ORC6_HUMAN
ID ORC6_HUMAN Reviewed; 252 AA.
AC Q9Y5N6; B3KN89;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Origin recognition complex subunit 6;
GN Name=ORC6; Synonyms=ORC6L;
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].
RA Dean F.B., O'Donnell M.;
RT "cDNA cloning of a homolog for Saccharomyces cerevisiae ORC6 from Homo
RT sapiens.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Testis;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-195, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP RECONSTITUTION OF THE ORC COMPLEX, AND DISASSEMBLY OF THE ORC COMPLEX.
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-229, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-195, AND IDENTIFICATION BY
RP 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 [10]
RP LACK OF BINDING TO HISTONE H3 AND H4 TRIMETHYLATION MARKS, AND FUNCTION.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-195, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-210, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 94-187, MUTAGENESIS OF GLN-129;
RP ARG-137 AND LYS-168, AND DNA-BINDING.
RX PubMed=21502537; DOI=10.1073/pnas.1013676108;
RA Liu S., Balasov M., Wang H., Wu L., Chesnokov I.N., Liu Y.;
RT "Structural analysis of human Orc6 protein reveals a homology with
RT transcription factor TFIIB.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:7373-7378(2011).
RN [14]
RP VARIANT MGORS3 SER-232.
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).
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. Does not bind histone H3 and H4
CC trimethylation marks H3K9me3, H3K27me3 and H4K20me3.
CC {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. Interacts
CC with DBF4 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9Y5N6; P17096: HMGA1; NbExp=4; IntAct=EBI-374840, EBI-746843;
CC Q9Y5N6; Q969G2: LHX4; NbExp=8; IntAct=EBI-374840, EBI-2865388;
CC Q9Y5N6; Q9UBD5: ORC3; NbExp=4; IntAct=EBI-374840, EBI-374916;
CC Q9Y5N6; O43929: ORC4; NbExp=2; IntAct=EBI-374840, EBI-374889;
CC Q9Y5N6; Q96R06: SPAG5; NbExp=4; IntAct=EBI-374840, EBI-413317;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Meier-Gorlin syndrome 3 (MGORS3) [MIM:613803]: 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:21358632}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ORC6 family. {ECO:0000305}.
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DR EMBL; AF139658; AAD32666.1; -; mRNA.
DR EMBL; AK024019; BAG51251.1; -; mRNA.
DR EMBL; CH471092; EAW82685.1; -; Genomic_DNA.
DR EMBL; BC039032; AAH39032.1; -; mRNA.
DR EMBL; BC063565; AAH63565.1; -; mRNA.
DR CCDS; CCDS10722.1; -.
DR RefSeq; NP_055136.1; NM_014321.3.
DR PDB; 3M03; X-ray; 2.50 A; A/B/C=94-187.
DR PDB; 6KVG; NMR; -; A=1-252.
DR PDBsum; 3M03; -.
DR PDBsum; 6KVG; -.
DR AlphaFoldDB; Q9Y5N6; -.
DR SMR; Q9Y5N6; -.
DR BioGRID; 117129; 44.
DR ComplexPortal; CPX-1880; Nuclear origin of replication recognition complex.
DR CORUM; Q9Y5N6; -.
DR DIP; DIP-29692N; -.
DR IntAct; Q9Y5N6; 23.
DR MINT; Q9Y5N6; -.
DR STRING; 9606.ENSP00000219097; -.
DR iPTMnet; Q9Y5N6; -.
DR PhosphoSitePlus; Q9Y5N6; -.
DR SwissPalm; Q9Y5N6; -.
DR BioMuta; ORC6; -.
DR DMDM; 8928274; -.
DR EPD; Q9Y5N6; -.
DR jPOST; Q9Y5N6; -.
DR MassIVE; Q9Y5N6; -.
DR MaxQB; Q9Y5N6; -.
DR PaxDb; Q9Y5N6; -.
DR PeptideAtlas; Q9Y5N6; -.
DR PRIDE; Q9Y5N6; -.
DR ProteomicsDB; 86456; -.
DR Antibodypedia; 4278; 244 antibodies from 35 providers.
DR DNASU; 23594; -.
DR Ensembl; ENST00000219097.7; ENSP00000219097.2; ENSG00000091651.9.
DR GeneID; 23594; -.
DR KEGG; hsa:23594; -.
DR MANE-Select; ENST00000219097.7; ENSP00000219097.2; NM_014321.4; NP_055136.1.
DR UCSC; uc002eeh.3; human.
DR CTD; 23594; -.
DR DisGeNET; 23594; -.
DR GeneCards; ORC6; -.
DR HGNC; HGNC:17151; ORC6.
DR HPA; ENSG00000091651; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MalaCards; ORC6; -.
DR MIM; 607213; gene.
DR MIM; 613803; phenotype.
DR neXtProt; NX_Q9Y5N6; -.
DR OpenTargets; ENSG00000091651; -.
DR Orphanet; 2554; Ear-patella-short stature syndrome.
DR PharmGKB; PA32813; -.
DR VEuPathDB; HostDB:ENSG00000091651; -.
DR eggNOG; KOG4557; Eukaryota.
DR GeneTree; ENSGT00390000007370; -.
DR InParanoid; Q9Y5N6; -.
DR OMA; RMFEKLL; -.
DR OrthoDB; 1522235at2759; -.
DR PhylomeDB; Q9Y5N6; -.
DR TreeFam; TF101096; -.
DR BRENDA; 3.6.4.B8; 2681.
DR PathwayCommons; Q9Y5N6; -.
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; Q9Y5N6; -.
DR SIGNOR; Q9Y5N6; -.
DR BioGRID-ORCS; 23594; 801 hits in 1088 CRISPR screens.
DR ChiTaRS; ORC6; human.
DR GeneWiki; ORC6; -.
DR GeneWiki; ORC6L; -.
DR GenomeRNAi; 23594; -.
DR Pharos; Q9Y5N6; Tbio.
DR PRO; PR:Q9Y5N6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9Y5N6; protein.
DR Bgee; ENSG00000091651; Expressed in oocyte and 179 other tissues.
DR ExpressionAtlas; Q9Y5N6; baseline and differential.
DR Genevisible; Q9Y5N6; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005664; C:nuclear origin of replication recognition complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000808; C:origin recognition complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IBA:GO_Central.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:CAFA.
DR InterPro; IPR008721; ORC6.
DR InterPro; IPR020529; ORC6_met/pln.
DR PANTHER; PTHR13394; PTHR13394; 1.
DR Pfam; PF05460; ORC6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; DNA replication; DNA-binding; Dwarfism;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..252
FT /note="Origin recognition complex subunit 6"
FT /id="PRO_0000127097"
FT REGION 188..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT CROSSLNK 210
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 32
FT /note="R -> W (in dbSNP:rs3218744)"
FT /id="VAR_029283"
FT VARIANT 138
FT /note="P -> Q (in dbSNP:rs3218745)"
FT /id="VAR_029284"
FT VARIANT 232
FT /note="Y -> S (in MGORS3; dbSNP:rs387906969)"
FT /evidence="ECO:0000269|PubMed:21358632"
FT /id="VAR_065487"
FT MUTAGEN 129
FT /note="Q->A: Abolished DNA binding."
FT /evidence="ECO:0000269|PubMed:21502537"
FT MUTAGEN 137
FT /note="R->A: Abolished DNA binding."
FT /evidence="ECO:0000269|PubMed:21502537"
FT MUTAGEN 168
FT /note="K->A: Abolished DNA binding."
FT /evidence="ECO:0000269|PubMed:21502537"
FT STRAND 1..3
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 4..9
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 18..34
FT /evidence="ECO:0007829|PDB:6KVG"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 44..58
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 65..71
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 138..151
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 158..163
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 169..183
FT /evidence="ECO:0007829|PDB:3M03"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:6KVG"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:6KVG"
FT HELIX 232..242
FT /evidence="ECO:0007829|PDB:6KVG"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:6KVG"
SQ SEQUENCE 252 AA; 28107 MW; 78840387605F45FE CRC64;
MGSELIGRLA PRLGLAEPDM LRKAEEYLRL SRVKCVGLSA RTTETSSAVM CLDLAASWMK
CPLDRAYLIK LSGLNKETYQ SCLKSFECLL GLNSNIGIRD LAVQFSCIEA VNMASKILKS
YESSLPQTQQ VDLDLSRPLF TSAALLSACK ILKLKVDKNK MVATSGVKKA IFDRLCKQLE
KIGQQVDREP GDVATPPRKR KKIVVEAPAK EMEKVEEMPH KPQKDEDLTQ DYEEWKRKIL
ENAASAQKAT AE
