O43929 (ORC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Origin recognition complex subunit 4

Gene names

Name:	ORC4
Synonyms:	ORC4L

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	436 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 DBF4 By similarity.
Subcellular location	Nucleus.
Involvement in disease	Defects in ORC4 are the cause of Meier-Gorlin syndrome type 2 (MGORS2) [MIM:613800]. MGORS2 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 cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. Ref.10 Ref.11
Sequence similarities	Belongs to the ORC4 family.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Ligand	ATP-binding DNA-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA-dependent DNA replication initiation Inferred from mutant phenotype Ref.1. Source: UniProtKB G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome 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
Cellular component	nuclear origin of replication recognition complex Inferred from direct assay. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA replication origin binding Inferred from mutant phenotype Ref.1. Source: UniProtKB nucleoside-triphosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 436	436	Origin recognition complex subunit 4		PRO_0000127087
Regions
	Nucleotide binding	67 – 74	8	ATP Potential
Natural variations
	Natural variant	56	1	L → V. Ref.4 Corresponds to variant rs2307397 [ dbSNP | Ensembl ].		VAR_014523
	Natural variant	78	1	N → S. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs2307394 [ dbSNP | Ensembl ].		VAR_019235
	Natural variant	174	1	Y → C in MGORS2. Ref.10 Ref.11		VAR_065486
Experimental info
	Mutagenesis	73	1	K → A or E: Impairs ORC complex formation. Ref.8
	Mutagenesis	159 – 160	2	DE → AA: Impairs ORC complex formation.

Sequences

	Sequence		Length	Mass (Da)
	O43929 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: A7020B6690E30B4E	FASTA	436	50,377
	10 20 30 40 50 60 MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES 70 80 90 100 110 120 NSVLIIGPRG SGKTMLINHA LKELMEIEEV SENVLQVHLN GLLQINDKIA LKEITRQLNL 130 140 150 160 170 180 ENVVGDKVFG SFAENLSFLL EALKKGDRTS SCPVIFILDE FDLFAHHKNQ TLLYNLFDIS 190 200 210 220 230 240 QSAQTPIAVI GLTCRLDILE LLEKRVKSRF SHRQIHLMNS FGFPQYVKIF KEQLSLPAEF 250 260 270 280 290 300 PDKVFAEKWN ENVQYLSEDR SVQEVLQKHF NISKNLRSLH MLLMLALNRV TASHPFMTAV 310 320 330 340 350 360 DLMEASQLCS MDSKANIVHG LSVLEICLII AMKHLNDIYE EEPFNFQMVY NEFQKFVQRK 370 380 390 400 410 420 AHSVYNFEKP VVMKAFEHLQ QLELIKPMER TSGNSQREYQ LMKLLLDNTQ IMNALQKYPN 430 CPTDVRQWAT SSLSWL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of HsORC4, a member of the human origin of replication recognition complex." Quintana D.G., Hou Z.H., Thome K.C., Hendricks M., Saha P., Dutta A. J. Biol. Chem. 272:28247-28251(1997) [PubMed: 9353276] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-78.
[2]	"The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p." Komrskova T., Yang H., Gavin K., Pappin D., Canas B., Kobayashi R., Hunt T., Stillman B. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-78.
[3]	"cDNA cloning of a homolog for S. cerevisiae ORC4 from H. sapiens." Dean F.B., O'Donnell M. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-78.
[4]	NIEHS SNPs program Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-56.
[5]	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], VARIANT SER-78.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	"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.
[8]	"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, MUTAGENESIS OF LYS-73 AND 159-ASP-GLU-160.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"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 MGORS2 CYS-174.
[11]	"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: VARIANT MGORS2 CYS-174.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF022108 mRNA. Translation: AAC01957.1. AF047598 mRNA. Translation: AAC80282.1. AF132596 mRNA. Translation: AAD22110.1. AY600302 Genomic DNA. Translation: AAS94326.1. CH471058 Genomic DNA. Translation: EAX11555.1. CH471058 Genomic DNA. Translation: EAX11556.1. CH471058 Genomic DNA. Translation: EAX11557.1. CH471058 Genomic DNA. Translation: EAX11558.1. BC014847 mRNA. Translation: AAH14847.1.
IPI	IPI00015164.
RefSeq	NP_001177808.1. NM_001190879.2. NP_002543.2. NM_002552.4. NP_859525.1. NM_181741.3. NP_859526.1. NM_181742.3.
UniGene	Hs.558364.
3D structure databases
ProteinModelPortal	O43929.
SMR	O43929. Positions 41-118.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29690N.
IntAct	O43929. 18 interactions.
MINT	MINT-1201591.
STRING	O43929.
Proteomic databases
PeptideAtlas	O43929.
PRIDE	O43929.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264169; ENSP00000264169; ENSG00000115947. ENST00000392857; ENSP00000376597; ENSG00000115947. ENST00000392858; ENSP00000376598; ENSG00000115947.
GeneID	5000.
KEGG	hsa:5000.
UCSC	uc002twi.1. human.
Organism-specific databases
CTD	5000.
GeneCards	GC02M148691.
H-InvDB	HIX0002492.
HGNC	HGNC:8490. ORC4.
HPA	CAB015124.
MIM	603056. gene. 613800. phenotype.
neXtProt	NX_O43929.
Orphanet	2554. Ear-patella-short stature syndrome.
PharmGKB	PA32811.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04148.
HOGENOM	HBG717246.
HOVERGEN	HBG000253.
InParanoid	O43929.
OMA	NEFQKFI.
OrthoDB	EOG49ZXP8.
PhylomeDB	O43929.
Enzyme and pathway databases
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1538. Cell Cycle Checkpoints. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	O43929.
Bgee	O43929.
CleanEx	HS_ORC4L.
Genevestigator	O43929.
GermOnline	ENSG00000115947. Homo sapiens.
Family and domain databases
InterPro	IPR003593. ATPase_AAA+_core. IPR003959. ATPase_AAA_core. IPR016527. ORC4. [Graphical view]
KO	K02606.
Pfam	PF00004. AAA. 1 hit. [Graphical view]
PIRSF	PIRSF007858. ORC4. 1 hit.
SMART	SM00382. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	19248.
SOURCE	Search...

Entry information

Entry name

ORC4_HUMAN

Accession

Primary (citable) accession number: O43929
Secondary accession number(s): D3DP86, Q96C42

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 7, 2005
Last modified:	December 14, 2011
This is version 105 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.