Q9Y6F1 (PARP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Poly [ADP-ribose] polymerase 3
Short name=PARP-3
Short name=hPARP-3
EC=2.4.2.30

Alternative name(s):
ADP-ribosyltransferase diphtheria toxin-like 3
Short name=ARTD3
IRT1
NAD(+) ADP-ribosyltransferase 3
Short name=ADPRT-3
Poly[ADP-ribose] synthase 3
Short name=pADPRT-3

Gene names

Name:	PARP3
Synonyms:	ADPRT3, ADPRTL3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing. Ref.7
Catalytic activity	NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor.
Subunit structure	Interacts with PRKDC and PARP1. Interacts with XRCC5; the interaction is dependent on nucleic acids. Interacts with XRCC6; the interaction is dependent on nucleic acids. Interacts with EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3 and LIG4. Ref.7
Subcellular location	Nucleus. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › centrosome › centriole. Note: Core component of the centrosome. Preferentially localized to the daughter centriole throughout the cell cycle. According to Ref.7, it is almost exclusively localized in the nucleus and appears in numerous small foci and a small number of larger foci whereas a centrosomal location has not been detected. Ref.3 Ref.7
Tissue specificity	Widely expressed; the highest levels are in the kidney, skeletal muscle, liver, heart and spleen; also detected in pancreas, lung, placenta, brain, leukocytes, colon, small intestine, ovary, testis, prostate and thymus.
Domain	According to Ref.2, the N-terminal domain (54 amino acids) of isoform 2 is responsible for its centrosomal localization. The C-terminal region contains the catalytic domain.
Post-translational modification	Auto-poly(ADP)-ribosylation.
Sequence similarities	Contains 1 PARP alpha-helical domain. Contains 1 PARP catalytic domain.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NAD
Molecular function	Glycosyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement PubMed 7260241. Source: ProtInc protein ADP-ribosylation Traceable author statement PubMed 10338144. Source: ProtInc
Cellular_component	centriole Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	NAD+ ADP-ribosyltransferase activity Inferred from electronic annotation. Source: EC catalytic activity Traceable author statement PubMed 10338144. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6F1-1)

Also known as: Short;

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.

Note: More abundant according to PubMed:16924674.

Isoform 2 (identifier: Q9Y6F1-2)

Also known as: Long;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSLLFLAM

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 533

533

Poly [ADP-ribose] polymerase 3

PRO_0000211329

Regions

Domain

182 – 300

119

PARP alpha-helical

Domain

313 – 533

221

PARP catalytic

Motif

14 – 20

7

Nuclear localization signal Potential

Natural variations

Alternative sequence

1

1

M → MSLLFLAM in isoform 2.

VSP_007863

Natural variant

91

1

S → N.
Corresponds to variant rs34224216 [ dbSNP | Ensembl ].

VAR_056643

Natural variant

100

1

H → R. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6
Corresponds to variant rs28547534 [ dbSNP | Ensembl ].

VAR_054622

Natural variant

269

1

Q → R.
Corresponds to variant rs323870 [ dbSNP | Ensembl ].

VAR_056644

Experimental info

Sequence conflict

80

1

N → K in AAD29855. Ref.2

Sequence conflict

171

1

G → A in AAD29855. Ref.2

Sequence conflict

411

1

K → E in CAB43246. Ref.6

Secondary structure

1

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533

Helix Strand Turn

Details...

Beta strand

50 – 53

4

Turn

54 – 56

3

Beta strand

61 – 74

14

Turn

75 – 78

4

Beta strand

79 – 89

11

Beta strand

95 – 100

6

Beta strand

111 – 117

7

Helix

118 – 133

16

Helix

140 – 142

3

Beta strand

147 – 149

3

Beta strand

151 – 153

3

Helix

187 – 196

10

Helix

199 – 208

10

Turn

213 – 215

3

Turn

218 – 220

3

Helix

223 – 240

18

Beta strand

246 – 248

3

Helix

250 – 260

11

Beta strand

265 – 268

4

Helix

276 – 299

24

Helix

303 – 307

5

Beta strand

309 – 311

3

Helix

314 – 322

9

Beta strand

325 – 328

4

Helix

336 – 346

11

Beta strand

349 – 351

3

Beta strand

354 – 362

9

Turn

364 – 366

3

Helix

367 – 371

5

Turn

372 – 375

4

Beta strand

379 – 386

8

Helix

388 – 390

3

Helix

391 – 397

7

Beta strand

411 – 418

8

Helix

419 – 423

5

Beta strand

429 – 431

3

Beta strand

434 – 445

12

Beta strand

448 – 454

7

Beta strand

467 – 471

5

Beta strand

474 – 477

4

Helix

479 – 481

3

Beta strand

483 – 487

5

Beta strand

490 – 494

5

Beta strand

499 – 501

3

Helix

503 – 505

3

Beta strand

514 – 519

6

Helix

520 – 522

3

Beta strand

523 – 532

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Short) [UniParc]. Last modified March 3, 2009. Version 3. Checksum: BF728C3D88722029	FASTA	533	60,070
	10 20 30 40 50 60 MAPKPKPWVQ TEGPEKKKGR QAGREEDPFR STAEALKAIP AEKRIIRVDP TCPLSSNPGT 70 80 90 100 110 120 QVYEDYNCTL NQTNIENNNN KFYIIQLLQD SNRFFTCWNH WGRVGEVGQS KINHFTRLED 130 140 150 160 170 180 AKKDFEKKFR EKTKNNWAER DHFVSHPGKY TLIEVQAEDE AQEAVVKVDR GPVRTVTKRV 190 200 210 220 230 240 QPCSLDPATQ KLITNIFSKE MFKNTMALMD LDVKKMPLGK LSKQQIARGF EALEALEEAL 250 260 270 280 290 300 KGPTDGGQSL EELSSHFYTV IPHNFGHSQP PPINSPELLQ AKKDMLLVLA DIELAQALQA 310 320 330 340 350 360 VSEQEKTVEE VPHPLDRDYQ LLKCQLQLLD SGAPEYKVIQ TYLEQTGSNH RCPTLQHIWK 370 380 390 400 410 420 VNQEGEEDRF QAHSKLGNRK LLWHGTNMAV VAAILTSGLR IMPHSGGRVG KGIYFASENS 430 440 450 460 470 480 KSAGYVIGMK CGAHHVGYMF LGEVALGREH HINTDNPSLK SPPPGFDSVI ARGHTEPDPT 490 500 510 520 530 QDTELELDGQ QVVVPQGQPV PCPEFSSSTF SQSEYLIYQE SQCRLRYLLE VHL
	Isoform 2 (Long) [UniParc]. Checksum: AF68D80A50A78BC8	FASTA	540	60,846
	10 20 30 40 50 60 MSLLFLAMAP KPKPWVQTEG PEKKKGRQAG REEDPFRSTA EALKAIPAEK RIIRVDPTCP 70 80 90 100 110 120 LSSNPGTQVY EDYNCTLNQT NIENNNNKFY IIQLLQDSNR FFTCWNHWGR VGEVGQSKIN 130 140 150 160 170 180 HFTRLEDAKK DFEKKFREKT KNNWAERDHF VSHPGKYTLI EVQAEDEAQE AVVKVDRGPV 190 200 210 220 230 240 RTVTKRVQPC SLDPATQKLI TNIFSKEMFK NTMALMDLDV KKMPLGKLSK QQIARGFEAL 250 260 270 280 290 300 EALEEALKGP TDGGQSLEEL SSHFYTVIPH NFGHSQPPPI NSPELLQAKK DMLLVLADIE 310 320 330 340 350 360 LAQALQAVSE QEKTVEEVPH PLDRDYQLLK CQLQLLDSGA PEYKVIQTYL EQTGSNHRCP 370 380 390 400 410 420 TLQHIWKVNQ EGEEDRFQAH SKLGNRKLLW HGTNMAVVAA ILTSGLRIMP HSGGRVGKGI 430 440 450 460 470 480 YFASENSKSA GYVIGMKCGA HHVGYMFLGE VALGREHHIN TDNPSLKSPP PGFDSVIARG 490 500 510 520 530 540 HTEPDPTQDT ELELDGQQVV VPQGQPVPCP EFSSSTFSQS EYLIYQESQC RLRYLLEVHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Koch-Nolte F. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-100.
[2]	"A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues." Johansson M. Genomics 57:442-445(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-100. Tissue: Fetal brain.
[3]	"PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression." Augustin A., Spenlehauer C., Dumond H., Menissier-de Murcia J., Piel M., Schmit A.-C., Apiou F., Vonesch J.-L., Kock M., Bornens M., de Murcia G.M. J. Cell Sci. 116:1551-1562(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-100, SUBCELLULAR LOCATION. Tissue: Frontal cortex.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1), VARIANT ARG-100. Tissue: B-cell.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 75-533 (ISOFORM 1), VARIANT ARG-100. Tissue: Kidney.
[7]	"PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery." Rouleau M., McDonald D., Gagne P., Ouellet M.E., Droit A., Hunter J.M., Dutertre S., Prigent C., Hendzel M.J., Poirier G.G. J. Cell. Biochem. 100:385-401(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRKDC; PARP1; EZH2; HDAC1; HDAC2; SUZ12; YY1; LRIG3 AND LIG4.
[8]	"Toward a unified nomenclature for mammalian ADP-ribosyltransferases." Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F. Trends Biochem. Sci. 35:208-219(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NOMENCLATURE.
[9]	"Human poly(ADP-ribose) polymerase 3, catalytic fragment in complex with an inhibitor 3-aminobenzoic acid." Structural genomics consortium (SGC) Submitted (APR-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 178-532 IN COMPLEX WITH THE INHIBITOR 3-AMINOBENZOIC ACID.
[10]	"Solution structure of the WGR domain from human poly [ADP-ribose] polymerase-3." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 41-157.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y16836 mRNA. Translation: CAC79988.1.
AF083068 mRNA. Translation: AAD29855.1.
AY126341 mRNA. Translation: AAM95460.1.
AC115284 Genomic DNA. No translation available.
BC014260 mRNA. Translation: AAH14260.1.
AL050034 mRNA. Translation: CAB43246.1.

IPI

IPI00023184.
IPI00333507.

PIR

T08713.

RefSeq

NP_001003931.2. NM_001003931.2.
NP_005476.3. NM_005485.4.

UniGene

Hs.271742.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EOC	NMR	-	A	41-157	[»]
3C49	X-ray	2.80	A	178-532	[»]
3C4H	X-ray	2.10	A	178-532	[»]
3CE0	X-ray	2.80	A	178-532	[»]
3FHB	X-ray	2.30	A	178-532	[»]

ProteinModelPortal

Q9Y6F1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000381740.

PTM databases

PhosphoSite

Q9Y6F1.

Polymorphism databases

DMDM

224471880.

Proteomic databases

PaxDb

Q9Y6F1.

PRIDE

Q9Y6F1.

Protocols and materials databases

DNASU

10039.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000398755; ENSP00000381740; ENSG00000041880.
ENST00000417220; ENSP00000395951; ENSG00000041880.
ENST00000431474; ENSP00000401511; ENSG00000041880.

GeneID

10039.

KEGG

hsa:10039.

UCSC

uc003dby.3. human.
uc003dbz.3. human.

Organism-specific databases

CTD

10039.

GeneCards

GC03P051951.

HGNC

HGNC:273. PARP3.

MIM

607726. gene.

neXtProt

NX_Q9Y6F1.

PharmGKB

PA24593.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG243963.

HOGENOM

HOG000173055.

HOVERGEN

HBG053514.

InParanoid

Q9Y6F1.

KO

K10798.

OMA

SEYLIYQ.

PhylomeDB

Q9Y6F1.

Enzyme and pathway databases

BRENDA

2.4.2.30. 2681.

Gene expression databases

ArrayExpress

Q9Y6F1.

Bgee

Q9Y6F1.

CleanEx

HS_PARP3.

Genevestigator

Q9Y6F1.

GermOnline

ENSG00000041880. Homo sapiens.

Family and domain databases

Gene3D

1.20.142.10. 1 hit.
2.20.140.10. 1 hit.

InterPro

IPR012317. Poly(ADP-ribose)pol_cat_dom.
IPR004102. Poly(ADP-ribose)pol_reg_dom.
IPR008893. WGR_domain.
[Graphical view]

Pfam

PF00644. PARP. 1 hit.
PF02877. PARP_reg. 1 hit.
PF05406. WGR. 1 hit.
[Graphical view]

SMART

SM00773. WGR. 1 hit.
[Graphical view]

SUPFAM

SSF47587. PARP_reg. 1 hit.
SSF142921. SSF142921. 1 hit.

PROSITE

PS51060. PARP_ALPHA_HD. 1 hit.
PS51059. PARP_CATALYTIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9Y6F1.

ChEMBL

CHEMBL5083.

EvolutionaryTrace

Q9Y6F1.

GenomeRNAi

10039.

NextBio

37913.

SOURCE

Search...

Entry information

Entry name

PARP3_HUMAN

Accession

Primary (citable) accession number: Q9Y6F1
Secondary accession number(s): Q8NER9, Q96CG2, Q9UG81

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	March 3, 2009
Last modified:	May 1, 2013
This is version 128 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.