CDK1 cyclin dependent kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDK1provided by HGNC
Official Full Name: cyclin dependent kinase 1provided by HGNC
Primary source: HGNC:HGNC:1722
See related: Ensembl:ENSG00000170312 MIM:116940
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CDC2; CDC28A; P34CDC2
Summary: The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
Expression: Broad expression in lymph node (RPKM 12.8), bone marrow (RPKM 12.8) and 18 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 10q21.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	10	NC_000010.11 (60778331..60794852)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (62538089..62554610)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inhibition of CDK1 can damage normal cells.
Title: CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner.
cyclin-dependent kinase 1 (Cdk1), a known target of E2F1, is involved in G1 checkpoint regulation, as Cdk1 knockdown hindered G1/S progression, while Cdk1 overexpression rescued RCC1 knockdown-mediated effect on G1 cell cycle progression.
Title: Regulator of chromatin condensation 1 abrogates the G1 cell cycle checkpoint via Cdk1 in human papillomavirus E7-expressing epithelium and cervical cancer cells.
Beside their direct functions in regulation of cell cycle progression, the complex of cyclin B1-CDK1 is able to coordinate the cell cycle events with enhanced mitochondrial bioenergetics. Such nucleus-mitochondria oscillation may play key roles in the flexible bioenergetics required for tumor cell survival and compromising the efficacy of anti-cancer therapy. [review]
Title: Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.
Point to differences in Cdk1-mediated mechanisms of regulation between human and yeast Cdc14 orthologues.
Title: Biochemical analyses reveal amino acid residues critical for cell cycle-dependent phosphorylation of human Cdc14A phosphatase by cyclin-dependent kinase 1.
CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling.
Title: CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling.
These findings uncover CDK1 as a new regulator of Sox2 during tumor initiation and implicate the CDK1-Sox2 interaction as a potential therapeutic target in cancer.
Title: CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma.
The cyclin dependent kinase 1 (CDK1) was identified as one of the binding candidates of miR-186. Experimental analysis showed that miR-186 bound the 3'-untranslated region (3'-UTR) of CDK1 and suppressed the level of CDK1 in NSCLC cells.
Title: Lycorine inhibited the cell growth of non-small cell lung cancer by modulating the miR-186/CDK1 axis.
Cdk1 phosphorylation of Nde1 stimulates CENP-F binding and is required for Nde1 targeting to the nuclear envelope and kinetochores in vivo.
Title: Cdk1 phosphorylation of the dynein adapter Nde1 controls cargo binding from G2 to anaphase.
The inactivation of CDK1 is the trigger that initiates remodeling of adhesion complexes and the actin cytoskeleton in preparation for rapid entry into mitosis.
Title: Cell adhesion is regulated by CDK1 during the cell cycle.
Depletion of TIAR accelerates mitotic entry and leads to chromosomal instability in response to replication stress, in a manner that can be alleviated by the concomitant depletion of Cdc25B or inhibition of CDK1. Since TIAR retains CDK1 in GMGs and attenuates CDK1 activity, we propose that the assembly of GMGs may represent a so far unrecognized mechanism that contributes to the activation of the G2/M checkpoint
Title: TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress.

Submit: New GeneRIF Correction See all GeneRIFs (368)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
A genome-wide association study for reading and language abilities in two population cohorts. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	In cultured neurons, HIV-1 gp120 increases transcription factor E2F1 levels in the nucleus, stimulates its transcriptional activity, and enhances the expression of the E2F1 target proteins Cdc2 and Puma	PubMed
	env	Cell-cell contact between T cells expressing HIV-1 gp120/gp41 and other T cells expressing CD4 receptors leads to the rapid accumulation of cyclin B and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2 phase	PubMed
Pr55(Gag)	gag	The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with CDC2	PubMed
Rev	rev	cdc2 has been shown to phosphorylate Rev in vitro	PubMed
Tat	tat	When expressed in astrocytes, neurons, and non-glial 293T cells, HIV-1 Tat interacts with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA	PubMed
	tat	Cdc2 activity is enhanced by HIV-1 Tat expression in Jurkat T cells and is associated with Tat-induced apoptosis	PubMed
Vif	vif	HIV-1 Vif-mediated G2 arrest involves the dysregulation of DK1-CyclinB1 nuclear translocation	PubMed
	vif	HIV-1 Vif inhibits CDK1 activation and subsequent nuclear translocation	PubMed
Vpr	vpr	HIV-1 Vpr inactivates the cdc2-cyclin B kinase complex by inhibiting the dephosphorylation of cdc2 tyrosine 15, leading to arrest in the G2 phase of the cell cycle	PubMed
	vpr	HIV-1 Vpr causes increased levels of CyclinB1, Plk1, and Cdk1 in a complex with the nuclear transport and spindle assembly protein, importin beta	PubMed
	vpr	Vpr-induced cell cycle G2/M arrest reveals a dramatic increase in the amount of Cdk1, Cdc25C, and CyclinB1 bound to 14-3-3 theta	PubMed
	vpr	The human Vpr interacting protein (hVIP/MOV34) is a likely cellular cofactor for HIV-1 Vpr inactivation of the cdc2-cyclin B kinase complex and induction of cell cycle arrest	PubMed
	vpr	Data suggests that HIV-1 Vpr transactivation of the HIV-LTR promoter occurs through the inhibition of p300-associated cdc2-cyclin B kinase complex activity which enhances transcriptional activation by Rel A and p300	PubMed
	vpr	Accumulation of the hypophosphorylated or active form of cdc2 kinase is not required for HIV-1 Vpr-induced apoptosis, however one report indicates cdc2 is activated in Vpr-induced apoptotic cells	PubMed
	vpr	Inactivation of the cdc2-cyclin B kinase complex by HIV-1 Vpr leads to the activation of Poly(A) polymerase	PubMed
	vpr	Inactivation of the cdc2-cyclin B kinase complex and arrest in the G2 phase of the cell cycle has been mapped to the C-terminus of HIV-1 Vpr, including amino acids 73, 80 and 84-96	PubMed
	vpr	HIV-1 Vpr inactivates the cdc2-cyclin B kinase complex by inactivating cdc25C, the phosphatase that dephosphorylates and activates cdc2	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

ksks369 (e-PCR)
- UniSTS:514418

SHGC-64950 (e-PCR)
- UniSTS:72564

SHGC-57924 (e-PCR)
- UniSTS:67283

RH71273 (e-PCR)
- UniSTS:82900

RH68267 (e-PCR)
- UniSTS:68335

Homology

Homologs of the CDK1 gene: The CDK1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, and frog.
Orthologs from Annotation Pipeline: 283 organisms have orthologs with human gene CDK1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
Hsp70 protein binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II CTD heptapeptide repeat kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
RNA polymerase II CTD heptapeptide repeat kinase activity	IDA Inferred from Direct Assay more info	PubMed
chromatin binding	IEA Inferred from Electronic Annotation more info
cyclin binding	IDA Inferred from Direct Assay more info	PubMed
cyclin binding	IPI Inferred from Physical Interaction more info	PubMed
cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
cyclin-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
cyclin-dependent protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
cyclin-dependent protein serine/threonine kinase activity	TAS Traceable Author Statement more info
histone kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	TAS Traceable Author Statement more info
virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	TAS Traceable Author Statement more info
DNA repair	TAS Traceable Author Statement more info	PubMed
DNA replication	TAS Traceable Author Statement more info	PubMed
G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
Golgi disassembly	ISS Inferred from Sequence or Structural Similarity more info
activation of MAPK activity	TAS Traceable Author Statement more info
anaphase-promoting complex-dependent catabolic process	TAS Traceable Author Statement more info
animal organ regeneration	IEA Inferred from Electronic Annotation more info
apoptotic process	IEA Inferred from Electronic Annotation more info
cell aging	IEA Inferred from Electronic Annotation more info
cell division	IEA Inferred from Electronic Annotation more info
cell migration	TAS Traceable Author Statement more info	PubMed
cell proliferation	IEA Inferred from Electronic Annotation more info
cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
centrosome cycle	TAS Traceable Author Statement more info	PubMed
chromosome condensation	IEA Inferred from Electronic Annotation more info
ciliary basal body-plasma membrane docking	TAS Traceable Author Statement more info
epithelial cell differentiation	IEP Inferred from Expression Pattern more info	PubMed
histone phosphorylation	IEA Inferred from Electronic Annotation more info
microtubule cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
mitotic G2 DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
mitotic nuclear envelope disassembly	TAS Traceable Author Statement more info
negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-threonine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of DNA replication	IEA Inferred from Electronic Annotation more info
positive regulation of G2/M transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cardiac muscle cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
positive regulation of mitochondrial ATP synthesis coupled electron transport	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
pronuclear fusion	TAS Traceable Author Statement more info	PubMed
protein deubiquitination	TAS Traceable Author Statement more info
protein localization to kinetochore	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein-containing complex assembly	IEA Inferred from Electronic Annotation more info
regulation of G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
regulation of Schwann cell differentiation	TAS Traceable Author Statement more info	PubMed
regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of embryonic development	TAS Traceable Author Statement more info	PubMed
regulation of mitotic cell cycle phase transition	TAS Traceable Author Statement more info
response to activity	IEA Inferred from Electronic Annotation more info
response to amine	IEA Inferred from Electronic Annotation more info
response to axon injury	IEA Inferred from Electronic Annotation more info
response to cadmium ion	IEA Inferred from Electronic Annotation more info
response to copper ion	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
rhythmic process	IEA Inferred from Electronic Annotation more info
transcription initiation from RNA polymerase II promoter	TAS Traceable Author Statement more info
ventricular cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
viral entry into host cell	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
centrosome	IDA Inferred from Direct Assay more info	PubMed
cyclin B1-CDK1 complex	IMP Inferred from Mutant Phenotype more info	PubMed
cyclin-dependent protein kinase holoenzyme complex	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
membrane	HDA more info	PubMed
midbody	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	TAS Traceable Author Statement more info	PubMed
mitotic spindle	IDA Inferred from Direct Assay more info	PubMed
nuclear chromosome, telomeric region	HDA more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
spindle microtubule	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cyclin-dependent kinase 1

Names: cell cycle controller CDC2; cell division control protein 2 homolog; cell division cycle 2, G1 to S and G2 to M; cell division protein kinase 1; p34 protein kinase

NP_001163877.1

EC 2.7.11.22

EC 2.7.11.23

NP_001163878.1

EC 2.7.11.22

EC 2.7.11.23

NP_001307847.1

EC 2.7.11.22

EC 2.7.11.23

NP_001777.1

EC 2.7.11.22

EC 2.7.11.23

NP_203698.1

EC 2.7.11.22

EC 2.7.11.23

XP_005270360.1

EC 2.7.11.22

EC 2.7.11.23

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029877.1 RefSeqGene

Range

5148..21522

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001170406.1 → NP_001163877.1 cyclin-dependent kinase 1 isoform 4

See identical proteins and their annotated locations for NP_001163877.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 1. Both variants 4 and 5 encode the same isoform (4).

Source sequence(s)

AA459484, AC022390, AK295741, DA823877

UniProtKB/TrEMBL

B7Z3D6

Conserved Domains (1) summary

cl21453
Location:3 → 106

PKc_like; Protein Kinases, catalytic domain
NM_001170407.1 → NP_001163878.1 cyclin-dependent kinase 1 isoform 4

See identical proteins and their annotated locations for NP_001163878.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 1. Both variants 4 and 5 encode the same isoform (4).

Source sequence(s)

AA459484, AC022390, AK295741, BG723076

UniProtKB/TrEMBL

B7Z3D6

Conserved Domains (1) summary

cl21453
Location:3 → 106

PKc_like; Protein Kinases, catalytic domain
NM_001320918.1 → NP_001307847.1 cyclin-dependent kinase 1 isoform 1

Status: REVIEWED

Source sequence(s)

BC014563, BQ308742, BU633268, DA823877

Consensus CDS

CCDS44408.1

UniProtKB/Swiss-Prot

P06493

Conserved Domains (1) summary

cd07861
Location:3 → 287

STKc_CDK1_euk; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes
NM_001786.5 → NP_001777.1 cyclin-dependent kinase 1 isoform 1

See identical proteins and their annotated locations for NP_001777.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC022390, BC107750, BG723076, X05360

Consensus CDS

CCDS44408.1

UniProtKB/Swiss-Prot

P06493

UniProtKB/TrEMBL

I6L9I5

Related

ENSP00000378699.3, ENST00000395284.8

Conserved Domains (1) summary

cd07861
Location:3 → 287

STKc_CDK1_euk; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes
NM_033379.4 → NP_203698.1 cyclin-dependent kinase 1 isoform 2

See identical proteins and their annotated locations for NP_203698.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as CDC2 delta T, lacks an alternate in-frame exon in the middle portion of the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AC022390, AW976143, BC107750, BG723076, D88357

Consensus CDS

CCDS7260.1

UniProtKB/Swiss-Prot

P06493

UniProtKB/TrEMBL

A0A024QZJ8, I6L9I5

Related

ENSP00000325970.4, ENST00000316629.8

Conserved Domains (1) summary

cl21453
Location:3 → 230

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p13 Primary Assembly

Range

60778331..60794852

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005270303.3 → XP_005270360.1 cyclin-dependent kinase 1 isoform X1

See identical proteins and their annotated locations for XP_005270360.1

UniProtKB/Swiss-Prot

P06493

Related

ENSP00000397973.2, ENST00000448257.6

Conserved Domains (1) summary

cd07861
Location:3 → 287

STKc_CDK1_euk; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001130829.1: Suppressed sequence

Description

NM_001130829.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.