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Protein

Tumor necrosis factor receptor superfamily member 4

Gene

TNFRSF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity.1 Publication
(Microbial infection) Acts as a receptor for human herpesvirus 6B/HHV-6B.1 Publication

GO - Molecular functioni

  • tumor necrosis factor-activated receptor activity Source: ProtInc
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:G66-30849-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiP43489.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 4
Alternative name(s):
ACT35 antigen
OX40L receptor
TAX transcriptionally-activated glycoprotein 1 receptor
CD_antigen: CD134
Gene namesi
Name:TNFRSF4
Synonyms:TXGP1L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:11918. TNFRSF4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 214ExtracellularSequence analysisAdd BLAST186
Transmembranei215 – 235HelicalSequence analysisAdd BLAST21
Topological domaini236 – 277CytoplasmicSequence analysisAdd BLAST42

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 16 (IMD16)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive primary immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell recall immune responses due to complete functional OX40 deficiency.
See also OMIM:615593
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07094265R → C in IMD16. 1 PublicationCorresponds to variant rs587777075dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7293.
MalaCardsiTNFRSF4.
MIMi615593. phenotype.
OpenTargetsiENSG00000186827.
PharmGKBiPA36611.

Chemistry databases

GuidetoPHARMACOLOGYi1873.

Polymorphism and mutation databases

BioMutaiTNFRSF4.
DMDMi1171933.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000003455429 – 277Tumor necrosis factor receptor superfamily member 4Add BLAST249

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 42PROSITE-ProRule annotation1 Publication
Disulfide bondi43 ↔ 56PROSITE-ProRule annotation1 Publication
Disulfide bondi46 ↔ 64PROSITE-ProRule annotation1 Publication
Disulfide bondi67 ↔ 81PROSITE-ProRule annotation1 Publication
Disulfide bondi84 ↔ 99PROSITE-ProRule annotation1 Publication
Disulfide bondi87 ↔ 107PROSITE-ProRule annotation1 Publication
Disulfide bondi109 ↔ 125PROSITE-ProRule annotation1 Publication
Disulfide bondi128 ↔ 141PROSITE-ProRule annotation1 Publication
Glycosylationi146N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi147 ↔ 166PROSITE-ProRule annotation
Glycosylationi160N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43489.
PeptideAtlasiP43489.
PRIDEiP43489.

Expressioni

Gene expression databases

BgeeiENSG00000186827.
CleanExiHS_TNFRSF4.
GenevisibleiP43489. HS.

Organism-specific databases

HPAiCAB016128.

Interactioni

Subunit structurei

Interacts with TRAF2, TRAF3 and TRAF5.3 Publications
(Microbial infection) Interacts with Human herpesvirus 6B/HHV-6B gQ1:gQ2 proteins.1 Publication

Protein-protein interaction databases

BioGridi113144. 6 interactors.
DIPiDIP-3024N.
STRINGi9606.ENSP00000368538.

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 38Combined sources6
Beta strandi41 – 44Combined sources4
Beta strandi50 – 54Combined sources5
Beta strandi58 – 60Combined sources3
Beta strandi63 – 66Combined sources4
Beta strandi77 – 79Combined sources3
Helixi89 – 91Combined sources3
Beta strandi93 – 97Combined sources5
Beta strandi106 – 109Combined sources4
Beta strandi113 – 116Combined sources4
Beta strandi118 – 120Combined sources3
Beta strandi123 – 127Combined sources5
Turni147 – 151Combined sources5
Beta strandi153 – 156Combined sources4
Beta strandi160 – 162Combined sources3
Beta strandi165 – 167Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0AX-ray2.00G/H/I/J/K/L262-266[»]
2HEVX-ray2.41R29-170[»]
2HEYX-ray2.00R/T29-170[»]
ProteinModelPortaliP43489.
SMRiP43489.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43489.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati30 – 65TNFR-Cys 1Add BLAST36
Repeati66 – 107TNFR-Cys 2Add BLAST42
Repeati108 – 126TNFR-Cys 3; truncatedAdd BLAST19
Repeati127 – 167TNFR-Cys 4Add BLAST41

Sequence similaritiesi

Contains 4 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J0US. Eukaryota.
ENOG4111DUJ. LUCA.
GeneTreeiENSGT00730000111452.
HOGENOMiHOG000049154.
HOVERGENiHBG005031.
InParanoidiP43489.
KOiK05142.
OMAiHHRAWRL.
OrthoDBiEOG091G03XW.
PhylomeDBiP43489.
TreeFamiTF330135.

Family and domain databases

InterProiIPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020445. TNFR_4.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSiPR01921. TNFACTORR4.
SMARTiSM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 3 hits.
[Graphical view]
PROSITEiPS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43489-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCVGARRLGR GPCAALLLLG LGLSTVTGLH CVGDTYPSND RCCHECRPGN
60 70 80 90 100
GMVSRCSRSQ NTVCRPCGPG FYNDVVSSKP CKPCTWCNLR SGSERKQLCT
110 120 130 140 150
ATQDTVCRCR AGTQPLDSYK PGVDCAPCPP GHFSPGDNQA CKPWTNCTLA
160 170 180 190 200
GKHTLQPASN SSDAICEDRD PPATQPQETQ GPPARPITVQ PTEAWPRTSQ
210 220 230 240 250
GPSTRPVEVP GGRAVAAILG LGLVLGLLGP LAILLALYLL RRDQRLPPDA
260 270
HKPPGGGSFR TPIQEEQADA HSTLAKI
Length:277
Mass (Da):29,341
Last modified:November 1, 1995 - v1
Checksum:i49F15525941550BF
GO

Sequence cautioni

The sequence AAB33944 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02516410R → C.1 PublicationCorresponds to variant rs35304565dbSNPEnsembl.1
Natural variantiVAR_07094265R → C in IMD16. 1 PublicationCorresponds to variant rs587777075dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75962 mRNA. Translation: CAA53576.1.
S76792 mRNA. Translation: AAB33944.1. Different initiation.
AJ277151 Genomic DNA. Translation: CAB96543.1.
DQ118974 Genomic DNA. Translation: AAZ15374.1.
AL162741 Genomic DNA. Translation: CAI23250.1.
BC105070 mRNA. Translation: AAI05071.1.
BC105072 mRNA. Translation: AAI05073.1.
CCDSiCCDS11.1.
PIRiI37552.
RefSeqiNP_003318.1. NM_003327.3.
XP_016857721.1. XM_017002232.1.
UniGeneiHs.129780.

Genome annotation databases

EnsembliENST00000379236; ENSP00000368538; ENSG00000186827.
GeneIDi7293.
KEGGihsa:7293.
UCSCiuc001ade.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75962 mRNA. Translation: CAA53576.1.
S76792 mRNA. Translation: AAB33944.1. Different initiation.
AJ277151 Genomic DNA. Translation: CAB96543.1.
DQ118974 Genomic DNA. Translation: AAZ15374.1.
AL162741 Genomic DNA. Translation: CAI23250.1.
BC105070 mRNA. Translation: AAI05071.1.
BC105072 mRNA. Translation: AAI05073.1.
CCDSiCCDS11.1.
PIRiI37552.
RefSeqiNP_003318.1. NM_003327.3.
XP_016857721.1. XM_017002232.1.
UniGeneiHs.129780.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1D0AX-ray2.00G/H/I/J/K/L262-266[»]
2HEVX-ray2.41R29-170[»]
2HEYX-ray2.00R/T29-170[»]
ProteinModelPortaliP43489.
SMRiP43489.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113144. 6 interactors.
DIPiDIP-3024N.
STRINGi9606.ENSP00000368538.

Chemistry databases

GuidetoPHARMACOLOGYi1873.

Polymorphism and mutation databases

BioMutaiTNFRSF4.
DMDMi1171933.

Proteomic databases

PaxDbiP43489.
PeptideAtlasiP43489.
PRIDEiP43489.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379236; ENSP00000368538; ENSG00000186827.
GeneIDi7293.
KEGGihsa:7293.
UCSCiuc001ade.4. human.

Organism-specific databases

CTDi7293.
DisGeNETi7293.
GeneCardsiTNFRSF4.
HGNCiHGNC:11918. TNFRSF4.
HPAiCAB016128.
MalaCardsiTNFRSF4.
MIMi600315. gene.
615593. phenotype.
neXtProtiNX_P43489.
OpenTargetsiENSG00000186827.
PharmGKBiPA36611.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0US. Eukaryota.
ENOG4111DUJ. LUCA.
GeneTreeiENSGT00730000111452.
HOGENOMiHOG000049154.
HOVERGENiHBG005031.
InParanoidiP43489.
KOiK05142.
OMAiHHRAWRL.
OrthoDBiEOG091G03XW.
PhylomeDBiP43489.
TreeFamiTF330135.

Enzyme and pathway databases

BioCyciZFISH:G66-30849-MONOMER.
ReactomeiR-HSA-5669034. TNFs bind their physiological receptors.
SIGNORiP43489.

Miscellaneous databases

EvolutionaryTraceiP43489.
GeneWikiiCD134.
GenomeRNAii7293.
PROiP43489.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186827.
CleanExiHS_TNFRSF4.
GenevisibleiP43489. HS.

Family and domain databases

InterProiIPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020445. TNFR_4.
IPR011641. Tyr-kin_ephrin_A/B_rcpt-like.
[Graphical view]
PfamiPF00020. TNFR_c6. 3 hits.
[Graphical view]
PRINTSiPR01921. TNFACTORR4.
SMARTiSM01411. Ephrin_rec_like. 2 hits.
SM00208. TNFR. 3 hits.
[Graphical view]
PROSITEiPS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNR4_HUMAN
AccessioniPrimary (citable) accession number: P43489
Secondary accession number(s): Q13663, Q2M312, Q5T7M0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 146 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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.