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O43557

- TNF14_HUMAN

UniProt

O43557 - TNF14_HUMAN

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Protein
Tumor necrosis factor ligand superfamily member 14
Gene
TNFSF14, HVEML, LIGHT, UNQ391/PRO726
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei82 – 832Cleavage Reviewed prediction

GO - Molecular functioni

  1. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  2. protein binding Source: IntAct
  3. receptor binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. T cell activation Source: UniProtKB
  2. T cell costimulation Source: Ensembl
  3. T cell homeostasis Source: UniProtKB
  4. T cell proliferation Source: UniProtKB
  5. apoptotic process Source: ProtInc
  6. cellular response to mechanical stimulus Source: UniProtKB
  7. immune response Source: InterPro
  8. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: GOC
  9. positive regulation of T cell chemotaxis Source: Ensembl
  10. release of cytoplasmic sequestered NF-kappaB Source: UniProtKB
  11. signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

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
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:11930. TNFSF14.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei38 – 5821Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini59 – 240182Extracellular Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. extracellular space Source: UniProtKB-KW
  3. integral component of membrane Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36622.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 240240Tumor necrosis factor ligand superfamily member 14, membrane form
PRO_0000034532Add
BLAST
Chaini?83 – 240158Tumor necrosis factor ligand superfamily member 14, soluble form
PRO_0000034533Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi102 – 1021N-linked (GlcNAc...)1 Publication
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.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43557.
PRIDEiO43557.

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

BgeeiO43557.
CleanExiHS_TNFSF14.
GenevestigatoriO43557.

Organism-specific databases

HPAiHPA012700.

Interactioni

Subunit structurei

Homotrimer.

Binary interactionsi

WithEntry#Exp.IntActNotes
TNFRSF14Q929562EBI-524131,EBI-1056653
TNFRSF6BO954072EBI-524131,EBI-524171

Protein-protein interaction databases

BioGridi114277. 8 interactions.
DIPiDIP-3016N.
IntActiO43557. 3 interactions.
STRINGi9606.ENSP00000245912.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi95 – 1028
Beta strandi107 – 1104
Beta strandi113 – 1153
Beta strandi122 – 1298
Beta strandi132 – 1376
Beta strandi139 – 15113
Beta strandi162 – 1698
Beta strandi173 – 1753
Beta strandi177 – 1848
Helixi186 – 1894
Beta strandi197 – 20913
Beta strandi214 – 2207
Helixi222 – 2243
Beta strandi232 – 2398

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliO43557.
SMRiO43557. Positions 93-240.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG40950.
HOVERGENiHBG061471.
InParanoidiO43557.
KOiK05477.
OMAiAGYYYIY.
OrthoDBiEOG7V4B0Q.
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. Align

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

MEESVVRPSV FVVDGQTDIP FTRLGRSHRR QSCSVARVGL GLLLLLMGAG    50
LAVQGWFLLQ LHWRLGEMVT RLPDGPAGSW EQLIQERRSH EVNPAAHLTG 100
ANSSLTGSGG PLLWETQLGL AFLRGLSYHD GALVVTKAGY YYIYSKVQLG 150
GVGCPLGLAS TITHGLYKRT PRYPEELELL VSQQSPCGRA TSSSRVWWDS 200
SFLGGVVHLE AGEKVVVRVL DERLVRLRDG TRSYFGAFMV 240
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti32 – 321S → L.
Corresponds to variant rs2291667 [ dbSNP | Ensembl ].
VAR_027677
Natural varianti120 – 1201L → V.
Corresponds to variant rs17851606 [ dbSNP | Ensembl ].
VAR_027678
Natural varianti214 – 2141K → E.5 Publications
Corresponds to variant rs344560 [ dbSNP | Ensembl ].
VAR_027679

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei38 – 7336Missing in isoform 2.
VSP_006452Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_003807.3. [O43557-1]
NP_742011.2. NM_172014.2. [O43557-2]
XP_005259727.1. XM_005259670.1. [O43557-2]
UniGeneiHs.129708.

Genome annotation databases

EnsembliENST00000245912; ENSP00000245912; ENSG00000125735. [O43557-2]
ENST00000326176; ENSP00000326940; ENSG00000125735. [O43557-2]
ENST00000599359; ENSP00000469049; ENSG00000125735. [O43557-1]
GeneIDi8740.
KEGGihsa:8740.
UCSCiuc002mfj.2. human. [O43557-2]
uc002mfk.2. human. [O43557-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS12171.1. [O43557-1 ]
CCDS45939.1. [O43557-2 ]
RefSeqi NP_003798.2. NM_003807.3. [O43557-1 ]
NP_742011.2. NM_172014.2. [O43557-2 ]
XP_005259727.1. XM_005259670.1. [O43557-2 ]
UniGenei Hs.129708.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4EN0 X-ray 2.59 A/B/C 83-240 [» ]
4J6G X-ray 2.40 A/B 83-240 [» ]
4KG8 X-ray 2.25 A/B/C 83-240 [» ]
4KGG X-ray 2.78 A/B 83-240 [» ]
4KGQ X-ray 2.27 A/B 83-240 [» ]
ProteinModelPortali O43557.
SMRi O43557. Positions 93-240.
ModBasei Search...

Protein-protein interaction databases

BioGridi 114277. 8 interactions.
DIPi DIP-3016N.
IntActi O43557. 3 interactions.
STRINGi 9606.ENSP00000245912.

Proteomic databases

PaxDbi O43557.
PRIDEi O43557.

Protocols and materials databases

DNASUi 8740.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000245912 ; ENSP00000245912 ; ENSG00000125735 . [O43557-2 ]
ENST00000326176 ; ENSP00000326940 ; ENSG00000125735 . [O43557-2 ]
ENST00000599359 ; ENSP00000469049 ; ENSG00000125735 . [O43557-1 ]
GeneIDi 8740.
KEGGi hsa:8740.
UCSCi uc002mfj.2. human. [O43557-2 ]
uc002mfk.2. human. [O43557-1 ]

Organism-specific databases

CTDi 8740.
GeneCardsi GC19M006663.
HGNCi HGNC:11930. TNFSF14.
HPAi HPA012700.
MIMi 604520. gene.
neXtProti NX_O43557.
PharmGKBi PA36622.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40950.
HOVERGENi HBG061471.
InParanoidi O43557.
KOi K05477.
OMAi AGYYYIY.
OrthoDBi EOG7V4B0Q.
PhylomeDBi O43557.
TreeFami TF332169.

Miscellaneous databases

GeneWikii TNFSF14.
GenomeRNAii 8740.
NextBioi 32787.
PROi O43557.
SOURCEi Search...

Gene expression databases

Bgeei O43557.
CleanExi HS_TNFSF14.
Genevestigatori O43557.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR006053. TNF.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
PRINTSi PR01234. TNECROSISFCT.
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator."
    Mauri D.N., Ebner R., Montgomery R.I., Kochel K.D., Cheung T.C., Yu G.-L., Ruben S., Murphy M., Eisenberg R.J., Cohen G.H., Spear P.G., Ware C.F.
    Immunity 8:21-30(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLU-214.
  2. "Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth."
    Harrop J.A., McDonnell P.C., Brigham-Burke M., Lyn S.D., Minton J., Tan K.B., Dede K., Spampanato J., Silverman C., Hensley P., DiPrinzio R., Emery J.G., Deen K., Eichman C., Chabot-Fletcher M., Truneh A., Young P.R.
    J. Biol. Chem. 273:27548-27556(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
    Tissue: Liver.
  3. "Genomic characterization of LIGHT reveals linkage to an immune response locus on chromosome 19p13.3 and distinct isoforms generated by alternate splicing or proteolysis."
    Granger S.W., Butrovich K.D., Houshmand P., Edwards W.R., Ware C.F.
    J. Immunol. 167:5122-5128(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING, VARIANT GLU-214.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-214.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Spleen.
  6. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-214.
  7. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-214.
  9. "Crystal structure of LIGHT."
    New York structural genomics research consortium (NYSGRC)
    Submitted (MAY-2012) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 83-240, GLYCOSYLATION AT ASN-102, DISULFIDE BOND.

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: July 9, 2014
This is version 144 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

External Data

Dasty 3

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