Q9Y5N6 (ORC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Origin recognition complex subunit 6

Gene names

Name:	ORC6
Synonyms:	ORC6L

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	252 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.5 Ref.7 Ref.8
Involvement in disease	Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:613803]. MGORS3 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.9
Sequence similarities	Belongs to the ORC6 family.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA replication Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement. Source: Reactome
Cellular component	nuclear origin of replication recognition complex Inferred from electronic annotation. Source: InterPro nucleoplasm Traceable author statement. Source: Reactome
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 252

252

Origin recognition complex subunit 6

PRO_0000127097

Amino acid modifications

Modified residue

195

1

Phosphothreonine Ref.5 Ref.8

Modified residue

229

1

Phosphothreonine Ref.7

Natural variations

Natural variant

32

1

R → W.
Corresponds to variant rs3218744 [ dbSNP | Ensembl ].

VAR_029283

Natural variant

138

1

P → Q.
Corresponds to variant rs3218745 [ dbSNP | Ensembl ].

VAR_029284

Natural variant

232

1

Y → S in MGORS3. Ref.9

VAR_065487

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

252

Helix Strand Turn

Details...

Helix

99 – 105

7

Helix

108 – 110

3

Helix

111 – 122

12

Helix

127 – 132

6

Helix

138 – 151

14

Helix

158 – 163

6

Helix

169 – 181

13

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5N6 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 78840387605F45FE	FASTA	252	28,107
	10 20 30 40 50 60 MGSELIGRLA PRLGLAEPDM LRKAEEYLRL SRVKCVGLSA RTTETSSAVM CLDLAASWMK 70 80 90 100 110 120 CPLDRAYLIK LSGLNKETYQ SCLKSFECLL GLNSNIGIRD LAVQFSCIEA VNMASKILKS 130 140 150 160 170 180 YESSLPQTQQ VDLDLSRPLF TSAALLSACK ILKLKVDKNK MVATSGVKKA IFDRLCKQLE 190 200 210 220 230 240 KIGQQVDREP GDVATPPRKR KKIVVEAPAK EMEKVEEMPH KPQKDEDLTQ DYEEWKRKIL 250 ENAASAQKAT AE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a homolog for Saccharomyces cerevisiae ORC6 from Homo sapiens." Dean F.B., O'Donnell M. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Cervix and Testis.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-195, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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.
[7]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-229, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-195, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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. , 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 MGORS3 SER-232.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF139658 mRNA. Translation: AAD32666.1.
AK024019 mRNA. Translation: BAG51251.1.
CH471092 Genomic DNA. Translation: EAW82685.1.
BC039032 mRNA. Translation: AAH39032.1.
BC063565 mRNA. Translation: AAH63565.1.

IPI

IPI00001641.

RefSeq

NP_055136.1. NM_014321.3.

UniGene

Hs.49760.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3M03	X-ray	2.50	A/B/C	94-187	[»]

ProteinModelPortal

Q9Y5N6.

SMR

Q9Y5N6. Positions 94-187.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29692N.

IntAct

Q9Y5N6. 8 interactions.

MINT

MINT-1202310.

STRING

Q9Y5N6.

PTM databases

PhosphoSite

Q9Y5N6.

Polymorphism databases

DMDM

8928274.

Proteomic databases

PRIDE

Q9Y5N6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219097; ENSP00000219097; ENSG00000091651.

GeneID

23594.

KEGG

hsa:23594.

UCSC

uc002eeh.1. human.

Organism-specific databases

CTD

23594.

GeneCards

GC16P046724.

H-InvDB

HIX0013002.

HGNC

HGNC:17151. ORC6.

HPA

CAB016330.

MIM

607213. gene.
613803. phenotype.

neXtProt

NX_Q9Y5N6.

Orphanet

2554. Ear-patella-short stature syndrome.

PharmGKB

PA32813.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000007370.

HOGENOM

HBG277971.

HOVERGEN

HBG007876.

InParanoid

Q9Y5N6.

OMA

RVKCVGL.

OrthoDB

EOG48SGTX.

PhylomeDB

Q9Y5N6.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpress

Q9Y5N6.

Bgee

Q9Y5N6.

CleanEx

HS_ORC6L.

Genevestigator

Q9Y5N6.

GermOnline

ENSG00000091651. Homo sapiens.

Family and domain databases

InterPro

IPR008721. ORC6.
IPR020529. ORC6_met/pln.
[Graphical view]

KO

K02608.

Pfam

PF05460. ORC6. 1 hit.
[Graphical view]

ProDom

PD315657. Origin_recog_cplx_su6-like. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other

NextBio

46248.

SOURCE

Search...

Entry information

Entry name

ORC6_HUMAN

Accession

Primary (citable) accession number: Q9Y5N6
Secondary accession number(s): B3KN89

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1999
Last modified:	December 14, 2011
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.