Human Gene ORC1 (ENST00000371568.8) from GENCODE V44
Description: Homo sapiens origin recognition complex subunit 1 (ORC1), transcript variant 1, mRNA. (from RefSeq NM_004153) RefSeq Summary (NM_004153): 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]. Gencode Transcript: ENST00000371568.8 Gencode Gene: ENSG00000085840.13 Transcript (Including UTRs) Position: hg38 chr1:52,372,829-52,404,423 Size: 31,595 Total Exon Count: 17 Strand: - Coding Region Position: hg38 chr1:52,373,181-52,402,223 Size: 29,043 Coding Exon Count: 16
ID:ORC1_HUMAN DESCRIPTION: RecName: Full=Origin recognition complex subunit 1; AltName: Full=Replication control protein 1; FUNCTION: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. SUBUNIT: ORC is composed of six subunits. In human, ORC is cell cycle-dependent regulated: it is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase. Interacts with CDC6 and KAT7/HBO1. INTERACTION: Q13416:ORC2; NbExp=6; IntAct=EBI-374847, EBI-374957; Q9UBD5:ORC3; NbExp=12; IntAct=EBI-374847, EBI-374916; O43913:ORC5; NbExp=5; IntAct=EBI-374847, EBI-374928; Q13309:SKP2; NbExp=2; IntAct=EBI-374847, EBI-456291; SUBCELLULAR LOCATION: Nucleus. DEVELOPMENTAL STAGE: Expression is cell-cycle regulated, it starts to accumulate in mid-G1 phase, reaches a peak at the G1/S boundary, and decreases to a basal level in S phase (at protein level). DOMAIN: The BAH domain mediates binding to dimethylated histone H4 'Lys-20' (H4K20me2), which is enriched at replication origins (By similarity). DISEASE: Defects in ORC1 are the cause of Meier-Gorlin syndrome type 1 (MGORS1) [MIM:224690]; also called ear patella short stature syndrome (EPS) or microtia absent patellae micrognathia syndrome. MGORS1 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all MGORS1 cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. SIMILARITY: Belongs to the ORC1 family. SIMILARITY: Contains 1 BAH domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00004 - ATPase family associated with various cellular activities (AAA) PF01426 - BAH domain PF09079 - CDC6, C terminal winged helix domain
ModBase Predicted Comparative 3D Structure on Q13415
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0006260 DNA replication GO:0006270 DNA replication initiation
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04110 - Cell cycle
BioCarta from NCI Cancer Genome Anatomy Project h_mcmPathway - CDK Regulation of DNA Replication
Reactome (by CSHL, EBI, and GO)
Protein Q13415 (Reactome details) participates in the following event(s):
R-HSA-68611 Orc1 associates with Orc4:Orc5:Orc3:Orc2:origin complexes R-HSA-68946 Phosphorylated Orc1 is ubiquitinated while still associated with chromatin R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2 R-HSA-68947 Ubiquitinated Orc1 enters the cytosol R-HSA-68688 CDC6 association with ORC:origin complexes mediated by MCM8 R-HSA-113638 Association of Cyclin B/Cdk1 with replicative origin inhibits pre-RC formation R-HSA-176973 Association of MCM8 with ORC:origin complex R-HSA-68615 Orc6 associates with Orc1:Orc4:Orc5:Orc3:Orc2:origin complexes, forming ORC:origin complexes R-HSA-68826 Free CDT1 associates with CDC6:ORC:origin complexes R-HSA-68849 Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) R-HSA-68919 Mcm10 associates with the pre-replicative complex, stabilizing Mcm2-7 R-HSA-68918 CDK and DDK associate with the Mcm10:pre-replicative complex R-HSA-68940 Cdt1 is displaced from the pre-replicative complex. R-HSA-68917 Cdc45 associates with the pre-replicative complex at the origin R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin R-HSA-176318 Loading of claspin onto DNA during replication origin firing R-HSA-176298 Activation of claspin R-HSA-68616 Assembly of the ORC complex at the origin of replication R-HSA-539107 Activation of E2F1 target genes at G1/S R-HSA-68949 Orc1 removal from chromatin R-HSA-68689 CDC6 association with the ORC:origin complex R-HSA-113507 E2F-enabled inhibition of pre-replication complex formation R-HSA-68867 Assembly of the pre-replicative complex R-HSA-69205 G1/S-Specific Transcription R-HSA-69052 Switching of origins to a post-replicative state R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex R-HSA-113510 E2F mediated regulation of DNA replication R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69239 Synthesis of DNA R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-68962 Activation of the pre-replicative complex R-HSA-69278 Cell Cycle (Mitotic) R-HSA-1640170 Cell Cycle R-HSA-176187 Activation of ATR in response to replication stress R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints
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