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Protein

Tumor necrosis factor ligand superfamily member 14

Gene

TNFSF14

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

Functioni

Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB, stimulates the proliferation of T-cells, and inhibits growth of the adenocarcinoma HT-29. Acts as a receptor for Herpes simplex virus.

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: ProtInc
  • cellular response to mechanical stimulus Source: UniProtKB
  • immune response Source: InterPro
  • positive regulation of myoblast differentiation Source: Ensembl
  • positive regulation of myoblast fusion Source: Ensembl
  • positive regulation of T cell chemotaxis Source: Ensembl
  • release of cytoplasmic sequestered NF-kappaB Source: UniProtKB
  • signal transduction Source: UniProtKB
  • T cell activation Source: UniProtKB
  • T cell costimulation Source: Ensembl
  • T cell homeostasis Source: UniProtKB
  • T cell proliferation Source: UniProtKB
  • tumor necrosis factor-mediated signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125735-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5669034. TNFs bind their physiological receptors.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiO43557.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor ligand superfamily member 14
Alternative name(s):
Herpes virus entry mediator ligand
Short name:
HVEM-L
Short name:
Herpesvirus entry mediator ligand
CD_antigen: CD258
Cleaved into the following 2 chains:
Gene namesi
Name:TNFSF14
Synonyms:HVEML, LIGHT
ORF Names:UNQ391/PRO726
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11930. TNFSF14.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37CytoplasmicSequence analysisAdd BLAST37
Transmembranei38 – 58Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini59 – 240ExtracellularSequence analysisAdd BLAST182

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi8740.
OpenTargetsiENSG00000125735.
PharmGKBiPA36622.

Polymorphism and mutation databases

BioMutaiTNFSF14.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000345321 – 240Tumor necrosis factor ligand superfamily member 14, membrane formAdd BLAST240
ChainiPRO_0000034533?83 – 240Tumor necrosis factor ligand superfamily member 14, soluble formAdd BLAST158

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi102N-linked (GlcNAc...)1 Publication1
Disulfide bondi154 ↔ 1871 Publication

Post-translational modificationi

N-glycosylated.1 Publication
The soluble form of isoform 1 derives from the membrane form by proteolytic processing.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei82 – 83CleavageSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43557.
PeptideAtlasiO43557.
PRIDEiO43557.

PTM databases

iPTMnetiO43557.
PhosphoSitePlusiO43557.
SwissPalmiO43557.

Expressioni

Tissue specificityi

Predominantly expressed in the spleen but also found in the brain. Weakly expressed in peripheral lymphoid tissues and in heart, placenta, liver, lung, appendix, and kidney, and no expression seen in fetal tissues, endocrine glands, or nonhematopoietic tumor lines.

Inductioni

Up-regulated after T-cell activation.

Gene expression databases

BgeeiENSG00000125735.
CleanExiHS_TNFSF14.
GenevisibleiO43557. HS.

Organism-specific databases

HPAiHPA012700.

Interactioni

Subunit structurei

Homotrimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
LTBRP369413EBI-524131,EBI-3509981
LtbrP502842EBI-524131,EBI-647023From a different organism.
TNFRSF14Q929565EBI-524131,EBI-1056653
Tnfrsf14Q71F552EBI-524131,EBI-11687219From a different organism.
TNFRSF6BO954072EBI-524131,EBI-524171

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114277. 8 interactors.
DIPiDIP-3016N.
IntActiO43557. 7 interactors.
STRINGi9606.ENSP00000469049.

Structurei

Secondary structure

1240
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi95 – 102Combined sources8
Beta strandi107 – 110Combined sources4
Beta strandi113 – 115Combined sources3
Beta strandi122 – 129Combined sources8
Beta strandi132 – 137Combined sources6
Beta strandi139 – 151Combined sources13
Beta strandi162 – 169Combined sources8
Beta strandi173 – 175Combined sources3
Beta strandi177 – 184Combined sources8
Helixi186 – 189Combined sources4
Beta strandi197 – 209Combined sources13
Beta strandi214 – 220Combined sources7
Helixi222 – 224Combined sources3
Beta strandi232 – 239Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4EN0X-ray2.59A/B/C83-240[»]
4J6GX-ray2.40A/B83-240[»]
4KG8X-ray2.25A/B/C83-240[»]
4KGGX-ray2.78A/B83-240[»]
4KGQX-ray2.27A/B83-240[»]
4RSUX-ray2.30A/B/C/G/H/I83-240[»]
ProteinModelPortaliO43557.
SMRiO43557.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IVET. Eukaryota.
ENOG41124FT. LUCA.
GeneTreeiENSGT00530000062992.
HOVERGENiHBG061471.
InParanoidiO43557.
KOiK05477.
OMAiQTDIPFR.
OrthoDBiEOG091G0MFC.
PhylomeDBiO43557.
TreeFamiTF332169.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS50049. TNF_2. 1 hit.
[Graphical view]

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: O43557-1) [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
MEESVVRPSV FVVDGQTDIP FTRLGRSHRR QSCSVARVGL GLLLLLMGAG
60 70 80 90 100
LAVQGWFLLQ LHWRLGEMVT RLPDGPAGSW EQLIQERRSH EVNPAAHLTG
110 120 130 140 150
ANSSLTGSGG PLLWETQLGL AFLRGLSYHD GALVVTKAGY YYIYSKVQLG
160 170 180 190 200
GVGCPLGLAS TITHGLYKRT PRYPEELELL VSQQSPCGRA TSSSRVWWDS
210 220 230 240
SFLGGVVHLE AGEKVVVRVL DERLVRLRDG TRSYFGAFMV
Length:240
Mass (Da):26,350
Last modified:November 30, 2010 - v2
Checksum:i49D0B1870F390B39
GO
Isoform 2 (identifier: O43557-2) [UniParc]FASTAAdd to basket
Also known as: LIGHT delta-TM

The sequence of this isoform differs from the canonical sequence as follows:
     38-73: Missing.

Show »
Length:204
Mass (Da):22,395
Checksum:iFF97FD515DB2EB11
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02767732S → L.Corresponds to variant rs2291667dbSNPEnsembl.1
Natural variantiVAR_027678120L → V.Corresponds to variant rs17851606dbSNPEnsembl.1
Natural variantiVAR_027679214K → E.5 PublicationsCorresponds to variant rs344560dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00645238 – 73Missing in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036581 mRNA. Translation: AAC39563.1.
AF064090 mRNA. Translation: AAC25169.1.
AY028261 mRNA. Translation: AAK26160.1.
AY358812 mRNA. Translation: AAQ89171.1.
AK292037 mRNA. Translation: BAF84726.1.
CR541854 mRNA. Translation: CAG46652.1.
CR541871 mRNA. Translation: CAG46669.1.
AC008760 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69072.1.
CCDSiCCDS12171.1. [O43557-1]
CCDS45939.1. [O43557-2]
RefSeqiNP_003798.2. NM_003807.4. [O43557-1]
NP_742011.2. NM_172014.3. [O43557-2]
XP_016882906.1. XM_017027417.1. [O43557-1]
UniGeneiHs.129708.

Genome annotation databases

EnsembliENST00000245912; ENSP00000245912; ENSG00000125735. [O43557-2]
ENST00000599359; ENSP00000469049; ENSG00000125735. [O43557-1]
GeneIDi8740.
KEGGihsa:8740.
UCSCiuc002mfk.3. human. [O43557-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036581 mRNA. Translation: AAC39563.1.
AF064090 mRNA. Translation: AAC25169.1.
AY028261 mRNA. Translation: AAK26160.1.
AY358812 mRNA. Translation: AAQ89171.1.
AK292037 mRNA. Translation: BAF84726.1.
CR541854 mRNA. Translation: CAG46652.1.
CR541871 mRNA. Translation: CAG46669.1.
AC008760 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69072.1.
CCDSiCCDS12171.1. [O43557-1]
CCDS45939.1. [O43557-2]
RefSeqiNP_003798.2. NM_003807.4. [O43557-1]
NP_742011.2. NM_172014.3. [O43557-2]
XP_016882906.1. XM_017027417.1. [O43557-1]
UniGeneiHs.129708.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4EN0X-ray2.59A/B/C83-240[»]
4J6GX-ray2.40A/B83-240[»]
4KG8X-ray2.25A/B/C83-240[»]
4KGGX-ray2.78A/B83-240[»]
4KGQX-ray2.27A/B83-240[»]
4RSUX-ray2.30A/B/C/G/H/I83-240[»]
ProteinModelPortaliO43557.
SMRiO43557.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114277. 8 interactors.
DIPiDIP-3016N.
IntActiO43557. 7 interactors.
STRINGi9606.ENSP00000469049.

PTM databases

iPTMnetiO43557.
PhosphoSitePlusiO43557.
SwissPalmiO43557.

Polymorphism and mutation databases

BioMutaiTNFSF14.

Proteomic databases

PaxDbiO43557.
PeptideAtlasiO43557.
PRIDEiO43557.

Protocols and materials databases

DNASUi8740.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245912; ENSP00000245912; ENSG00000125735. [O43557-2]
ENST00000599359; ENSP00000469049; ENSG00000125735. [O43557-1]
GeneIDi8740.
KEGGihsa:8740.
UCSCiuc002mfk.3. human. [O43557-1]

Organism-specific databases

CTDi8740.
DisGeNETi8740.
GeneCardsiTNFSF14.
HGNCiHGNC:11930. TNFSF14.
HPAiHPA012700.
MIMi604520. gene.
neXtProtiNX_O43557.
OpenTargetsiENSG00000125735.
PharmGKBiPA36622.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVET. Eukaryota.
ENOG41124FT. LUCA.
GeneTreeiENSGT00530000062992.
HOVERGENiHBG061471.
InParanoidiO43557.
KOiK05477.
OMAiQTDIPFR.
OrthoDBiEOG091G0MFC.
PhylomeDBiO43557.
TreeFamiTF332169.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000125735-MONOMER.
ReactomeiR-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5669034. TNFs bind their physiological receptors.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiO43557.

Miscellaneous databases

GeneWikiiTNFSF14.
GenomeRNAii8740.
PROiO43557.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125735.
CleanExiHS_TNFSF14.
GenevisibleiO43557. HS.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNF14_HUMAN
AccessioniPrimary (citable) accession number: O43557
Secondary accession number(s): A8K7M2
, C9J5H4, O75476, Q6FHA1, Q8WVF8, Q96LD2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 163 of the entry and version 2 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 19
    Human chromosome 19: 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.