P08543 (RIR1_HHV11) 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):
ICP6
Ribonucleotide reductase 136 kDa subunit
Ribonucleotide reductase large subunit

Gene names

ORF Names:

UL39

Organism

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]

Taxonomic identifier

10299 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 1

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	1137 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.
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
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.
Domain	Contains an alpha-crystallin domain homologous to small heat-shock proteins By similarity.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family.

Ontologies

Keywords
Biological process	DNA replication Host-virus interaction
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	ribonucleoside-diphosphate reductase complex Inferred from electronic annotation. Source: InterPro
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 – 1137	1137	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187236
Regions
	Region	287 – 393	107	alpha-crystallin domain By similarity
	Region	581 – 582	2	Substrate binding By similarity
	Region	791 – 795	5	Substrate binding By similarity
	Region	968 – 972	5	Substrate binding By similarity
	Compositional bias	150 – 154	5	Poly-Pro
	Compositional bias	190 – 239	50	Asp/Ser-rich
Sites
	Active site	791	1	Proton acceptor By similarity
	Active site	793	1	Cysteine radical intermediate By similarity
	Active site	795	1	Proton acceptor By similarity
	Binding site	566	1	Substrate By similarity
	Binding site	612	1	Substrate; via amide nitrogen By similarity
	Site	582	1	Important for hydrogen atom transfer By similarity
	Site	808	1	Important for hydrogen atom transfer By similarity
	Site	1111	1	Important for electron transfer By similarity
	Site	1112	1	Important for electron transfer By similarity
	Site	1132	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	1135	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	582 ↔ 808		Redox-active By similarity
Natural variations
	Natural variant	70	1	N → S in strain: Nonneuroinvasive mutant HF10, 17 syn+ and Isolate pYN1.
	Natural variant	1133	1	M → T in strain: Nonneuroinvasive mutant HF10.
Experimental info
	Sequence conflict	1034	1	A → P in AAA45805. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P08543 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: 8A3777F4C22D8F85	FASTA	1,137	124,051
	10 20 30 40 50 60 MASRPAASSP VEARAPVGGQ EAGGPSAATQ GEAAGAPLAH GHHVYCQRVN GVMVLSDKTP 70 80 90 100 110 120 GSASYRISDN NFVQCGSNCT MIIDGDVVRG RPQDPGAAAS PAPFVAVTNI GAGSDGGTAV 130 140 150 160 170 180 VAFGGTPRRS AGTSTGTQTA DVPTEALGGP PPPPRFTLGG GCCSCRDTRR RSAVFGGEGD 190 200 210 220 230 240 PVGPAEFVSD DRSSDSDSDD SEDTDSETLS HASSDVSGGA TYDDALDSDS SSDDSLQIDG 250 260 270 280 290 300 PVCRPWSNDT APLDVCPGTP GPGADAGGPS AVDPHAPTPE AGAGLAADPA VARDDAEGLS 310 320 330 340 350 360 DPRPRLGTGT AYPVPLELTP ENAEAVARFL GDAVNREPAL MLEYFCRCAR EETKRVPPRT 370 380 390 400 410 420 FGSPPRLTED DFGLLNYALV EMQRLCLDVP PVPPNAYMPY YLREYVTRLV NGFKPLVSRS 430 440 450 460 470 480 ARLYRILGVL VHLRIRTREA SFEEWLRSKE VALDFGLTER LREHEAQLVI LAQALDHYDC 490 500 510 520 530 540 LIHSTPHTLV ERGLQSALKY EEFYLKRFGG HYMESVFQMY TRIAGFLACR ATRGMRHIAL 550 560 570 580 590 600 GREGSWWEMF KFFFHRLYDH QIVPSTPAML NLGTRNYYTS SCYLVNPQAT TNKATLRAIT 610 620 630 640 650 660 SNVSAILARN GGIGLCVQAF NDSGPGTASV MPALKVLDSL VAAHNKESAR PTGACVYLEP 670 680 690 700 710 720 WHTDVRAVLR MKGVLAGEEA QRCDNIFSAL WMPDLFFKRL IRHLDGEKNV TWTLFDRDTS 730 740 750 760 770 780 MSLADFHGEE FEKLYQHLEV MGFGEQIPIQ ELAYGIVRSA ATTGSPFVMF KDAVNRHYIY 790 800 810 820 830 840 DTQGAAIAGS NLCTEIVHPA SKRSSGVCNL GSVNLARCVS RQTFDFGRLR DAVQACVLMV 850 860 870 880 890 900 NIMIDSTLQP TPQCTRGNDN LRSMGIGMQG LHTACLKLGL DLESAEFQDL NKHIAEVMLL 910 920 930 940 950 960 SAMKTSNALC VRGARPFNHF KRSMYRAGRF HWERFPDARP RYEGEWEMLR QSMMKHGLRN 970 980 990 1000 1010 1020 SQFVALMPTA ASAQISDVSE GFAPLFTNLF SKVTRDGETL RPNTLLLKEL ERTFSGKRLL 1030 1040 1050 1060 1070 1080 EVMDSLDAKQ WSVAQALPCL EPTHPLRRFK TAFDYDQKLL IDLCADRAPY VDHSQSMTLY 1090 1100 1110 1120 1130 VTEKADGTLP ASTLVRLLVH AYKRGLKTGM YYCKVRKATN SGVFGGDDNI VCMSCAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1." McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P. J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Structural features of ribonucleotide reductase." Nikas I., McLauchlan J., Davison A.J., Taylor W.R., Clements J.B. Proteins 1:376-384(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Isolate pYN1.
[3]	"Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus." Ushijima Y., Luo C., Goshima F., Yamauchi Y., Kimura H., Nishiyama Y. Microbes Infect. 9:142-149(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Nonneuroinvasive mutant HF10.
[4]	"Herpes simplex virus type 1 bacterial artificial chromosome." Cunningham C., Davison A.J. Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: 17 syn+.
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X14112 Genomic DNA. Translation: CAA32314.1. M18410 Genomic DNA. Translation: AAA45805.1. DQ889502 Genomic DNA. Translation: ABI63501.1. FJ593289 Genomic DNA. Translation: ACM62262.1.
PIR	WMBEB1. A26536.
RefSeq	NP_044641.1. NC_001806.1.
3D structure databases
ProteinModelPortal	P08543.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-6732628.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	2703361.
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...
Other
BindingDB	P08543.
ChEMBL	CHEMBL3840.

Entry information

Entry name

RIR1_HHV11

Accession

Primary (citable) accession number: P08543
Secondary accession number(s): B9VQG7, Q09I94

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	July 1, 1989
Last modified:	April 3, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program