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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Ref.9
Subcellular location	Nucleus.
Involvement in disease	Meier-Gorlin syndrome 2 (MGORS2) [MIM:613800]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14
Sequence similarities	Belongs to the ORC4 family.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Ligand	ATP-binding DNA-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 PubMed 20932478. 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 nucleotide binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORC2	Q13416	6	EBI-374889,EBI-374957
ORC3	Q9UBD5	12	EBI-374889,EBI-374916
ORC5	O43913	2	EBI-374889,EBI-374928

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43929-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43929-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O43929-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-74: Missing.

Note: No experimental confirmation available.

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
	Alternative sequence	1 – 84	84	Missing in isoform 2.		VSP_045199
	Alternative sequence	1 – 74	74	Missing in isoform 3.		VSP_046437
	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.7 Corresponds to variant rs2307394 [ dbSNP | Ensembl ].		VAR_019235
	Natural variant	174	1	Y → C in MGORS2. Ref.13 Ref.14		VAR_065486
Experimental info
	Mutagenesis	73	1	K → A or E: Impairs ORC complex formation. Ref.10
	Mutagenesis	159 – 160	2	DE → AA: Impairs ORC complex formation.
	Sequence conflict	135	1	N → S in BAH12887. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2 [UniParc]. Checksum: EE1B23556EB4AA9E	FASTA	352	40,870
	10 20 30 40 50 60 MEIEEVSENV LQVHLNGLLQ INDKIALKEI TRQLNLENVV GDKVFGSFAE NLSFLLEALK 70 80 90 100 110 120 KGDRTSSCPV IFILDEFDLF AHHKNQTLLY NLFDISQSAQ TPIAVIGLTC RLDILELLEK 130 140 150 160 170 180 RVKSRFSHRQ IHLMNSFGFP QYVKIFKEQL SLPAEFPDKV FAEKWNENVQ YLSEDRSVQE 190 200 210 220 230 240 VLQKHFNISK NLRSLHMLLM LALNRVTASH PFMTAVDLME ASQLCSMDSK ANIVHGLSVL 250 260 270 280 290 300 EICLIIAMKH LNDIYEEEPF NFQMVYNEFQ KFVQRKAHSV YNFEKPVVMK AFEHLQQLEL 310 320 330 340 350 IKPMERTSGN SQREYQLMKL LLDNTQIMNA LQKYPNCPTD VRQWATSSLS WL
	Isoform 3 [UniParc]. Checksum: FB95A4CFA5AB1CB3	FASTA	362	42,034
	10 20 30 40 50 60 MLINHALKEL MEIEEVSENV LQVHLNGLLQ INDKIALKEI TRQLNLENVV GDKVFGSFAE 70 80 90 100 110 120 NLSFLLEALK KGDRTSSCPV IFILDEFDLF AHHKNQTLLY NLFDISQSAQ TPIAVIGLTC 130 140 150 160 170 180 RLDILELLEK RVKSRFSHRQ IHLMNSFGFP QYVKIFKEQL SLPAEFPDKV FAEKWNENVQ 190 200 210 220 230 240 YLSEDRSVQE VLQKHFNISK NLRSLHMLLM LALNRVTASH PFMTAVDLME ASQLCSMDSK 250 260 270 280 290 300 ANIVHGLSVL EICLIIAMKH LNDIYEEEPF NFQMVYNEFQ KFVQRKAHSV YNFEKPVVMK 310 320 330 340 350 360 AFEHLQQLEL IKPMERTSGN SQREYQLMKL LLDNTQIMNA LQKYPNCPTD VRQWATSSLS WL

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] (ISOFORM 1), 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] (ISOFORM 1), 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]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). Tissue: Hippocampus.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[9]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE ORC COMPLEX, MASS SPECTROMETRY, ASSEMBLY OF THE ORC COMPLEX.
[10]	"ATP-dependent assembly of the human origin recognition complex." Siddiqui K., Stillman B. J. Biol. Chem. 282:32370-32383(2007) [PubMed] [Europe PMC] [Abstract] Cited for: RECONSTITUTION OF THE ORC COMPLEX, DISASSEMBLY OF THE ORC COMPLEX, MUTAGENESIS OF LYS-73 AND 159-ASP-GLU-160.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANT MGORS2 CYS-174.
[14]	"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] [Europe PMC] [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. AK295721 mRNA. Translation: BAH12166.1. AK298862 mRNA. Translation: BAH12887.1. AC009480 Genomic DNA. No translation available. AC019226 Genomic DNA. No translation available. 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. IPI00980783. IPI00983461.
RefSeq	NP_001177808.1. NM_001190879.2. NP_001177810.1. NM_001190881.2. 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.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29690N.
IntAct	O43929. 19 interactions.
MINT	MINT-1201591.
PTM databases
PhosphoSite	O43929.
Proteomic databases
PaxDb	O43929.
PeptideAtlas	O43929.
PRIDE	O43929.
Protocols and materials databases
DNASU	5000.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264169; ENSP00000264169; ENSG00000115947. ENST00000392857; ENSP00000376597; ENSG00000115947. ENST00000392858; ENSP00000376598; ENSG00000115947. ENST00000535373; ENSP00000441953; ENSG00000115947. ENST00000536575; ENSP00000441502; ENSG00000115947. ENST00000540442; ENSP00000438326; ENSG00000115947.
GeneID	5000.
KEGG	hsa:5000.
UCSC	uc002twi.3. human.
Organism-specific databases
CTD	5000.
GeneCards	GC02M148691.
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	NOG289784.
HOGENOM	HOG000007226.
HOVERGEN	HBG000253.
InParanoid	O43929.
KO	K02606.
OMA	FQKFIQR.
OrthoDB	EOG49ZXP8.
PhylomeDB	O43929.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases. 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. AAA+_ATPase. IPR016527. ORC4. [Graphical view]
PIRSF	PIRSF007858. ORC4. 1 hit.
SMART	SM00382. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ORC4. human.
GenomeRNAi	5000.
NextBio	19248.
SOURCE	Search...

Entry information

Entry name

ORC4_HUMAN

Accession

Primary (citable) accession number: O43929
Secondary accession number(s): B7Z3D0 , B7Z5F1, D3DP86, F5H069, Q96C42

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 7, 2005
Last modified:	May 1, 2013
This is version 119 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.