UniProtKB - Q92956 (TNR14_HUMAN)
Tumor necrosis factor receptor superfamily member 14
TNFRSF14
Functioni
Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signaling network (PubMed:9462508, PubMed:10754304, PubMed:18193050, PubMed:23761635).
Signals via the TRAF2-TRAF3 E3 ligase pathway to promote immune cell survival and differentiation (PubMed:19915044, PubMed:9153189, PubMed:9162022).
Participates in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. In response to ligation of TNFSF14/LIGHT, delivers costimulatory signals to T cells, promoting cell proliferation and effector functions (PubMed:10754304).
Interacts with CD160 on NK cells, enhancing IFNG production and anti-tumor immune response (PubMed:23761635).
In the context of bacterial infection, acts as a signaling receptor on epithelial cells for CD160 from intraepithelial lymphocytes, triggering the production of antimicrobial proteins and proinflammatory cytokines (By similarity).
Upon binding to CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050).
May interact in cis (on the same cell) or in trans (on other cells) with BTLA (PubMed:19915044) (By similarity).
In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells (PubMed:19915044) (By similarity).
By similarity7 Publications(Microbial infection) Acts as a receptor for Herpes simplex virus 1/HHV-1.
2 Publications(Microbial infection) Acts as a receptor for Herpes simplex virus 2/HHV-2.
2 PublicationsGO - Molecular functioni
- cytokine binding Source: UniProtKB
- tumor necrosis factor-activated receptor activity Source: ProtInc
- ubiquitin protein ligase binding Source: UniProtKB
- virus receptor activity Source: UniProtKB-KW
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- cell surface receptor signaling pathway Source: ProtInc
- defense response to Gram-negative bacterium Source: GO_Central
- defense response to Gram-positive bacterium Source: GO_Central
- immune response Source: ProtInc
- innate immune response Source: UniProtKB-KW
- negative regulation of adaptive immune memory response Source: UniProtKB
- negative regulation of alpha-beta T cell proliferation Source: GO_Central
- positive regulation of cytokine production involved in immune response Source: GO_Central
- positive regulation of peptidyl-tyrosine phosphorylation Source: GO_Central
- positive regulation of T cell migration Source: GO_Central
- T cell costimulation Source: UniProtKB
Keywordsi
Molecular function | Host cell receptor for virus entry, Receptor |
Biological process | Adaptive immunity, Host-virus interaction, Immunity, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | Q92956 |
Reactomei | R-HSA-388841, Costimulation by the CD28 family R-HSA-5669034, TNFs bind their physiological receptors |
SignaLinki | Q92956 |
SIGNORi | Q92956 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor necrosis factor receptor superfamily member 14Alternative name(s): Herpes virus entry mediator A1 Publication Short name: Herpesvirus entry mediator A1 Publication Short name: HveA1 Publication Tumor necrosis factor receptor-like 2 Short name: TR21 Publication CD_antigen: CD270 |
Gene namesi | ORF Names:UNQ329/PRO509 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11912, TNFRSF14 |
MIMi | 602746, gene |
neXtProti | NX_Q92956 |
VEuPathDBi | HostDB:ENSG00000157873 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein Curated
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 39 – 202 | ExtracellularSequence analysisAdd BLAST | 164 | |
Transmembranei | 203 – 223 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 224 – 283 | CytoplasmicSequence analysisAdd BLAST | 60 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 61 | Y → A: Abolishes cis interactions with BTLA. 1 Publication | 1 | |
Mutagenesisi | 61 | Y → F: Does not affect cis interactions with BTLA. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8764 |
OpenTargetsi | ENSG00000157873 |
PharmGKBi | PA36605 |
Miscellaneous databases
Pharosi | Q92956, Tbio |
Genetic variation databases
BioMutai | TNFRSF14 |
DMDMi | 13878821 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 38 | 1 PublicationAdd BLAST | 38 | |
ChainiPRO_0000034590 | 39 – 283 | Tumor necrosis factor receptor superfamily member 14Add BLAST | 245 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 42 ↔ 53 | 1 Publication | ||
Disulfide bondi | 54 ↔ 67 | 1 Publication | ||
Disulfide bondi | 57 ↔ 75 | 1 Publication | ||
Disulfide bondi | 78 ↔ 93 | 1 Publication | ||
Disulfide bondi | 96 ↔ 111 | 1 Publication | ||
Disulfide bondi | 99 ↔ 119 | 1 Publication | ||
Glycosylationi | 110 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 121 ↔ 138 | 1 Publication | ||
Disulfide bondi | 127 ↔ 135 | 1 Publication | ||
Glycosylationi | 173 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 240 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q92956 |
jPOSTi | Q92956 |
MassIVEi | Q92956 |
PaxDbi | Q92956 |
PeptideAtlasi | Q92956 |
PRIDEi | Q92956 |
ProteomicsDBi | 75630 [Q92956-1] |
PTM databases
GlyGeni | Q92956, 2 sites |
iPTMneti | Q92956 |
PhosphoSitePlusi | Q92956 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000157873, Expressed in muscle layer of sigmoid colon and 198 other tissues |
ExpressionAtlasi | Q92956, baseline and differential |
Genevisiblei | Q92956, HS |
Organism-specific databases
HPAi | ENSG00000157873, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with TRAF2, TRAF3 and TRAF5 (PubMed:9153189, PubMed:9162022).
Interacts (via CRD1/TNFR-Cys 1) with CD160; this interaction is direct (PubMed:18193050, PubMed:23761635).
Interacts with LTA and TNFSF14 (PubMed:9462508).
Interacts (via CRD1/TNFR-Cys 1) in cis and trans with BTLA; the cis interactions inhibits the trans interactions (PubMed:19915044, PubMed:16169851).
7 Publications(Microbial infection) Interacts with herpes simplex virus 1/HHV-1 envelope glycoprotein D.
2 Publications(Microbial infection) Interacts with herpes simplex virus 2/HHV-2 envelope glycoprotein D.
2 PublicationsBinary interactionsi
Q92956
Isoform 2 [Q92956-2]
With | #Exp. | IntAct |
---|---|---|
TARDBP [Q13148] | 6 | EBI-25985089,EBI-372899 |
GO - Molecular functioni
- cytokine binding Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114298, 31 interactors |
DIPi | DIP-34779N |
ELMi | Q92956 |
IntActi | Q92956, 31 interactors |
MINTi | Q92956 |
STRINGi | 9606.ENSP00000347948 |
Miscellaneous databases
RNActi | Q92956, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q92956 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q92956 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 42 – 75 | TNFR-Cys 1Add BLAST | 34 | |
Repeati | 78 – 119 | TNFR-Cys 2Add BLAST | 42 | |
Repeati | 121 – 162 | TNFR-Cys 3Add BLAST | 42 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502S1XZ, Eukaryota |
GeneTreei | ENSGT00940000162427 |
InParanoidi | Q92956 |
OMAi | GWELPPW |
PhylomeDBi | Q92956 |
TreeFami | TF331157 |
Family and domain databases
CDDi | cd10582, TNFRSF14, 1 hit |
InterProi | View protein in InterPro IPR001368, TNFR/NGFR_Cys_rich_reg IPR022332, TNFR_14 IPR034031, TNFRSF14/UL144_N |
Pfami | View protein in Pfam PF00020, TNFR_c6, 1 hit |
PRINTSi | PR01965, TNFACTORR14 |
SMARTi | View protein in SMART SM00208, TNFR, 3 hits |
PROSITEi | View protein in PROSITE PS00652, TNFR_NGFR_1, 1 hit PS50050, TNFR_NGFR_2, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF6Q0M4 | F6Q0M4_HUMAN | Tumor necrosis factor receptor supe... | TNFRSF14 | 231 | Annotation score: | ||
F6UPZ7 | F6UPZ7_HUMAN | Tumor necrosis factor receptor supe... | TNFRSF14 | 183 | Annotation score: | ||
B9A034 | B9A034_HUMAN | Tumor necrosis factor receptor supe... | TNFRSF14 | 193 | Annotation score: | ||
A0A0D9SF52 | A0A0D9SF52_HUMAN | Tumor necrosis factor receptor supe... | TNFRSF14 | 25 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 135 | C → R in AAH29848 (Ref. 10) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_013007 | 17 | K → R3 PublicationsCorresponds to variant dbSNP:rs4870EnsemblClinVar. | 1 | |
Natural variantiVAR_018955 | 117 | A → T1 PublicationCorresponds to variant dbSNP:rs2234163EnsemblClinVar. | 1 | |
Natural variantiVAR_018956 | 174 | G → E1 PublicationCorresponds to variant dbSNP:rs11573986EnsemblClinVar. | 1 | |
Natural variantiVAR_013440 | 241 | V → I2 PublicationsCorresponds to variant dbSNP:rs2234167EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054186 | 1 – 100 | MEPPG…CQMCD → MVSRPPRTPLSPSSWT in isoform 2. 2 PublicationsAdd BLAST | 100 |
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 No translation available. CH471183 Genomic DNA Translation: EAW56089.1 CH471183 Genomic DNA Translation: EAW56090.1 BC002794 mRNA Translation: AAH02794.1 BC029848 mRNA Translation: AAH29848.1 |
CCDSi | CCDS44046.1 [Q92956-1] |
RefSeqi | NP_003811.2, NM_003820.3 [Q92956-1] XP_016858209.1, XM_017002720.1 [Q92956-2] |
Genome annotation databases
Ensembli | ENST00000355716; ENSP00000347948; ENSG00000157873 ENST00000621877; ENSP00000478308; ENSG00000273936 |
GeneIDi | 8764 |
KEGGi | hsa:8764 |
MANE-Selecti | ENST00000355716.5; ENSP00000347948.4; NM_003820.4; NP_003811.2 |
UCSCi | uc001ajr.4, human [Q92956-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
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 No translation available. CH471183 Genomic DNA Translation: EAW56089.1 CH471183 Genomic DNA Translation: EAW56090.1 BC002794 mRNA Translation: AAH02794.1 BC029848 mRNA Translation: AAH29848.1 |
CCDSi | CCDS44046.1 [Q92956-1] |
RefSeqi | NP_003811.2, NM_003820.3 [Q92956-1] XP_016858209.1, XM_017002720.1 [Q92956-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1JMA | X-ray | 2.65 | B | 39-199 | [»] | |
2AW2 | X-ray | 2.80 | B/Y | 39-142 | [»] | |
4FHQ | X-ray | 2.25 | A | 39-162 | [»] | |
4RSU | X-ray | 2.30 | D/E/F/J/K/L | 39-162 | [»] | |
5T2Q | X-ray | 1.90 | A/B | 39-142 | [»] | |
5T2R | X-ray | 2.10 | A/B | 39-142 | [»] | |
6NG3 | X-ray | 2.88 | A | 39-143 | [»] | |
7MSG | X-ray | 3.50 | D/E/F | 39-143 | [»] | |
SMRi | Q92956 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114298, 31 interactors |
DIPi | DIP-34779N |
ELMi | Q92956 |
IntActi | Q92956, 31 interactors |
MINTi | Q92956 |
STRINGi | 9606.ENSP00000347948 |
PTM databases
GlyGeni | Q92956, 2 sites |
iPTMneti | Q92956 |
PhosphoSitePlusi | Q92956 |
Genetic variation databases
BioMutai | TNFRSF14 |
DMDMi | 13878821 |
Proteomic databases
EPDi | Q92956 |
jPOSTi | Q92956 |
MassIVEi | Q92956 |
PaxDbi | Q92956 |
PeptideAtlasi | Q92956 |
PRIDEi | Q92956 |
ProteomicsDBi | 75630 [Q92956-1] |
Protocols and materials databases
Antibodypediai | 1626, 784 antibodies from 45 providers |
CPTCi | Q92956, 1 antibody |
DNASUi | 8764 |
Genome annotation databases
Ensembli | ENST00000355716; ENSP00000347948; ENSG00000157873 ENST00000621877; ENSP00000478308; ENSG00000273936 |
GeneIDi | 8764 |
KEGGi | hsa:8764 |
MANE-Selecti | ENST00000355716.5; ENSP00000347948.4; NM_003820.4; NP_003811.2 |
UCSCi | uc001ajr.4, human [Q92956-1] |
Organism-specific databases
CTDi | 8764 |
DisGeNETi | 8764 |
GeneCardsi | TNFRSF14 |
HGNCi | HGNC:11912, TNFRSF14 |
HPAi | ENSG00000157873, Low tissue specificity |
MIMi | 602746, gene |
neXtProti | NX_Q92956 |
OpenTargetsi | ENSG00000157873 |
PharmGKBi | PA36605 |
VEuPathDBi | HostDB:ENSG00000157873 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S1XZ, Eukaryota |
GeneTreei | ENSGT00940000162427 |
InParanoidi | Q92956 |
OMAi | GWELPPW |
PhylomeDBi | Q92956 |
TreeFami | TF331157 |
Enzyme and pathway databases
PathwayCommonsi | Q92956 |
Reactomei | R-HSA-388841, Costimulation by the CD28 family R-HSA-5669034, TNFs bind their physiological receptors |
SignaLinki | Q92956 |
SIGNORi | Q92956 |
Miscellaneous databases
BioGRID-ORCSi | 8764, 5 hits in 1035 CRISPR screens |
ChiTaRSi | TNFRSF14, human |
EvolutionaryTracei | Q92956 |
GeneWikii | TNFRSF14 |
GenomeRNAii | 8764 |
Pharosi | Q92956, Tbio |
PROi | PR:Q92956 |
RNActi | Q92956, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000157873, Expressed in muscle layer of sigmoid colon and 198 other tissues |
ExpressionAtlasi | Q92956, baseline and differential |
Genevisiblei | Q92956, HS |
Family and domain databases
CDDi | cd10582, TNFRSF14, 1 hit |
InterProi | View protein in InterPro IPR001368, TNFR/NGFR_Cys_rich_reg IPR022332, TNFR_14 IPR034031, TNFRSF14/UL144_N |
Pfami | View protein in Pfam PF00020, TNFR_c6, 1 hit |
PRINTSi | PR01965, TNFACTORR14 |
SMARTi | View protein in SMART SM00208, TNFR, 3 hits |
PROSITEi | View protein in PROSITE PS00652, TNFR_NGFR_1, 1 hit PS50050, TNFR_NGFR_2, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | TNR14_HUMAN | |
Accessioni | Q92956Primary (citable) accession number: Q92956 Secondary accession number(s): B3KW30 Q9UM65 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | April 27, 2001 | |
Last modified: | February 23, 2022 | |
This is version 217 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families