P16778 (VGLI_HCMVA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
UL37 immediate early glycoprotein

Gene names

Name:

UL37

Organism

Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) [Complete proteome]

Taxonomic identifier

10360 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Betaherpesvirinae › Cytomegalovirus › Human cytomegalovirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	487 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	Isoform vMIA sequesters proapoptotic BAX at the outer mitochondrial membrane and prevents cytochrome c release and subsequent initiation of the proapoptotic cascade. Also provoques a calcium efflux from host endoplasmic reticulum and F-actin cytoskeleton disruption. Participates in the increase of host mitochondrial biogenesis, thus promoting viral replication by efficient use of newly made mitochondria. Ref.6 Ref.7 Ref.11 Isoform gpUL37 may play a role in escape from the host antiviral response. Ref.6 Ref.7 Ref.11
Subunit structure	Isofom vMIA interacts with host BAX. Isoform vMIA interacts with host RSAD2/viperin; this interaction results in RSAD2/viperin relocalization from the endoplasmic reticulum to the mitochondria, actin cytoskeleton disruption and enhancement of infection. Ref.6 Ref.10
Subcellular location	Isoform gpUL37: Host membrane; Single-pass membrane protein. Host endoplasmic reticulum membrane; Single-pass membrane protein. Host Golgi apparatus membrane; Single-pass membrane protein. Host mitochondrion membrane; Single-pass membrane protein. Note: The C-terminal fragment localizes to the endoplasmic reticulum while the N-terminal fragment is stable and traffics to mitochondria. Ref.5 Ref.8 Ref.9 Isoform vMIA: Host mitochondrion membrane; Single-pass membrane protein. Host endoplasmic reticulum membrane; Single-pass membrane protein. Note: Transported from the endoplasmic reticulum (ER) through the mitochondrial associated membrane (MAMs) to the mitochondrial outer membrane. Associates with internal lipid rafts (LRs) in the MAM. Ref.5 Ref.8 Ref.9 Isoform pUL37m: Host mitochondrion membrane; Single-pass membrane protein. Host endoplasmic reticulum membrane; Single-pass membrane protein. Note: Not cleaved or N-glycosylated. Ref.5 Ref.8 Ref.9
Sequence similarities	Belongs to the immediate early glycoprotein family.

Ontologies

Keywords
Biological process	Host-virus interaction Modulation of host cell apoptosis by virus
Cellular component	Host Golgi apparatus Host endoplasmic reticulum Host membrane Host mitochondrion Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	modulation by virus of host apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform gpUL37 (identifier: P16778-1)

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.

Isoform vMIA (identifier: P16778-2)

The sequence of this isoform differs from the canonical sequence as follows:
     163-163: H → Q
     164-487: Missing.

Isoform pUL37m (identifier: P16778-3)

The sequence of this isoform differs from the canonical sequence as follows:
     178-262: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 487

465

UL37 immediate early glycoprotein

PRO_0000037455

Regions

Transmembrane

433 – 459

27

Helical; Potential

Compositional bias

97 – 108

12

Poly-Glu

Sites

Site

193 – 194

2

Cleavage site

Amino acid modifications

Glycosylation

206

1

N-linked (GlcNAc...); by host Potential

Glycosylation

210

1

N-linked (GlcNAc...); by host Potential

Glycosylation

219

1

N-linked (GlcNAc...); by host Potential

Glycosylation

223

1

N-linked (GlcNAc...); by host Potential

Glycosylation

242

1

N-linked (GlcNAc...); by host Potential

Glycosylation

246

1

N-linked (GlcNAc...); by host Potential

Glycosylation

275

1

N-linked (GlcNAc...); by host Potential

Glycosylation

281

1

N-linked (GlcNAc...); by host Potential

Glycosylation

294

1

N-linked (GlcNAc...); by host Potential

Glycosylation

297

1

N-linked (GlcNAc...); by host Potential

Glycosylation

306

1

N-linked (GlcNAc...); by host Potential

Glycosylation

333

1

N-linked (GlcNAc...); by host Potential

Glycosylation

337

1

N-linked (GlcNAc...); by host Potential

Glycosylation

343

1

N-linked (GlcNAc...); by host Potential

Glycosylation

379

1

N-linked (GlcNAc...); by host Potential

Glycosylation

384

1

N-linked (GlcNAc...); by host Potential

Glycosylation

391

1

N-linked (GlcNAc...); by host Potential

Natural variations

Alternative sequence

163

1

H → Q in isoform vMIA.

VSP_044014

Alternative sequence

164 – 487

324

Missing in isoform vMIA.

VSP_044015

Alternative sequence

178 – 262

85

Missing in isoform pUL37m.

VSP_044016

Secondary structure

1

.

.

.

.

487

Helix Strand Turn

Details...

Helix

138 – 145

8

Beta strand

146 – 148

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform gpUL37 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: FA39A37C51FFB4A3	FASTA	487	56,125
	10 20 30 40 50 60 MSPVYVNLLG SVGLLAFWYF SYRWIQRKRL EDPLPPWLRK KKACALTRRS RHRLRRQHGV 70 80 90 100 110 120 IDGENSETER SVDLVAALLA EAGEESVTED TEREDTEEER EDEEEENEAR TPEVNPIDAE 130 140 150 160 170 180 GLSGLAREAC EALKKALRRH RFLWQRRQRA RMLQHNGPQQ SHHAAVFCRV HGLRGFQVSV 190 200 210 220 230 240 WLLLTLLWST GHGVSVRCTY HGTDVNRTSN TTSMNCHLNC TRNHTQIYNG PCLGTEARLP 250 260 270 280 290 300 LNVTFNQSRR KWHSVMLKFG FQYHLEGWFP LRVLNESREI NVTEVHGEVA CFRNDTNVTV 310 320 330 340 350 360 GQLTLNFTGH SYVLRAIAHT SPFESYVRWE ETNVTDNATS SENTTTVMST LTKYAESDYI 370 380 390 400 410 420 FLQDMCPRFL KRTVKLTRNK TKHNVTVTGN NMTTLPVWTP ECKGWTYWTT LSVMWRNRRS 430 440 450 460 470 480 ALLRAKSRAL GHWALLSICT VAAGSIALLS LFCILLIGLR RDLLEDFRYI CRDEGSSSTK NDVHRIV
	Isoform vMIA [UniParc]. Checksum: B657342BB57AEC21	FASTA	163	19,115
	10 20 30 40 50 60 MSPVYVNLLG SVGLLAFWYF SYRWIQRKRL EDPLPPWLRK KKACALTRRS RHRLRRQHGV 70 80 90 100 110 120 IDGENSETER SVDLVAALLA EAGEESVTED TEREDTEEER EDEEEENEAR TPEVNPIDAE 130 140 150 160 GLSGLAREAC EALKKALRRH RFLWQRRQRA RMLQHNGPQQ SHQ
	Isoform pUL37m [UniParc]. Checksum: BDFD81E69DC4753E	FASTA	402	46,435
	10 20 30 40 50 60 MSPVYVNLLG SVGLLAFWYF SYRWIQRKRL EDPLPPWLRK KKACALTRRS RHRLRRQHGV 70 80 90 100 110 120 IDGENSETER SVDLVAALLA EAGEESVTED TEREDTEEER EDEEEENEAR TPEVNPIDAE 130 140 150 160 170 180 GLSGLAREAC EALKKALRRH RFLWQRRQRA RMLQHNGPQQ SHHAAVFCRV HGLRGFQYHL 190 200 210 220 230 240 EGWFPLRVLN ESREINVTEV HGEVACFRND TNVTVGQLTL NFTGHSYVLR AIAHTSPFES 250 260 270 280 290 300 YVRWEETNVT DNATSSENTT TVMSTLTKYA ESDYIFLQDM CPRFLKRTVK LTRNKTKHNV 310 320 330 340 350 360 TVTGNNMTTL PVWTPECKGW TYWTTLSVMW RNRRSALLRA KSRALGHWAL LSICTVAAGS 370 380 390 400 IALLSLFCIL LIGLRRDLLE DFRYICRDEG SSSTKNDVHR IV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"An immediate early gene of human cytomegalovirus encodes a potential membrane glycoprotein." Kouzarides T., Bankier A.T., Satchwell S.C., Preddy E., Barrell B.G. Virology 165:151-164(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169." Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R., Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A., Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G. Curr. Top. Microbiol. Immunol. 154:125-169(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ISOFORM PUL37M, ISOFORM VMIA.
[3]	"The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome." Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:17-28(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION.
[4]	Erratum Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:1053-1053(2003)
[5]	"The human cytomegalovirus UL37 immediate-early regulatory protein is an integral membrane N-glycoprotein which traffics through the endoplasmic reticulum and Golgi apparatus." Al-Barazi H.O., Colberg-Poley A.M. J. Virol. 70:7198-7208(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"An anti-apoptotic viral protein that recruits Bax to mitochondria." Poncet D., Larochette N., Pauleau A.L., Boya P., Jalil A.A., Cartron P.F., Vallette F., Schnebelen C., Bartle L.M., Skaletskaya A., Boutolleau D., Martinou J.C., Goldmacher V.S., Kroemer G., Zamzami N. J. Biol. Chem. 279:22605-22614(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HOST BAX.
[7]	"Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria." Arnoult D., Bartle L.M., Skaletskaya A., Poncet D., Zamzami N., Park P.U., Sharpe J., Youle R.J., Goldmacher V.S. Proc. Natl. Acad. Sci. U.S.A. 101:7988-7993(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Internal cleavage of the human cytomegalovirus UL37 immediate-early glycoprotein and divergent trafficking of its proteolytic fragments." Mavinakere M.S., Colberg-Poley A.M. J. Gen. Virol. 85:1989-1994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE SITE, SUBCELLULAR LOCATION.
[9]	"Trafficking of UL37 proteins into mitochondrion-associated membranes during permissive human cytomegalovirus infection." Bozidis P., Williamson C.D., Wong D.S., Colberg-Poley A.M. J. Virol. 84:7898-7903(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Human cytomegalovirus directly induces the antiviral protein viperin to enhance infectivity." Seo J.Y., Yaneva R., Hinson E.R., Cresswell P. Science 332:1093-1097(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST RSAD2.
[11]	"Human cytomegalovirus infection increases mitochondrial biogenesis." Kaarbo M., Ager-Wick E., Osenbroch P.O., Kilander A., Skinnes R., Muller F., Eide L. Mitochondrion 11:935-945(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X17403 Genomic DNA. Translation: CAA35396.1.
BK000394 Genomic DNA. Translation: DAA00142.1.

PIR

QQBEU5. S09801.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LR1	NMR	-	B	130-150	[»]

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR010880. Herpes_UL37_HHV-5-rel.
[Graphical view]

Pfam

PF07413. Herpes_UL37_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

VGLI_HCMVA

Accession

Primary (citable) accession number: P16778
Secondary accession number(s): P87887, Q7M6P6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	May 30, 2000
Last modified:	April 3, 2013
This is version 55 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program