Ribonucleoside-diphosphate reductase large subunit

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Reviewed, UniProtKB/Swiss-Prot P23921 (RIR1_HUMAN)

Last modified June 16, 2009. Version 97. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Ribonucleoside-diphosphate reductase large subunit
    EC=1.17.4.1
Alternative name(s):
    Ribonucleoside-diphosphate reductase subunit M1
    Ribonucleotide reductase large subunit

Gene names

Name:	RRM1
Synonyms:	RR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	792 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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 the binding of deoxynucleoside triphosphates and ATP to binding sites on the M1 subunit.
Pathway	Genetic information processing; DNA replication.
Subunit structure	Heterodimer of a large and a small subunit. Interacts with RRM2B. Ref.6
Subcellular location	Cytoplasm.
Involvement in disease	Ribonucleotide reductase is thought to mediate the pathogenesis of the immunodeficiency of adenosine deaminase or purine nucleoside phosphorylase. The deoxynucleotides that accumulate in the lymphoid cells of these patients are thought to feed-back inhibit ribonucleotide reductase, preventing DNA replication and cell proliferation.
Miscellaneous	Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2. The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.

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Ontologies

Keywords
Biological process	DNA replication
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
Technical term	3D-structure Allosteric enzyme
Gene Ontology (GO)
Biological process	DNA replication Non-traceable author statement. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome ribonucleoside-diphosphate reductase complex Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 792

792

Ribonucleoside-diphosphate reductase large subunit

PRO_0000187190

Regions

Domain

1 – 92

ATP-cone

Sites

Active site

218

Hydrogen atom transfer By similarity

Active site

427

Proton acceptor By similarity

Active site

429

Proton acceptor By similarity

Active site

431

Proton acceptor By similarity

Active site

444

Hydrogen atom transfer By similarity

Active site

737

Electron transfer By similarity

Active site

738

Electron transfer By similarity

Site

226

Allosteric effector binding By similarity

Site

256

Allosteric effector binding By similarity

Site

787

Interacts with thioredoxin/glutaredoxin By similarity

Site

790

Interacts with thioredoxin/glutaredoxin By similarity

Natural variations

Natural variant

590

K → Q: dbSNP rs2228123.

VAR_052052

Natural variant

778

V → A: dbSNP rs2229196.

VAR_052053

Experimental info

Sequence conflict

R → Q in AAD37491. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

P23921-1 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: 4470A76C61E8F86A
Show »

FASTA

792

90,070

        10         20         30         40         50         60 
MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA 

        70         80         90        100        110        120 
AETAATLTTK HPDYAILAAR IAVSNLHKET KKVFSDVMED LYNYINPHNG KHSPMVAKST 

       130        140        150        160        170        180 
LDIVLANKDR LNSAIIYDRD FSYNYFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK 

       190        200        210        220        230        240 
EDIDAAIETY NLLSERWFTH ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL 

       250        260        270        280        290        300 
ISKSAGGIGV AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY 

       310        320        330        340        350        360 
LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL MCPNECPGLD 

       370        380        390        400        410        420 
EVWGEEFEKL YASYEKQGRV RKVVKAQQLW YAIIESQTET GTPYMLYKDS CNRKSNQQNL 

       430        440        450        460        470        480 
GTIKCSNLCT EIVEYTSKDE VAVCNLASLA LNMYVTSEHT YDFKKLAEVT KVVVRNLNKI 

       490        500        510        520        530        540 
IDINYYPVPE ACLSNKRHRP IGIGVQGLAD AFILMRYPFE SAEAQLLNKQ IFETIYYGAL 

       550        560        570        580        590        600 
EASCDLAKEQ GPYETYEGSP VSKGILQYDM WNVTPTDLWD WKVLKEKIAK YGIRNSLLIA 

       610        620        630        640        650        660 
PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WHEEMKNQII 

       670        680        690        700        710        720 
ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL 

       730        740        750        760        770        780 
TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKVSKEEEEK ERNTAAMVCS 

       790 
LENRDECLMC GS

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human M1 subunit of ribonucleotide reductase: cDNA sequence and expression in stimulated lymphocytes." Parker N.J., Begley C.G., Fox R.M. Nucleic Acids Res. 19:3741-3741(1991) [PubMed: 1840662] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone marrow.
[2]	"Sequence analysis of the large and small subunits of human ribonucleotide reductase." Pavloff N., Rivard D., Masson S., Shen S.-H., Mes-Masson A.-M. DNA Seq. 2:227-234(1992) [PubMed: 1627826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary carcinoma.
[3]	"A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region." Bepler G., O'Briant K.C., Kim Y.-C., Schreiber G., Pitterle D.M. Genomics 55:164-175(1999) [PubMed: 9933563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[5]	"Human R1 subunit of ribonucleotide reductase (RRM1): 5' flanking region of the gene." Parker N.J., Begley C.G., Fox R.M. Genomics 19:91-96(1994) [PubMed: 8188248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6. Tissue: Placenta.
[6]	"Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits." Xue L., Zhou B., Liu X., Qiu W., Jin Z., Yen Y. Cancer Res. 63:980-986(2003) [PubMed: 12615712] [Abstract] Cited for: INTERACTION WITH RRM2B.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

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Web resources

Wikipedia

Ribonucleotide reductase entry

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Cross-references

Sequence databases

X59543 mRNA. Translation: CAA42118.1.
X59617 mRNA. Translation: CAA42180.1.
AF107045 Genomic DNA. Translation: AAD37491.1.
BC006498 mRNA. Translation: AAH06498.1.
L10342 Genomic DNA. No translation available.

IPI

IPI00013871.

PIR

S16680.

RefSeq

NP_001024.1.

UniGene

Hs.445705

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WGH	X-ray	2.30	A/B	75-742	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24233N.

IntAct

P23921. 9 interactions.

PTM databases

PhosphoSite

P23921.

Proteomic databases

PeptideAtlas

P23921.

PRIDE

P23921.

Genome annotation databases

Ensembl

ENSG00000167325. Homo sapiens. [Contig view]

GeneID

6240.

KEGG

hsa:6240.

NMPDR

fig|9606.3.peg.5072.

Organism-specific databases

GeneCards

GC11P004072.

H-InvDB

HIX0009381.

HGNC

HGNC:10451. RRM1.

MIM

180410. gene.

PharmGKB

PA298.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P23921.

HOVERGEN

P23921.

OMA

P23921. GSLWSKG.

Enzyme and pathway databases

BRENDA

1.17.4.1. 247.

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

P23921.

Bgee

P23921.

CleanEx

HS_RRM1.

GermOnline

ENSG00000167325. Homo sapiens.

Family and domain databases

InterPro

IPR005144. ATP-cone.
IPR013346. NrdE_NrdA.
IPR013509. Ribncl_Rdtase_lsu_N.
IPR000788. Ribncl_red_lg_C.
[Graphical view]

PANTHER

PTHR11573. Ribncl_red_lg_C. 1 hit.

Pfam

PF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]

PRINTS

PR01183. RIBORDTASEM1.

TIGRFAMs

TIGR02506. NrdE_NrdA. 1 hit.

PROSITE

PS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00631. Clofarabine.
DB01073. Fludarabine.
DB00441. Gemcitabine.
DB01005. Hydroxyurea.

NextBio

24233.

SOURCE

Search...

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Entry information

Entry name

RIR1_HUMAN

Accession

Primary (citable) accession number: P23921
Secondary accession number(s): Q9UNN2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	June 16, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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