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FLASH GENE

Symbol

RRM2

contributors: mct - updated : 13-07-2017

HGNC name	ribonucleotide reductase M2 polypeptide
HGNC id	10452

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	8.85 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (CAAT box) (TATA box)
text structure	TATA box upstream the first initiation site 3 consensus CAAT boxes between the two transcription start sites

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_001165931 10 - 3452 NP_001159403 - 449 - 2001 11978970 NM_001034 10 - 3284 NP_001025 - 389 - 2001 11978970

EXPRESSION

Type

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 blood / hematopoietic thymus       highly Digestive intestine large intestine colon   highly   intestine small intestine     highly   liver       lowly   stomach         Lymphoid/Immune lymph node           spleen         Reproductive male system testis     highly Respiratory lung       lowly

cell lineage

cell lines

fluid/secretion

at STAGE

cell cycle

cell cycle, S

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a Cyclin F-binding motif, in a region of RRM2 located between amino acids 40-65, containing two putative CY motifs

HOMOLOGY

interspecies

homolog to murine Rrm2

Homologene

FAMILY

ribonucleoside diphosphate reductase small chain family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
text	is largely cytoplasmic
	its expression is S phase-specific and required for DNA replication

basic FUNCTION	ribonucleoside diphosphate reductase activity
	promoter responsible for cell-cycle specific expression
	plays an active role in tumor progression
	its activity is a prosurvival function inactivated by proteolysis during apoptosis
	plays a significant role in the regulation of cell invasiveness, cell migration and tumor metastasis

CELLULAR PROCESS

nucleotide, replication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

purine/pyrimidine

signaling

pyrimidine biosynthetic pathway

a component

component of the ribonucleotide reductase

INTERACTION

DNA

RNA

small molecule	metal binding,
	binding two iron ions

protein	heterodimerizing with RRM1
	positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of THBS1 and VEGFA
	is a new interactor of the F-box protein CCNF
	Cyclin F directly controls the ubiquitin-mediated degradation of RRM2
	RRM2 regulates BCL2 protein stability, with RRM2 suppression leading to increased BCL2 degradation, and critical link between RRM2 and BCL2 in apoptosis signaling
	E2F1 can promote colorectal cancer proliferation, migration, invasion and metastasis by regulating RRM2 transactivation
	CDKL3 is a promotor for glioma, probably through the regulation of RRM2 and activation of the JNK signalling pathway

cell & other

REGULATION

Other

regulated in a cell cycle dependent manner

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   associated with poor prognosis of gastric cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive stomach RRM2 is a novel target for effective diagnosis and treatment of gastric cancer cancer skin   inhibition of RRM2 converts the transient response of melanoma cells to BRAF inhibitor to a stable response and may be a novel combinatorial strategy to prolong therapeutic response of melanoma patients cancer reproductive uterus inhibition of RRM2 activity may be a novel therapeutic strategy for human cervical cancer cancer digestive colon novel therapeutic target, thus highlighting the potential utility of RRM2 inhibitors in colorectal cancer with oncogenic KRAS

ANIMAL & CELL MODELS