P32984 (RIR1_VAR67) 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

ORF Names:

I4L, K4L, ORF3L

Organism

Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus) [Reference proteome]

Taxonomic identifier

587200 [NCBI]

Taxonomic lineage

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

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

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

General annotation (Comments)

Function	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
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, 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.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.

Ontologies

Keywords
Biological process	DNA replication
Developmental stage	Early protein
Ligand	ATP-binding 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-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 – 771	771	Ribonucleoside-diphosphate reductase large subunit		PRO_0000187233
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
Natural variations
	Natural variant	509	1	D → Y in strain: Garcia-1966.
	Natural variant	764	1	E → K in strain: Garcia-1966.

Sequences

	Sequence		Length	Mass (Da)
	P32984 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: E628AAA9AD95A8CD	FASTA	771	87,761
	10 20 30 40 50 60 MFVIKRNGYK ENVMFDKITS RIRKLCYGLN TDHIDPIKIA MKVIQGIYNG VTTVELDTLT 70 80 90 100 110 120 AEIAATCTTQ HPDYAILAAR IAVSNLHKET KKLFSEVMKD LFNYVNPKNG KHSPIISSIT 130 140 150 160 170 180 MDVVNKYKDK LNSVIIYERD FSYNYFGFKT LEKSYLLKIN NKIVERPQHM LMRVAVGIHQ 190 200 210 220 230 240 WDIDSAIETY NLLSEKWFTH ASPTLFNAGT SRHQMSSCFL LNMMDDSIEG IYDTLKRCAL 250 260 270 280 290 300 ISKMAGGIGL SISNIRASGS YISGTNGASN GIIPMLRVYN NTARYIDQGG NKRPGVMTIY 310 320 330 340 350 360 LEPWHSDIMA FLDLKKNTGN EEHRTRDLFI ALWIPDLFMK RVKDDGEWSL MCPDECPGLD 370 380 390 400 410 420 NVWGDEFERL YTLYEREKRY KSIIKARVVW KAIIESQIET GTPFILYKDA CNKKSNQQNL 430 440 450 460 470 480 GTIKCSNLCT EIIQYADANE VAVCNLASIA LNMFVIDGQF 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 NDEIKNRIMV 670 680 690 700 710 720 DGGSIQNTNL PEDIKRVYKT IWEIPQKTII KMAADRGAFI DQSQSMNIHI ADPSYSKLTS 730 740 750 760 770 MHFYGWSLGL KTGMYYLRTK PASAPIQFTL DKDKIKPLVV CDSEICTSCS G

References

[1]	"Analysis of the nucleotide sequence of a 43 kbp segment of the genome of variola virus India-1967 strain." Shchelkunov S.N., Blinov V.M., Resenchuk S.M., Totmenin A.V., Sandakhchiev L.S. Virus Res. 30:239-258(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: India-1967 / Isolate Ind3.
[2]	"Nucleotide sequence analysis of variola virus HindIII M, L, I genome fragments." Shchelkunov S.N., Blinov V.M., Totmenin A.V., Marennikova S.S., Kolykhalov A.A., Frolov I.V., Chizhikov V.E., Gytorov V.V., Gashikov P.V., Belanov E.F., Belavin P.A., Resenchuk S.M., Andzhaparidze O.G., Sandakhchiev L.S. Virus Res. 27:25-35(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: India-1967 / Isolate Ind3.
[3]	"Genes of variola and vaccinia viruses necessary to overcome the host protective mechanisms." Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S. FEBS Lett. 319:80-83(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: India-1967 / Isolate Ind3.
[4]	"Potential virulence determinants in terminal regions of variola smallpox virus genome." Massung R.F., Esposito J.J., Liu L.I., Qi J., Utterback T.R., Knight J.C., Aubin L., Yuran T.E., Parsons J.M., Loparev V.N., Selivanov N.A., Cavallaro K.F., Kerlavage A.R., Mahy B.W.J., Venter J.C. Nature 366:748-751(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Bangladesh-1975.
[5]	Shchelkunov S.N., Chizhikov V.E., Totmenin A.V., Resenchuk S.M., Blinov V.M., Sandakhchiev L.S. Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Garcia-1966.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X67119 Genomic DNA. Translation: CAA47558.1. X69198 Genomic DNA. Translation: CAA48999.1. L22579 Genomic DNA. Translation: AAA60806.1. X76263 Genomic DNA. Translation: CAA53832.1.
PIR	B36843. T28496.
RefSeq	NP_042102.1. NC_001611.1.
3D structure databases
ProteinModelPortal	P32984.
SMR	P32984. Positions 15-752.
ModBase	Search...
Proteomic databases
PRIDE	P32984.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1486459.
Phylogenomic databases
ProtClustDB	CLSP2509774.
Enzyme and pathway databases
UniPathway	UPA00326.
Family and domain databases
InterPro	IPR005144. ATP-cone. IPR013346. NrdE_NrdA. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. IPR008926. RNR_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_VAR67

Accession

Primary (citable) accession number: P32984

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	April 3, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program