Q92956 · TNR14_HUMAN
- ProteinTumor necrosis factor receptor superfamily member 14
- GeneTNFRSF14
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids283 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:10754304, PubMed:18193050, PubMed:23761635, PubMed:9462508).
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 pro-inflammatory 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 (By similarity) (PubMed:19915044).
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 (By similarity) (PubMed:19915044).
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 pro-inflammatory 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 (By similarity) (PubMed:19915044).
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 (By similarity) (PubMed:19915044).
(Microbial infection) Acts as a receptor for Herpes simplex virus 1/HHV-1.
(Microbial infection) Acts as a receptor for Herpes simplex virus 2/HHV-2.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | plasma membrane | |
Molecular Function | cytokine binding | |
Molecular Function | tumor necrosis factor receptor activity | |
Molecular Function | ubiquitin protein ligase binding | |
Molecular Function | virus receptor activity | |
Biological Process | adaptive immune response | |
Biological Process | cell surface receptor signaling pathway | |
Biological Process | defense response to Gram-negative bacterium | |
Biological Process | defense response to Gram-positive bacterium | |
Biological Process | immune response | |
Biological Process | innate immune response | |
Biological Process | negative regulation of adaptive immune memory response | |
Biological Process | negative regulation of alpha-beta T cell proliferation | |
Biological Process | positive regulation of cytokine production involved in immune response | |
Biological Process | positive regulation of peptidyl-tyrosine phosphorylation | |
Biological Process | positive regulation of T cell migration | |
Biological Process | T cell costimulation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTumor necrosis factor receptor superfamily member 14
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ92956
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 39-202 | Extracellular | ||||
Sequence: LPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWV | ||||||
Transmembrane | 203-223 | Helical | ||||
Sequence: WWFLSGSLVIVIVCSTVGLII | ||||||
Topological domain | 224-283 | Cytoplasmic | ||||
Sequence: CVKRRKPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPPDVTTVAVEETIPSFTGRSPNH |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_013007 | 17 | in dbSNP:rs4870 | |||
Sequence: K → R | ||||||
Mutagenesis | 61 | Abolishes cis interactions with BTLA. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 61 | Does not affect cis interactions with BTLA. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_018955 | 117 | in dbSNP:rs2234163 | |||
Sequence: A → T | ||||||
Natural variant | VAR_018956 | 174 | in dbSNP:rs11573986 | |||
Sequence: G → E | ||||||
Natural variant | VAR_013440 | 241 | in dbSNP:rs2234167 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 845 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-38 | |||||
Sequence: MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPA | ||||||
Chain | PRO_0000034590 | 39-283 | Tumor necrosis factor receptor superfamily member 14 | |||
Sequence: LPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWVWWFLSGSLVIVIVCSTVGLIICVKRRKPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPPDVTTVAVEETIPSFTGRSPNH | ||||||
Disulfide bond | 42↔53 | |||||
Sequence: CKEDEYPVGSEC | ||||||
Disulfide bond | 54↔67 | |||||
Sequence: CPKCSPGYRVKEAC | ||||||
Disulfide bond | 57↔75 | |||||
Sequence: CSPGYRVKEACGELTGTVC | ||||||
Disulfide bond | 78↔93 | |||||
Sequence: CPPGTYIAHLNGLSKC | ||||||
Disulfide bond | 96↔111 | |||||
Sequence: CQMCDPAMGLRASRNC | ||||||
Disulfide bond | 99↔119 | |||||
Sequence: CDPAMGLRASRNCSRTENAVC | ||||||
Glycosylation | 110 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 121↔138 | |||||
Sequence: CSPGHFCIVQDGDHCAAC | ||||||
Disulfide bond | 127↔135 | |||||
Sequence: CIVQDGDHC | ||||||
Glycosylation | 173 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 240 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
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:16169851, PubMed:19915044).
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:16169851, PubMed:19915044).
(Microbial infection) Interacts with herpes simplex virus 1/HHV-1 envelope glycoprotein D.
(Microbial infection) Interacts with herpes simplex virus 2/HHV-2 envelope glycoprotein D.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q92956 | FOXD4L6 Q3SYB3 | 3 | EBI-1056653, EBI-6425864 | |
BINARY | Q92956 | TNFSF14 O43557 | 5 | EBI-1056653, EBI-524131 | |
BINARY | Q92956 | TRAF2 Q12933 | 2 | EBI-1056653, EBI-355744 | |
BINARY | Q92956 | TRAF2 Q12933-2 | 4 | EBI-1056653, EBI-355760 | |
BINARY | Q92956 | TRAF5 O00463 | 5 | EBI-1056653, EBI-523498 | |
BINARY | Q92956-2 | TARDBP Q13148 | 6 | EBI-25985089, EBI-372899 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 42-75 | TNFR-Cys 1 | ||||
Sequence: CKEDEYPVGSECCPKCSPGYRVKEACGELTGTVC | ||||||
Repeat | 78-119 | TNFR-Cys 2 | ||||
Sequence: CPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVC | ||||||
Repeat | 121-162 | TNFR-Cys 3 | ||||
Sequence: CSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLC |
Domain
The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for interaction with BY55 and BTLA.
Sequence similarities
Belongs to the tumor necrosis factor receptor superfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q92956-1
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.
- Name1
- Length283
- Mass (Da)30,392
- Last updated2001-04-27 v3
- Checksum46CE13C2C70242C1
Q92956-2
- Name2
- Differences from canonical
- 1-100: MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCD → MVSRPPRTPLSPSSWT
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6UPZ7 | F6UPZ7_HUMAN | TNFRSF14 | 183 | ||
A0A0D9SF52 | A0A0D9SF52_HUMAN | TNFRSF14 | 25 | ||
B9A034 | B9A034_HUMAN | TNFRSF14 | 193 | ||
F6Q0M4 | F6Q0M4_HUMAN | TNFRSF14 | 231 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054186 | 1-100 | in isoform 2 | |||
Sequence: MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCD → MVSRPPRTPLSPSSWT | ||||||
Sequence conflict | 135 | in Ref. 10; AAH29848 | ||||
Sequence: C → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U70321 EMBL· GenBank· DDBJ | AAB58354.1 EMBL· GenBank· DDBJ | mRNA | ||
U81232 EMBL· GenBank· DDBJ | AAD00505.1 EMBL· GenBank· DDBJ | mRNA | ||
AF153978 EMBL· GenBank· DDBJ | AAF75588.1 EMBL· GenBank· DDBJ | mRNA | ||
AF373877 EMBL· GenBank· DDBJ | AAL47717.1 EMBL· GenBank· DDBJ | mRNA | ||
AF373878 EMBL· GenBank· DDBJ | AAL47718.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358879 EMBL· GenBank· DDBJ | AAQ89238.1 EMBL· GenBank· DDBJ | mRNA | ||
AK124010 EMBL· GenBank· DDBJ | BAG53992.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456909 EMBL· GenBank· DDBJ | CAG33190.1 EMBL· GenBank· DDBJ | mRNA | ||
AY466111 EMBL· GenBank· DDBJ | AAR23264.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL139246 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471183 EMBL· GenBank· DDBJ | EAW56089.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471183 EMBL· GenBank· DDBJ | EAW56090.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002794 EMBL· GenBank· DDBJ | AAH02794.1 EMBL· GenBank· DDBJ | mRNA | ||
BC029848 EMBL· GenBank· DDBJ | AAH29848.1 EMBL· GenBank· DDBJ | mRNA |