ORC1

Protein identityUniProt · HPA

UniProt accession

Q13415

Gene

ORC1

Ensembl

ENSG00000085840

Chromosome

1

Canonical length

861 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the ORC complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MyST2/HBO1), a protein involved in control of transcription silencing. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

Canonical amino-acid sequenceUniProt

861 residues, UniProt reviewed canonical sequence.

>Q13415|ORC1
     1  MAHYPTRLKT RKTYSWVGRP LLDRKLHYQT YREMCVKTEG CSTEIHIQIG QFVLIEGDDD
    61  ENPYVAKLLE LFEDDSDPPP KKRARVQWFV RFCEVPACKR HLLGRKPGAQ EIFWYDYPAC
   121  DSNINAETII GLVRVIPLAP KDVVPTNLKN EKTLFVKLSW NEKKFRPLSS ELFAELNKPQ
   181  ESAAKCQKPV RAKSKSAESP SWTPAEHVAK RIESRHSASK SRQTPTHPLT PRARKRLELG
   241  NLGNPQMSQQ TSCASLDSPG RIKRKVAFSE ITSPSKRSQP DKLQTLSPAL KAPEKTRETG
   301  LSYTEDDKKA SPEHRIILRT RIAASKTIDI REERTLTPIS GGQRSSVVPS VILKPENIKK
   361  RDAKEAKAQN EATSTPHRIR RKSSVLTMNR IRQQLRFLGN SKSDQEEKEI LPAAEISDSS
   421  SDEEEASTPP LPRRAPRTVS RNLRSSLKSS LHTLTKVPKK SLKPRTPRCA APQIRSRSLA
   481  AQEPASVLEE ARLRLHVSAV PESLPCREQE FQDIYNFVES KLLDHTGGCM YISGVPGTGK
   541  TATVHEVIRC LQQAAQANDV PPFQYIEVNG MKLTEPHQVY VQILQKLTGQ KATANHAAEL
   601  LAKQFCTRGS PQETTVLLVD ELDLLWTHKQ DIMYNLFDWP THKEARLVVL AIANTMDLPE
   661  RIMMNRVSSR LGLTRMCFQP YTYSQLQQIL RSRLKHLKAF EDDAIQLVAR KVAALSGDAR
   721  RCLDICRRAT EICEFSQQKP DSPGLVTIAH SMEAVDEMFS SSYITAIKNS SVLEQSFLRA
   781  ILAEFRRSGL EEATFQQIYS QHVALCRMEG LPYPTMSETM AVCSHLGSCR LLLVEPSRND
   841  LLLRVRLNVS QDDVLYALKD E

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ORC1 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)

0.45

Highest tissue expression

27 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ORC1.

Disease | AllUniProt

Conditions ORC1 is implicated in, by any mechanism.

• Meier-Gorlin syndrome 1 (MGORS1) MIM:224690

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 436 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Meier-Gorlin syndrome 1
• Inborn genetic diseases
• Meier-Gorlin syndrome
• ORC1-related disorder
• Fetal anomalies with a likely genetic cause

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)

0.88

gnomAD pLI

0

gnomAD missense Z

0.24

DepMap mean gene effect

-1.08

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA replication initiation
• mitotic DNA replication checkpoint signaling

Molecular functions

• ATP binding
• ATP hydrolysis activity
• chromatin binding
• DNA binding
• DNA replication origin binding
• metal ion binding

Cellular components

• chromosome, telomeric region
• cytosol
• nuclear origin of replication recognition complex
• nucleoplasm
• nucleus
• origin recognition complex

Protein domainsUniProt · Pfam · InterPro

• Bromo adjacent homology (BAH) domain
• AAA+ ATPase domain
• ATPase, AAA-type, core
• Cdc6, C-terminal
• P-loop containing nucleoside triphosphate hydrolase
• Bromo adjacent homology (BAH) domain superfamily
• Origin recognition complex 1/Cell division control protein 6
• ATPase family associated with various cellular activities (AAA)
• BAH domain
• CDC6, C terminal winged helix domain
• AAA lid domain
• AAA lid domain

KeywordsUniProt

• Acetylation
• ATP-binding
• DNA replication
• DNA-binding
• Dwarfism
• Magnesium
• Metal-binding
• Nucleotide-binding
• Nucleus
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of ORC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CDC6
• SKP2
• KAT7
• ORC2
• ORC3
• ORC4
• ORC5
• TERF2