Skip Header

Contribute Send feedback
Read comments (?) or add your own

O43929 (ORC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 105. 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·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)
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, 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.

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

Natural variant561L → V. Ref.4
Corresponds to variant rs2307397 [ dbSNP | Ensembl ].
VAR_014523
Natural variant781N → S. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs2307394 [ dbSNP | Ensembl ].
VAR_019235
Natural variant1741Y → C in MGORS2. Ref.10 Ref.11
VAR_065486

Experimental info

Mutagenesis731K → A or E: Impairs ORC complex formation. Ref.8
Mutagenesis159 – 1602DE → AA: Impairs ORC complex formation.

Sequences

Sequence LengthMass (Da)Tools
O43929 [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

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: 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. 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.
[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. 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: 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. expand/collapse author list , 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

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.
IPIIPI00015164.
RefSeqNP_001177808.1. NM_001190879.2.
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 41-118.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29690N.
IntActO43929. 18 interactions.
MINTMINT-1201591.
STRINGO43929.

Proteomic databases

PeptideAtlasO43929.
PRIDEO43929.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264169; ENSP00000264169; ENSG00000115947.
ENST00000392857; ENSP00000376597; ENSG00000115947.
ENST00000392858; ENSP00000376598; ENSG00000115947.
GeneID5000.
KEGGhsa:5000.
UCSCuc002twi.1. human.

Organism-specific databases

CTD5000.
GeneCardsGC02M148691.
H-InvDBHIX0002492.
HGNCHGNC:8490. ORC4.
HPACAB015124.
MIM603056. gene.
613800. phenotype.
neXtProtNX_O43929.
Orphanet2554. Ear-patella-short stature syndrome.
PharmGKBPA32811.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG04148.
HOGENOMHBG717246.
HOVERGENHBG000253.
InParanoidO43929.
OMANEFQKFI.
OrthoDBEOG49ZXP8.
PhylomeDBO43929.

Enzyme and pathway databases

ReactomeREACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressO43929.
BgeeO43929.
CleanExHS_ORC4L.
GenevestigatorO43929.
GermOnlineENSG00000115947. Homo sapiens.

Family and domain databases

InterProIPR003593. ATPase_AAA+_core.
IPR003959. ATPase_AAA_core.
IPR016527. ORC4.
[Graphical view]
KOK02606.
PfamPF00004. AAA. 1 hit.
[Graphical view]
PIRSFPIRSF007858. ORC4. 1 hit.
SMARTSM00382. AAA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio19248.
SOURCESearch...

Entry information

Entry nameORC4_HUMAN
AccessionPrimary (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 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

Human chromosome 2

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families