P89462 (RIR1_HHV2H) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonucleoside-diphosphate reductase large subunit
Short name=R1
EC=1.17.4.1

Alternative name(s):
ICP10
Ribonucleotide reductase 136 kDa subunit
Ribonucleotide reductase large subunit

Gene names

ORF Names:

UL39

Organism

Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2) [Reference proteome]

Taxonomic identifier

10315 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 2

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1142 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Ribonucleoside-diphosphate reductase holoenzyme provides the precursors necessary for viral DNA synthesis. Allows virus growth in non-dividing cells, as well as reactivation from latency in infected hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. The N-terminal region confers antiapoptotic activity in differentiated cells such as neurons and is important for viral reactivation to increase neural survivability By similarity. Ref.3
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin. ATP + a protein = ADP + a phosphoprotein.
Pathway	Genetic information processing; DNA replication.
Subunit structure	Heterotetramer composed of a homodimer of the large subunit UL39 (R1) and a homodimer of the small subunit UL40 (R2). Larger multisubunit protein complex are also active, composed of (R1)n(R2)n By similarity.
Subcellular location	Host cell membrane. Host endosome membrane. Note: Associates with the host cytoskeleton Potential. Ref.2
Domain	Contains an alpha-crystallin domain homologous to small heat-shock proteins. Ref.4
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family.

Ontologies

Keywords
Biological process	DNA replication Host-virus interaction
Cellular component	Host cell membrane Host endosome Host membrane Membrane
Developmental stage	Early protein
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1142	1142	Ribonucleoside-diphosphate reductase large subunit		PRO_0000385162
Regions
	Region	294 – 400	107	alpha-crystallin domain
	Region	586 – 587	2	Substrate binding By similarity
	Region	796 – 800	5	Substrate binding By similarity
	Region	973 – 977	5	Substrate binding By similarity
	Compositional bias	151 – 159	9	Poly-Pro
	Compositional bias	186 – 239	54	Asp/Ser-rich
Sites
	Active site	796	1	Proton acceptor By similarity
	Active site	798	1	Cysteine radical intermediate By similarity
	Active site	800	1	Proton acceptor By similarity
	Binding site	571	1	Substrate By similarity
	Binding site	617	1	Substrate; via amide nitrogen By similarity
	Site	587	1	Important for hydrogen atom transfer By similarity
	Site	813	1	Important for hydrogen atom transfer By similarity
	Site	1116	1	Important for electron transfer By similarity
	Site	1117	1	Important for electron transfer By similarity
	Site	1137	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	1140	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	587 ↔ 813		Redox-active By similarity

Sequences

	Sequence		Length	Mass (Da)
	P89462 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 5A46D3985338BB21	FASTA	1,142	124,923
	10 20 30 40 50 60 MANRPAASAL AGARSPSERQ EPREPEVAPP GGDHVFCRKV SGVMVLSSDP PGPAAYRISD 70 80 90 100 110 120 SSFVQCGSNC SMIIDGDVAR GHLRDLEGAT STGAFVAISN VAAGGDGRTA VVALGGTSGP 130 140 150 160 170 180 SATTSVGTQT SGEFLHGNPR TPEPQGPQAV PPPPPPPFPW GHECCARRDA RGGAEKDVGA 190 200 210 220 230 240 AESWSDGPSS DSETEDSDSS DEDTGSETLS RSSSIWAAGA TDDDDSDSDS RSDDSVQPDV 250 260 270 280 290 300 VVRRRWSDGP APVAFPKPRR PGDSPGNPGL GAGTGPGSAT DPRASADSDS AAHAAAPQAD 310 320 330 340 350 360 VAPVLDSQPT VGTDPGYPVP LELTPENAEA VARFLGDAVD REPALMLEYF CRCAREESKR 370 380 390 400 410 420 VPPRTFGSAP RLTEDDFGLL NYALAEMRRL CLDLPPVPPN AYTPYHLREY ATRLVNGFKP 430 440 450 460 470 480 LVRRSARLYR ILGVLVHLRI RTREASFEEW MRSKEVDLDF GLTERLREHE AQLMILAQAL 490 500 510 520 530 540 NPYDCLIHST PNTLVERGLQ SALKYEEFYL KRFGGHYMES VFQMYTRIAG FLACRATRGM 550 560 570 580 590 600 RHIALGRQGS WWEMFKFFFH RLYDHQIVPS TPAMLNLGTR NYYTSSCYLV NPQATTNQAT 610 620 630 640 650 660 LRAITGNVSA ILARNGGIGL CMQAFNDASP GTASIMPALK VLDSLVAAHN KQSTRPTGAC 670 680 690 700 710 720 VYLEPWHSDV RAVLRMKGVL AGEEAQRCDN IFSALWMPDL FFKRLIRHLD GEKNVTWSLF 730 740 750 760 770 780 DRDTSMSLAD FHGEEFEKLY EHLEAMGFGE TIPIQDLAYA IVRSAATTGS PFIMFKDAVN 790 800 810 820 830 840 RHYIYDTQGA AIAGSNLCTE IVHPASKRSS GVCNLGSVNL ARCVSRQTFD FGRLRDAVQA 850 860 870 880 890 900 CVLMVNIMID STLQPTPQCT RGNDNLRSMG IGMQGLHTAC LKMGLDLESA EFRDLNTHIA 910 920 930 940 950 960 EVMLLAAMKT SNALCVRGAR PFSHFKRSMY RAGRFHWERF SNASPRYEGE WEMLRQSMMK 970 980 990 1000 1010 1020 HGLRNSQFIA LMPTAASAQI SDVSEGFAPL FTNLFSKVTR DGETLRPNTL LLKELERTFG 1030 1040 1050 1060 1070 1080 GKRLLDAMDG LEAKQWSVAQ ALPCLDPAHP LRRFKTAFDY DQELLIDLCA DRAPYVDHSQ 1090 1100 1110 1120 1130 1140 SMTLYVTEKA DGTLPASTLV RLLVHAYKRG LKTGMYYCKV RKATNSGVFA GDDNIVCTSC AL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome sequence of herpes simplex virus type 2." Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J. J. Virol. 72:2010-2021(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Intracellular internalization and signaling pathways triggered by the large subunit of HSV-2 ribonucleotide reductase (ICP10)." Hunter J.C., Smith C.C., Bose D., Kulka M., Broderick R., Aurelian L. Virology 210:345-360(1995) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[3]	"The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway." Perkins D., Pereira E.F., Gober M., Yarowsky P.J., Aurelian L. J. Virol. 76:1435-1449(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"The R1 subunit of herpes simplex virus ribonucleotide reductase has chaperone-like activity similar to Hsp27." Chabaud S., Lambert H., Sasseville A.M., Lavoie H., Guilbault C., Massie B., Landry J., Langelier Y. FEBS Lett. 545:213-218(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ALPHA-CRYSTALLIN DOMAIN.
[5]	"Tinkering with a viral ribonucleotide reductase." Lembo D., Brune W. Trends Biochem. Sci. 34:25-32(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z86099 Genomic DNA. Translation: CAB06725.1.
PIR	A05247.
RefSeq	NP_044509.1. NC_001798.1.
3D structure databases
ProteinModelPortal	P89462.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1487325.
Phylogenomic databases
ProtClustDB	CLSP2509601.
Enzyme and pathway databases
UniPathway	UPA00326.
Family and domain databases
InterPro	IPR013346. NrdE_NrdA. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. [Graphical view]
Pfam	PF02867. Ribonuc_red_lgC. 1 hit. PF00317. Ribonuc_red_lgN. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
TIGRFAMs	TIGR02506. NrdE_NrdA. 1 hit.
PROSITE	PS00089. RIBORED_LARGE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

RIR1_HHV2H

Accession

Primary (citable) accession number: P89462

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 22, 2009
Last sequence update:	May 1, 1997
Last modified:	May 29, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program