Q92956 (TNR14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 14

Alternative name(s):
Herpes virus entry mediator A
Short name=Herpesvirus entry mediator A
Short name=HveA
Tumor necrosis factor receptor-like 2
Short name=TR2
CD_antigen=CD270

Gene names

Name:	TNFRSF14
Synonyms:	HVEA, HVEM
ORF Names:	UNQ329/PRO509

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	283 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for BTLA. Receptor for TNFSF14/LIGHT and homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte activation. Plays an important role in HSV pathogenesis because it enhanced the entry of several wild-type HSV strains of both serotypes into CHO cells, and mediated HSV entry into activated human T-cells. Ref.1
Subunit structure	Interacts with TRAF2, TRAF3 and TRAF5. Interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 1 (HHV-2) envelope glycoprotein D; functions as an entry receptor for these viruses. Ref.12 Ref.13 Ref.14
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
Tissue specificity	Widely expressed, with the highest expression in lung, spleen and thymus.
Post-translational modification	N-glycosylated. Ref.16
Sequence similarities	Contains 3 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Host cell receptor for virus entry Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	T cell costimulation Traceable author statement. Source: Reactome immune response Traceable author statement Ref.13. Source: ProtInc negative regulation of alpha-beta T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred by curator Ref.12. Source: ProtInc
Molecular_function	tumor necrosis factor-activated receptor activity Traceable author statement Ref.12. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFSF14	O43557	2	EBI-1056653,EBI-524131
TRAF2	Q12933-2	4	EBI-1056653,EBI-355760
TRAF5	O00463	5	EBI-1056653,EBI-523498

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 38

38

Ref.11

Chain

39 – 283

245

Tumor necrosis factor receptor superfamily member 14

PRO_0000034590

Regions

Topological domain

39 – 202

164

Extracellular Potential

Transmembrane

203 – 223

21

Helical; Potential

Topological domain

224 – 283

60

Cytoplasmic Potential

Repeat

42 – 75

34

TNFR-Cys 1

Repeat

78 – 119

42

TNFR-Cys 2

Repeat

121 – 162

42

TNFR-Cys 3

Amino acid modifications

Glycosylation

110

1

N-linked (GlcNAc...) Ref.16

Glycosylation

173

1

N-linked (GlcNAc...) Potential

Disulfide bond

42 ↔ 53

Disulfide bond

54 ↔ 67

Disulfide bond

57 ↔ 75

Disulfide bond

78 ↔ 93

Disulfide bond

96 ↔ 111

Disulfide bond

99 ↔ 119

Disulfide bond

121 ↔ 138

Disulfide bond

127 ↔ 135

Natural variations

Natural variant

17

1

K → R. Ref.4 Ref.5 Ref.7
Corresponds to variant rs4870 [ dbSNP | Ensembl ].

VAR_013007

Natural variant

117

1

A → T. Ref.7
Corresponds to variant rs2234163 [ dbSNP | Ensembl ].

VAR_018955

Natural variant

174

1

G → E. Ref.7
Corresponds to variant rs11573986 [ dbSNP | Ensembl ].

VAR_018956

Natural variant

241

1

V → I. Ref.4 Ref.7
Corresponds to variant rs2234167 [ dbSNP | Ensembl ].

VAR_013440

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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283

Helix Strand Turn

Details...

Beta strand

46 – 49

4

Beta strand

52 – 55

4

Beta strand

61 – 65

5

Beta strand

69 – 71

3

Beta strand

74 – 77

4

Beta strand

86 – 88

3

Helix

101 – 103

3

Beta strand

105 – 109

5

Beta strand

113 – 115

3

Beta strand

118 – 121

4

Beta strand

125 – 131

7

Beta strand

134 – 140

7

Sequences

	Sequence		Length	Mass (Da)
	Q92956 [UniParc]. Last modified April 27, 2001. Version 3. Checksum: 46CE13C2C70242C1	FASTA	283	30,392
	10 20 30 40 50 60 MEPPGDWGPP PWRSTPKTDV LRLVLYLTFL GAPCYAPALP SCKEDEYPVG SECCPKCSPG 70 80 90 100 110 120 YRVKEACGEL TGTVCEPCPP GTYIAHLNGL SKCLQCQMCD PAMGLRASRN CSRTENAVCG 130 140 150 160 170 180 CSPGHFCIVQ DGDHCAACRA YATSSPGQRV QKGGTESQDT LCQNCPPGTF SPNGTLEECQ 190 200 210 220 230 240 HQTKCSWLVT KAGAGTSSSH WVWWFLSGSL VIVIVCSTVG LIICVKRRKP RGDVVKVIVS 250 260 270 280 VQRKRQEAEG EATVIEALQA PPDVTTVAVE ETIPSFTGRS PNH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family." Montgomery R.I., Warner M.S., Lum B.J., Spear P.G. Cell 87:427-436(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION AS A RECEPTOR FOR HHV-1. Tissue: Cervix adenocarcinoma.
[2]	"A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation." Kwon B.S., Tan K.B., Ni J., Oh K.-O., Lee Z.H., Kim K.K., Kim Y.-J., Wang S., Gentz R., Yu G.-L., Harrop J., Lyn S.D., Silverman C., Porter T.G., Truneh A., Young P.R. J. Biol. Chem. 272:14272-14276(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Zhang W., Wan T., Cao X. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Search for polymorphisms in the genes for herpesvirus entry mediator, Nectin-1, and Nectin-2 in immune seronegative individuals." Struyf F., Posavad C.M., Keyaerts E., Van Ranst M., Corey L., Spear P.G. J. Infect. Dis. 185:36-44(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-17 AND ILE-241.
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-17.
[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].
[7]	NIEHS SNPs program Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-17; THR-117; GLU-174 AND ILE-241.
[8]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[11]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 39-53.
[12]	"ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5." Hsu H., Solovyev I., Colombero A., Elliott R., Kelley M., Boyle W.J. J. Biol. Chem. 272:13471-13474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF2 AND TRAF5.
[13]	"Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1." Marsters S.A., Ayres T.M., Skubatch M., Gray C.L., Rothe M., Ashkenazi A. J. Biol. Chem. 272:14029-14032(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRAF3 AND TRAF5.
[14]	"Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry." Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J. J. Virol. 72:7064-7074(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HHV-1 AND HHV-2 GLYCOPROTEIN D.
[15]	"Herpes simplex virus glycoprotein D bound to the human receptor HveA." Carfi A., Willis S.H., Whitbeck J.C., Krummenacher C., Cohen G.H., Eisenberg R.J., Wiley D.C. Mol. Cell 8:169-179(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 39-200 IN COMPLEX WITH HUMAN HERPESVIRUS 1 GLYCOPROTEIN.
[16]	"Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex." Compaan D.M., Gonzalez L.C., Tom I., Loyet K.M., Eaton D., Hymowitz S.G. J. Biol. Chem. 280:39553-39561(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-137 IN COMPLEX WITH BTLA, GLYCOSYLATION AT ASN-110.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CR456909 mRNA. Translation: CAG33190.1.
AY466111 Genomic DNA. Translation: AAR23264.1.
AL139246 Genomic DNA. Translation: CAX30824.1.
CH471183 Genomic DNA. Translation: EAW56089.1.
BC002794 mRNA. Translation: AAH02794.1.

IPI

IPI00024331.

RefSeq

NP_003811.2. NM_003820.2.

UniGene

Hs.512898.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JMA	X-ray	2.65	B	39-200	[»]
2AW2	X-ray	2.80	B/Y	39-142	[»]
4FHQ	X-ray	2.25	A	39-162	[»]

ProteinModelPortal

Q92956.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34779N.
DIP-6233N.

IntAct

Q92956. 16 interactions.

MINT

MINT-208002.

STRING

9606.ENSP00000347948.

Polymorphism databases

DMDM

13878821.

Proteomic databases

PaxDb

Q92956.

PRIDE

Q92956.

Protocols and materials databases

DNASU

8764.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355716; ENSP00000347948; ENSG00000157873.

GeneID

8764.

KEGG

hsa:8764.

UCSC

uc001ajr.3. human.

Organism-specific databases

CTD

8764.

GeneCards

GC01P002487.

HGNC

HGNC:11912. TNFRSF14.

HPA

CAB026150.
CAB030007.
HPA006404.

MIM

602746. gene.

neXtProt

NX_Q92956.

PharmGKB

PA36605.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40150.

HOGENOM

HOG000065766.

HOVERGEN

HBG072084.

InParanoid

Q92956.

KO

K05152.

OMA

GHFCIVQ.

PhylomeDB

Q92956.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q92956.

Bgee

Q92956.

CleanEx

HS_TNFRSF14.

Genevestigator

Q92956.

GermOnline

ENSG00000157873. Homo sapiens.

Family and domain databases

InterPro

IPR001368. TNFR/NGFR_Cys_rich_reg.
IPR022332. TNFR_14.
[Graphical view]

Pfam

PF00020. TNFR_c6. 1 hit.
[Graphical view]

PRINTS

PR01965. TNFACTORR14.

SMART

SM00208. TNFR. 3 hits.
[Graphical view]

PROSITE

PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TNFRSF14. human.

EvolutionaryTrace

Q92956.

GenomeRNAi

8764.

NextBio

32872.

SOURCE

Search...

Entry information

Entry name

TNR14_HUMAN

Accession

Primary (citable) accession number: Q92956
Secondary accession number(s): B9DI89 , Q6IB95, Q8WXR1, Q96J31, Q9UM65

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 148 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.