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O43929 (ORC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Origin recognition complex subunit 4
Gene names
Name:ORC4
Synonyms:ORC4L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length436 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3. Ref.13

Subunit structure

Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. 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.14 Ref.15

Sequence similarities

Belongs to the ORC4 family.

Binary interactions

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 436436Origin recognition complex subunit 4
PRO_0000127087

Regions

Nucleotide binding67 – 748ATP Potential

Natural variations

Alternative sequence1 – 8484Missing in isoform 2.
VSP_045199
Alternative sequence1 – 7474Missing in isoform 3.
VSP_046437
Natural variant561L → V. Ref.4
Corresponds to variant rs2307397 [ dbSNP | Ensembl ].
VAR_014523
Natural variant781N → S. Ref.1 Ref.2 Ref.3 Ref.7
Corresponds to variant rs2307394 [ dbSNP | Ensembl ].
VAR_019235
Natural variant1741Y → C in MGORS2. Ref.14 Ref.15
VAR_065486

Experimental info

Mutagenesis731K → A or E: Impairs ORC complex formation. Ref.10
Mutagenesis159 – 1602DE → AA: Impairs ORC complex formation.
Sequence conflict1351N → S in BAH12887. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: A7020B6690E30B4E

FASTA43650,377
        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 

« Hide

Isoform 2 [UniParc].

Checksum: EE1B23556EB4AA9E
Show »

FASTA35240,870
Isoform 3 [UniParc].

Checksum: FB95A4CFA5AB1CB3
Show »

FASTA36242,034

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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]"Leucine-rich repeat and WD repeat-containing protein 1 is recruited to pericentric heterochromatin by trimethylated lysine 9 of histone H3 and maintains heterochromatin silencing."
Chan K.M., Zhang Z.
J. Biol. Chem. 287:15024-15033(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BINDING TO HISTONE H3 AND H4 TRIMETHYLATION MARKS.
[14]"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. expand/collapse author list , 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.
[15]"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. expand/collapse author list , 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

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.
RefSeqNP_001177808.1. NM_001190879.2.
NP_001177810.1. NM_001190881.2.
NP_001177811.1. NM_001190882.2.
NP_002543.2. NM_002552.4.
NP_859525.1. NM_181741.3.
NP_859526.1. NM_181742.3.
UniGeneHs.558364.

3D structure databases

ProteinModelPortalO43929.
SMRO43929. Positions 43-215.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111042. 30 interactions.
DIPDIP-29690N.
IntActO43929. 20 interactions.
MINTMINT-1201591.

PTM databases

PhosphoSiteO43929.

Proteomic databases

PaxDbO43929.
PeptideAtlasO43929.
PRIDEO43929.

Protocols and materials databases

DNASU5000.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264169; ENSP00000264169; ENSG00000115947. [O43929-1]
ENST00000392857; ENSP00000376597; ENSG00000115947. [O43929-1]
ENST00000392858; ENSP00000376598; ENSG00000115947. [O43929-1]
ENST00000535373; ENSP00000441953; ENSG00000115947. [O43929-1]
ENST00000536575; ENSP00000441502; ENSG00000115947. [O43929-2]
ENST00000540442; ENSP00000438326; ENSG00000115947. [O43929-3]
GeneID5000.
KEGGhsa:5000.
UCSCuc002twi.3. human. [O43929-1]

Organism-specific databases

CTD5000.
GeneCardsGC02M148691.
HGNCHGNC:8490. ORC4.
HPACAB015124.
MIM603056. gene.
613800. phenotype.
neXtProtNX_O43929.
Orphanet2554. Ear-patella-short stature syndrome.
PharmGKBPA32811.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289784.
HOGENOMHOG000007226.
HOVERGENHBG000253.
InParanoidO43929.
KOK02606.
OMAFQKFIQR.
OrthoDBEOG72NRPZ.
PhylomeDBO43929.
TreeFamTF101094.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressO43929.
BgeeO43929.
CleanExHS_ORC4L.
GenevestigatorO43929.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR016527. ORC4.
IPR027417. P-loop_NTPase.
[Graphical view]
PIRSFPIRSF007858. ORC4. 1 hit.
SMARTSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSORC4. human.
GeneWikiORC4.
ORC4L.
GenomeRNAi5000.
NextBio19248.
PROO43929.
SOURCESearch...

Entry information

Entry nameORC4_HUMAN
AccessionPrimary (citable) accession number: O43929
Secondary accession number(s): B7Z3D0 expand/collapse secondary AC list , B7Z5F1, D3DP86, F5H069, Q96C42
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 7, 2005
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM