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Protein

Cell division control protein 6 homolog

Gene

CDC6

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

Functioni

Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi202 – 209ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase binding Source: BHF-UCL
  • nucleotide binding Source: ProtInc

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to angiotensin Source: Ensembl
  • cellular response to vasopressin Source: Ensembl
  • DNA replication Source: Reactome
  • DNA replication checkpoint Source: ProtInc
  • DNA replication initiation Source: InterPro
  • G1/S transition of mitotic cell cycle Source: Reactome
  • mitotic cell cycle Source: UniProtKB
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of DNA replication Source: ProtInc
  • positive regulation of chromosome segregation Source: BHF-UCL
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  • positive regulation of cytokinesis Source: BHF-UCL
  • positive regulation of fibroblast proliferation Source: Ensembl
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
  • regulation of mitotic metaphase/anaphase transition Source: BHF-UCL
  • regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
  • traversing start control point of mitotic cell cycle Source: ProtInc

Keywordsi

Biological processCell cycle, Cell division, DNA replication, Mitosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-539107 Activation of E2F1 target genes at G1/S
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
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
SignaLinkiQ99741
SIGNORiQ99741

Names & Taxonomyi

Protein namesi
Recommended name:
Cell division control protein 6 homolog
Alternative name(s):
CDC6-related protein
Cdc18-related protein
Short name:
HsCdc18
p62(cdc6)
Short name:
HsCDC6
Gene namesi
Name:CDC6
Synonyms:CDC18L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000094804.9
HGNCiHGNC:1744 CDC6
MIMi602627 gene
neXtProtiNX_Q99741

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

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Meier-Gorlin syndrome 5 (MGORS5)1 Publication
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:613805
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065493323T → R in MGORS5. 1 PublicationCorresponds to variant dbSNP:rs387906842EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi990
MalaCardsiCDC6
MIMi613805 phenotype
OpenTargetsiENSG00000094804
Orphaneti2554 Ear-patella-short stature syndrome
PharmGKBiPA26271

Chemistry databases

ChEMBLiCHEMBL2311228

Polymorphism and mutation databases

BioMutaiCDC6
DMDMi50400620

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001509791 – 560Cell division control protein 6 homologAdd BLAST560

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45PhosphoserineCombined sources1
Modified residuei54PhosphoserineCombined sources1
Modified residuei67PhosphothreonineBy similarity1
Modified residuei74PhosphoserineBy similarity1
Modified residuei106PhosphoserineCombined sources1
Modified residuei127PhosphoserineCombined sources1
Modified residuei419PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99741
MaxQBiQ99741
PaxDbiQ99741
PeptideAtlasiQ99741
PRIDEiQ99741
ProteomicsDBi78452

PTM databases

iPTMnetiQ99741
PhosphoSitePlusiQ99741

Miscellaneous databases

PMAP-CutDBiQ99741

Expressioni

Gene expression databases

BgeeiENSG00000094804
CleanExiHS_CDC6
ExpressionAtlasiQ99741 baseline and differential
GenevisibleiQ99741 HS

Organism-specific databases

HPAiHPA050114
HPA065070

Interactioni

Subunit structurei

Interacts with PCNA, ORC1, cyclin-CDK (PubMed:9566895). Interacts with HUWE1 (PubMed:17567951). Interacts with ANKRD17 (PubMed:23711367). Interacts with GRWD1; origin binding of GRWD1 is dependent on CDC6 (PubMed:25990725). Interacts with CDT1; are mutually dependent on one another for loading MCM complexes onto chromatin (PubMed:14672932).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107426, 76 interactors
CORUMiQ99741
DIPiDIP-28154N
ELMiQ99741
IntActiQ99741, 26 interactors
MINTiQ99741
STRINGi9606.ENSP00000209728

Structurei

3D structure databases

ProteinModelPortaliQ99741
SMRiQ99741
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99741

Family & Domainsi

Sequence similaritiesi

Belongs to the CDC6/cdc18 family.Curated

Phylogenomic databases

eggNOGiKOG2227 Eukaryota
COG1474 LUCA
GeneTreeiENSGT00530000063498
HOGENOMiHOG000045316
HOVERGENiHBG050860
InParanoidiQ99741
KOiK02213
OMAiTGWPTDQ
OrthoDBiEOG091G0AXO
PhylomeDBiQ99741
TreeFamiTF101051

Family and domain databases

CDDicd08768 Cdc6_C, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR016314 Cdc6/18
IPR015163 Cdc6_C
IPR027417 P-loop_NTPase
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF13401 AAA_22, 1 hit
PF09079 Cdc6_C, 1 hit
PIRSFiPIRSF001767 Cdc6, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM01074 Cdc6_C, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF52540 SSF52540, 1 hit

Sequencei

Sequence statusi: Complete.

Q99741-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPQTRSQAQA TISFPKRKLS RALNKAKNSS DAKLEPTNVQ TVTCSPRVKA
60 70 80 90 100
LPLSPRKRLG DDNLCNTPHL PPCSPPKQGK KENGPPHSHT LKGRRLVFDN
110 120 130 140 150
QLTIKSPSKR ELAKVHQNKI LSSVRKSQEI TTNSEQRCPL KKESACVRLF
160 170 180 190 200
KQEGTCYQQA KLVLNTAVPD RLPAREREMD VIRNFLREHI CGKKAGSLYL
210 220 230 240 250
SGAPGTGKTA CLSRILQDLK KELKGFKTIM LNCMSLRTAQ AVFPAIAQEI
260 270 280 290 300
CQEEVSRPAG KDMMRKLEKH MTAEKGPMIV LVLDEMDQLD SKGQDVLYTL
310 320 330 340 350
FEWPWLSNSH LVLIGIANTL DLTDRILPRL QAREKCKPQL LNFPPYTRNQ
360 370 380 390 400
IVTILQDRLN QVSRDQVLDN AAVQFCARKV SAVSGDVRKA LDVCRRAIEI
410 420 430 440 450
VESDVKSQTI LKPLSECKSP SEPLIPKRVG LIHISQVISE VDGNRMTLSQ
460 470 480 490 500
EGAQDSFPLQ QKILVCSLML LIRQLKIKEV TLGKLYEAYS KVCRKQQVAA
510 520 530 540 550
VDQSECLSLS GLLEARGILG LKRNKETRLT KVFFKIEEKE IEHALKDKAL
560
IGNILATGLP
Length:560
Mass (Da):62,720
Last modified:May 1, 1997 - v1
Checksum:i3ED7DE4AF80CB017
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019349238T → A1 PublicationCorresponds to variant dbSNP:rs4135010EnsemblClinVar.1
Natural variantiVAR_019350295D → N1 PublicationCorresponds to variant dbSNP:rs4135012EnsemblClinVar.1
Natural variantiVAR_019351299T → M1 PublicationCorresponds to variant dbSNP:rs4135013EnsemblClinVar.1
Natural variantiVAR_065493323T → R in MGORS5. 1 PublicationCorresponds to variant dbSNP:rs387906842EnsemblClinVar.1
Natural variantiVAR_019352378R → H1 PublicationCorresponds to variant dbSNP:rs4135016Ensembl.1
Natural variantiVAR_019353441V → I2 PublicationsCorresponds to variant dbSNP:rs13706EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77949 mRNA Translation: AAB38317.1
AF022109 mRNA Translation: AAC52071.1
AY150310 Genomic DNA Translation: AAN10296.1
BC025232 mRNA Translation: AAH25232.1
CCDSiCCDS11365.1
RefSeqiNP_001245.1, NM_001254.3
UniGeneiHs.405958

Genome annotation databases

EnsembliENST00000209728; ENSP00000209728; ENSG00000094804
GeneIDi990
KEGGihsa:990
UCSCiuc002huj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCDC6_HUMAN
AccessioniPrimary (citable) accession number: Q99741
Secondary accession number(s): Q8TB30
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1997
Last modified: July 18, 2018
This is version 169 of the entry and version 1 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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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