P09853 (RIR1_HHV23) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Ribonucleoside-diphosphate reductase large subunit EC=1.17.4.1 Alternative name(s): Ribonucleotide reductase 136 kDa subunit Ribonucleotide reductase large subunit
Organism	Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2)
Taxonomic identifier	10313 [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	1144 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.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family.

Ontologies

Keywords
Biological process	DNA replication
Developmental stage	Early protein
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway
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 – 1144	1144	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187237
Regions
	Region	588 – 589	2	Substrate binding By similarity
	Region	798 – 802	5	Substrate binding By similarity
	Region	975 – 979	5	Substrate binding By similarity
	Compositional bias	151 – 159	9	Poly-Pro
	Compositional bias	224 – 231	8	Poly-Asp
Sites
	Active site	798	1	Proton acceptor By similarity
	Active site	800	1	Cysteine radical intermediate By similarity
	Active site	802	1	Proton acceptor By similarity
	Binding site	573	1	Substrate By similarity
	Binding site	619	1	Substrate; via amide nitrogen By similarity
	Site	589	1	Important for hydrogen atom transfer By similarity
	Site	815	1	Important for hydrogen atom transfer By similarity
	Site	1118	1	Important for electron transfer By similarity
	Site	1119	1	Important for electron transfer By similarity
	Site	1139	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	1142	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	589 ↔ 815		Redox-active By similarity

Sequences

	Sequence		Length	Mass (Da)
	P09853 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 4771481C3103FC78	FASTA	1,144	125,093
	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 DEDTGSGSET LSRSSSIWAA GATDDDDSDS DSRSDDSVQP 250 260 270 280 290 300 DVVVRRRWSD GPAPVAFPKP RRPGDSPGNP GLGAGTGPGS ATDPRASADS DSAAHAAAPQ 310 320 330 340 350 360 ADVAPVLDSQ PTVGTDPGYP VPLELTPENA EAVARFLGDA VDREPALMLE YFCRCAREES 370 380 390 400 410 420 KRVPPRTFGS APRLTEDDFG LLNYALAEMR RLCLDLPPVP PNAYTPYHLR EYATRLVNGF 430 440 450 460 470 480 KPLVRRSARL YRILGILVHL RIRTREASFE EWMRSKEVDL DFGLTERLRE HEAQLMILAQ 490 500 510 520 530 540 ALNPYDCLIH STPNTLVERG LQSALKYEEF YLKRFGGHYM ESVFQMYTRI AGFLACRATR 550 560 570 580 590 600 GMRHIALGRQ GSWWEMFKFF FHRLYDHQIV PSTPAMLNLG TRNYYTSSCY LVNPQATTNQ 610 620 630 640 650 660 ATLRAITGNV SAILARNGGI GLCMQAFNDA SPGTASIMPA LKVLDSLVAA HNKQSTRPTG 670 680 690 700 710 720 ACVYLEPWHS DVRAVLRMKG VLAGEEAQRC DNIFSALWMP DLFFKRLIRH LDGEKNVTWS 730 740 750 760 770 780 LFDRDTSMSL ADFHGEEFEK LYEHLEAMGF GETIPIQDLA YAIVRSAATT GSPFIMFKDA 790 800 810 820 830 840 VNRHYIYDTQ GAAIAGSNLC TEIVHPSSKR SSGVCNLGSV NLARCVSRRT FDFGMLRDAV 850 860 870 880 890 900 QACVLMVNIM IDSTLQPTPQ CARGHDNLRS MGIGMQGLHT ACLKMGLDLE SAEFRDLNTH 910 920 930 940 950 960 IAEVMLLAAM KTSNALCVRG ARPFSHFKRS MYRAGRFHWE RFSNASPRYE GEWEMLRQSM 970 980 990 1000 1010 1020 MKHGLRNSQF IALMPTAASA QISDVSEGFA PLFTNLFSKV TRDGETLRPN TLLLKELERT 1030 1040 1050 1060 1070 1080 FGGKRLLDAM DGLEAKQWSV AQALPCLDPA HPLRRFKTAF DYDQELLIDL CADRAPYVDH 1090 1100 1110 1120 1130 1140 SQSMTLYVTE KADGTLPAST LVRLLVHAYK RGLKTGMYYC KVRKATNSGV FAGDDNIVCT SCAL

References

[1]	"Herpes simplex virus specifies two subunits of ribonucleotide reductase encoded by 3'-coterminal transcripts." Swain M.A., Galloway D.A. J. Virol. 57:802-808(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Organization of the left-hand end of the herpes simplex virus type 2 BglII N fragment." Galloway D.A., Swain M.A. J. Virol. 49:724-730(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 981-1144.
[3]	"DNA sequence homology between two co-linear loci on the HSV genome which have different transforming abilities." McLauchlan J., Clements J.B. EMBO J. 2:1953-1961(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1036-1144.
[4]	"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	M12700 Genomic DNA. Translation: AAA45806.1. X00048 Genomic DNA. Translation: CAA24929.1.
3D structure databases
ProteinModelPortal	P09853.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
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	P09853.
ChEMBL	CHEMBL3104.

Entry information

Entry name

RIR1_HHV23

Accession

Primary (citable) accession number: P09853

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program