P12848 (RIR1_VACCW) 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 large subunit

Gene names

Ordered Locus Names:	VACWR073
ORF Names:	I4L

Organism

Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain WR))

Taxonomic identifier

10254 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Poxviridae › Chordopoxvirinae › Orthopoxvirus › Vaccinia virus

Virus host

Bos taurus (Bovine) [TaxID: 9913]

Protein attributes

Sequence length	771 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ribonucleoside-diphosphate reductase holoenzyme provides the precursors necessary for viral DNA synthesis. Allows virus growth in non-dividing cells. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides By similarity.
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
Cofactor	Maximal ribonucleotide reductase activity requires the presence of magnesium ions. Ref.4
Enzyme regulation	Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, whereas dGTP favors ADP reduction and dTTP favors GDP reduction By similarity.
Pathway	Genetic information processing; DNA replication.
Subunit structure	Heterotetramer composed of a homodimer of the large subunit (R1) and a homodimer of the small subunit (R2). Larger multisubunit protein complex are also active, composed of (R1)n(R2)n By similarity.
Induction	Expressed early in the viral replicative cycle. Ref.1
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.
Biophysicochemical properties	pH dependence: Optimum pH is 8.0 and above. Ref.4

Ontologies

Keywords
Biological process	DNA replication
Developmental stage	Early protein
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA replication 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 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 – 771	771	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187232
Regions
	Domain	1 – 92	92	ATP-cone
	Region	217 – 218	2	Substrate binding By similarity
	Region	427 – 431	5	Substrate binding By similarity
	Region	602 – 606	5	Substrate binding By similarity
Sites
	Active site	427	1	Proton acceptor By similarity
	Active site	429	1	Cysteine radical intermediate By similarity
	Active site	431	1	Proton acceptor By similarity
	Binding site	202	1	Substrate By similarity
	Binding site	247	1	Substrate; via amide nitrogen By similarity
	Site	218	1	Important for hydrogen atom transfer By similarity
	Site	226	1	Allosteric effector binding By similarity
	Site	256	1	Allosteric effector binding By similarity
	Site	444	1	Important for hydrogen atom transfer By similarity
	Site	735	1	Important for electron transfer By similarity
	Site	736	1	Important for electron transfer By similarity
	Site	766	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	769	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	218 ↔ 444		Redox-active By similarity
Experimental info
	Sequence conflict	447	1	A → G in AAA48274. Ref.2
	Sequence conflict	467	1	D → V in AAA48274. Ref.2
	Sequence conflict	526	1	L → I in AAA48274. Ref.2
	Sequence conflict	601 – 606	6	MPTAST → LPLHQH in AAA48274. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P12848 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 6CA07F0C58F6A8F9	FASTA	771	87,738
	10 20 30 40 50 60 MFVIKRNGYK ENVMFDKITS RIRKLCYGLN TDHIDPIKIA MKVIQGIYNG VTTVELDTLA 70 80 90 100 110 120 AEIAATCTTQ HPDYAILAAR IAVSNLHKET KKLFSEVMED LFNYVNPKNG KHSPIISSIT 130 140 150 160 170 180 MDIVNKYKDK LNSVIIYERD FSYNYFGFKT LEKSYLLKIN NKIVERPQHM LMRVAVGIHQ 190 200 210 220 230 240 WDIDSAIETY NLLSEKWFTH ASPTLFNAGT SRHQMSSCFL LNMIDDSIEG IYDTLKRCAL 250 260 270 280 290 300 ISKMAGGIGL SISNIRASGS YISGTNGISN GIIPMLRVYN NTARYIDQGG NKRPGVMAIY 310 320 330 340 350 360 LEPWHSDIMA FLDLKKNTGN EEHRTRDLFI ALWIPDLFMK RVKDDGEWSL MCPDECPGLD 370 380 390 400 410 420 NVWGDEFERL YTLYERERRY KSIIKARVVW KAIIESQIET GTPFILYKDA CNKKSNQQNL 430 440 450 460 470 480 GTIKCSNLCT EIIQYADANE VAVCNLASVA LNMFVIDGRF DFLKLKDVVK VIVRNLNKII 490 500 510 520 530 540 DINYYPIPEA EISNKRHRPI GIGVQGLADA FILLNYPFDS LEAQDLNKKI FETIYYGALE 550 560 570 580 590 600 ASCELAEKEG PYDTYVGSYA SNGILQYDLW NVVPSDLWNW EPLKDKIRTY GLRNSLLVAP 610 620 630 640 650 660 MPTASTAQIL GNNESVEPYT SNIYTRRVLS GEFQVVNPHL LRVLTERKLW NDEIKNRIMA 670 680 690 700 710 720 DGGSIQNTNL PEDIKRVYKT IWEIPQKTII KMAADRGAFI DQSQSMNIHI ADPSYSKLTS 730 740 750 760 770 MHFYGWSLGL KTGMYYLRTK PASAPIQFTL DKDKIKPPVV CDSEICTSCS G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and transcriptional analysis of the vaccinia virus HindIII I fragment." Schmitt J.F.C., Stunnenberg H.G. J. Virol. 62:1889-1897(1988) [PubMed: 2835495] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION.
[2]	"Nucleotide sequence and molecular genetic analysis of the large subunit of ribonucleotide reductase encoded by vaccinia virus." Tengelsen L.A., Slabaugh M.B., Bibler J.K., Hruby D.E. Virology 164:121-131(1988) [PubMed: 3284177] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Sequencing of the coding region of Vaccinia-WR to an average 9-fold redundancy and an error rate of 0.16/10kb." Esposito J.J., Frace A.M., Sammons S.A., Olsen-Rasmussen M., Osborne J., Wohlhueter R. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Vaccinia virus ribonucleotide reductase expression and isolation of the recombinant large subunit." Slabaugh M.B., Davis R.E., Roseman N.A., Mathews C.K. J. Biol. Chem. 268:17803-17810(1993) [PubMed: 8349665] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03399 Genomic DNA. Translation: AAB59806.1. M20299 Genomic DNA. Translation: AAA48274.1. AY243312 Genomic DNA. Translation: AAO89352.1.
PIR	WZVZH4. A28611.
RefSeq	YP_232955.1. NC_006998.1.
3D structure databases
ProteinModelPortal	P12848.
SMR	P12848. Positions 15-752.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2158N.
MINT	MINT-131002.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	3707606.
Phylogenomic databases
ProtClustDB	CLSP2509774.
Family and domain databases
InterPro	IPR005144. ATP-cone. IPR013346. NrdE_NrdA. IPR013509. Ribncl_Rdtase_lsu_N. IPR000788. Ribncl_red_lg_C. IPR008926. Ribnucl_Rdtase_R1-su_N. [Graphical view]
Pfam	PF03477. ATP-cone. 1 hit. PF02867. Ribonuc_red_lgC. 1 hit. PF00317. Ribonuc_red_lgN. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
SUPFAM	SSF48168. Ribonucleo_red_N. 1 hit.
TIGRFAMs	TIGR02506. NrdE_NrdA. 1 hit.
PROSITE	PS51161. ATP_CONE. 1 hit. PS00089. RIBORED_LARGE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

RIR1_VACCW

Accession

Primary (citable) accession number: P12848
Secondary accession number(s): Q76ZU9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	September 21, 2011
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program