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Protein

Tumor necrosis factor ligand superfamily member 14

Gene

TNFSF14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000125735.10
HGNCiHGNC:11930 TNFSF14
MIMi604520 gene
neXtProtiNX_O43557

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 domaini1 – 37CytoplasmicSequence analysisAdd BLAST37
Transmembranei38 – 58Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini59 – 240ExtracellularSequence analysisAdd BLAST182

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi8740
OpenTargetsiENSG00000125735
PharmGKBiPA36622

Chemistry databases

ChEMBLiCHEMBL3712914

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...) asparagine1 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
ProteomicsDBi49049
49050 [O43557-2]

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 Expressed in 106 organ(s), highest expression level in right lobe of liver
CleanExiHS_TNFSF14
GenevisibleiO43557 HS

Organism-specific databases

HPAiHPA012700

Interactioni

Subunit structurei

Homotrimer.

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114277, 16 interactors
DIPiDIP-3016N
IntActiO43557, 23 interactors
STRINGi9606.ENSP00000469049

Structurei

Secondary structure

1240
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS50049 TNF_2, 1 hit

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 dbSNP:rs2291667Ensembl.1
Natural variantiVAR_027678120L → V. Corresponds to variant dbSNP:rs17851606Ensembl.1
Natural variantiVAR_027679214K → E5 PublicationsCorresponds to variant dbSNP:rs344560Ensembl.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

Similar proteinsi

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, 16 interactors
DIPiDIP-3016N
IntActiO43557, 23 interactors
STRINGi9606.ENSP00000469049

Chemistry databases

ChEMBLiCHEMBL3712914

PTM databases

iPTMnetiO43557
PhosphoSitePlusiO43557
SwissPalmiO43557

Polymorphism and mutation databases

BioMutaiTNFSF14

Proteomic databases

PaxDbiO43557
PeptideAtlasiO43557
PRIDEiO43557
ProteomicsDBi49049
49050 [O43557-2]

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
EuPathDBiHostDB:ENSG00000125735.10
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

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
PROiPR:O43557
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125735 Expressed in 106 organ(s), highest expression level in right lobe of liver
CleanExiHS_TNFSF14
GenevisibleiO43557 HS

Family and domain databases

CDDicd00184 TNF, 1 hit
Gene3Di2.60.120.40, 1 hit
InterProiView protein in InterPro
IPR006053 TNF
IPR006052 TNF_dom
IPR008983 Tumour_necrosis_fac-like_dom
PfamiView protein in Pfam
PF00229 TNF, 1 hit
PRINTSiPR01234 TNECROSISFCT
SMARTiView protein in SMART
SM00207 TNF, 1 hit
SUPFAMiSSF49842 SSF49842, 1 hit
PROSITEiView protein in PROSITE
PS50049 TNF_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTNF14_HUMAN
AccessioniPrimary (citable) accession number: O43557
Secondary accession number(s): A8K7M2
, C9J5H4, O75476, Q6FHA1, Q8WVF8, Q96LD2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 30, 2010
Last modified: September 12, 2018
This is version 173 of the entry and version 2 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, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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