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92  structures 268  species 2  interactions 1951  sequences 267  architectures

Family: PARP (PF00644)

Summary: Poly(ADP-ribose) polymerase catalytic domain

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Poly(ADP-ribose) polymerase catalytic domain Provide feedback

Poly(ADP-ribose) polymerase catalyses the covalent attachment of ADP-ribose units from NAD+ to itself and to a limited number of other DNA binding proteins, which decreases their affinity for DNA. Poly(ADP-ribose) polymerase is a regulatory component induced by DNA damage. The carboxyl-terminal region is the most highly conserved region of the protein. Experiments have shown that a carboxyl 40 kDa fragment is still catalytically active [2].

Literature references

  1. Ruf A, Mennissier de Murcia J, de Murcia G, Schulz GE; , Proc Natl Acad Sci U S A 1996;93:7481-7485.: Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken. PUBMED:8755499 EPMC:8755499

  2. Simonin F, Hofferer L, Panzeter PL, Muller S, de Murcia G, Althaus FR; , J Biol Chem 1993;268:13454-13461.: The carboxyl-terminal domain of human poly(ADP-ribose) polymerase. Overproduction in Escherichia coli, large scale purification, and characterization. PUBMED:8390463 EPMC:8390463

  3. Ruf A, de Murcia G, Schulz GE; , Biochemistry 1998;37:3893-3900.: Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. PUBMED:9521710 EPMC:9521710


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR012317

Poly(ADP-ribose) polymerases (PARP) are a family of enzymes present in eukaryotes, which catalyze the poly(ADP-ribosyl)ation of a limited number of proteins involved in chromatin architecture, DNA repair, or in DNA metabolism, including PARP itself. PARP, also known as poly(ADP-ribose) synthetase and poly(ADP-ribose) transferase, transfers the ADP-ribose moiety from its substrate, nicotinamide adenine dinucleotide (NAD), to carboxylate groups of aspartic and glutamic residues. Whereas some PARPs might function in genome protection, others appear to play different roles in the cell, including telomere replication and cellular transport. PARP-1 is a multifunctional enzyme. The polypeptide has a highly conserved modular organisation consisting of an N-terminal DNA-binding domain, a central regulating segment, and a C-terminal or F region accommodating the catalytic centre. The F region is composed of two parts: a purely alpha-helical N- terminal domain (alpha-hd), and the mixed alpha/beta C-terminal catalytic domain bearing the putative NAD binding site. Although proteins of the PARP family are related through their PARP catalytic domain, they do not resemble each other outside of that region, but rather, they contain unique domains that distinguish them from each other and hint at their discrete functions. Domains with which the PARP catalytic domain is found associated include zinc fingers, SAP, ankyrin, BRCT, Macro, SAM, WWE and UIM domains [PUBMED:8016868, PUBMED:15273990, PUBMED:15561303].

The alpha-hd domain is about 130 amino acids in length and consists of an up-up-down-up-down-down motif of helices. It is thought to relay the activation signal issued on binding to damaged DNA [PUBMED:8755499, PUBMED:14739238]. The PARP catalytic domain is about 230 residues in length. Its core consists of a five-stranded antiparallel beta-sheet and four-stranded mixed beta-sheet. The two sheets are consecutive and are connected via a single pair of hydrogen bonds between two strands that run at an angle of 90 degrees. These central beta-sheets are surrounded by five alpha-helices, three 3(10)-helices, and by a three- and a two-stranded beta-sheet in a 37-residue excursion between two central beta-strands [PUBMED:8755499, PUBMED:14739238]. The active site, known as the 'PARP signature' is formed by a block of 50 amino acids that is strictly conserved among the vertebrates and highly conserved among all species. The 'PARP signature' is characteristic of all PARP protein family members. It is formed by a segment of conserved amino acid residues formed by a beta-sheet, an alpha-helix, a 3(10)-helix, a beta-sheet, and an alpha-helix [PUBMED:15561303].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ADP-ribosyl (CL0084), which contains the following 6 members:

ADPrib_exo_Tox ART Diphtheria_C Enterotoxin_a PARP Pertussis_S1

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(28)
Full
(1951)
Representative proteomes NCBI
(1843)
Meta
(56)
RP15
(534)
RP35
(710)
RP55
(997)
RP75
(1317)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Format an alignment

  Seed
(28)
Full
(1951)
Representative proteomes NCBI
(1843)
Meta
(56)
RP15
(534)
RP35
(710)
RP55
(997)
RP75
(1317)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(28)
Full
(1951)
Representative proteomes NCBI
(1843)
Meta
(56)
RP15
(534)
RP35
(710)
RP55
(997)
RP75
(1317)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Family
Author: Bateman A, Griffiths-Jones SR
Number in seed: 28
Number in full: 1951
Average length of the domain: 176.60 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 23.35 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.9 23.9
Trusted cut-off 23.9 24.0
Noise cut-off 23.6 23.8
Model length: 206
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

PARP PARP_reg

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PARP domain has been found. There are 92 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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