CDK2AP1 cyclin dependent kinase 2 associated protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDK2AP1provided by HGNC
Official Full Name: cyclin dependent kinase 2 associated protein 1provided by HGNC
Primary source: HGNC:HGNC:14002
See related: Ensembl:ENSG00000111328 MIM:602198; AllianceGenome:HGNC:14002
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: DOC1; ST19; DORC1; doc-1; p12DOC-1
Summary: The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggests a regulatory role in DNA replication during the S-phase of the cell cycle. This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NURD) complex that epigenetically regulates embryonic stem cell differentiation. This gene thus plays a role in both cell-cycle and epigenetic regulation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]
Expression: Ubiquitous expression in brain (RPKM 57.9), endometrium (RPKM 35.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.31

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (123260976..123272240, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (123257499..123268761, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (123745523..123756787, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs.
Title: The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs.
The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer.
Title: The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer.
A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumour-suppressive function.
Title: mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters.
Knockdown of CDK2AP1 in hESCs results in increased p53 and enhances differentiation and favors it over a self-renewal fate.
Title: Knockdown of CDK2AP1 in human embryonic stem cells reduces the threshold of differentiation.
DOC1 re-expression in oral cancer cells causes a reversal of EMT. DOC1 promotes NURD binding to a subset of target loci.
Title: DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells.
The simultaneous overexpression of p12CDK2-AP1 and CD82 significantly suppressed the in vivo tumor growth.
Title: p12CDK2-AP1 interacts with CD82 to regulate the proliferation and survival of human oral squamous cell carcinoma cells.
knockdown of CDK2AP1 in primary human fibroblasts reduced proliferation and induced premature senescence, with the observed phenotype being p53 dependent
Title: Knockdown of CDK2AP1 in primary human fibroblasts induces p53 dependent senescence.
In summary, p12CDK2AP1 expression in myxofibrosarcoma cells induces G0/G1 arrest and mitochondria dependent proapoptotic activity and down-regulation of p12CDK2AP1 by shRNAi results in up-regulation of the CDK2 transcript and protein.
Title: Clinical aggressiveness of myxofibrosarcomas associates with down-regulation of p12CDK2AP1: prognostic implication of a putative tumor suppressor that induces cell cycle arrest and apoptosis via mitochondrial pathway.
Study reports that knockdown of CDK2AP1 by RNAi in glioma cells could effectively inhibit cell proliferation by inducing cell cycle arrest and apoptosis
Title: Knockdown of CDK2AP1 by RNA interference inhibits cell growth and tumorigenesis of human glioma.
CDK2AP1 plays an important role in modulating the growth and tumorigenesis of lung cancer cells.
Title: Cyclin-dependent kinase 2-associated protein 1 suppresses growth and tumorigenesis of lung cancer.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 13 new risk loci for schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. EBI GWAS Catalog EBI GWAS 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH15673 (e-PCR)
- UniSTS:42756

SGC31687 (e-PCR)
- UniSTS:59773

G62121 (e-PCR)
- UniSTS:139171

D11S4467 (e-PCR)
- UniSTS:473580

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA polymerase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA-templated DNA replication	NAS Non-traceable Author Statement more info	PubMed
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of NuRD complex	IDA Inferred from Direct Assay more info	PubMed
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cyclin-dependent kinase 2-associated protein 1

Names: CDK2-associated protein 1; Deleted in oral cancer-1; deleted in oral cancer 1; putative oral cancer suppressor

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.

mRNA and Protein(s)

NM_001270433.2 → NP_001257362.1 cyclin-dependent kinase 2-associated protein 1 isoform 2

See identical proteins and their annotated locations for NP_001257362.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region and represents the use of an alternate promoter, compared to variant 1. This difference results in the use of an in-frame downstream start codon and a protein (isoform 2) with a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same protein (isoform 2).

Source sequence(s)

AA477326, AC068768, AF006484, BP290637

Consensus CDS

CCDS58289.1

UniProtKB/Swiss-Prot

O14519

Related

ENSP00000442502.1, ENST00000538446.5

Conserved Domains (1) summary

pfam09806
Location:34 → 86

CDK2AP; Cyclin-dependent kinase 2-associated protein
NM_001270434.2 → NP_001257363.1 cyclin-dependent kinase 2-associated protein 1 isoform 2

See identical proteins and their annotated locations for NP_001257363.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding region and represents the use of an alternate promoter, compared to variant 1. This difference results in the use of an in-frame downstream start codon and a protein (isoform 2) with a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same protein (isoform 2).

Source sequence(s)

AA295789, AA477326, AC068768, AF006484, N41298

Consensus CDS

CCDS58289.1

UniProtKB/Swiss-Prot

O14519

Related

ENSP00000479982.1, ENST00000618072.4

Conserved Domains (1) summary

pfam09806
Location:34 → 86

CDK2AP; Cyclin-dependent kinase 2-associated protein
NM_004642.4 → NP_004633.1 cyclin-dependent kinase 2-associated protein 1 isoform 1

See identical proteins and their annotated locations for NP_004633.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AA477326, AF006484

Consensus CDS

CCDS9245.1

UniProtKB/Swiss-Prot

F5GYA4, O14519

Related

ENSP00000261692.2, ENST00000261692.7

Conserved Domains (1) summary

pfam09806
Location:62 → 114

CDK2AP; Cyclin-dependent kinase 2-associated protein

RNA

NR_073007.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and represents the use of an alternate promoter, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AA477326, AF006484, DR759851
NR_073008.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and represents the use of an alternate promoter, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AA477326, AC068768, AF006484, CB964037