P11103 (PARP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Poly [ADP-ribose] polymerase 1
Short name=PARP-1
EC=2.4.2.30

Alternative name(s):
ADP-ribosyltransferase diphtheria toxin-like 1
Short name=ARTD1
NAD(+) ADP-ribosyltransferase 1
Short name=ADPRT 1
Poly[ADP-ribose] synthase 1
Short name=msPARP

Gene names

Name:	Parp1
Synonyms:	Adprp, Adprt, Adprt1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1013 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production By similarity. 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. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR.
Catalytic activity	NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor.
Subunit structure	Component of a base excision repair (BER) complex, containing at least XRCC1, PARP2, POLB and LRIG3. Homo- and heterodimer with PARP2. Interacts with PARP3, APTX and SRY Interacts (when poly-ADP-ribosylated) with CHD1L. Interacts with the DNA polymerase alpha catalytic subunit POLA1; this interaction functions as part of the control of replication fork progression By similarity. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with TIAM2 and ZNF423. Interacts with RNF4. Interacts with EEF1A1 and TXK By similarity. Interacts with RNF146 By similarity. Interacts with SNAI1 (via zinc fingers); the interaction requires SNAI1 to be poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B. Ref.3 Ref.6 Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus. Nucleus › nucleolus By similarity.
Tissue specificity	Widely expressed. Expression is correlated with proliferation, with higher levels occurring during early fetal development and organogenesis and in the highly proliferative cell compartments of adult. Expressed in B-cells that have been induced to switch to various Ig isotypes. Ref.3
Developmental stage	At stage E12.5, expressed at high level in the developing liver and kidneys. Expressed at higher level in the genital ridge and the spinal ganglia. At E18.5, preferentially expressed in the thymus and in regions of the nervous system. Within the developing trunk, preferential expression persisted in the liver and became restricted to the cortical region of the kidney, spleen, adrenal gland, and to stomach and intestinal epithelia. From E14.5 to E18.5, as well as in the adult, expressed at the highest level in thymus. Expression is particularly high in the subcapsular zone of the thymus where immature lymphocytes proliferate. Expressed at high level in the seminiferous tubules of the developing testis. Ref.5
Post-translational modification	Phosphorylated by PRKDC and TXK. Poly-ADP-ribosylated by PARP2. Poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites By similarity. S-nitrosylated, leading to inhibit transcription regulation activity.
Disruption phenotype	Mice show a complete lack of nuclear poly(ADP-ribosyl)ation. Mice are however viable and fertile. Moreover, repair of UV and MNNG induced DNA damage are not affected. However, about 30% of the mutant mice developed pathological skin aberrations on a mixed 129/Sv x C57B1/6 genetic background. Ref.4
Miscellaneous	The ADP-D-ribosyl group of NAD+ is transferred to an acceptor carboxyl group on a histone or the enzyme itself, and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units.
Sequence similarities	Contains 1 BRCT domain. Contains 1 PARP alpha-helical domain. Contains 1 PARP catalytic domain. Contains 2 PARP-type zinc fingers.
Sequence caution	The sequence AAF61293.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative initiation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding NAD Zinc
Molecular function	Glycosyltransferase Transferase
PTM	ADP-ribosylation Acetylation Phosphoprotein S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	base-excision repair Inferred from mutant phenotype Ref.5. Source: MGI protein ADP-ribosylation Inferred from electronic annotation. Source: InterPro regulation of growth rate Inferred from mutant phenotype PubMed 12707040. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW telomere maintenance Inferred from mutant phenotype PubMed 12707040. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 19470756. Source: BHF-UCL nucleolus Inferred from direct assay PubMed 15615785. Source: MGI nucleoplasm Inferred from direct assay PubMed 15615785. Source: MGI protein complex Inferred from direct assay PubMed 19796622. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW NAD binding Inferred from electronic annotation. Source: InterPro NAD+ ADP-ribosyltransferase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arntl	Q9WTL8	7	EBI-642213,EBI-644534
Casp3	P70677	3	EBI-642213,EBI-1790419
Casp7	P97864	3	EBI-642213,EBI-5307197
Pou5f1	P20263	2	EBI-642213,EBI-1606219

Alternative products

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

Isoform 1 (identifier: P11103-1)

Also known as: Long;

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.

Isoform 2 (identifier: P11103-2)

Also known as: Short; sPARP-1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-521: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1013	1012	Poly [ADP-ribose] polymerase 1		PRO_0000023259
Regions
	Domain	385 – 476	92	BRCT
	Domain	661 – 778	118	PARP alpha-helical
	Domain	787 – 1013	227	PARP catalytic
	DNA binding	2 – 372	371
	Zinc finger	9 – 93	85	PARP-type 1
	Zinc finger	113 – 203	91	PARP-type 2
	Region	373 – 523	151	Automodification domain
	Motif	207 – 209	3	Nuclear localization signal
	Motif	221 – 226	6	Nuclear localization signal
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	41	1	Phosphoserine By similarity
	Modified residue	97	1	N6-acetyllysine By similarity
	Modified residue	105	1	N6-acetyllysine By similarity
	Modified residue	131	1	N6-acetyllysine By similarity
	Modified residue	179	1	Phosphoserine By similarity
	Modified residue	407	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	413	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	435	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	437	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	444	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	445	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	448	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	456	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	484	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	488	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	491	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	512	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	513	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	519	1	PolyADP-ribosyl glutamic acid Potential
	Modified residue	599	1	N6-acetyllysine By similarity
	Modified residue	620	1	N6-acetyllysine By similarity
	Modified residue	781	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 521	521	Missing in isoform 2.		VSP_018970
Experimental info
	Sequence conflict	114	1	A → L AA sequence Ref.3
	Sequence conflict	591	1	L → V in AAF61293. Ref.2
	Sequence conflict	608	1	E → D in AAF61293. Ref.2
	Sequence conflict	612	1	Q → H in AAF61293. Ref.2
	Sequence conflict	629	1	N → D in AAF61293. Ref.2
	Sequence conflict	679	1	D → E in AAF61293. Ref.2
	Sequence conflict	717	1	Q → E in AAF61293. Ref.2
	Sequence conflict	758	1	Q → L in AAF61293. Ref.2
	Sequence conflict	982	1	A → C in AAF61293. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 5E54C3E5F60BB922	FASTA	1,013	113,100
	10 20 30 40 50 60 MAEASERLYR VQYAKSGRAS CKKCSESIPK DSLRMAIMVQ SPMFDGKVPH WYHFSCFWKV 70 80 90 100 110 120 GQSIRHPDVE VDGFSELRWD DQQKVKKTAE AGGVAGKGQD GSGGKAEKTL GDFAAEYAKS 130 140 150 160 170 180 NRSMCKGCLE KIEKGQMRLS KKMVDPEKPQ LGMIDRWYHP TCFVKKRDEL GFRPEYSASQ 190 200 210 220 230 240 LKGFSLLSAE DKEALKKQLP AIKNEGKRKG DEVDGTDEVA KKKSRKETDK YSKLEKALKA 250 260 270 280 290 300 QNELIWNIKD ELKKACSTND LKELLIFNQQ QVPSGESAIL DRVADGMAFG ALLPCKECSG 310 320 330 340 350 360 QLVFKSDAYY CTGDVTAWTK CMVKTQNPSR KEWVTPKEFR EISYLKKLKV KKQDRIFPPE 370 380 390 400 410 420 SSAPITVHWP LSVTSAPTAV NSSAPADKPL SNMKILTLGK LSQNKDEAKA VIEKLGGKLT 430 440 450 460 470 480 GSANKASLCI SIKKEVEKMN KKMEEVKEAN IRVVSEDFLQ DVSASTKSLQ DLLSAHSLSP 490 500 510 520 530 540 WGAEVKAEPG EVVAPRGKSA APSKKSKGCF KEEGVNKSEK RMKLTLKGGA AVDPDSGLEH 550 560 570 580 590 600 SAHVLEKGGK VFSATLGLVD IVKGTNSYYK LQLLEDDKES RYWIFRSWGR LGTVIGSNKL 610 620 630 640 650 660 EQMPSKEEAV EQFMKLYEEK TGNAWHSKNF TKYPKKFYPL EIDYGQDEEA VKKLTVKPGT 670 680 690 700 710 720 KSKLPKPVQE LVGMIFDVDS MKKALVEYEI DLQKMPLGKL SRRQIQAAYS ILSEVQQPVS 730 740 750 760 770 780 QGSSESQILD LSNRFYTLIP HDFGMKKPPL LNNADSVQAK VEMLDNLLDI EVAYSLLRGG 790 800 810 820 830 840 SDDSSKDPID VNYEKLKTDI KVVDRDSEEA EVIRKYVKNT HATTHNAYDL EVIDIFKIER 850 860 870 880 890 900 EGESQRYKPF RQLHNRRLLW HGSRTTNFAG ILSQGLRIAP PEAPVTGYMF GKGIYFADMV 910 920 930 940 950 960 SKSANYCHTS QGDPIGLIML GEVALGNMYE LKHASHISKL PKGKHSVKGL GKTTPDPSAS 970 980 990 1000 1010 ITLEGVEVPL GTGIPSGVND TALLYNEYIV YDIAQVNLKY LLKLKFNFKT SLW
	Isoform 2 (Short) (sPARP-1) [UniParc]. Checksum: 6F429A5F21D15246	FASTA	492	55,237
	10 20 30 40 50 60 MKLTLKGGAA VDPDSGLEHS AHVLEKGGKV FSATLGLVDI VKGTNSYYKL QLLEDDKESR 70 80 90 100 110 120 YWIFRSWGRL GTVIGSNKLE QMPSKEEAVE QFMKLYEEKT GNAWHSKNFT KYPKKFYPLE 130 140 150 160 170 180 IDYGQDEEAV KKLTVKPGTK SKLPKPVQEL VGMIFDVDSM KKALVEYEID LQKMPLGKLS 190 200 210 220 230 240 RRQIQAAYSI LSEVQQPVSQ GSSESQILDL SNRFYTLIPH DFGMKKPPLL NNADSVQAKV 250 260 270 280 290 300 EMLDNLLDIE VAYSLLRGGS DDSSKDPIDV NYEKLKTDIK VVDRDSEEAE VIRKYVKNTH 310 320 330 340 350 360 ATTHNAYDLE VIDIFKIERE GESQRYKPFR QLHNRRLLWH GSRTTNFAGI LSQGLRIAPP 370 380 390 400 410 420 EAPVTGYMFG KGIYFADMVS KSANYCHTSQ GDPIGLIMLG EVALGNMYEL KHASHISKLP 430 440 450 460 470 480 KGKHSVKGLG KTTPDPSASI TLEGVEVPLG TGIPSGVNDT ALLYNEYIVY DIAQVNLKYL 490 LKLKFNFKTS LW

References

[1]	"Sequence and organization of the mouse poly (ADP-ribose) polymerase gene." Huppi K., Bhatia K., Siwarski D., Klinman D., Cherney B., Smulson M. Nucleic Acids Res. 17:3387-3401(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BXSB.
[2]	"Characterization of sPARP-1. An alternative product of PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks." Sallmann F.R., Vodenicharov M.D., Wang Z.-Q., Poirier G.G. J. Biol. Chem. 275:15504-15511(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION. Strain: C57BL/6 X 129/Sv. Tissue: Fibroblast.
[3]	"A B-cell-specific DNA recombination complex." Borggrefe T., Wabl M., Akhmedov A.T., Jessberger R. J. Biol. Chem. 273:17025-17035(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 109-119 AND 865-875, SUBUNIT, TISSUE SPECIFICITY. Strain: C57BL/6. Tissue: Spleen.
[4]	"On the biological role of the nuclear polymerizing NAD+: protein(ADP-ribosyl) transferase (ADPRT): ADPRT from Dictyostelium discoideum and inactivation of the ADPRT gene in the mouse." Auer B., Flick K., Wang Z.Q., Haidacher D., Jaeger S., Berghammer H., Kofler B., Schweiger M., Wagner E.F. Biochimie 77:444-449(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[5]	"Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1." Schreiber V., Ame J.-C., Dolle P., Schultz I., Rinaldi B., Fraulob V., Menissier-de Murcia J., de Murcia G.M. J. Biol. Chem. 277:23028-23036(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[6]	"Poly(ADP-ribose) polymerase 1 interacts with OAZ and regulates BMP-target genes." Ku M.-C., Stewart S., Hata A. Biochem. Biophys. Res. Commun. 311:702-707(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZNF423.
[7]	"Nitric oxide-dependent negative feedback of PARP-1 trans-activation of the inducible nitric-oxide synthase gene." Yu Z., Kuncewicz T., Dubinsky W.P., Kone B.C. J. Biol. Chem. 281:9101-9109(2006) [PubMed] [Europe PMC] [Abstract] Cited for: S-NITROSYLATION.
[8]	"Rho-kinase modulates the function of STEF, a Rac GEF, through its phosphorylation." Takefuji M., Mori K., Morita Y., Arimura N., Nishimura T., Nakayama M., Hoshino M., Iwamatsu A., Murohara T., Kaibuchi K., Amano M. Biochem. Biophys. Res. Commun. 355:788-794(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TIAM2.
[9]	"PARP-1 transcriptional activity is regulated by sumoylation upon heat shock." Martin N., Schwamborn K., Schreiber V., Werner A., Guillier C., Zhang X.D., Bischof O., Seeler J.S., Dejean A. EMBO J. 28:3534-3548(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF4.
[10]	"Poly(ADP-ribose)-dependent regulation of Snail1 protein stability." Rodriguez M.I., Gonzalez-Flores A., Dantzer F., Collard J., de Herreros A.G., Oliver F.J. Oncogene 30:4365-4372(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X14206 mRNA. Translation: CAA32421.1. AF126717 mRNA. Translation: AAF61293.1. Different initiation.
IPI	IPI00112473. IPI00759945.
PIR	S04200.
UniGene	Mm.277779.
3D structure databases
ProteinModelPortal	P11103.
SMR	P11103. Positions 5-94, 108-200, 234-359, 388-486, 519-1010.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-39371N.
IntAct	P11103. 9 interactions.
MINT	MINT-237428.
PTM databases
PhosphoSite	P11103.
Proteomic databases
PaxDb	P11103.
PRIDE	P11103.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:1340806. Parp1.
Phylogenomic databases
eggNOG	NOG243963.
HOVERGEN	HBG053513.
InParanoid	P11103.
OrthoDB	EOG4PG609.
Gene expression databases
CleanEx	MM_PARP1.
Genevestigator	P11103.
GermOnline	ENSMUSG00000026496. Mus musculus.
Family and domain databases
Gene3D	1.20.142.10. 1 hit. 2.20.140.10. 1 hit. 3.30.1740.10. 2 hits.
InterPro	IPR001357. BRCT_dom. IPR008288. NAD_ADPRT. IPR012982. PADR1. IPR012317. Poly(ADP-ribose)pol_cat_dom. IPR004102. Poly(ADP-ribose)pol_reg_dom. IPR008893. WGR_domain. IPR001510. Znf_PARP. [Graphical view]
Pfam	PF00533. BRCT. 1 hit. PF08063. PADR1. 1 hit. PF00644. PARP. 1 hit. PF02877. PARP_reg. 1 hit. PF05406. WGR. 1 hit. PF00645. zf-PARP. 2 hits. [Graphical view]
PIRSF	PIRSF000489. NAD_ADPRT. 1 hit.
SMART	SM00292. BRCT. 1 hit. SM00773. WGR. 1 hit. [Graphical view]
SUPFAM	SSF52113. BRCT. 1 hit. SSF47587. PARP_reg. 1 hit. SSF142921. SSF142921. 1 hit.
PROSITE	PS50172. BRCT. 1 hit. PS51060. PARP_ALPHA_HD. 1 hit. PS51059. PARP_CATALYTIC. 1 hit. PS00347. PARP_ZN_FINGER_1. 2 hits. PS50064. PARP_ZN_FINGER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P11103.
ChEMBL	CHEMBL3740.
SOURCE	Search...

Entry information

Entry name

PARP1_MOUSE

Accession

Primary (citable) accession number: P11103
Secondary accession number(s): Q9JLX4, Q9QVQ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 147 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program