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Protein

Tumor necrosis factor receptor superfamily member 14

Gene

TNFRSF14

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

Functioni

Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells.1 Publication
(Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 and herpes simplex virus 1/HHV-2.2 Publications

GO - Molecular functioni

  • tumor necrosis factor-activated receptor activity Source: ProtInc
  • ubiquitin protein ligase binding Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-388841. Costimulation by the CD28 family.
R-HSA-5669034. TNFs bind their physiological receptors.
SignaLinkiQ92956.
SIGNORiQ92956.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 14
Alternative name(s):
Herpes virus entry mediator A
Short name:
Herpesvirus entry mediator A
Short name:
HveA
Tumor necrosis factor receptor-like 2
Short name:
TR2
CD_antigen: CD270
Gene namesi
Name:TNFRSF14
Synonyms:HVEA, HVEM
ORF Names:UNQ329/PRO509
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000157873.17.
HGNCiHGNC:11912. TNFRSF14.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini39 – 202ExtracellularIEP:Add BLAST164
Transmembranei203 – 223HelicalIEP:Add BLAST21
Topological domaini224 – 283CytoplasmicIEP:Add BLAST60

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8764.
OpenTargetsiENSG00000157873.
PharmGKBiPA36605.

Polymorphism and mutation databases

BioMutaiTNFRSF14.
DMDMi13878821.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 381 PublicationAdd BLAST38
ChainiPRO_000003459039 – 283Tumor necrosis factor receptor superfamily member 14Add BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 53
Disulfide bondi54 ↔ 67
Disulfide bondi57 ↔ 75
Disulfide bondi78 ↔ 93
Disulfide bondi96 ↔ 111
Disulfide bondi99 ↔ 119
Glycosylationi110N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi121 ↔ 138
Disulfide bondi127 ↔ 135
Glycosylationi173N-linked (GlcNAc...) asparagineIEP:1
Modified residuei240PhosphoserineND:1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ92956.
PaxDbiQ92956.
PeptideAtlasiQ92956.
PRIDEiQ92956.

PTM databases

iPTMnetiQ92956.
PhosphoSitePlusiQ92956.

Expressioni

Tissue specificityi

Widely expressed, with the highest expression in lung, spleen and thymus.

Gene expression databases

BgeeiENSG00000157873.
CleanExiHS_TNFRSF14.
ExpressionAtlasiQ92956. baseline and differential.
GenevisibleiQ92956. HS.

Organism-specific databases

HPAiCAB026150.
CAB030007.
HPA006404.

Interactioni

Subunit structurei

Interacts with TRAF2, TRAF3 and TRAF5.3 Publications
(Microbial infection) Interacts with herpes simplex virus 1/HHV-1 and herpes simplex virus 1/HHV-2 envelope glycoprotein D (PubMed:11511370, PubMed:9696799).2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114298. 30 interactors.
DIPiDIP-34779N.
ELMiQ92956.
IntActiQ92956. 29 interactors.
MINTiMINT-208002.
STRINGi9606.ENSP00000347948.

Structurei

Secondary structure

1283
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi46 – 49ND:4
Beta strandi52 – 55ND:4
Beta strandi61 – 65ND:5
Beta strandi69 – 71ND:3
Beta strandi74 – 77ND:4
Beta strandi86 – 88ND:3
Helixi101 – 103ND:3
Beta strandi105 – 109ND:5
Beta strandi113 – 115ND:3
Beta strandi118 – 121ND:4
Beta strandi125 – 131ND:7
Beta strandi134 – 140ND:7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JMAX-ray2.65B39-199[»]
2AW2X-ray2.80B/Y39-142[»]
4FHQX-ray2.25A39-162[»]
4RSUX-ray2.30D/E/F/J/K/L39-162[»]
ProteinModelPortaliQ92956.
SMRiQ92956.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92956.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati42 – 75TNFR-Cys 1Add BLAST34
Repeati78 – 119TNFR-Cys 2Add BLAST42
Repeati121 – 162TNFR-Cys 3Add BLAST42

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IX15. Eukaryota.
ENOG410ZEC2. LUCA.
GeneTreeiENSGT00760000119204.
HOGENOMiHOG000065766.
HOVERGENiHBG072084.
InParanoidiQ92956.
KOiK05152.
OMAiCRVCDPA.
OrthoDBiEOG091G03XW.
PhylomeDBiQ92956.
TreeFamiTF331157.

Family and domain databases

CDDicd10582. TNFRSF14. 1 hit.
InterProiView protein in InterPro
IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022332. TNFR_14.
IPR034031. TNFRSF14/UL144_N.
PfamiView protein in Pfam
PF00020. TNFR_c6. 1 hit.
PRINTSiPR01965. TNFACTORR14.
SMARTiView protein in SMART
SM00208. TNFR. 3 hits.
PROSITEiView protein in PROSITE
PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92956-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPPGDWGPP PWRSTPKTDV LRLVLYLTFL GAPCYAPALP SCKEDEYPVG
60 70 80 90 100
SECCPKCSPG YRVKEACGEL TGTVCEPCPP GTYIAHLNGL SKCLQCQMCD
110 120 130 140 150
PAMGLRASRN CSRTENAVCG CSPGHFCIVQ DGDHCAACRA YATSSPGQRV
160 170 180 190 200
QKGGTESQDT LCQNCPPGTF SPNGTLEECQ HQTKCSWLVT KAGAGTSSSH
210 220 230 240 250
WVWWFLSGSL VIVIVCSTVG LIICVKRRKP RGDVVKVIVS VQRKRQEAEG
260 270 280
EATVIEALQA PPDVTTVAVE ETIPSFTGRS PNH
Length:283
Mass (Da):30,392
Last modified:April 27, 2001 - v3
Checksum:i46CE13C2C70242C1
GO
Isoform 2 (identifier: Q92956-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: MEPPGDWGPP...SKCLQCQMCD → MVSRPPRTPLSPSSWT

Show »
Length:199
Mass (Da):21,351
Checksum:iB14A3275B16BBD66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135C → R in AAH29848 (Ref. 10) IKR:1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01300717K → R3 PublicationsCorresponds to variant dbSNP:rs4870Ensembl.1
Natural variantiVAR_018955117A → T1 PublicationCorresponds to variant dbSNP:rs2234163Ensembl.1
Natural variantiVAR_018956174G → E1 PublicationCorresponds to variant dbSNP:rs11573986Ensembl.1
Natural variantiVAR_013440241V → I2 PublicationsCorresponds to variant dbSNP:rs2234167Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0541861 – 100MEPPG…CQMCD → MVSRPPRTPLSPSSWT in isoform 2. IBD:Add BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70321 mRNA. Translation: AAB58354.1.
U81232 mRNA. Translation: AAD00505.1.
AF153978 mRNA. Translation: AAF75588.1.
AF373877 mRNA. Translation: AAL47717.1.
AF373878 mRNA. Translation: AAL47718.1.
AY358879 mRNA. Translation: AAQ89238.1.
AK124010 mRNA. Translation: BAG53992.1.
CR456909 mRNA. Translation: CAG33190.1.
AY466111 Genomic DNA. Translation: AAR23264.1.
AL139246 Genomic DNA. Translation: CAX30824.1.
CH471183 Genomic DNA. Translation: EAW56089.1.
CH471183 Genomic DNA. Translation: EAW56090.1.
BC002794 mRNA. Translation: AAH02794.1.
BC029848 mRNA. Translation: AAH29848.1.
CCDSiCCDS44046.1. [Q92956-1]
RefSeqiNP_003811.2. NM_003820.3. [Q92956-1]
XP_016858209.1. XM_017002720.1. [Q92956-2]
UniGeneiHs.512898.
Hs.682060.

Genome annotation databases

EnsembliENST00000355716; ENSP00000347948; ENSG00000157873. [Q92956-1]
ENST00000621877; ENSP00000478308; ENSG00000273936. [Q92956-1]
GeneIDi8764.
KEGGihsa:8764.
UCSCiuc001ajr.4. human. [Q92956-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTNR14_HUMAN
AccessioniPrimary (citable) accession number: Q92956
Secondary accession number(s): B3KW30
, B9DI89, Q6IB95, Q8N634, Q8WXR1, Q96J31, Q9UM65
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: October 25, 2017
This is version 190 of the entry and version 3 of the sequence. See 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, Direct protein sequencing, 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