PNKP polynucleotide kinase 3'-phosphatase [Homo sapiens (human)] - Gene

Summary

Official Symbol: PNKPprovided by HGNC
Official Full Name: polynucleotide kinase 3'-phosphataseprovided by HGNC
Primary source: HGNC:HGNC:9154
See related: Ensembl:ENSG00000039650 MIM:605610; AllianceGenome:HGNC:9154
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: PNK; AOA4; MCSZ; CMT2B2; EIEE10
Summary: This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]
Expression: Ubiquitous expression in spleen (RPKM 18.2), adrenal (RPKM 13.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.33

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (49861204..49867576, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (52861341..52867713, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (50364461..50370833, complement)

Chromosome 19 - NC_000019.10 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?

Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.
Title: Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.
Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans.
Title: Functional analysis of a conserved site mutation in the DNA end processing enzyme PNKP leading to ataxia with oculomotor apraxia type 4 in humans.
Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP.
Title: Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP.
Characteristics of epilepsy secondary to mutations in the PNKP gene.
Title: Characteristics of epilepsy secondary to mutations in the PNKP gene.
The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort.
Title: The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort.
The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability.
Title: The FHA domain of PNKP is essential for its recruitment to DNA damage sites and maintenance of genome stability.
PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.
Title: PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington's disease.
Mutational survivorship bias: The case of PNKP.
Title: Mutational survivorship bias: The case of PNKP.
Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair.
Title: Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair.
Study provides evidence that wild-type ATXN3 plays an important role in error-free repair of DNA double-strand breaks in the transcribed genes. In contrast, mutant ATXN3 blocks the activity of a DNA end-processing enzyme, polynucleotide kinase 3'-phosphatase (PNKP), leading to progressive accumulation of double-strand breaks and abrogation of global transcription.
Title: Deficiency in classical nonhomologous end-joining-mediated repair of transcribed genes is linked to SCA3 pathogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (45)

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

Associated conditions

Description	Tests
Ataxia - oculomotor apraxia type 4 MedGen: C4225397 OMIM: 616267 GeneReviews: Not available	Compare labs
Charcot-Marie-Tooth disease type 2B2 MedGen: C1854150 OMIM: 605589 GeneReviews: Not available	Compare labs
Microcephaly, seizures, and developmental delay MedGen: C3150667 OMIM: 613402 GeneReviews: Not available	Compare labs

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
Rev	rev	HIV-1 Rev interacting protein, polynucleotide kinase 3'-phosphatase (PNKP), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	NAS Non-traceable Author Statement more info	PubMed
enables ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables damaged DNA binding	NAS Non-traceable Author Statement more info	PubMed
enables double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables double-stranded DNA binding	TAS Traceable Author Statement more info	PubMed
enables endonuclease activity	NAS Non-traceable Author Statement more info	PubMed
enables polynucleotide 3'-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables polynucleotide 3'-phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables polynucleotide 3'-phosphatase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables purine nucleotide binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA ligation involved in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IGI Inferred from Genetic Interaction more info	PubMed
involved_in DNA-templated DNA replication	NAS Non-traceable Author Statement more info	PubMed
involved_in base-excision repair, gap-filling	TAS Traceable Author Statement more info
involved_in double-strand break repair via nonhomologous end joining	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein ADP-ribosylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-excision repair	TAS Traceable Author Statement more info	PubMed
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomerase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomere capping	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomere maintenance via telomerase	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to radiation	NAS Non-traceable Author Statement more info	PubMed
involved_in response to radiation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	HDA more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement 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
is_active_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bifunctional polynucleotide phosphatase/kinase

Names: DNA 5'-kinase/3'-phosphatase; Homo sapiens polynucleotide kinase 3'-phosphatase (PNKP)

NP_009185.2

EC 2.7.1.78

EC 3.1.3.32

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_027717.1 RefSeqGene

Range

4990..11362

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_007254.4 → NP_009185.2 bifunctional polynucleotide phosphatase/kinase

See identical proteins and their annotated locations for NP_009185.2

Status: REVIEWED

Source sequence(s)

AC118341, BC033822, BU541073

Consensus CDS

CCDS12783.1

UniProtKB/Swiss-Prot

Q96T60, Q9BUL2, Q9P1V2, Q9UKU8, Q9UNF8, Q9UNI0

UniProtKB/TrEMBL

A0A1S5RA93

Related

ENSP00000323511.2, ENST00000322344.8

Conserved Domains (3) summary

cd01427
Location:170 → 289

HAD_like; Haloacid dehalogenase-like hydrolases. The haloacid dehalogenase-like (HAD) superfamily includes L-2-haloacid dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, and many others, ...

TIGR01663
Location:2 → 521

PNK-3'Pase; polynucleotide 5'-kinase 3'-phosphatase

cl17190
Location:367 → 465

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...