ORC4_HUMAN
ID ORC4_HUMAN Reviewed; 436 AA.
AC O43929; B7Z3D0; B7Z5F1; D3DP86; F5H069; Q96C42;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Origin recognition complex subunit 4;
GN Name=ORC4; Synonyms=ORC4L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78.
RX PubMed=9353276; DOI=10.1074/jbc.272.45.28247;
RA Quintana D.G., Hou Z.H., Thome K.C., Hendricks M., Saha P., Dutta A.;
RT "Identification of HsORC4, a member of the human origin of replication
RT recognition complex.";
RL J. Biol. Chem. 272:28247-28251(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78.
RA Komrskova T., Yang H., Gavin K., Pappin D., Canas B., Kobayashi R.,
RA Hunt T., Stillman B.;
RT "The Orc4p and Orc5p subunits of the Xenopus and human origin recognition
RT complex are related to Orc1p and Cdc6p.";
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78.
RA Dean F.B., O'Donnell M.;
RT "cDNA cloning of a homolog for S. cerevisiae ORC4 from H. sapiens.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-56.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-78.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP IDENTIFICATION IN THE ORC COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP ASSEMBLY OF THE ORC COMPLEX.
RX PubMed=12909626; DOI=10.1074/jbc.m307535200;
RA Ohta S., Tatsumi Y., Fujita M., Tsurimoto T., Obuse C.;
RT "The ORC1 cycle in human cells: II. Dynamic changes in the human ORC
RT complex during the cell cycle.";
RL J. Biol. Chem. 278:41535-41540(2003).
RN [10]
RP RECONSTITUTION OF THE ORC COMPLEX, DISASSEMBLY OF THE ORC COMPLEX, AND
RP MUTAGENESIS OF LYS-73 AND 159-ASP-GLU-160.
RX PubMed=17716973; DOI=10.1074/jbc.m705905200;
RA Siddiqui K., Stillman B.;
RT "ATP-dependent assembly of the human origin recognition complex.";
RL J. Biol. Chem. 282:32370-32383(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP FUNCTION, AND BINDING TO HISTONE H3 AND H4 TRIMETHYLATION MARKS.
RX PubMed=22427655; DOI=10.1074/jbc.m111.337980;
RA Chan K.M., Zhang Z.;
RT "Leucine-rich repeat and WD repeat-containing protein 1 is recruited to
RT pericentric heterochromatin by trimethylated lysine 9 of histone H3 and
RT maintains heterochromatin silencing.";
RL J. Biol. Chem. 287:15024-15033(2012).
RN [14]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [15]
RP INTERACTION WITH POLQ.
RX PubMed=24989122; DOI=10.1038/ncomms5285;
RA Fernandez-Vidal A., Guitton-Sert L., Cadoret J.C., Drac M., Schwob E.,
RA Baldacci G., Cazaux C., Hoffmann J.S.;
RT "A role for DNA polymerase theta in the timing of DNA replication.";
RL Nat. Commun. 5:4285-4285(2014).
RN [16]
RP VARIANT MGORS2 CYS-174.
RX PubMed=21358632; DOI=10.1038/ng.775;
RA Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., Harley M.E.,
RA Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., van Bokhoven H., Dean J.,
RA Edrees A.Y., Feingold M., Fryer A., Hoefsloot L.H., Kau N., Knoers N.V.,
RA Mackenzie J., Opitz J.M., Sarda P., Ross A., Temple I.K., Toutain A.,
RA Wise C.A., Wright M., Jackson A.P.;
RT "Mutations in the pre-replication complex cause Meier-Gorlin syndrome.";
RL Nat. Genet. 43:356-359(2011).
RN [17]
RP VARIANT MGORS2 CYS-174.
RX PubMed=21358631; DOI=10.1038/ng.777;
RA Guernsey D.L., Matsuoka M., Jiang H., Evans S., Macgillivray C.,
RA Nightingale M., Perry S., Ferguson M., LeBlanc M., Paquette J., Patry L.,
RA Rideout A.L., Thomas A., Orr A., McMaster C.R., Michaud J.L., Deal C.,
RA Langlois S., Superneau D.W., Parkash S., Ludman M., Skidmore D.L.,
RA Samuels M.E.;
RT "Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin
RT syndrome.";
RL Nat. Genet. 43:360-364(2011).
CC -!- FUNCTION: Component of the origin recognition complex (ORC) that binds
CC origins of replication. DNA-binding is ATP-dependent. The specific DNA
CC sequences that define origins of replication have not been identified
CC yet. ORC is required to assemble the pre-replication complex necessary
CC to initiate DNA replication. Binds histone H3 and H4 trimethylation
CC marks H3K9me3, H3K27me3 and H4K20me3. {ECO:0000269|PubMed:22427655}.
CC -!- SUBUNIT: Component of ORC, a complex composed of at least 6 subunits:
CC ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle
CC dependent manner. It is sequentially assembled at the exit from
CC anaphase of mitosis and disassembled as cells enter S phase
CC (PubMed:12909626, PubMed:17716973). Interacts with DBF4 (By
CC similarity). Interacts with POLQ (PubMed:24989122).
CC {ECO:0000250|UniProtKB:O88708, ECO:0000269|PubMed:12909626,
CC ECO:0000269|PubMed:17716973, ECO:0000269|PubMed:24989122}.
CC -!- INTERACTION:
CC O43929; Q13416: ORC2; NbExp=12; IntAct=EBI-374889, EBI-374957;
CC O43929; Q9UBD5: ORC3; NbExp=12; IntAct=EBI-374889, EBI-374916;
CC O43929; O43913: ORC5; NbExp=2; IntAct=EBI-374889, EBI-374928;
CC O43929; Q9Y5N6: ORC6; NbExp=2; IntAct=EBI-374889, EBI-374840;
CC O43929; Q7LG56: RRM2B; NbExp=4; IntAct=EBI-374889, EBI-9009083;
CC O43929; P15884: TCF4; NbExp=3; IntAct=EBI-374889, EBI-533224;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O43929-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43929-2; Sequence=VSP_045199;
CC Name=3;
CC IsoId=O43929-3; Sequence=VSP_046437;
CC -!- DISEASE: Meier-Gorlin syndrome 2 (MGORS2) [MIM:613800]: A syndrome
CC characterized by bilateral microtia, aplasia/hypoplasia of the
CC patellae, and severe intrauterine and postnatal growth retardation with
CC short stature and poor weight gain. Additional clinical findings
CC include anomalies of cranial sutures, microcephaly, apparently low-set
CC and simple ears, microstomia, full lips, highly arched or cleft palate,
CC micrognathia, genitourinary tract anomalies, and various skeletal
CC anomalies. While almost all cases have primordial dwarfism with
CC substantial prenatal and postnatal growth retardation, not all cases
CC have microcephaly, and microtia and absent/hypoplastic patella are
CC absent in some. Despite the presence of microcephaly, intellect is
CC usually normal. {ECO:0000269|PubMed:21358631,
CC ECO:0000269|PubMed:21358632}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ORC4 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/orc4l/";
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DR EMBL; AF022108; AAC01957.1; -; mRNA.
DR EMBL; AF047598; AAC80282.1; -; mRNA.
DR EMBL; AF132596; AAD22110.1; -; mRNA.
DR EMBL; AY600302; AAS94326.1; -; Genomic_DNA.
DR EMBL; AK295721; BAH12166.1; -; mRNA.
DR EMBL; AK298862; BAH12887.1; -; mRNA.
DR EMBL; AC009480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11555.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11556.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11557.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11558.1; -; Genomic_DNA.
DR EMBL; BC014847; AAH14847.1; -; mRNA.
DR CCDS; CCDS2187.1; -. [O43929-1]
DR CCDS; CCDS54404.1; -. [O43929-2]
DR CCDS; CCDS54405.1; -. [O43929-3]
DR RefSeq; NP_001177808.1; NM_001190879.2. [O43929-1]
DR RefSeq; NP_001177810.1; NM_001190881.2. [O43929-2]
DR RefSeq; NP_001177811.1; NM_001190882.2. [O43929-3]
DR RefSeq; NP_002543.2; NM_002552.4. [O43929-1]
DR RefSeq; NP_859525.1; NM_181741.3. [O43929-1]
DR RefSeq; NP_859526.1; NM_181742.3. [O43929-1]
DR RefSeq; XP_011509557.1; XM_011511255.2. [O43929-1]
DR RefSeq; XP_016859715.1; XM_017004226.1.
DR RefSeq; XP_016859716.1; XM_017004227.1.
DR PDB; 5UJ7; X-ray; 3.39 A; C/D=1-436.
DR PDB; 5UJM; EM; 18.00 A; D=1-436.
DR PDB; 7CTE; EM; 3.80 A; D=1-436.
DR PDB; 7CTF; EM; 4.80 A; D=1-436.
DR PDB; 7CTG; EM; 5.00 A; D=1-436.
DR PDB; 7JPO; EM; 3.20 A; D=1-436.
DR PDB; 7JPP; EM; 3.70 A; D=1-436.
DR PDB; 7JPQ; EM; 3.50 A; D=1-436.
DR PDB; 7JPR; EM; 4.00 A; D=1-436.
DR PDB; 7JPS; EM; 4.40 A; D=1-436.
DR PDBsum; 5UJ7; -.
DR PDBsum; 5UJM; -.
DR PDBsum; 7CTE; -.
DR PDBsum; 7CTF; -.
DR PDBsum; 7CTG; -.
DR PDBsum; 7JPO; -.
DR PDBsum; 7JPP; -.
DR PDBsum; 7JPQ; -.
DR PDBsum; 7JPR; -.
DR PDBsum; 7JPS; -.
DR AlphaFoldDB; O43929; -.
DR SMR; O43929; -.
DR BioGRID; 111042; 140.
DR ComplexPortal; CPX-1880; Nuclear origin of replication recognition complex.
DR CORUM; O43929; -.
DR DIP; DIP-29690N; -.
DR IntAct; O43929; 45.
DR MINT; O43929; -.
DR STRING; 9606.ENSP00000441953; -.
DR iPTMnet; O43929; -.
DR PhosphoSitePlus; O43929; -.
DR SwissPalm; O43929; -.
DR BioMuta; ORC4; -.
DR EPD; O43929; -.
DR jPOST; O43929; -.
DR MassIVE; O43929; -.
DR MaxQB; O43929; -.
DR PaxDb; O43929; -.
DR PeptideAtlas; O43929; -.
DR PRIDE; O43929; -.
DR ProteomicsDB; 25248; -.
DR ProteomicsDB; 49241; -. [O43929-1]
DR ProteomicsDB; 6510; -.
DR Antibodypedia; 4189; 252 antibodies from 33 providers.
DR DNASU; 5000; -.
DR Ensembl; ENST00000264169.6; ENSP00000264169.2; ENSG00000115947.14. [O43929-1]
DR Ensembl; ENST00000392857.10; ENSP00000376597.5; ENSG00000115947.14. [O43929-1]
DR Ensembl; ENST00000535373.5; ENSP00000441953.1; ENSG00000115947.14. [O43929-1]
DR Ensembl; ENST00000536575.5; ENSP00000441502.1; ENSG00000115947.14. [O43929-2]
DR Ensembl; ENST00000540442.5; ENSP00000438326.1; ENSG00000115947.14. [O43929-3]
DR GeneID; 5000; -.
DR KEGG; hsa:5000; -.
DR MANE-Select; ENST00000392857.10; ENSP00000376597.5; NM_181741.4; NP_859525.1.
DR UCSC; uc002twi.4; human. [O43929-1]
DR CTD; 5000; -.
DR DisGeNET; 5000; -.
DR GeneCards; ORC4; -.
DR HGNC; HGNC:8490; ORC4.
DR HPA; ENSG00000115947; Low tissue specificity.
DR MalaCards; ORC4; -.
DR MIM; 603056; gene.
DR MIM; 613800; phenotype.
DR neXtProt; NX_O43929; -.
DR OpenTargets; ENSG00000115947; -.
DR Orphanet; 2554; Ear-patella-short stature syndrome.
DR PharmGKB; PA32811; -.
DR VEuPathDB; HostDB:ENSG00000115947; -.
DR eggNOG; KOG2228; Eukaryota.
DR GeneTree; ENSGT00390000016542; -.
DR HOGENOM; CLU_007115_0_1_1; -.
DR InParanoid; O43929; -.
DR OMA; KVSTTMQ; -.
DR OrthoDB; 1543398at2759; -.
DR PhylomeDB; O43929; -.
DR TreeFam; TF101094; -.
DR BRENDA; 3.6.4.B8; 2681.
DR PathwayCommons; O43929; -.
DR Reactome; R-HSA-113507; E2F-enabled inhibition of pre-replication complex formation.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-68616; Assembly of the ORC complex at the origin of replication.
DR Reactome; R-HSA-68689; CDC6 association with the ORC:origin complex.
DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex.
DR Reactome; R-HSA-68949; Orc1 removal from chromatin.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR SignaLink; O43929; -.
DR SIGNOR; O43929; -.
DR BioGRID-ORCS; 5000; 439 hits in 1059 CRISPR screens.
DR ChiTaRS; ORC4; human.
DR GeneWiki; ORC4; -.
DR GeneWiki; ORC4L; -.
DR GenomeRNAi; 5000; -.
DR Pharos; O43929; Tbio.
DR PRO; PR:O43929; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43929; protein.
DR Bgee; ENSG00000115947; Expressed in calcaneal tendon and 203 other tissues.
DR ExpressionAtlas; O43929; baseline and differential.
DR Genevisible; O43929; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005664; C:nuclear origin of replication recognition complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000808; C:origin recognition complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003688; F:DNA replication origin binding; IMP:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041664; AAA_16.
DR InterPro; IPR016527; ORC4.
DR InterPro; IPR032705; ORC4_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR12087; PTHR12087; 1.
DR Pfam; PF13191; AAA_16; 1.
DR Pfam; PF14629; ORC4_C; 1.
DR PIRSF; PIRSF007858; ORC4; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Disease variant;
KW DNA replication; DNA-binding; Dwarfism; Methylation; Nucleotide-binding;
KW Nucleus; Reference proteome.
FT CHAIN 1..436
FT /note="Origin recognition complex subunit 4"
FT /id="PRO_0000127087"
FT BINDING 67..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 7
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045199"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046437"
FT VARIANT 56
FT /note="L -> V (in dbSNP:rs2307397)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014523"
FT VARIANT 78
FT /note="N -> S (in dbSNP:rs2307394)"
FT /evidence="ECO:0000269|PubMed:9353276, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.7"
FT /id="VAR_019235"
FT VARIANT 174
FT /note="Y -> C (in MGORS2; dbSNP:rs387906847)"
FT /evidence="ECO:0000269|PubMed:21358631,
FT ECO:0000269|PubMed:21358632"
FT /id="VAR_065486"
FT MUTAGEN 73
FT /note="K->A,E: Impairs ORC complex formation."
FT /evidence="ECO:0000269|PubMed:17716973"
FT MUTAGEN 159..160
FT /note="DE->AA: Impairs ORC complex formation."
FT /evidence="ECO:0000269|PubMed:17716973"
FT CONFLICT 135
FT /note="N -> S (in Ref. 5; BAH12887)"
FT /evidence="ECO:0000305"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:7JPO"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 41..56
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 73..86
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 88..92
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:7JPO"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 107..117
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 132..140
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 154..160
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 171..182
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 223..233
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 243..257
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 260..272
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 276..287
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 313..319
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 323..338
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 346..359
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:5UJ7"
FT HELIX 369..381
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:7JPO"
FT TURN 392..394
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:7JPO"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 408..416
FT /evidence="ECO:0007829|PDB:7JPO"
FT HELIX 423..430
FT /evidence="ECO:0007829|PDB:7JPO"
SQ SEQUENCE 436 AA; 50377 MW; A7020B6690E30B4E CRC64;
MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES
NSVLIIGPRG SGKTMLINHA LKELMEIEEV SENVLQVHLN GLLQINDKIA LKEITRQLNL
ENVVGDKVFG SFAENLSFLL EALKKGDRTS SCPVIFILDE FDLFAHHKNQ TLLYNLFDIS
QSAQTPIAVI GLTCRLDILE LLEKRVKSRF SHRQIHLMNS FGFPQYVKIF KEQLSLPAEF
PDKVFAEKWN ENVQYLSEDR SVQEVLQKHF NISKNLRSLH MLLMLALNRV TASHPFMTAV
DLMEASQLCS MDSKANIVHG LSVLEICLII AMKHLNDIYE EEPFNFQMVY NEFQKFVQRK
AHSVYNFEKP VVMKAFEHLQ QLELIKPMER TSGNSQREYQ LMKLLLDNTQ IMNALQKYPN
CPTDVRQWAT SSLSWL
