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Q96T60 (PNKP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional polynucleotide phosphatase/kinase
Alternative name(s):
DNA 5'-kinase/3'-phosphatase
Polynucleotide kinase-3'-phosphatase

Including the following 2 domains:

  1. Polynucleotide 3'-phosphatase
    EC=3.1.3.32
    Alternative name(s):
    2'(3')-polynucleotidase
  2. Polynucleotide 5'-hydroxyl-kinase
    EC=2.7.1.78
Gene names
Name:PNKP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length521 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

A 3'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.

ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.

Subunit structure

Monomer By similarity.

Subcellular location

Nucleus Ref.2.

Tissue specificity

Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine (Ref.1). Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver (Ref.2). Ref.1 Ref.2

Domain

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. Ref.16

Involvement in disease

Epileptic encephalopathy, early infantile, 10 (EIEE10) [MIM:613402]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Sequence similarities

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

Contains 1 FHA domain.

Sequence caution

The sequence AAD47379.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Primary microcephaly
   LigandATP-binding
Nucleotide-binding
   Molecular functionHydrolase
Kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, detection of DNA damage

Inferred from direct assay Ref.1. Source: UniProtKB

DNA-dependent DNA replication

Non-traceable author statement Ref.1. Source: UniProtKB

nucleotide-excision repair, DNA damage removal

Non-traceable author statement Ref.2. Source: UniProtKB

response to oxidative stress

Inferred from direct assay Ref.1. Source: UniProtKB

response to radiation

Non-traceable author statement Ref.2. Source: UniProtKB

   Cellular_componentnucleolus

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Non-traceable author statement Ref.1. Source: UniProtKB

ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

damaged DNA binding

Non-traceable author statement Ref.2. Source: UniProtKB

double-stranded DNA binding

Traceable author statement Ref.2. Source: UniProtKB

endonuclease activity

Non-traceable author statement Ref.1. Source: UniProtKB

nucleotide kinase activity

Inferred from direct assay Ref.1Ref.2. Source: UniProtKB

polynucleotide 3'-phosphatase activity

Inferred from direct assay Ref.1Ref.2. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 521521Bifunctional polynucleotide phosphatase/kinase
PRO_0000058478

Regions

Domain6 – 110105FHA
Nucleotide binding372 – 3798ATP Potential
Region146 – 337192Phosphatase By similarity
Region341 – 516176Kinase By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.15
Modified residue1141Phosphoserine Ref.14
Modified residue1181Phosphothreonine Ref.9 Ref.11 Ref.12 Ref.14
Modified residue1221Phosphothreonine Ref.8 Ref.9 Ref.11

Natural variations

Natural variant201P → S. Ref.5
Corresponds to variant rs3739168 [ dbSNP | Ensembl ].
VAR_019260
Natural variant631A → V. Ref.5
Corresponds to variant rs3739173 [ dbSNP | Ensembl ].
VAR_019261
Natural variant1761L → F in EIEE10. Ref.17
VAR_063835
Natural variant1801R → S. Ref.5
Corresponds to variant rs3739185 [ dbSNP | Ensembl ].
VAR_019262
Natural variant1961Y → N. Ref.5
Corresponds to variant rs3739186 [ dbSNP | Ensembl ].
VAR_019263
Natural variant3261E → K in EIEE10. Ref.17
VAR_063836
Natural variant4781V → G. Ref.5
Corresponds to variant rs3739206 [ dbSNP | Ensembl ].
VAR_019264

Experimental info

Sequence conflict61A → P in AAD50639. Ref.2
Sequence conflict181G → E in AAD51135. Ref.1
Sequence conflict4581R → C in AAD47379. Ref.3

Secondary structure

................... 521
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96T60 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 22B5C94D41E62516

FASTA52157,076
        10         20         30         40         50         60 
MGEVEAPGRL WLESPPGGAP PIFLPSDGQA LVLGRGPLTQ VTDRKCSRTQ VELVADPETR 

        70         80         90        100        110        120 
TVAVKQLGVN PSTTGTQELK PGLEGSLGVG DTLYLVNGLH PLTLRWEETR TPESQPDTPP 

       130        140        150        160        170        180 
GTPLVSQDEK RDAELPKKRM RKSNPGWENL EKLLVFTAAG VKPQGKVAGF DLDGTLITTR 

       190        200        210        220        230        240 
SGKVFPTGPS DWRILYPEIP RKLRELEAEG YKLVIFTNQM SIGRGKLPAE EFKAKVEAVV 

       250        260        270        280        290        300 
EKLGVPFQVL VATHAGLYRK PVTGMWDHLQ EQANDGTPIS IGDSIFVGDA AGRPANWAPG 

       310        320        330        340        350        360 
RKKKDFSCAD RLFALNLGLP FATPEEFFLK WPAAGFELPA FDPRTVSRSG PLCLPESRAL 

       370        380        390        400        410        420 
LSASPEVVVA VGFPGAGKST FLKKHLVSAG YVHVNRDTLG SWQRCVTTCE TALKQGKRVA 

       430        440        450        460        470        480 
IDNTNPDAAS RARYVQCARA AGVPCRCFLF TATLEQARHN NRFREMTDSS HIPVSDMVMY 

       490        500        510        520 
GYRKQFEAPT LAEGFSAILE IPFRLWVEPR LGRLYCQFSE G 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage."
Jilani A., Ramotar D., Slack C., Ong C., Yang X.M., Scherer S.W., Lasko D.D.
J. Biol. Chem. 274:24176-24186(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]"Molecular characterization of a human DNA kinase."
Karimi-Busheri F., Daly G., Robins P., Canas B., Pappin D.J.C., Sgouros J., Miller G.G., Fakhrai H., Davis E.M., Le Beau M.M., Weinfeld M.
J. Biol. Chem. 274:24187-24194(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, CHARACTERIZATION.
[3]"Cloning a cDNA which is differently expressed in malignancies."
Yang H.W., Piao H.Y., Chen Y.Z., Hayashi Y.
Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Genomic organization, physical mapping and expression analysis of the human polynucleotide kinase-3'-phosphatase (PNKP) gene."
Scorilas A., Katsaros N.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-20; VAL-63; SER-180; ASN-196 AND GLY-478.
[6]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Blood.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-122, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118 AND THR-122, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118 AND THR-122, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114 AND THR-118, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK."
Ali A.A., Jukes R.M., Pearl L.H., Oliver A.W.
Nucleic Acids Res. 37:1701-1712(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-110 ALONE AND IN COMPLEX WITH XRCC1 PHOSPHOPEPTIDE, DOMAIN FHA.
[17]"Mutations in PNKP cause microcephaly, seizures and defects in DNA repair."
Shen J., Gilmore E.C., Marshall C.A., Haddadin M., Reynolds J.J., Eyaid W., Bodell A., Barry B., Gleason D., Allen K., Ganesh V.S., Chang B.S., Grix A., Hill R.S., Topcu M., Caldecott K.W., Barkovich A.J., Walsh C.A.
Nat. Genet. 42:245-249(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE10 PHE-176 AND LYS-326.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
BC033822 mRNA. Translation: AAH33822.1.
RefSeqNP_009185.2. NM_007254.3.
UniGeneHs.78016.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BRFX-ray1.40A1-110[»]
2W3OX-ray1.85A/B1-110[»]
ProteinModelPortalQ96T60.
SMRQ96T60. Positions 8-108, 146-521.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116440. 48 interactions.
IntActQ96T60. 12 interactions.
MINTMINT-1199136.
STRING9606.ENSP00000323511.

PTM databases

PhosphoSiteQ96T60.

Polymorphism databases

DMDM50401132.

Proteomic databases

PaxDbQ96T60.
PRIDEQ96T60.

Protocols and materials databases

DNASU11284.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322344; ENSP00000323511; ENSG00000039650.
ENST00000596014; ENSP00000472300; ENSG00000039650.
GeneID11284.
KEGGhsa:11284.
UCSCuc002pqg.3. human.

Organism-specific databases

CTD11284.
GeneCardsGC19M050364.
HGNCHGNC:9154. PNKP.
HPAHPA006782.
MIM605610. gene.
613402. phenotype.
neXtProtNX_Q96T60.
Orphanet228418. Microcephaly - seizures - developmental delay.
PharmGKBPA33477.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0241.
HOGENOMHOG000031466.
HOVERGENHBG053624.
InParanoidQ96T60.
KOK08073.
OMADIYRKPR.
OrthoDBEOG7HQN87.
PhylomeDBQ96T60.
TreeFamTF313738.

Gene expression databases

ArrayExpressQ96T60.
BgeeQ96T60.
CleanExHS_PNKP.
GenevestigatorQ96T60.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
3.40.50.1000. 1 hit.
InterProIPR000253. FHA_dom.
IPR023214. HAD-like_dom.
IPR006549. HAD-SF_hydro_IIIA.
IPR027417. P-loop_NTPase.
IPR013954. PNK3P.
IPR006550. PNK_3Pase_met.
IPR006551. Polynucleotide_phosphatase.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamPF08645. PNK3P. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF56784. SSF56784. 1 hit.
TIGRFAMsTIGR01664. DNA-3'-Pase. 1 hit.
TIGR01662. HAD-SF-IIIA. 1 hit.
TIGR01663. PNK-3'Pase. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ96T60.
GeneWikiPNKP.
GenomeRNAi11284.
NextBio42959.
PROQ96T60.
SOURCESearch...

Entry information

Entry namePNKP_HUMAN
AccessionPrimary (citable) accession number: Q96T60
Secondary accession number(s): Q9P1V2 expand/collapse secondary AC list , Q9UKU8, Q9UNF8, Q9UNI0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: March 19, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM