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P11103 (PARP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1013 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites By similarity.

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. Interacts (when poly-ADP-ribosylated) with PARP9 By similarity. Ref.3 Ref.6 Ref.8 Ref.9 Ref.10

Subcellular location

Nucleus. Nucleusnucleolus By similarity. Note: Localizes at sites of DNA damage 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 processDNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative initiation
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
NAD
Zinc
   Molecular functionGlycosyltransferase
Transferase
   PTMAcetylation
ADP-ribosylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA metabolic process

Inferred from mutant phenotype PubMed 11756244PubMed 12707040. Source: MGI

DNA repair

Traceable author statement PubMed 12065591. Source: MGI

base-excision repair

Inferred from mutant phenotype Ref.5. Source: MGI

double-strand break repair

Inferred from sequence or structural similarity. Source: UniProtKB

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-templated

Inferred from electronic annotation. Source: UniProtKB-KW

telomere maintenance

Inferred from mutant phenotype PubMed 12707040. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

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

nucleus

Inferred from direct assay PubMed 19470756. Source: BHF-UCL

protein complex

Inferred from direct assay PubMed 19796622. Source: MGI

   Molecular_functionDNA 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: UniProtKB-EC

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

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:
     2-521: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 10131012Poly [ADP-ribose] polymerase 1
PRO_0000023259

Regions

Domain385 – 47692BRCT
Domain661 – 778118PARP alpha-helical
Domain787 – 1013227PARP catalytic
DNA binding2 – 372371
Zinc finger9 – 9385PARP-type 1
Zinc finger113 – 20391PARP-type 2
Region373 – 523151Automodification domain
Motif207 – 2093Nuclear localization signal
Motif221 – 2266Nuclear localization signal

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue411Phosphoserine By similarity
Modified residue971N6-acetyllysine Ref.11
Modified residue1051N6-acetyllysine By similarity
Modified residue1311N6-acetyllysine By similarity
Modified residue1791Phosphoserine By similarity
Modified residue4071PolyADP-ribosyl glutamic acid Potential
Modified residue4131PolyADP-ribosyl glutamic acid Potential
Modified residue4351PolyADP-ribosyl glutamic acid Potential
Modified residue4371PolyADP-ribosyl glutamic acid Potential
Modified residue4441PolyADP-ribosyl glutamic acid Potential
Modified residue4451PolyADP-ribosyl glutamic acid Potential
Modified residue4481PolyADP-ribosyl glutamic acid Potential
Modified residue4561PolyADP-ribosyl glutamic acid Potential
Modified residue4841PolyADP-ribosyl glutamic acid Potential
Modified residue4881PolyADP-ribosyl glutamic acid Potential
Modified residue4911PolyADP-ribosyl glutamic acid Potential
Modified residue5121PolyADP-ribosyl glutamic acid Potential
Modified residue5131PolyADP-ribosyl glutamic acid Potential
Modified residue5191PolyADP-ribosyl glutamic acid Potential
Modified residue5991N6-acetyllysine By similarity
Modified residue6201N6-acetyllysine By similarity
Modified residue7811Phosphoserine By similarity

Natural variations

Alternative sequence2 – 521520Missing in isoform 2.
VSP_018970

Experimental info

Sequence conflict1141A → L AA sequence Ref.3
Sequence conflict5911L → V in AAF61293. Ref.2
Sequence conflict6081E → D in AAF61293. Ref.2
Sequence conflict6121Q → H in AAF61293. Ref.2
Sequence conflict6291N → D in AAF61293. Ref.2
Sequence conflict6791D → E in AAF61293. Ref.2
Sequence conflict7171Q → E in AAF61293. Ref.2
Sequence conflict7581Q → L in AAF61293. Ref.2
Sequence conflict9821A → C in AAF61293. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 5E54C3E5F60BB922

FASTA1,013113,100
        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 

« Hide

Isoform 2 (Short) (sPARP-1) [UniParc].

Checksum: FBD0D37BA9E04DC7
Show »

FASTA49355,368

References

« Hide 'large scale' 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.
[11]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14206 mRNA. Translation: CAA32421.1.
AF126717 mRNA. Translation: AAF61293.1. Different initiation.
PIRS04200.
UniGeneMm.277779.

3D structure databases

ProteinModelPortalP11103.
SMRP11103. Positions 5-94, 108-200, 234-359, 388-486, 519-1010.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-39371N.
IntActP11103. 12 interactions.
MINTMINT-237428.

Chemistry

BindingDBP11103.
ChEMBLCHEMBL3740.

PTM databases

PhosphoSiteP11103.

Proteomic databases

PaxDbP11103.
PRIDEP11103.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1340806. Parp1.

Phylogenomic databases

eggNOGNOG243963.
HOVERGENHBG053513.
InParanoidP11103.
PhylomeDBP11103.

Gene expression databases

CleanExMM_PARP1.
GenevestigatorP11103.

Family and domain databases

Gene3D1.20.142.10. 1 hit.
2.20.140.10. 1 hit.
3.30.1740.10. 2 hits.
3.40.50.10190. 1 hit.
3.90.228.10. 1 hit.
InterProIPR001357. 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]
PfamPF00533. 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]
PIRSFPIRSF000489. NAD_ADPRT. 1 hit.
SMARTSM00292. BRCT. 1 hit.
SM00773. WGR. 1 hit.
[Graphical view]
SUPFAMSSF142921. SSF142921. 1 hit.
SSF47587. SSF47587. 1 hit.
SSF52113. SSF52113. 1 hit.
PROSITEPS50172. 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]
ProtoNetSearch...

Other

PROP11103.
SOURCESearch...

Entry information

Entry namePARP1_MOUSE
AccessionPrimary (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 16, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot