Q13415 (ORC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Origin recognition complex subunit 1

Alternative name(s):
Replication control protein 1

Gene names

Name:	ORC1
Synonyms:	ORC1L, PARC1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	861 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	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. Ref.5 Ref.6
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). Ref.7
Involvement in 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. Ref.14 Ref.15 Ref.16
Sequence similarities	Belongs to the ORC1 family. Contains 1 BAH domain.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Ligand	ATP-binding DNA-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication initiation Traceable author statement. Source: ProtInc M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement. Source: Reactome regulation of transcription involved in G1/S phase of mitotic cell cycle Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nuclear origin of replication recognition complex Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Traceable author statement. Source: ProtInc nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORC2	Q13416	3	EBI-374847,EBI-374957
SKP2	Q13309	2	EBI-374847,EBI-456291

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 861	861	Origin recognition complex subunit 1		PRO_0000127067
Regions
	Domain	45 – 171	127	BAH
	Nucleotide binding	534 – 541	8	ATP Potential
	Region	501 – 861	361	Necessary and sufficient for ORC complex assembly
Amino acid modifications
	Modified residue	196	1	Phosphoserine Ref.11
	Modified residue	203	1	Phosphothreonine Ref.11
	Modified residue	273	1	Phosphoserine Ref.12
	Modified residue	287	1	Phosphoserine Ref.12
	Modified residue	326	1	N6-acetyllysine Ref.13
	Modified residue	337	1	Phosphothreonine Ref.11
	Modified residue	340	1	Phosphoserine Ref.11
	Modified residue	417	1	Phosphoserine Ref.9 Ref.11
	Modified residue	419	1	Phosphoserine Ref.9
	Modified residue	420	1	Phosphoserine Ref.9 Ref.11
	Modified residue	421	1	Phosphoserine Ref.9 Ref.11
	Modified residue	427	1	Phosphoserine Ref.11
	Modified residue	478	1	Phosphoserine Ref.11
Natural variations
	Natural variant	19	1	R → S. Corresponds to variant rs3087473 [ dbSNP | Ensembl ].		VAR_014507
	Natural variant	89	1	F → S in MGORS1. Ref.14		VAR_065481
	Natural variant	105	1	R → Q in MGORS1. Ref.14 Ref.15 Ref.16		VAR_065482
	Natural variant	127	1	E → G in MGORS1. Ref.14		VAR_065483
	Natural variant	180	1	Q → H. Corresponds to variant rs3087482 [ dbSNP | Ensembl ].		VAR_014508
	Natural variant	190	1	V → M. Corresponds to variant rs3087477 [ dbSNP | Ensembl ].		VAR_014509
	Natural variant	372	1	A → V. Corresponds to variant rs3087476 [ dbSNP | Ensembl ].		VAR_014510
	Natural variant	441	1	R → M. Corresponds to variant rs3087472 [ dbSNP | Ensembl ].		VAR_014511
	Natural variant	456	1	K → E. Corresponds to variant rs3087470 [ dbSNP | Ensembl ].		VAR_014512
	Natural variant	466	1	T → M. Corresponds to variant rs3087481 [ dbSNP | Ensembl ].		VAR_014513
	Natural variant	469	1	C → Y. Corresponds to variant rs3087483 [ dbSNP | Ensembl ].		VAR_014514
	Natural variant	666	1	R → W in MGORS1. Ref.16		VAR_065484
	Natural variant	720	1	R → Q in MGORS1. Ref.14		VAR_065485
	Natural variant	816	1	M → T. Corresponds to variant rs34521609 [ dbSNP | Ensembl ].		VAR_050426
Experimental info
	Sequence conflict	582	1	Q → H in AAC50325. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q13415 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 5C594553F7F808E2	FASTA	861	97,350
	10 20 30 40 50 60 MAHYPTRLKT RKTYSWVGRP LLDRKLHYQT YREMCVKTEG CSTEIHIQIG QFVLIEGDDD 70 80 90 100 110 120 ENPYVAKLLE LFEDDSDPPP KKRARVQWFV RFCEVPACKR HLLGRKPGAQ EIFWYDYPAC 130 140 150 160 170 180 DSNINAETII GLVRVIPLAP KDVVPTNLKN EKTLFVKLSW NEKKFRPLSS ELFAELNKPQ 190 200 210 220 230 240 ESAAKCQKPV RAKSKSAESP SWTPAEHVAK RIESRHSASK SRQTPTHPLT PRARKRLELG 250 260 270 280 290 300 NLGNPQMSQQ TSCASLDSPG RIKRKVAFSE ITSPSKRSQP DKLQTLSPAL KAPEKTRETG 310 320 330 340 350 360 LSYTEDDKKA SPEHRIILRT RIAASKTIDI REERTLTPIS GGQRSSVVPS VILKPENIKK 370 380 390 400 410 420 RDAKEAKAQN EATSTPHRIR RKSSVLTMNR IRQQLRFLGN SKSDQEEKEI LPAAEISDSS 430 440 450 460 470 480 SDEEEASTPP LPRRAPRTVS RNLRSSLKSS LHTLTKVPKK SLKPRTPRCA APQIRSRSLA 490 500 510 520 530 540 AQEPASVLEE ARLRLHVSAV PESLPCREQE FQDIYNFVES KLLDHTGGCM YISGVPGTGK 550 560 570 580 590 600 TATVHEVIRC LQQAAQANDV PPFQYIEVNG MKLTEPHQVY VQILQKLTGQ KATANHAAEL 610 620 630 640 650 660 LAKQFCTRGS PQETTVLLVD ELDLLWTHKQ DIMYNLFDWP THKEARLVVL AIANTMDLPE 670 680 690 700 710 720 RIMMNRVSSR LGLTRMCFQP YTYSQLQQIL RSRLKHLKAF EDDAIQLVAR KVAALSGDAR 730 740 750 760 770 780 RCLDICRRAT EICEFSQQKP DSPGLVTIAH SMEAVDEMFS SSYITAIKNS SVLEQSFLRA 790 800 810 820 830 840 ILAEFRRSGL EEATFQQIYS QHVALCRMEG LPYPTMSETM AVCSHLGSCR LLLVEPSRND 850 860 LLLRVRLNVS QDDVLYALKD E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Conserved initiator proteins in eukaryotes." Gavin K.A., Hidaka M., Stillman B.D. Science 270:1667-1671(1995) [PubMed: 7502077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Wolf D.A., McKeon F. Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase." Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A. Mol. Cell. Biol. 18:2758-2767(1998) [PubMed: 9566895] [Abstract] Cited for: INTERACTION WITH CDC6.
[6]	"Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein." Iizuka M., Stillman B. J. Biol. Chem. 274:23027-23034(1999) [PubMed: 10438470] [Abstract] Cited for: INTERACTION WITH KAT7.
[7]	"The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1." Tatsumi Y., Ohta S., Kimura H., Tsurimoto T., Obuse C. J. Biol. Chem. 278:41528-41534(2003) [PubMed: 12909627] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[8]	"The ORC1 cycle in human cells: II. Dynamic changes in the human ORC complex during the cell cycle." Ohta S., Tatsumi Y., Fujita M., Tsurimoto T., Obuse C. J. Biol. Chem. 278:41535-41540(2003) [PubMed: 12909626] [Abstract] Cited for: IDENTIFICATION IN THE ORC COMPLEX, MASS SPECTROMETRY, ASSEMBLY OF THE ORC COMPLEX.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417; SER-419; SER-420 AND SER-421, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"ATP-dependent assembly of the human origin recognition complex." Siddiqui K., Stillman B. J. Biol. Chem. 282:32370-32383(2007) [PubMed: 17716973] [Abstract] Cited for: RECONSTITUTION OF THE ORC COMPLEX, DISASSEMBLY OF THE ORC COMPLEX.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196; THR-203; THR-337; SER-340; SER-417; SER-420; SER-421; SER-427 AND SER-478, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-273 AND SER-287, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-326, MASS SPECTROMETRY.
[14]	"Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome." Bicknell L.S., Walker S., Klingseisen A., Stiff T., Leitch A., Kerzendorfer C., Martin C.A., Yeyati P., Al Sanna N., Bober M., Johnson D., Wise C., Jackson A.P., O'Driscoll M., Jeggo P.A. Nat. Genet. 43:350-355(2011) [PubMed: 21358633] [Abstract] Cited for: VARIANTS MGORS1 SER-89; GLN-105; GLY-127 AND GLN-720.
[15]	"Mutations in the pre-replication complex cause Meier-Gorlin syndrome." Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., Harley M.E., Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., van Bokhoven H., Dean J., Edrees A.Y., Feingold M., Fryer A., Hoefsloot L.H., Kau N., Knoers N.V. , Mackenzie J., Opitz J.M., Sarda P., Ross A., Temple I.K., Toutain A., Wise C.A., Wright M., Jackson A.P. Nat. Genet. 43:356-359(2011) [PubMed: 21358632] [Abstract] Cited for: VARIANT MGORS1 GLN-105.
[16]	"Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome." Guernsey D.L., Matsuoka M., Jiang H., Evans S., Macgillivray C., Nightingale M., Perry S., Ferguson M., LeBlanc M., Paquette J., Patry L., Rideout A.L., Thomas A., Orr A., McMaster C.R., Michaud J.L., Deal C., Langlois S. , Superneau D.W., Parkash S., Ludman M., Skidmore D.L., Samuels M.E. Nat. Genet. 43:360-364(2011) [PubMed: 21358631] [Abstract] Cited for: VARIANTS MGORS1 GLN-105 AND TRP-666.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U40152 mRNA. Translation: AAC50325.1. U43416 mRNA. Translation: AAA86260.1. AL513218 Genomic DNA. Translation: CAI12288.1. CH471059 Genomic DNA. Translation: EAX06783.1. CH471059 Genomic DNA. Translation: EAX06784.1.
IPI	IPI00013215.
PIR	G02329.
RefSeq	NP_001177747.1. NM_001190818.1. NP_001177748.1. NM_001190819.1. NP_004144.2. NM_004153.3.
UniGene	Hs.17908.
3D structure databases
ProteinModelPortal	Q13415.
SMR	Q13415. Positions 9-168, 492-861.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29688N.
IntAct	Q13415. 16 interactions.
MINT	MINT-1201992.
STRING	Q13415.
PTM databases
PhosphoSite	Q13415.
Polymorphism databases
DMDM	76803807.
Proteomic databases
PRIDE	Q13415.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371566; ENSP00000360621; ENSG00000085840. ENST00000371568; ENSP00000360623; ENSG00000085840.
GeneID	4998.
KEGG	hsa:4998.
NMPDR	fig|9606.3.peg.1166.
UCSC	uc001ctt.1. human.
Organism-specific databases
CTD	4998.
GeneCards	GC01M052839.
H-InvDB	HIX0000584.
HGNC	HGNC:8487. ORC1.
HPA	HPA027450.
MIM	224690. phenotype. 601902. gene.
neXtProt	NX_Q13415.
Orphanet	2554. Ear-patella-short stature syndrome.
PharmGKB	PA32808.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18890.
HOGENOM	HBG717572.
HOVERGEN	HBG007873.
InParanoid	Q13415.
OMA	SWNEKKF.
OrthoDB	EOG40K7ZJ.
PhylomeDB	Q13415.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	Q13415.
Bgee	Q13415.
CleanEx	HS_ORC1L.
Genevestigator	Q13415.
GermOnline	ENSG00000085840. Homo sapiens.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR003959. ATPase_AAA_core. IPR001025. BAH_dom. IPR015163. Cdc6_C_dom. IPR020793. ORC1. [Graphical view]
KO	K02603.
PANTHER	PTHR10763:SF6. ORC1. 1 hit.
Pfam	PF00004. AAA. 1 hit. PF01426. BAH. 1 hit. PF09079. Cdc6_C. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. SM00439. BAH. 1 hit. SM01074. Cdc6_C. 1 hit. [Graphical view]
PROSITE	PS51038. BAH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	19240.
SOURCE	Search...

Entry information

Entry name

ORC1_HUMAN

Accession

Primary (citable) accession number: Q13415
Secondary accession number(s): D3DQ34, Q13471, Q5T0F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 27, 2005
Last modified:	January 25, 2012
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.