RRM2B

Protein identityUniProt · HPA

UniProt accession

Q7LG56

Gene

RRM2B

Ensembl

ENSG00000048392

Chromosome

8

Canonical length

351 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. This heterotetrameric enzyme catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The product of this reaction is necessary for DNA synthesis. Mutations in this gene have been associated with autosomal recessive mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia-5, and mitochondrial neurogastrointestinal encephalopathy. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

Canonical amino-acid sequenceUniProt

351 residues, UniProt reviewed canonical sequence.

>Q7LG56|RRM2B
     1  MGDPERPEAA GLDQDERSSS DTNESEIKSN EEPLLRKSSR RFVIFPIQYP DIWKMYKQAQ
    61  ASFWTAEEVD LSKDLPHWNK LKADEKYFIS HILAFFAASD GIVNENLVER FSQEVQVPEA
   121  RCFYGFQILI ENVHSEMYSL LIDTYIRDPK KREFLFNAIE TMPYVKKKAD WALRWIADRK
   181  STFGERVVAF AAVEGVFFSG SFAAIFWLKK RGLMPGLTFS NELISRDEGL HCDFACLMFQ
   241  YLVNKPSEER VREIIVDAVK IEQEFLTEAL PVGLIGMNCI LMKQYIEFVA DRLLVELGFS
   301  KVFQAENPFD FMENISLEGK TNFFEKRVSE YQRFAVMAET TDNVFTLDAD F

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RRM2B can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

42 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RRM2B.

Disease | AllUniProt

Conditions RRM2B is implicated in, by any mechanism.

• Mitochondrial DNA depletion syndrome 8A (MTDPS8A) MIM:612075
• Mitochondrial DNA depletion syndrome 8B (MTDPS8B) MIM:612075
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5 (PEOA5) MIM:613077
• Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD) MIM:268315

Disease | GeneticClinVar

45 pathogenic / likely-pathogenic of 463 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial DNA depletion syndrome 8a
• RRM2B-related mitochondrial disease
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5
• Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction
• Mitochondrial disease

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.7

gnomAD pLI

0

gnomAD missense Z

1.21

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2'-deoxyribonucleotide biosynthetic process
• deoxyribonucleotide biosynthetic process
• DNA repair
• DNA synthesis involved in DNA repair
• kidney development
• mitochondrial DNA replication
• negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator
• positive regulation of G0 to G1 transition
• positive regulation of G2/M transition of mitotic cell cycle
• renal system process
• response to amine
• response to oxidative stress
• ribonucleoside diphosphate metabolic process
• deoxyribonucleoside triphosphate metabolic process

Molecular functions

• identical protein binding
• metal ion binding
• ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor

Cellular components

• cytosol
• mitochondrion
• nucleoplasm
• ribonucleoside-diphosphate reductase complex

Protein domainsUniProt · Pfam · InterPro

• Ribonucleotide reductase small subunit family
• Ferritin-like superfamily
• Ribonucleotide reductase-like
• Ribonucleotide reductase small subunit, acitve site
• Ribonucleotide reductase small subunit
• Ribonucleotide reductase, small chain

KeywordsUniProt

• Cytoplasm
• Deafness
• Deoxyribonucleotide synthesis
• DNA damage
• DNA repair
• Iron
• Metal-binding
• Neuropathy
• Nucleus
• Oxidoreductase
• Primary mitochondrial disease
• Progressive external ophthalmoplegia

InteractionsUniProt · HPA

Protein binding partners of RRM2B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RRM1