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93  structures 2806  species 1  interaction 5297  sequences 119  architectures

Family: Macro (PF01661)

Summary: Macro domain

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Macro domain Provide feedback

This domain is an ADP-ribose binding module. It is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein Q02874. This domain is found in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alphaviruses P03317. This domain is also found on its own in a family of proteins from bacteria P75918 archaebacteria O59182 and eukaryotes Q17432.

Literature references

  1. Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM; , Science 1999;286:1153-1155.: A biochemical genomics approach for identifying genes by the activity of their products. PUBMED:10550052 EPMC:10550052

  2. Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG; , EMBO J 2005;24:1911-1920.: The macro domain is an ADP-ribose binding module. PUBMED:15902274 EPMC:15902274

  3. Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM; , Science 1999;286:1153-1155.: A biochemical genomics approach for identifying genes by the activity of their products. PUBMED:10550052 EPMC:10550052

  4. Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG; , EMBO J 2005;24:1911-1920.: The macro domain is an ADP-ribose binding module. PUBMED:15902274 EPMC:15902274

  5. Till S, Ladurner AG;, Front Biosci. 2009;14:3246-3258.: Sensing NAD metabolites through macro domains. PUBMED:19273270 EPMC:19273270


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002589

The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose, an NAD metabolite or related ligands. Binding to ADP-ribose could be either covalent or non-covalent [PUBMED:16959969]: in certain cases it is believed to bind non-covalently [PUBMED:18983849]; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein [PUBMED:18172500]. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein [PUBMED:10550052]. The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A [PUBMED:11343911, PUBMED:12842467]. Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses, Rubella and Hepatitis E viruses. In vertebrates the domain occurs e.g. in histone macroH2A, in predicted poly-ADP-ribose polymerases (PARPs) and in B aggressive lymphoma (BAL) protein. The macro domain can be associated with catalytic domains, such as PARP, or sirtuin. The Macro domain can recognise ADP-ribose or in some cases poly-ADP-ribose, which can be involved in ADP-ribosylation reactions that occur in important processes, such as chromatin biology, DNA repair and transcription regulation [PUBMED:15902274]. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose [PUBMED:15965484]. The Macro domain has been suggested to play a regulatory role in ADP-ribosylation, which is involved in inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis.

The 3D structure of the Macro domain has a mixed alpha/beta fold of a mixed beta sheet sandwiched between four helices. Several Macro domain only domains are shorter than the structure of AF1521 and lack either the first strand or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [PUBMED:12842467, PUBMED:15902274, PUBMED:15965484, PUBMED:16912299].

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 MACRO (CL0223), which has the following description:

This superfamily includes the Macro domain as well as the amino terminal domain from peptidase M17 proteins.

The clan contains the following 3 members:

Macro Macro_2 Peptidase_M17_N

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
(124)
Full
(5297)
Representative proteomes NCBI
(4535)
Meta
(236)
RP15
(543)
RP35
(862)
RP55
(1216)
RP75
(1542)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(124)
Full
(5297)
Representative proteomes NCBI
(4535)
Meta
(236)
RP15
(543)
RP35
(862)
RP55
(1216)
RP75
(1542)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(124)
Full
(5297)
Representative proteomes NCBI
(4535)
Meta
(236)
RP15
(543)
RP35
(862)
RP55
(1216)
RP75
(1542)
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.

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: Pfam-B_434 (release 4.1)
Previous IDs: DUF27;A1pp;
Type: Domain
Author: Bateman A, Mistry J, Wood V
Number in seed: 124
Number in full: 5297
Average length of the domain: 112.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 10.96 %

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 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 118
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Macro

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 Macro domain has been found. There are 93 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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