF-UCL
  30. positive regulation of immunoglobulin secretion Source: BHF-UCL
  31. positive regulation of inflammatory response Source: BHF-UCL
  32. positive regulation of interferon-gamma production Source: BHF-UCL
  33. positive regulation of interleukin-10 production Source: BHF-UCL
  34. positive regulation of interleukin-12 production Source: BHF-UCL
  35. positive regulation of interleukin-13 production Source: BHF-UCL
  36. positive regulation of interleukin-2 production Source: Ensembl
  37. positive regulation of interleukin-4 production Source: BHF-UCL
  38. positive regulation of interleukin-4-dependent isotype switching to IgE isotypes Source: BHF-UCL
  39. positive regulation of interleukin-6 production Source: BHF-UCL
  40. positive regulation of memory T cell activation Source: Ensembl
  41. positive regulation of memory T cell differentiation Source: BHF-UCL
  42. positive regulation of type 2 immune response Source: BHF-UCL
  43. regulation of adaptive immune response Source: BHF-UCL
  44. regulation of inflammatory response Source: BHF-UCL
  45. response to nitrogen dioxide Source: BHF-UCL
  46. response to virus Source: BHF-UCL
  47. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Names & Taxonomyi

Protein namesi
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 namesi
Name:TNFSF4
Synonyms:TXGP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:11934. TNFSF4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2323Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei24 – 5027Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini51 – 183133Extracellular Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. extracellular space Source: BHF-UCL
  3. integral component of plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

MIMi152700. phenotype.
Orphaneti2073. Narcolepsy-cataplexy.
536. Systemic lupus erythematosus.
PharmGKBiPA36625.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 183183Tumor necrosis factor ligand superfamily member 4
PRO_0000185493Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi90 – 901N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi97 ↔ 1811 Publication
Glycosylationi114 – 1141N-linked (GlcNAc...) Reviewed prediction
Glycosylationi152 – 1521N-linked (GlcNAc...)1 Publication
Glycosylationi157 – 1571N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP23510.
PRIDEiP23510.

PTM databases

PhosphoSiteiP23510.

Expressioni

Inductioni

By HTLV-1 transactivator p40-Tax.

Gene expression databases

ArrayExpressiP23510.
BgeeiP23510.
CleanExiHS_TNFSF4.
GenevestigatoriP23510.

Organism-specific databases

HPAiHPA059579.

Interactioni

Subunit structurei

Homotrimer.1 Publication

Protein-protein interaction databases

DIPiDIP-3023N.
STRINGi9606.ENSP00000281834.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi61 – 7010
Turni71 – 733
Beta strandi74 – 785
Beta strandi92 – 943
Beta strandi99 – 12022
Beta strandi126 – 14318
Beta strandi148 – 1558
Beta strandi165 – 17410

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2HEVX-ray2.41F51-183[»]
ProteinModelPortaliP23510.
SMRiP23510. Positions 58-183.

Miscellaneous databases

EvolutionaryTraceiP23510.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG47572.
HOGENOMiHOG000076309.
HOVERGENiHBG056457.
InParanoidiP23510.
KOiK05469.
OMAiMEGVQPL.
PhylomeDBiP23510.
TreeFamiTF336384.

Family and domain databases

InterProiIPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23510-1 [UniParc]FASTAAdd to Basket

« Hide

MERVQPLEEN VGNAARPRFE RNKLLLVASV IQGLGLLLCF TYICLHFSAL    50
QVSHRYPRIQ SIKVQFTEYK KEKGFILTSQ KEDEIMKVQN NSVIINCDGF 100
YLISLKGYFS QEVNISLHYQ KDEEPLFQLK KVRSVNSLMV ASLTYKDKVY 150
LNVTTDNTSL DDFHVNGGEL ILIHQNPGEF CVL 183
Length:183
Mass (Da):21,050
Last modified:November 1, 1991 - v1
Checksum:i0D5604AD29D529CF
GO

Sequence cautioni

The sequence CAA18438.2 differs from that shown. Reason: Erroneous gene model prediction.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS1306.1.
PIRiA39680.
RefSeqiNP_003317.1. NM_003326.3.
UniGeneiHs.181097.

Genome annotation databases

EnsembliENST00000281834; ENSP00000281834; ENSG00000117586.
GeneIDi7292.
KEGGihsa:7292.
UCSCiuc001giw.3. human.

Polymorphism databases

DMDMi121540.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS1306.1.
PIRi A39680.
RefSeqi NP_003317.1. NM_003326.3.
UniGenei Hs.181097.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2HEV X-ray 2.41 F 51-183 [» ]
ProteinModelPortali P23510.
SMRi P23510. Positions 58-183.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-3023N.
STRINGi 9606.ENSP00000281834.

PTM databases

PhosphoSitei P23510.

Polymorphism databases

DMDMi 121540.

Proteomic databases

PaxDbi P23510.
PRIDEi P23510.

Protocols and materials databases

DNASUi 7292.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000281834 ; ENSP00000281834 ; ENSG00000117586 .
GeneIDi 7292.
KEGGi hsa:7292.
UCSCi uc001giw.3. human.

Organism-specific databases

CTDi 7292.
GeneCardsi GC01M173152.
HGNCi HGNC:11934. TNFSF4.
HPAi HPA059579.
MIMi 152700. phenotype.
603594. gene.
neXtProti NX_P23510.
Orphaneti 2073. Narcolepsy-cataplexy.
536. Systemic lupus erythematosus.
PharmGKBi PA36625.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG47572.
HOGENOMi HOG000076309.
HOVERGENi HBG056457.
InParanoidi P23510.
KOi K05469.
OMAi MEGVQPL.
PhylomeDBi P23510.
TreeFami TF336384.

Miscellaneous databases

ChiTaRSi TNFSF4. human.
EvolutionaryTracei P23510.
GenomeRNAii 7292.
NextBioi 28511.
PROi P23510.
SOURCEi Search...

Gene expression databases

ArrayExpressi P23510.
Bgeei P23510.
CleanExi HS_TNFSF4.
Genevestigatori P23510.

Family and domain databases

InterProi IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS00251. TNF_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiTNFL4_HUMAN
AccessioniPrimary (citable) accession number: P23510
Secondary accession number(s): Q5JZA5, Q9HCN9
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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