ORC4

Protein identityUniProt · HPA

UniProt accession

O43929

Gene

ORC4

Ensembl

ENSG00000115947

Chromosome

2

Canonical length

436 aa

Protein class

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

Subcellular location

Nucleoplasm,Nucleoli

OverviewNCBI Gene

The origin recognition complex (ORC) is a highly conserved six subunit 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. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]

Canonical amino-acid sequenceUniProt

436 residues, UniProt reviewed canonical sequence.

>O43929|ORC4
     1  MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES
    61  NSVLIIGPRG SGKTMLINHA LKELMEIEEV SENVLQVHLN GLLQINDKIA LKEITRQLNL
   121  ENVVGDKVFG SFAENLSFLL EALKKGDRTS SCPVIFILDE FDLFAHHKNQ TLLYNLFDIS
   181  QSAQTPIAVI GLTCRLDILE LLEKRVKSRF SHRQIHLMNS FGFPQYVKIF KEQLSLPAEF
   241  PDKVFAEKWN ENVQYLSEDR SVQEVLQKHF NISKNLRSLH MLLMLALNRV TASHPFMTAV
   301  DLMEASQLCS MDSKANIVHG LSVLEICLII AMKHLNDIYE EEPFNFQMVY NEFQKFVQRK
   361  AHSVYNFEKP VVMKAFEHLQ QLELIKPMER TSGNSQREYQ LMKLLLDNTQ IMNALQKYPN
   421  CPTDVRQWAT SSLSWL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ORC4 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

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ORC4.

Disease | AllUniProt

Conditions ORC4 is implicated in, by any mechanism.

• Meier-Gorlin syndrome 2 (MGORS2) MIM:613800

Disease | GeneticClinVar

23 pathogenic / likely-pathogenic of 239 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Meier-Gorlin syndrome 2

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)

1.13

gnomAD pLI

0

gnomAD missense Z

-0.2

DepMap mean gene effect

-0.54

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
• polar body extrusion after meiotic divisions
• protein polymerization

Molecular functions

• ATP binding
• DNA replication origin binding
• nucleotide binding

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• AAA+ ATPase domain
• P-loop containing nucleoside triphosphate hydrolase
• Orc1-like, AAA ATPase domain
• AAA ATPase domain
• Origin recognition complex subunit 4
• Origin recognition complex subunit 4, C-terminal
• Origin recognition complex (ORC) subunit 4 C-terminus

KeywordsUniProt

• ATP-binding
• DNA replication
• DNA-binding
• Dwarfism
• Methylation
• Nucleotide-binding
• Nucleus

InteractionsUniProt · HPA

Protein binding partners of ORC4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DBF4
• POLQ
• ORC1
• ORC2
• ORC3
• ORC5
• ORC6