ORC1 origin recognition complex subunit 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ORC1provided by HGNC
Official Full Name: origin recognition complex subunit 1provided by HGNC
Primary source: HGNC:HGNC:8487
See related: Ensembl:ENSG00000085840 MIM:601902; AllianceGenome:HGNC:8487
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ORC1L; PARC1; HSORC1
Summary: 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]
Expression: Biased expression in bone marrow (RPKM 7.3), lymph node (RPKM 2.5) and 10 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 1p32.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (52372829..52409503, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (52254294..52290972, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (52838501..52870095, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
Title: Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.
Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer.
Title: Origin recognition complex subunit 1(ORC1) is a potential biomarker and therapeutic target in cancer.
Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling.
Title: Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling.
Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
Title: Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication.
Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway.
Title: Origin recognition complex subunit 1 regulates cell growth and metastasis in glioma by altering activation of ERK and JNK signaling pathway.
Authors report the crystal structure of Cyclin A-CDK2 complex bound to a peptide derived from ORC1 at 2.54 a resolution; structure revealed that the ORC1 peptide interacts with a hydrophobic groove, termed cyclin binding groove, of Cyclin A via a KXL motif.
Title: Structural basis for the ORC1-Cyclin A association.
The opposing effects of ORC1 (represor) and CDC6 (gene activator) in controlling the level of Cyclin E ensures genome stability and a mechanism for linking directly DNA replication and cell division commitment.
Title: Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription.
The authors have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1.
Title: Two subunits of human ORC are dispensable for DNA replication and proliferation.
Orc1 acts as a nucleating center for origin recognition complex assembly and then pre-replication complex assembly by binding to mitotic chromosomes, followed by gradual removal from chromatin during the G1 phase.
Title: Orc1 Binding to Mitotic Chromosomes Precedes Spatial Patterning during G1 Phase and Assembly of the Origin Recognition Complex in Human Cells.
ORC1 harbors a G-rich RNA/ssDNA-binding domain, which may be involved in the preferential binding to G-quadruplex-formable RNA/DNA by ORC. Structure modeling predicts the structural similarity between the G-rich RNA/ssDNA-binding domain of ORC1 and part of mammalian DNA methyltransferase 1.
Title: Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Meier-Gorlin syndrome 1 MedGen: C4552001 OMIM: 224690 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH120149 (e-PCR)
- UniSTS:132354

RH79919 (e-PCR)
- UniSTS:83720

A009U12 (e-PCR)
- UniSTS:5696

csnporc1l-pcr10-1 (e-PCR)
- UniSTS:243061

csnporc1l-pcr11-1 (e-PCR)
- UniSTS:243062

csnporc1l-pcr14-1 (e-PCR)
- UniSTS:243063

csnporc1l-pcr16-1 (e-PCR)
- UniSTS:243064

csnporc1l-pcr17-1 (e-PCR)
- UniSTS:243065

csnporc1l-pcr2-1 (e-PCR)
- UniSTS:243066

csnporc1l-pcr5-1 (e-PCR)
- UniSTS:243067

csnporc1l-pcr6-1 (e-PCR)
- UniSTS:243068

csnporc1l-pcr7-1 (e-PCR)
- UniSTS:243069

csnporc1l-pcr8-1 (e-PCR)
- UniSTS:243070

csnporc1l-pcr9-1 (e-PCR)
- UniSTS:243071

PMC303366P7 (e-PCR)
- UniSTS:272514

G32836 (e-PCR)
- UniSTS:117415

RH70495 (e-PCR)
- UniSTS:29114

RH80351 (e-PCR)
- UniSTS:89283

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA replication origin binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in mitotic DNA replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromosome, telomeric region	HDA more info	PubMed
colocalizes_with chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of nuclear origin of replication recognition complex	IBA Inferred from Biological aspect of Ancestor more info
part_of nuclear origin of replication recognition complex	IDA Inferred from Direct Assay more info	PubMed
part_of nuclear origin of replication recognition complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of origin recognition complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: origin recognition complex subunit 1

Names: origin recognition complex, subunit 1 homolog; replication control protein 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028251.2 RefSeqGene

Range

10080..41674

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001190818.2 → NP_001177747.1 origin recognition complex subunit 1 isoform 1

See identical proteins and their annotated locations for NP_001177747.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate splice site in the 5' UTR, resulting in 3 nt fewer than variant 1. Variants 1 and 2 encode the same isoform 1.

Source sequence(s)

BC011539, BP280383, U43416

Consensus CDS

CCDS566.1

UniProtKB/Swiss-Prot

D3DQ34, Q13415, Q13471, Q5T0F5

UniProtKB/TrEMBL

A8K794, Q96F82

Related

ENSP00000360621.1, ENST00000371566.1

Conserved Domains (4) summary

PRK10811
Location:362 → 487

rne; ribonuclease E; Reviewed

cd04719
Location:44 → 170

BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...

PTZ00112
Location:495 → 743

PTZ00112; origin recognition complex 1 protein; Provisional

pfam09079
Location:778 → 857

Cdc6_C; CDC6, C terminal winged helix domain
NM_001190819.2 → NP_001177748.1 origin recognition complex subunit 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate splice site in the CDS, resulting in 15 nt fewer than variant 1. The resulting isoform (2) lacks internal 5 aa, as compared to isoform 1.

Source sequence(s)

AK303420, DB156841, U43416

UniProtKB/TrEMBL

B7Z8H0

Conserved Domains (4) summary

cd04719
Location:44 → 170

BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...

pfam09079
Location:773 → 846

Cdc6_C; CDC6, C terminal

pfam13191
Location:499 → 549

AAA_16; AAA ATPase domain

cl21455
Location:525 → 670

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_004153.4 → NP_004144.2 origin recognition complex subunit 1 isoform 1

See identical proteins and their annotated locations for NP_004144.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longest transcript and encodes the longer isoform (1).

Source sequence(s)

U40152, U43416

Consensus CDS

CCDS566.1

UniProtKB/Swiss-Prot

D3DQ34, Q13415, Q13471, Q5T0F5

UniProtKB/TrEMBL

A8K794, Q96F82

Related

ENSP00000360623.3, ENST00000371568.8

Conserved Domains (4) summary

PRK10811
Location:362 → 487

rne; ribonuclease E; Reviewed

cd04719
Location:44 → 170

BAH_Orc1p_animal; BAH, or Bromo Adjacent Homology domain, as present in animal homologs of Saccharomyces cerevisiae Orc1p. Orc1 is part of the Yeast Sir1-origin recognition complex. The Orc1p BAH doman functions in epigenetic silencing. In vertebrates, a similar ORC ...

PTZ00112
Location:495 → 743

PTZ00112; origin recognition complex 1 protein; Provisional

pfam09079
Location:778 → 857

Cdc6_C; CDC6, C terminal winged helix domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

52372829..52409503 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421674.1 → XP_047277630.1 origin recognition complex subunit 1 isoform X1

UniProtKB/Swiss-Prot

D3DQ34, Q13415, Q13471, Q5T0F5
XM_047421680.1 → XP_047277636.1 origin recognition complex subunit 1 isoform X2
XM_017001388.3 → XP_016856877.1 origin recognition complex subunit 1 isoform X2

UniProtKB/TrEMBL

A8K794, Q96F82
XM_011541527.4 → XP_011539829.1 origin recognition complex subunit 1 isoform X3

Conserved Domains (4) summary

pfam09079
Location:418 → 491

Cdc6_C; CDC6, C terminal

pfam13191
Location:144 → 194

AAA_16; AAA ATPase domain

pfam15091
Location:34 → 159

DUF4554; Domain of unknown function (DUF4554)

cl21455
Location:170 → 315

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

52254294..52290972 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054336824.1 → XP_054192799.1 origin recognition complex subunit 1 isoform X1

UniProtKB/Swiss-Prot

D3DQ34, Q13415, Q13471, Q5T0F5
XM_054336826.1 → XP_054192801.1 origin recognition complex subunit 1 isoform X2
XM_054336825.1 → XP_054192800.1 origin recognition complex subunit 1 isoform X2
XM_054336827.1 → XP_054192802.1 origin recognition complex subunit 1 isoform X3