RRM1

Protein identityUniProt · HPA

UniProt accession

P23921

Gene

RRM1

Ensembl

ENSG00000167325

Chromosome

11

Canonical length

792 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Plasma membrane,Centriolar satellite,Basal body,Cytosol

OverviewNCBI Gene

This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Canonical amino-acid sequenceUniProt

792 residues, UniProt reviewed canonical sequence.

>P23921|RRM1
     1  MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA
    61  AETAATLTTK HPDYAILAAR IAVSNLHKET KKVFSDVMED LYNYINPHNG KHSPMVAKST
   121  LDIVLANKDR LNSAIIYDRD FSYNYFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK
   181  EDIDAAIETY NLLSERWFTH ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL
   241  ISKSAGGIGV AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY
   301  LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL MCPNECPGLD
   361  EVWGEEFEKL YASYEKQGRV RKVVKAQQLW YAIIESQTET GTPYMLYKDS CNRKSNQQNL
   421  GTIKCSNLCT EIVEYTSKDE VAVCNLASLA LNMYVTSEHT YDFKKLAEVT KVVVRNLNKI
   481  IDINYYPVPE ACLSNKRHRP IGIGVQGLAD AFILMRYPFE SAEAQLLNKQ IFETIYYGAL
   541  EASCDLAKEQ GPYETYEGSP VSKGILQYDM WNVTPTDLWD WKVLKEKIAK YGIRNSLLIA
   601  PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WHEEMKNQII
   661  ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL
   721  TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKVSKEEEEK ERNTAAMVCS
   781  LENRDECLMC GS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RRM1 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)

0.21

Highest tissue expression

53 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RRM1.

Disease | AllUniProt

Conditions RRM1 is implicated in, by any mechanism.

• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6 (PEOB6) MIM:620647

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 83 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6
• RRM1-related disorder

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)

0.1

gnomAD pLI

1

gnomAD missense Z

3.99

DepMap mean gene effect

-2.86

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 2'-deoxyribonucleotide biosynthetic process
• cell proliferation in forebrain
• deoxyribonucleotide biosynthetic process
• DNA repair
• DNA synthesis involved in DNA repair
• male gonad development
• mitochondrial DNA replication
• positive regulation of G0 to G1 transition
• positive regulation of G1/S transition of mitotic cell cycle
• positive regulation of G2/M transition of mitotic cell cycle
• protein heterotetramerization
• pyrimidine nucleobase metabolic process
• response to ionizing radiation
• retina development in camera-type eye
• ribonucleoside diphosphate metabolic process

Molecular functions

• ATP binding
• disordered domain specific binding
• identical protein binding
• ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
• ribonucleoside-diphosphate reductase activity

Cellular components

• centriolar satellite
• ciliary basal body
• cytosol
• mitochondrion
• neuronal cell body
• nuclear envelope
• ribonucleoside-diphosphate reductase complex

Protein domainsUniProt · Pfam · InterPro

• Ribonucleotide reductase large subunit, C-terminal
• ATP-cone domain
• Ribonucleotide reductase R1 subunit, N-terminal
• Ribonucleotide reductase, class I, alpha subunit, C-terminal
• Ribonucleotide reductase large subunit, N-terminal
• Ribonucleoside-diphosphate reductase large subunit
• Ribonucleotide reductase, all-alpha domain
• Ribonucleotide reductase, barrel domain
• ATP cone domain

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• ATP-binding
• Cytoplasm
• Deoxyribonucleotide synthesis
• Disulfide bond
• Nucleotide-binding
• Oxidoreductase
• Phosphoprotein
• Primary mitochondrial disease
• Progressive external ophthalmoplegia

InteractionsUniProt · HPA

Protein binding partners of RRM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RRM2B
• AHCYL1
• PARP1
• RRM2