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CDC7 (human)

Overview CDC7 an evolutionarily conserved serine/threonine protein kinase of the CDC7 family. Predominantly localized in the nucleus, it plays a pivotal role in linking cell cycle regulation to genome duplication, being essential for the firing of DNA replication origins. Plays an essential role in initiating DNA replication at replication origins by phosphorylating the MCM2 and MCM4 subunits of the MCM2-7 helicase complex. The human protein requires phosphorylation by CDK1 at T376 and binding to activator of S-phase kinase (ASK)/DBF4B to be fully activated. The interaction between Cdc7 and DBFK subunits facilitates ATP binding and substrate recognition by the Cdc7 kinase. Although CDC7 expression levels appear to be constant throughout the cell cycle, the expression levels of DBF4B is cell cycle-regulated. Thus, the CDC7 activity is activated during S phase in eukaryotes. The Cdc7/ DBF4B complex regulates initiation of DNA replication by phosphorylating chromatin-bound mini-chromosome maintenance protein 2 (MCM2). Impaired Cdc7 kinase activity leads to S-phase arrest. Plays a role in the TGF-beta regulation of smooth muscle cell (SMC) differentiation. Interacts with Smad3 to facilitate Smad3 binding to SMC marker promoter, leading to the activation of SMC marker gene transcription. Note: This description may include information from UniProtKB. Protein type: EC 2.7.11.1; Protein kinase, Other; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Other group; CDC7 family Cellular Component: nucleoplasm; cytoplasm; nucleus Molecular Function: protein serine/threonine kinase activity; metal ion binding; kinase activity; ATP binding Biological Process: M/G1 transition of mitotic cell cycle; cell division; regulation of S phase; positive regulation of cell proliferation; mitotic cell cycle; DNA replication; cell cycle checkpoint; G1/S transition of mitotic cell cycle Reference #:  O00311 (UniProtKB) Alt. Names/Synonyms: CDC7; CDC7 (cell division cycle 7, S. cerevisiae, homolog)-like 1; CDC7-related kinase; CDC7L1; cell division cycle 7 homolog (S. cerevisiae); cell division cycle 7-like protein 1; Cell division cycle 7-related protein kinase; HsCdc7; Hsk1; huCdc7; MGC117361; MGC126237; MGC126238 Gene Symbols: CDC7 Molecular weight: 63,888 Da Basal Isoelectric point: 8.96  Predict pI for various phosphorylation states Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below CDC7 4F99 - A=530-574 (human) 4F9A - A/C=530-574 (human) 4F9B - A/C=530-574 (human) 4F9C - A=530-574 (human)

STRING  |  Scansite  |  KinBase  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 4F99 4F9A 4F9B 4F9C  |  ENZYME  |  DISEASE  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene

	Sites Implicated In
enzymatic activity, induced: T376‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		S16-p	MDEPMAFsPQRDRFQ
0	3		S27-p	DRFQAEGsLKkNEQN
0	1		K30-u	QAEGsLKkNEQNFKL
0	1		S181-p	VHRDVKPsNFLYNRR
0	1		K212-u	DTKIELLkFVQSEAQ
0	1		S302-p	HSSISHEsPAVKLMK
0	1		K331-a	KKKAISTkVMNSAVM
2	12		T376-p	QVAPRAGtPGFRAPE
0	1		T386-p	FRAPEVLtKCPNQTT
0	1		Y415-p	LSGRYPFyKASDDLT
0	1		T472-p	LRGMDSStPKLTSDI
0	1		S484-p	SDIQGHAsHQPAISE
0	2		S498-p	EKTDHKAsCLVQtPP
0	2		T503-p	KAsCLVQtPPGQYsG
0	2		S509-p	QtPPGQYsGNSFKKG
0	1		S556-p	LLDLNPAsRItAEEA
0	1		T559-p	LNPAsRItAEEALLH
0	1		S573-p	HPFFKDMsL______

	mouse
S8	MEEPMAFSSLRGSDR
S21	DRCPADDSLKKYEQS
K24	PADDSLKKYEQSVKL
S175	VHRDVKPSNFLYNRR
K206	DTKIELLKFVQSEAQ
S294	HSSISHESPAEKLIK
K323	KKTAISTKAMNSVMR
T367-p	QVAPRAGtPGFRAPE
T377	FRAPEVLTKCPDQTT
Y406	LSGRYPFYKASDDLT
T463	LRGLDSTTPRSASGP
S475	SGPPGNASYDPAASK
S489	KNTDHKASRVQAAQA
A493	HKASRVQAAQAQHsE
S499-p	QAAQAQHsEDSLYKR
S546	LLDLNPASRITAEAA
T549	LNPASRITAEAALLH
C563	HAFFKDMCS______

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