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FLASH GENE

Symbol

RRM2B

contributors: mct - updated : 22-10-2015

HGNC name	ribonucleotide reductase M2 B (TP53 inducible)
HGNC id	17296

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MDDS5 mitochondrial DNA depletion syndrome, encephalomyopathic form PEO5 progressive external ophthalmoplegia 5
Location	8q22.3      Physical location : 103.216.728 - 103.251.346
Synonym name	p53-inducible ribonucleotide reductase small subunit 2 long form
	p53-inducible ribonucleotide reductase small subunit 2 short form gamma
Synonym symbol(s)	P53R2, DKFZp686M05248, MGC102856, MGC42116, MTDPS8A, MTDPS8B
EC.number	1.17.4.1

DNA

TYPE	functioning gene
STRUCTURE	34.62 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001172478 8 - 4776 NP_001165949 - 299 - 2000 10716435 NM_015713 9 - 4932 NP_056528 40.7 351 - 2000 10716435 NM_001172477 9 - 4913 NP_001165948 - 423 - 2000 10716435

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine parathyroid           thyroid         Lymphoid/Immune lymph node

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly

cell lineage

cell lines

fluid/secretion

at STAGE

cell cycle

cell cycle

life cycle

quiescence

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

intraspecies

homolog to RRM2 (80p 100)

Homologene

FAMILY

ribonucleoside diphosphate reductase small chain family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	is expressed throughout the cell cycle and in quiescent cells where it provides dNTPs for mitochondrial DNA synthesis

basic FUNCTION	TP53-controled small ribonucleotide reductase, catalyzing the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
	direct interaction of TP53 with RRM2 and the nuclear accumulation of ribonucleotide reductase subunits after UV exposure might play a pivotal role in DNA repair
	play essential roles in DNA repair, mtDNA synthesis, and protection against oxidative stress
	play key roles in forming ribonucleotide reductase holoenzyme and supplying nucleotide precursors for DNA replication and repair
	may play a key role in defending oxidative stress by scavenging ROS, and this antioxidant property is also important for its enzymatic activity
	plays critical roles not only in DNA damage repair but also in proliferation of cancer cells
	required for mitochondrial DNA replication and DNA repair in quiescent cells
	in postmitotic mammalian cells, RRM2B substitutes for protein R2 as a subunit of ribonucleotide reductase
	its activity is required for the stability of the mt genome in differentiated tissues, shifting the attention from DNA repair to mtDNA maintenance
	DNA damage-inducible small subunit of ribonucleotide reductase, the rate-limiting enzyme in de novo deoxyribonucleoside triphosphate synthesis
	plays a crucial role in maintaining chromosomal stability and preventing chronic-inflammation-associated tumorigenesis
	its activity is a prosurvival function inactivated by proteolysis during apoptosis
	critical ribonucleotide reductase (RR) subunit that exists as TP53-inducible and TP53-dependent molecule
	critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a TP53-independent manner

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

heterodimer of a large (M1) and a small chain (M2)

INTERACTION

DNA

RNA

small molecule	metal binding,
	binds 2 iron ions per subunit

protein	interacting with RRM1
	direct interaction with TP53 and RRM2
	TP53-inducible ribonucleotide reductase
	RRM2B as well as its heterodimeric partner RRM1, are associated with ATM
	MAP2K2 is an endogenous regulator of RRM2B, suggesting that it may associate with RRM2B and upregulate its activity
	transcriptionally and functionally regulated independent of TP53 pathway by FOXO3
	role of E2F1 in the regulation of RRM2B expression in DNA damage response (DDR)
	FOXO3 was identified as a novel regulator of RRM2B

cell & other

REGULATION

induced by	by ultraviolet light in a p53-dependent manner
		by stress signals prior to the onset of senescence and prevents premature oxidative stress-induced senescence

Other	regulated by p53 for supplying nucleotides to repair damaged DNA
	regulation of its activity via ATM-mediated phosphorylation at Ser(72) and MDM2-dependent turnover of RRM2B dephosphorylated at the same residue

ASSOCIATED DISORDERS

corresponding disease(s)

MDDS5 , PEO5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis, in esophageal squamous cell carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     is a potential target for cancer therapy cancer     potential target for anticancer drugs as well as a diagnostic marker in cancer

ANIMAL & CELL MODELS