Reviewed, UniProtKB/Swiss-Prot Q96T60 (PNKP_HUMAN)

Names and origin

Protein names

Recommended name:
    Bifunctional polynucleotide phosphatase/kinase
Alternative name(s):
    Polynucleotide kinase-3'-phosphatase
    DNA 5'-kinase/3'-phosphatase
Including the following 2 domains:
    1- Recommended name:
            Polynucleotide 3'-phosphatase
              EC=3.1.3.32
        Alternative name(s):
            2'(3')-polynucleotidase
    2- Recommended name:
            Polynucleotide 5'-hydroxyl-kinase
              EC=2.7.1.78

Gene names

Name:

PNKP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the phosphorylation of DNA at 5'-hydroxyl termini and can dephosphorylate its 3'-phosphate termini. Plays an important function in DNA repair following ionizing radiation or oxidative damage. Ref.1
Catalytic activity	A 3'-phosphopolynucleotide + H2O = a polynucleotide + phosphate. ATP + 5'-dephospho-DNA = ADP + 5'-phospho-DNA.
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
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8 Ref.9 Ref.10
Sequence similarities	In the N-terminal section; belongs to the DNA 3' phosphatase family.
Sequence caution	The sequence AAD47379.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	DNA damage response, detection of DNA damage Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB DNA-dependent DNA replication Ref.1 Non-traceable author statement. Source: UniProtKB dephosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB nucleotide phosphorylation Ref.2 Inferred from direct assay. Source: UniProtKB nucleotide-excision repair, DNA damage removal Ref.2 Non-traceable author statement. Source: UniProtKB response to oxidative stress Ref.1 Inferred from direct assay. Source: UniProtKB response to radiation Ref.1 Ref.2 Traceable author statement. Source: UniProtKB
Cellular component	nucleolus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Ref.1 Non-traceable author statement. Source: UniProtKB ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity Ref.2 Inferred from direct assay. Source: UniProtKB damaged DNA binding Ref.2 Non-traceable author statement. Source: UniProtKB double-stranded DNA binding Ref.2 Traceable author statement. Source: UniProtKB endonuclease activity Ref.1 Non-traceable author statement. Source: UniProtKB nucleotide kinase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB polynucleotide 3'-phosphatase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DDX20	Q9UHI6	1	EBI-1045072,EBI-347658
HEATR2	Q86Y56	1	EBI-1045072,EBI-719966
LAS1L	Q9Y4W2	1	EBI-1045072,EBI-1051591
LIG3	P49916	1	EBI-1045072,EBI-1753381
LIG4	P49917	1	EBI-1045072,EBI-847896
MCM3	P25205	1	EBI-1045072,EBI-355153
NOL3	O60936	1	EBI-1045072,EBI-740992
NUP93	Q8N1F7	1	EBI-1045072,EBI-1042703
SLC25A12	O75746	1	EBI-1045072,EBI-1047585
XRCC1	P18887	1	EBI-1045072,EBI-947466
XRCC4	Q13426	1	EBI-1045072,EBI-717592
YWHAQ	P27348	1	EBI-1045072,EBI-359854

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 521

521

Bifunctional polynucleotide phosphatase/kinase

PRO_0000058478

Regions

Nucleotide binding

372 – 379

8

ATP Potential

Amino acid modifications

Modified residue

114

1

Phosphoserine Ref.9

Modified residue

118

1

Phosphothreonine Ref.8 Ref.9 Ref.10

Modified residue

122

1

Phosphothreonine Ref.8 Ref.10

Modified residue

126

1

Phosphoserine Ref.9

Natural variations

Natural variant

20

1

P → S: dbSNP rs3739168. Ref.5

VAR_019260

Natural variant

63

1

A → V: dbSNP rs3739173. Ref.5

VAR_019261

Natural variant

180

1

R → S: dbSNP rs3739185. Ref.5

VAR_019262

Natural variant

196

1

Y → N: dbSNP rs3739186. Ref.5

VAR_019263

Natural variant

478

1

V → G: dbSNP rs3739206. Ref.5

VAR_019264

Experimental info

Sequence conflict

6

1

A → P in AAD50639. Ref.2

Sequence conflict

18

1

G → E in AAD51135. Ref.1

Sequence conflict

458

1

R → C in AAD47379. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

521

Helix Strand Turn

Details...

Beta strand

9 – 13

5

Beta strand

31 – 33

3

Turn

37 – 40

4

Beta strand

51 – 56

6

Turn

57 – 60

4

Beta strand

61 – 66

6

Beta strand

68 – 70

3

Beta strand

84 – 88

5

Beta strand

92 – 96

5

Beta strand

99 – 107

9

Sequences

	Sequence		Length	Mass (Da)
	Q96T60-1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 22B5C94D41E62516	FASTA	521	57,076
	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

References

	« Hide 'large scale' referencesShow '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: 10446192] [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: 10446193] [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. , 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: 15057824] [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: 15489334] [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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118 AND THR-122, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; THR-118 AND SER-126, MASS SPECTROMETRY.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118 AND THR-122, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00290684.

RefSeq

NP_009185.2.

UniGene

Hs.78016

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BRF	X-ray	1.40	A	1-110	[»]
2W3O	X-ray	1.85	A/B	1-110	[»]

SMR

Q96T60. Positions 141-521.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96T60. 19 interactions.

STRING

Q96T60.

Proteomic databases

PRIDE

Q96T60.

Genome annotation databases

Ensembl

ENST00000322344; ENSP00000323511; ENSG00000039650; Homo sapiens. [Genome view]

GeneID

11284.

KEGG

hsa:11284.

UCSC

uc002pqh.1. human.

Organism-specific databases

CTD

11284.

GeneCards

GC19M055056.

H-InvDB

HIX0015348.

HGNC

HGNC:9154. PNKP.

HPA

HPA006782.

MIM

605610. gene.

PharmGKB

PA33477.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96T60.

HOVERGEN

Q96T60.

OMA

SWQRCVT.

Enzyme and pathway databases

BRENDA

2.7.1.78. 247.
3.1.3.32. 247.

Gene expression databases

ArrayExpress

Q96T60.

Bgee

Q96T60.

CleanEx

HS_PNKP.

Genevestigator

Q96T60.

GermOnline

ENSG00000039650. Homo sapiens.

Family and domain databases

InterPro

IPR006551. DNA-3-Pase.
IPR006549. HAD-SF_hydro_IIIA.
IPR006550. PNK-3Pase.
IPR013954. PNK3P_central-region.
IPR015636. PNK_3Pase.
[Graphical view]

PANTHER

PTHR12083. PNK_3Pase. 1 hit.

Pfam

PF08645. PNK3P. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01664. DNA-3_-Pase. 1 hit.
TIGR01662. HAD-SF-IIIA. 1 hit.
TIGR01663. PNK-3_Pase. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

42959.

SOURCE

Search...

Entry information

Entry name

PNKP_HUMAN

Accession

Primary (citable) accession number: Q96T60
Secondary accession number(s): Q9P1V2 , Q9UKU8, Q9UNF8, Q9UNI0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	December 1, 2001
Last modified:	November 3, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.