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Protein

Origin recognition complex subunit 4

Gene

ORC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 H4K20me3.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi67 – 74ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DNA replication origin binding Source: UniProtKB
  • nucleotide binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processDNA replication
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-113507 E2F-enabled inhibition of pre-replication complex formation
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-68616 Assembly of the ORC complex at the origin of replication
R-HSA-68689 CDC6 association with the ORC:origin complex
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-68962 Activation of the pre-replicative complex

Names & Taxonomyi

Protein namesi
Recommended name:
Origin recognition complex subunit 4
Gene namesi
Name:ORC4
Synonyms:ORC4L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115947.13
HGNCiHGNC:8490 ORC4
MIMi603056 gene
neXtProtiNX_O43929

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Meier-Gorlin syndrome 2 (MGORS2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065486174Y → C in MGORS2. 2 PublicationsCorresponds to variant dbSNP:rs387906847EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73K → A or E: Impairs ORC complex formation. 1 Publication1
Mutagenesisi159 – 160DE → AA: Impairs ORC complex formation. 1 Publication2

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi5000
MalaCardsiORC4
MIMi613800 phenotype
OpenTargetsiENSG00000115947
Orphaneti2554 Ear-patella-short stature syndrome
PharmGKBiPA32811

Polymorphism and mutation databases

BioMutaiORC4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001270871 – 436Origin recognition complex subunit 4Add BLAST436

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7N6-methyllysineCombined sources1

Keywords - PTMi

Methylation

Proteomic databases

EPDiO43929
MaxQBiO43929
PaxDbiO43929
PeptideAtlasiO43929
PRIDEiO43929
ProteomicsDBi49241

PTM databases

iPTMnetiO43929
PhosphoSitePlusiO43929

Expressioni

Gene expression databases

BgeeiENSG00000115947 Expressed in 222 organ(s), highest expression level in kidney
CleanExiHS_ORC4L
ExpressionAtlasiO43929 baseline and differential
GenevisibleiO43929 HS

Organism-specific databases

HPAiCAB015124
HPA064562

Interactioni

Subunit structurei

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 (PubMed:12909626, PubMed:17716973). Interacts with DBF4 (By similarity). Interacts with POLQ (PubMed:24989122).By similarity3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi111042, 54 interactors
ComplexPortaliCPX-1880 Nuclear origin of replication recognition complex
CORUMiO43929
DIPiDIP-29690N
IntActiO43929, 36 interactors
MINTiO43929
STRINGi9606.ENSP00000264169

Structurei

Secondary structure

1436
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43929
SMRiO43929
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ORC4 family.Curated

Phylogenomic databases

eggNOGiKOG2228 Eukaryota
ENOG410XSK0 LUCA
GeneTreeiENSGT00390000016542
HOGENOMiHOG000007226
HOVERGENiHBG000253
InParanoidiO43929
KOiK02606
OMAiFQKFIQR
OrthoDBiEOG091G0842
PhylomeDBiO43929
TreeFamiTF101094

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR016527 ORC4
IPR032705 ORC4_C
IPR027417 P-loop_NTPase
PANTHERiPTHR12087 PTHR12087, 1 hit
PfamiView protein in Pfam
PF14629 ORC4_C, 1 hit
PIRSFiPIRSF007858 ORC4, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O43929-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL
60 70 80 90 100
LKRTALHGES NSVLIIGPRG SGKTMLINHA LKELMEIEEV SENVLQVHLN
110 120 130 140 150
GLLQINDKIA LKEITRQLNL ENVVGDKVFG SFAENLSFLL EALKKGDRTS
160 170 180 190 200
SCPVIFILDE FDLFAHHKNQ TLLYNLFDIS QSAQTPIAVI GLTCRLDILE
210 220 230 240 250
LLEKRVKSRF SHRQIHLMNS FGFPQYVKIF KEQLSLPAEF PDKVFAEKWN
260 270 280 290 300
ENVQYLSEDR SVQEVLQKHF NISKNLRSLH MLLMLALNRV TASHPFMTAV
310 320 330 340 350
DLMEASQLCS MDSKANIVHG LSVLEICLII AMKHLNDIYE EEPFNFQMVY
360 370 380 390 400
NEFQKFVQRK AHSVYNFEKP VVMKAFEHLQ QLELIKPMER TSGNSQREYQ
410 420 430
LMKLLLDNTQ IMNALQKYPN CPTDVRQWAT SSLSWL
Length:436
Mass (Da):50,377
Last modified:June 7, 2005 - v2
Checksum:iA7020B6690E30B4E
GO
Isoform 2 (identifier: O43929-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:352
Mass (Da):40,870
Checksum:iEE1B23556EB4AA9E
GO
Isoform 3 (identifier: O43929-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:362
Mass (Da):42,034
Checksum:iFB95A4CFA5AB1CB3
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q53SE3Q53SE3_HUMAN
Origin recognition complex subunit ...
ORC4 ORC4L
145Annotation score:
C9JGH7C9JGH7_HUMAN
Origin recognition complex subunit ...
ORC4
127Annotation score:
C9J2X8C9J2X8_HUMAN
Origin recognition complex subunit ...
ORC4
128Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135N → S in BAH12887 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01452356L → V1 PublicationCorresponds to variant dbSNP:rs2307397EnsemblClinVar.1
Natural variantiVAR_01923578N → S4 PublicationsCorresponds to variant dbSNP:rs2307394EnsemblClinVar.1
Natural variantiVAR_065486174Y → C in MGORS2. 2 PublicationsCorresponds to variant dbSNP:rs387906847EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0451991 – 84Missing in isoform 2. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_0464371 – 74Missing in isoform 3. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS2187.1 [O43929-1]
CCDS54404.1 [O43929-2]
CCDS54405.1 [O43929-3]
RefSeqiNP_001177808.1, NM_001190879.2 [O43929-1]
NP_001177810.1, NM_001190881.2 [O43929-2]
NP_001177811.1, NM_001190882.2 [O43929-3]
NP_002543.2, NM_002552.4 [O43929-1]
NP_859525.1, NM_181741.3 [O43929-1]
NP_859526.1, NM_181742.3 [O43929-1]
XP_011509557.1, XM_011511255.2 [O43929-1]
XP_016859715.1, XM_017004226.1 [O43929-1]
XP_016859716.1, XM_017004227.1
UniGeneiHs.558364

Genome annotation databases

EnsembliENST00000264169; ENSP00000264169; ENSG00000115947 [O43929-1]
ENST00000392857; ENSP00000376597; ENSG00000115947 [O43929-1]
ENST00000535373; ENSP00000441953; ENSG00000115947 [O43929-1]
ENST00000536575; ENSP00000441502; ENSG00000115947 [O43929-2]
ENST00000540442; ENSP00000438326; ENSG00000115947 [O43929-3]
GeneIDi5000
KEGGihsa:5000
UCSCiuc002twi.4 human [O43929-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS2187.1 [O43929-1]
CCDS54404.1 [O43929-2]
CCDS54405.1 [O43929-3]
RefSeqiNP_001177808.1, NM_001190879.2 [O43929-1]
NP_001177810.1, NM_001190881.2 [O43929-2]
NP_001177811.1, NM_001190882.2 [O43929-3]
NP_002543.2, NM_002552.4 [O43929-1]
NP_859525.1, NM_181741.3 [O43929-1]
NP_859526.1, NM_181742.3 [O43929-1]
XP_011509557.1, XM_011511255.2 [O43929-1]
XP_016859715.1, XM_017004226.1 [O43929-1]
XP_016859716.1, XM_017004227.1
UniGeneiHs.558364

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5UJ7X-ray3.39C/D1-436[»]
5UJMelectron microscopy18.00D1-436[»]
ProteinModelPortaliO43929
SMRiO43929
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111042, 54 interactors
ComplexPortaliCPX-1880 Nuclear origin of replication recognition complex
CORUMiO43929
DIPiDIP-29690N
IntActiO43929, 36 interactors
MINTiO43929
STRINGi9606.ENSP00000264169

PTM databases

iPTMnetiO43929
PhosphoSitePlusiO43929

Polymorphism and mutation databases

BioMutaiORC4

Proteomic databases

EPDiO43929
MaxQBiO43929
PaxDbiO43929
PeptideAtlasiO43929
PRIDEiO43929
ProteomicsDBi49241

Protocols and materials databases

DNASUi5000
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264169; ENSP00000264169; ENSG00000115947 [O43929-1]
ENST00000392857; ENSP00000376597; ENSG00000115947 [O43929-1]
ENST00000535373; ENSP00000441953; ENSG00000115947 [O43929-1]
ENST00000536575; ENSP00000441502; ENSG00000115947 [O43929-2]
ENST00000540442; ENSP00000438326; ENSG00000115947 [O43929-3]
GeneIDi5000
KEGGihsa:5000
UCSCiuc002twi.4 human [O43929-1]

Organism-specific databases

CTDi5000
DisGeNETi5000
EuPathDBiHostDB:ENSG00000115947.13
GeneCardsiORC4
HGNCiHGNC:8490 ORC4
HPAiCAB015124
HPA064562
MalaCardsiORC4
MIMi603056 gene
613800 phenotype
neXtProtiNX_O43929
OpenTargetsiENSG00000115947
Orphaneti2554 Ear-patella-short stature syndrome
PharmGKBiPA32811
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2228 Eukaryota
ENOG410XSK0 LUCA
GeneTreeiENSGT00390000016542
HOGENOMiHOG000007226
HOVERGENiHBG000253
InParanoidiO43929
KOiK02606
OMAiFQKFIQR
OrthoDBiEOG091G0842
PhylomeDBiO43929
TreeFamiTF101094

Enzyme and pathway databases

ReactomeiR-HSA-113507 E2F-enabled inhibition of pre-replication complex formation
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-68616 Assembly of the ORC complex at the origin of replication
R-HSA-68689 CDC6 association with the ORC:origin complex
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-68962 Activation of the pre-replicative complex

Miscellaneous databases

ChiTaRSiORC4 human
GeneWikiiORC4
ORC4L
GenomeRNAii5000
PROiPR:O43929
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115947 Expressed in 222 organ(s), highest expression level in kidney
CleanExiHS_ORC4L
ExpressionAtlasiO43929 baseline and differential
GenevisibleiO43929 HS

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR016527 ORC4
IPR032705 ORC4_C
IPR027417 P-loop_NTPase
PANTHERiPTHR12087 PTHR12087, 1 hit
PfamiView protein in Pfam
PF14629 ORC4_C, 1 hit
PIRSFiPIRSF007858 ORC4, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiORC4_HUMAN
AccessioniPrimary (citable) accession number: O43929
Secondary accession number(s): B7Z3D0
, B7Z5F1, D3DP86, F5H069, Q96C42
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 7, 2005
Last modified: November 7, 2018
This is version 170 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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