Reviewed, UniProtKB/Swiss-Prot Q7LG56 (RIR2B_HUMAN)

Names and origin

Protein names

Recommended name:
    Ribonucleoside-diphosphate reductase subunit M2 B
    EC=1.17.4.1
Alternative name(s):
    TP53-inducible ribonucleotide reductase M2 B
    p53-inducible ribonucleotide reductase small subunit 2-like protein
      Short name=p53R2

Gene names

Name:	RRM2B
Synonyms:	P53R2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage. Ref.1 Ref.7 Ref.8
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
Cofactor	Binds 2 iron ions per subunit By similarity.
Pathway	Genetic information processing; DNA replication.
Subunit structure	Heterotetramer with large (RRM1) subunit. Interacts with p53/TP53. Interacts with RRM1 in response to DNA damage. Ref.7 Ref.9
Subcellular location	Cytoplasm. Nucleus. Note: Translocates from cytoplasm to nucleus in response to DNA damage. Ref.8 Ref.9
Tissue specificity	Widely expressed at a high level in skeletal muscle and at a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma. Ref.10
Induction	In response to DNA damage in a wild-type p53/TP53-dependent manner. Ref.1
Involvement in disease	Defects in RRM2B are the cause of encephalomyopathic mitochondrial depletion syndrome with renal tubulopathy (EMDSRT) [MIM:612075]. Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. The encephalomyopathic form with renal tubulopathy is presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. Ref.12 Ref.13
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase small chain family.

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	Iron Metal-binding
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW deoxyribonucleoside diphosphate metabolic process Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoside-diphosphate reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7LG56-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q7LG56-2)

Also known as: Long form;

The sequence of this isoform differs from the canonical sequence as follows:
     17-68: Missing.

Isoform 3 (identifier: Q7LG56-3)

Also known as: Short form gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     17-228: Missing.

Isoform 4 (identifier: Q7LG56-4)

Also known as: Short form beta;

The sequence of this isoform differs from the canonical sequence as follows:
     17-301: Missing.

Isoform 5 (identifier: Q7LG56-5)

Also known as: Short form;

The sequence of this isoform differs from the canonical sequence as follows:
     42-43: FV → SF
     44-351: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 351

351

Ribonucleoside-diphosphate reductase subunit M2 B

PRO_0000228150

Sites

Active site

138

1

By similarity

Metal binding

100

1

Iron 1 By similarity

Metal binding

131

1

Iron 1 By similarity

Metal binding

131

1

Iron 2 By similarity

Metal binding

134

1

Iron 1 By similarity

Metal binding

194

1

Iron 2 By similarity

Metal binding

228

1

Iron 2 By similarity

Metal binding

231

1

Iron 2 By similarity

Natural variations

Alternative sequence

17 – 301

285

Missing in isoform 4.

VSP_017668

Alternative sequence

17 – 228

212

Missing in isoform 3.

VSP_017669

Alternative sequence

17 – 68

52

Missing in isoform 2.

VSP_017670

Alternative sequence

42 – 43

2

FV → SF in isoform 5.

VSP_017671

Alternative sequence

44 – 351

308

Missing in isoform 5.

VSP_017672

Natural variant

64

1

W → R in EMDSRT. Ref.12

VAR_046217

Natural variant

85

1

Missing in EMDSRT.

VAR_046218

Natural variant

115

1

V → L in colorectal adenocarcinomas cell line; loss of ribonucleotide reductase activity. Ref.8

VAR_025699

Natural variant

194

1

E → G in EMDSRT. Ref.12

VAR_046219

Natural variant

194

1

E → K in EMDSRT. Ref.12

VAR_046220

Natural variant

224

1

I → S in EMDSRT; without tubulopathy. Ref.13

VAR_046221

Natural variant

236

1

C → F in EMDSRT. Ref.12

VAR_046222

Natural variant

282

1

M → I in EMDSRT; without tubulopathy. Ref.13

VAR_046223

Natural variant

317

1

L → V in EMDSRT; without tubulopathy. Ref.13

VAR_046224

Experimental info

Sequence conflict

277

1

M → V in BAA92005. Ref.3

Secondary structure

1

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351

Helix Strand Turn

Details...

Turn

33 – 35

3

Helix

50 – 61

12

Helix

66 – 68

3

Helix

75 – 80

6

Helix

83 – 98

16

Helix

107 – 114

8

Helix

118 – 145

28

Helix

149 – 161

13

Helix

163 – 175

13

Turn

176 – 178

3

Helix

183 – 195

13

Turn

196 – 198

3

Helix

199 – 210

12

Helix

215 – 239

25

Helix

248 – 267

20

Helix

272 – 275

4

Helix

279 – 296

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 6D008687EEF40994	FASTA	351	40,737
	10 20 30 40 50 60 MGDPERPEAA GLDQDERSSS DTNESEIKSN EEPLLRKSSR RFVIFPIQYP DIWKMYKQAQ 70 80 90 100 110 120 ASFWTAEEVD LSKDLPHWNK LKADEKYFIS HILAFFAASD GIVNENLVER FSQEVQVPEA 130 140 150 160 170 180 RCFYGFQILI ENVHSEMYSL LIDTYIRDPK KREFLFNAIE TMPYVKKKAD WALRWIADRK 190 200 210 220 230 240 STFGERVVAF AAVEGVFFSG SFAAIFWLKK RGLMPGLTFS NELISRDEGL HCDFACLMFQ 250 260 270 280 290 300 YLVNKPSEER VREIIVDAVK IEQEFLTEAL PVGLIGMNCI LMKQYIEFVA DRLLVELGFS 310 320 330 340 350 KVFQAENPFD FMENISLEGK TNFFEKRVSE YQRFAVMAET TDNVFTLDAD F
	Isoform 2 (Long form). Checksum: 4705C44389EB689B	FASTA	299	34,529
	10 20 30 40 50 60 MGDPERPEAA GLDQDEVDLS KDLPHWNKLK ADEKYFISHI LAFFAASDGI VNENLVERFS 70 80 90 100 110 120 QEVQVPEARC FYGFQILIEN VHSEMYSLLI DTYIRDPKKR EFLFNAIETM PYVKKKADWA 130 140 150 160 170 180 LRWIADRKST FGERVVAFAA VEGVFFSGSF AAIFWLKKRG LMPGLTFSNE LISRDEGLHC 190 200 210 220 230 240 DFACLMFQYL VNKPSEERVR EIIVDAVKIE QEFLTEALPV GLIGMNCILM KQYIEFVADR 250 260 270 280 290 LLVELGFSKV FQAENPFDFM ENISLEGKTN FFEKRVSEYQ RFAVMAETTD NVFTLDADF
	Isoform 3 (Short form gamma). Checksum: E80F65CB030E89B5	FASTA	139	15,963
	10 20 30 40 50 60 MGDPERPEAA GLDQDEGLHC DFACLMFQYL VNKPSEERVR EIIVDAVKIE QEFLTEALPV 70 80 90 100 110 120 GLIGMNCILM KQYIEFVADR LLVELGFSKV FQAENPFDFM ENISLEGKTN FFEKRVSEYQ 130 RFAVMAETTD NVFTLDADF
	Isoform 4 (Short form beta). Checksum: D432147F4FC35499	FASTA	66	7,602
	10 20 30 40 50 60 MGDPERPEAA GLDQDEVFQA ENPFDFMENI SLEGKTNFFE KRVSEYQRFA VMAETTDNVF TLDADF
	Isoform 5 (Short form). Checksum: 29373C73112CBE75	FASTA	43	4,852
	10 20 30 40 MGDPERPEAA GLDQDERSSS DTNESEIKSN EEPLLRKSSR RSF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage." Tanaka H., Arakawa H., Yamaguchi T., Shiraishi K., Fukuda S., Matsui K., Takei Y., Nakamura Y. Nature 404:42-49(2000) [PubMed: 10716435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INDUCTION.
[2]	"Homo sapiens p53-inducible ribonucleotide reductase small subunit 2 splicing variants." Ugai H., Yokoyama K.K. Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Amygdala.
[5]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Brain and Eye.
[7]	"Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells." Guittet O., Haakansson P., Voevodskaya N., Fridd S., Graeslund A., Arakawa H., Nakamura Y., Thelander L. J. Biol. Chem. 276:40647-40651(2001) [PubMed: 11517226] [Abstract] Cited for: FUNCTION, SUBUNIT.
[8]	"p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint." Yamaguchi T., Matsuda K., Sagiya Y., Iwadate M., Fujino M.A., Nakamura Y., Arakawa H. Cancer Res. 61:8256-8262(2001) [PubMed: 11719458] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT LEU-115.
[9]	"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: SUBCELLULAR LOCATION, INTERACTION WITH TP53 AND RRM1.
[10]	"The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53." Zhou B., Liu X., Mo X., Xue L., Darwish D., Qiu W., Shih J., Hwu E.B., Luh F., Yen Y. Cancer Res. 63:6583-6594(2003) [PubMed: 14583450] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion." Bourdon A., Minai L., Serre V., Jais J.-P., Sarzi E., Aubert S., Chretien D., de Lonlay P., Paquis-Flucklinger V., Arakawa H., Nakamura Y., Munnich A., Roetig A. Nat. Genet. 39:776-780(2007) [PubMed: 17486094] [Abstract] Cited for: VARIANTS EMDSRT ARG-64; GLU-85 DEL; GLY-194; LYS-194 AND PHE-236.
[13]	"Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene." Bornstein B., Area E., Flanigan K.M., Ganesh J., Jayakar P., Swoboda K.J., Coku J., Naini A., Shanske S., Tanji K., Hirano M., DiMauro S. Neuromuscul. Disord. 18:453-459(2008) [PubMed: 18504129] [Abstract] Cited for: VARIANTS EMDSRT SER-224; ILE-282 AND VAL-317.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB036063 mRNA. Translation: BAA92434.1.
AB036532 Genomic DNA. Translation: BAA92493.1.
AB163437 mRNA. Translation: BAD11774.1.
AB163438 mRNA. Translation: BAD11775.1.
AB166669 mRNA. Translation: BAD12265.1.
AB166670 mRNA. Translation: BAD12266.1.
AB166671 mRNA. Translation: BAD12267.1.
AK001965 mRNA. Translation: BAA92005.1.
AL137348 mRNA. Translation: CAB70703.2.
DQ027001 Genomic DNA. Translation: AAY29059.1.
BC042468 mRNA. Translation: AAH42468.1.
BC108261 mRNA. Translation: AAI08262.1.
BC117496 mRNA. Translation: AAI17497.1.
BC130628 mRNA. Translation: AAI30629.1.

IPI

IPI00100213.
IPI00438859.
IPI00438860.
IPI00735900.
IPI00741117.

PIR

T46249.

RefSeq

NP_056528.2.

UniGene

Hs.512592

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VUX	X-ray	2.80	A/B	20-322	[»]

SMR

Q7LG56. Positions 31-313.

ModBase

Search...

Protein-protein interaction databases

STRING

Q7LG56.

PTM databases

PhosphoSite

Q7LG56.

Proteomic databases

PRIDE

Q7LG56.

Genome annotation databases

Ensembl

ENST00000251810; ENSP00000251810; ENSG00000048392; Homo sapiens. [Genome view]
ENST00000395908; ENSP00000379244; ENSG00000048392; Homo sapiens. [Genome view]
ENST00000395910; ENSP00000379246; ENSG00000048392; Homo sapiens. [Genome view]
ENST00000395912; ENSP00000379248; ENSG00000048392; Homo sapiens. [Genome view]

GeneID

50484.

KEGG

hsa:50484.

UCSC

uc003ykn.1. human.
uc010mbv.1. human.

Organism-specific databases

CTD

50484.

GeneCards

GC08M103285.

H-InvDB

HIX0007697.

HGNC

HGNC:17296. RRM2B.

HPA

CAB006854.

MIM

604712. gene.
612075. phenotype.

PharmGKB

PA34866.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q7LG56.

OMA

ENLVQRF.

Enzyme and pathway databases

BRENDA

1.17.4.1. 247.

Reactome

REACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpress

Q7LG56.

Bgee

Q7LG56.

Genevestigator

Q7LG56.

GermOnline

ENSG00000048392. Homo sapiens.

Family and domain databases

InterPro

IPR012348. Ribncl_red_rel.
IPR000358. Ribonucl_redctse.
[Graphical view]

Gene3D

G3DSA:1.10.620.20. Ribncl_red_rel. 1 hit.

PANTHER

PTHR23409. Ribonucl_redctse. 1 hit.

Pfam

PF00268. Ribonuc_red_sm. 1 hit.
[Graphical view]

PROSITE

PS00368. RIBORED_SMALL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

53036.

SOURCE

Search...

Entry information

Entry name

RIR2B_HUMAN

Accession

Primary (citable) accession number: Q7LG56
Secondary accession number(s): Q17R22 , Q75PQ6, Q75PQ7, Q75PY8, Q75PY9, Q86YE3, Q9NPD6, Q9NTD8, Q9NUW3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	July 5, 2004
Last modified:	November 3, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.