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Protein

Bifunctional polynucleotide phosphatase/kinase

Gene

PNKP

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

Functioni

Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone.1 Publication

Catalytic activityi

A 3'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.
ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi372 – 379ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Kinase, Multifunctional enzyme, Transferase
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.78 2681
3.1.3.32 2681
ReactomeiR-HSA-5649702 APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
SIGNORiQ96T60

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional polynucleotide phosphatase/kinase
Alternative name(s):
DNA 5'-kinase/3'-phosphatase
Polynucleotide kinase-3'-phosphatase
Including the following 2 domains:
Polynucleotide 3'-phosphatase (EC:3.1.3.32)
Alternative name(s):
2'(3')-polynucleotidase
Polynucleotide 5'-hydroxyl-kinase (EC:2.7.1.78)
Gene namesi
Name:PNKP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000039650.9
HGNCiHGNC:9154 PNKP
MIMi605610 gene
neXtProtiNX_Q96T60

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

Nucleus

Pathology & Biotechi

Involvement in diseasei

Microcephaly, seizures, and developmental delay (MCSZ)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by infantile-onset seizures, microcephaly, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly.
See also OMIM:613402
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063835176L → F in MCSZ. 1 PublicationCorresponds to variant dbSNP:rs267606957EnsemblClinVar.1
Natural variantiVAR_063836326E → K in MCSZ. 1 PublicationCorresponds to variant dbSNP:rs267606956EnsemblClinVar.1
Natural variantiVAR_076537462R → P in MCSZ; atypical phenotype. 1 PublicationCorresponds to variant dbSNP:rs376854895EnsemblClinVar.1
Ataxia-oculomotor apraxia 4 (AOA4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy.
See also OMIM:616267
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073369375G → W in AOA4. 1 PublicationCorresponds to variant dbSNP:rs786203983EnsemblClinVar.1
Natural variantiVAR_073370408Missing in AOA4. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation, Neurodegeneration, Primary microcephaly

Organism-specific databases

DisGeNETi11284
MalaCardsiPNKP
MIMi613402 phenotype
616267 phenotype
OpenTargetsiENSG00000039650
Orphaneti459033 Ataxia-oculomotor apraxia type 4
1934 Early infantile epileptic encephalopathy
PharmGKBiPA33477

Polymorphism and mutation databases

BioMutaiPNKP
DMDMi50401132

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000584781 – 521Bifunctional polynucleotide phosphatase/kinaseAdd BLAST521

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei114PhosphoserineCombined sources1
Modified residuei118PhosphothreonineCombined sources1
Modified residuei122PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96T60
MaxQBiQ96T60
PaxDbiQ96T60
PeptideAtlasiQ96T60
PRIDEiQ96T60
ProteomicsDBi78199

PTM databases

DEPODiQ96T60
iPTMnetiQ96T60
PhosphoSitePlusiQ96T60

Expressioni

Tissue specificityi

Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine (PubMed:10446192). Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver (PubMed:10446193).2 Publications

Gene expression databases

BgeeiENSG00000039650 Expressed in 204 organ(s), highest expression level in left adrenal gland
CleanExiHS_PNKP
ExpressionAtlasiQ96T60 baseline and differential
GenevisibleiQ96T60 HS

Organism-specific databases

HPAiHPA006782

Interactioni

Subunit structurei

Monomer.By similarity

Binary interactionsi

Protein-protein interaction databases

BioGridi116440, 67 interactors
CORUMiQ96T60
IntActiQ96T60, 47 interactors
MINTiQ96T60
STRINGi9606.ENSP00000323511

Structurei

Secondary structure

1521
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96T60
SMRiQ96T60
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96T60

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 110FHAAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni146 – 337PhosphataseBy similarityAdd BLAST192
Regioni341 – 516KinaseBy similarityAdd BLAST176

Domaini

The FHA domain binds threonine-phosphorylated peptides from XRCC1/4, and is responsible for the recruitment of PNKP to the sites of DNA repair. The affinity is ten times greater if peptides are also phosphorylated on the serine preceeding the phosphothreonine.1 Publication

Sequence similaritiesi

In the N-terminal section; belongs to the DNA 3' phosphatase family.Curated

Phylogenomic databases

eggNOGiKOG2134 Eukaryota
COG0241 LUCA
GeneTreeiENSGT00570000079163
HOGENOMiHOG000031466
HOVERGENiHBG053624
InParanoidiQ96T60
KOiK08073
OMAiSCSDRNF
OrthoDBiEOG091G0A9X
PhylomeDBiQ96T60
TreeFamiTF313738

Family and domain databases

Gene3Di3.40.50.1000, 1 hit
InterProiView protein in InterPro
IPR036412 HAD-like_sf
IPR006549 HAD-SF_hydro_IIIA
IPR023214 HAD_sf
IPR027417 P-loop_NTPase
IPR013954 PNK3P
IPR006550 PNK_3Pase_met
IPR006551 Polynucleotide_phosphatase
IPR008984 SMAD_FHA_dom_sf
PfamiView protein in Pfam
PF08645 PNK3P, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF52540 SSF52540, 1 hit
SSF56784 SSF56784, 1 hit
TIGRFAMsiTIGR01664 DNA-3'-Pase, 1 hit
TIGR01662 HAD-SF-IIIA, 1 hit
TIGR01663 PNK-3'Pase, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 15 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96T60-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGEVEAPGRL WLESPPGGAP PIFLPSDGQA LVLGRGPLTQ VTDRKCSRTQ
60 70 80 90 100
VELVADPETR TVAVKQLGVN PSTTGTQELK PGLEGSLGVG DTLYLVNGLH
110 120 130 140 150
PLTLRWEETR TPESQPDTPP GTPLVSQDEK RDAELPKKRM RKSNPGWENL
160 170 180 190 200
EKLLVFTAAG VKPQGKVAGF DLDGTLITTR SGKVFPTGPS DWRILYPEIP
210 220 230 240 250
RKLRELEAEG YKLVIFTNQM SIGRGKLPAE EFKAKVEAVV EKLGVPFQVL
260 270 280 290 300
VATHAGLYRK PVTGMWDHLQ EQANDGTPIS IGDSIFVGDA AGRPANWAPG
310 320 330 340 350
RKKKDFSCAD RLFALNLGLP FATPEEFFLK WPAAGFELPA FDPRTVSRSG
360 370 380 390 400
PLCLPESRAL LSASPEVVVA VGFPGAGKST FLKKHLVSAG YVHVNRDTLG
410 420 430 440 450
SWQRCVTTCE TALKQGKRVA IDNTNPDAAS RARYVQCARA AGVPCRCFLF
460 470 480 490 500
TATLEQARHN NRFREMTDSS HIPVSDMVMY GYRKQFEAPT LAEGFSAILE
510 520
IPFRLWVEPR LGRLYCQFSE G
Length:521
Mass (Da):57,076
Last modified:December 1, 2001 - v1
Checksum:i22B5C94D41E62516
GO
Isoform 2 (identifier: Q96T60-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: MGEVEAPGRLWLESPPGGAPPIFLPSDGQALVLGRGPLTQVTDRKCSRTQ → MQILTPPLQSS

Note: No experimental confirmation available.
Show »
Length:482
Mass (Da):53,004
Checksum:iD079EBCC7DAD8402
GO

Computationally mapped potential isoform sequencesi

There are 15 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R3C8M0R3C8_HUMAN
Bifunctional polynucleotide phospha...
PNKP
455Annotation score:
M0QYI1M0QYI1_HUMAN
Bifunctional polynucleotide phospha...
PNKP
247Annotation score:
M0QYH2M0QYH2_HUMAN
Bifunctional polynucleotide phospha...
PNKP
490Annotation score:
M0R000M0R000_HUMAN
Bifunctional polynucleotide phospha...
PNKP
176Annotation score:
A0A0D9SFL2A0A0D9SFL2_HUMAN
Bifunctional polynucleotide phospha...
PNKP
485Annotation score:
M0QX49M0QX49_HUMAN
Bifunctional polynucleotide phospha...
PNKP
51Annotation score:
A0A0D9SFD6A0A0D9SFD6_HUMAN
Bifunctional polynucleotide phospha...
PNKP
256Annotation score:
A0A0D9SFU1A0A0D9SFU1_HUMAN
Bifunctional polynucleotide phospha...
PNKP
87Annotation score:
M0R097M0R097_HUMAN
Bifunctional polynucleotide phospha...
PNKP
56Annotation score:
A0A0D9SEV0A0A0D9SEV0_HUMAN
Bifunctional polynucleotide phospha...
PNKP
174Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence AAD47379 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6A → P in AAD50639 (PubMed:10446193).Curated1
Sequence conflicti18G → E in AAD51135 (PubMed:10446192).Curated1
Sequence conflicti458R → C in AAD47379 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01926020P → S1 PublicationCorresponds to variant dbSNP:rs3739168EnsemblClinVar.1
Natural variantiVAR_01926163A → V1 PublicationCorresponds to variant dbSNP:rs3739173EnsemblClinVar.1
Natural variantiVAR_063835176L → F in MCSZ. 1 PublicationCorresponds to variant dbSNP:rs267606957EnsemblClinVar.1
Natural variantiVAR_019262180R → S1 PublicationCorresponds to variant dbSNP:rs3739185EnsemblClinVar.1
Natural variantiVAR_019263196Y → N1 PublicationCorresponds to variant dbSNP:rs3739186EnsemblClinVar.1
Natural variantiVAR_063836326E → K in MCSZ. 1 PublicationCorresponds to variant dbSNP:rs267606956EnsemblClinVar.1
Natural variantiVAR_073369375G → W in AOA4. 1 PublicationCorresponds to variant dbSNP:rs786203983EnsemblClinVar.1
Natural variantiVAR_073370408Missing in AOA4. 1 Publication1
Natural variantiVAR_076537462R → P in MCSZ; atypical phenotype. 1 PublicationCorresponds to variant dbSNP:rs376854895EnsemblClinVar.1
Natural variantiVAR_019264478V → G1 PublicationCorresponds to variant dbSNP:rs3739206EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555001 – 50MGEVE…CSRTQ → MQILTPPLQSS in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126486 mRNA Translation: AAD51135.1
AF125807 mRNA Translation: AAD50639.1
AF120499 mRNA Translation: AAD47379.1 Frameshift.
AF354258 Genomic DNA Translation: AAK57340.1
AY133033 Genomic DNA Translation: AAM82170.1
AC018766 Genomic DNA Translation: AAF44716.1
BC002519 mRNA Translation: AAH02519.2
BC033822 mRNA Translation: AAH33822.1
CCDSiCCDS12783.1 [Q96T60-1]
RefSeqiNP_009185.2, NM_007254.3 [Q96T60-1]
UniGeneiHs.78016

Genome annotation databases

EnsembliENST00000322344; ENSP00000323511; ENSG00000039650 [Q96T60-1]
ENST00000596014; ENSP00000472300; ENSG00000039650 [Q96T60-1]
GeneIDi11284
KEGGihsa:11284
UCSCiuc002pqj.4 human [Q96T60-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF126486 mRNA Translation: AAD51135.1
AF125807 mRNA Translation: AAD50639.1
AF120499 mRNA Translation: AAD47379.1 Frameshift.
AF354258 Genomic DNA Translation: AAK57340.1
AY133033 Genomic DNA Translation: AAM82170.1
AC018766 Genomic DNA Translation: AAF44716.1
BC002519 mRNA Translation: AAH02519.2
BC033822 mRNA Translation: AAH33822.1
CCDSiCCDS12783.1 [Q96T60-1]
RefSeqiNP_009185.2, NM_007254.3 [Q96T60-1]
UniGeneiHs.78016

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BRFX-ray1.40A1-110[»]
2W3OX-ray1.85A/B1-110[»]
ProteinModelPortaliQ96T60
SMRiQ96T60
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116440, 67 interactors
CORUMiQ96T60
IntActiQ96T60, 47 interactors
MINTiQ96T60
STRINGi9606.ENSP00000323511

PTM databases

DEPODiQ96T60
iPTMnetiQ96T60
PhosphoSitePlusiQ96T60

Polymorphism and mutation databases

BioMutaiPNKP
DMDMi50401132

Proteomic databases

EPDiQ96T60
MaxQBiQ96T60
PaxDbiQ96T60
PeptideAtlasiQ96T60
PRIDEiQ96T60
ProteomicsDBi78199

Protocols and materials databases

DNASUi11284
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322344; ENSP00000323511; ENSG00000039650 [Q96T60-1]
ENST00000596014; ENSP00000472300; ENSG00000039650 [Q96T60-1]
GeneIDi11284
KEGGihsa:11284
UCSCiuc002pqj.4 human [Q96T60-1]

Organism-specific databases

CTDi11284
DisGeNETi11284
EuPathDBiHostDB:ENSG00000039650.9
GeneCardsiPNKP
HGNCiHGNC:9154 PNKP
HPAiHPA006782
MalaCardsiPNKP
MIMi605610 gene
613402 phenotype
616267 phenotype
neXtProtiNX_Q96T60
OpenTargetsiENSG00000039650
Orphaneti459033 Ataxia-oculomotor apraxia type 4
1934 Early infantile epileptic encephalopathy
PharmGKBiPA33477
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2134 Eukaryota
COG0241 LUCA
GeneTreeiENSGT00570000079163
HOGENOMiHOG000031466
HOVERGENiHBG053624
InParanoidiQ96T60
KOiK08073
OMAiSCSDRNF
OrthoDBiEOG091G0A9X
PhylomeDBiQ96T60
TreeFamiTF313738

Enzyme and pathway databases

BRENDAi2.7.1.78 2681
3.1.3.32 2681
ReactomeiR-HSA-5649702 APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
SIGNORiQ96T60

Miscellaneous databases

EvolutionaryTraceiQ96T60
GeneWikiiPNKP
GenomeRNAii11284
PROiPR:Q96T60
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000039650 Expressed in 204 organ(s), highest expression level in left adrenal gland
CleanExiHS_PNKP
ExpressionAtlasiQ96T60 baseline and differential
GenevisibleiQ96T60 HS

Family and domain databases

Gene3Di3.40.50.1000, 1 hit
InterProiView protein in InterPro
IPR036412 HAD-like_sf
IPR006549 HAD-SF_hydro_IIIA
IPR023214 HAD_sf
IPR027417 P-loop_NTPase
IPR013954 PNK3P
IPR006550 PNK_3Pase_met
IPR006551 Polynucleotide_phosphatase
IPR008984 SMAD_FHA_dom_sf
PfamiView protein in Pfam
PF08645 PNK3P, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF52540 SSF52540, 1 hit
SSF56784 SSF56784, 1 hit
TIGRFAMsiTIGR01664 DNA-3'-Pase, 1 hit
TIGR01662 HAD-SF-IIIA, 1 hit
TIGR01663 PNK-3'Pase, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPNKP_HUMAN
AccessioniPrimary (citable) accession number: Q96T60
Secondary accession number(s): Q9BUL2
, Q9P1V2, Q9UKU8, Q9UNF8, Q9UNI0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: November 7, 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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