Summary: Macro domain
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Macro domain Edit Wikipedia article
| Macro | |||||||||
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 Crystal structure of the macro-domain of human core histone variant macroh2a1.1 | |||||||||
| Identifiers | |||||||||
| Symbol | Macro | ||||||||
| Pfam | PF01661 | ||||||||
| Pfam clan | CL0223 | ||||||||
| InterPro | IPR002589 | ||||||||
| SCOP2 | 1vhu / SCOPe / SUPFAM | ||||||||
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In molecular biology, 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 can be either covalent or non-covalent: [1] in certain cases it is believed to bind non-covalently, [2] 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.[3]
The domain was described originally in association with the ADP-ribose 1-phosphate (Appr-1-P)-processing activity (A1pp) of the yeast YBR022W protein and called A1pp.[4] However, the domain has been re-named Macro as it is the C-terminal domain of mammalian core histone macro-H2A.[5][6] 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 in e.g. histone macroH2A, predicted poly-ADP-ribose polymerases (PARPs) and B aggressive lymphoma (BAL) protein.
ADP-ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, regulation of transcription, chromatin biology, maintenance of genomic stability, telomere dynamics,[7] cell differentiation and proliferation,[8] necrosis and apoptosis, [9]and long-term memory formation.[10] The Macro domain recognises the ADP-ribose nucleotide and in some cases poly-ADP-ribose, and is thus a high-affinity ADP-ribose-binding module found in a number of otherwise unrelated proteins.[11] The Macro domain from human, macroH2A1.1, binds an NAD metabolite O-acetyl-ADP-ribose.[12]
The 3D structure of the Macro domain describes a mixed alpha/beta fold of a mixed beta sheet sandwiched between four helices with the ligand-binding pocket lies within the fold. [11]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.[6][11][12][13]
References
- ^ Hassa PO, Haenni SS, Elser M, Hottiger MO (2006). "Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?". Microbiol. Mol. Biol. Rev. 70 (3): 789–829. doi:10.1128/MMBR.00040-05. PMC 1594587. PMID 16959969.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Neuvonen M, Ahola T (2009). "Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites". J. Mol. Biol. 385 (1): 212–25. doi:10.1016/j.jmb.2008.10.045. PMID 18983849.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC (2008). "Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins". Nature. 451 (7174): 81–5. doi:10.1038/nature06420. PMID 18172500.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM (1999). "A biochemical genomics approach for identifying genes by the activity of their products". Science. 286 (5442): 1153–5. PMID 10550052.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Aravind L (2001). "The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation". Trends Biochem. Sci. 26 (5): 273–5. PMID 11343911.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ a b Allen MD, Buckle AM, Cordell SC, Löwe J, Bycroft M (2003). "The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A". J. Mol. Biol. 330 (3): 503–11. PMID 12842467.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Tennen RI, Chua KF (2011). "Chromatin regulation and genome maintenance by mammalian SIRT6". Trends in Biochemical Sciences. 36 (1): 39–46. doi:10.1016/j.tibs.2010.07.009. PMID 20729089.
{{cite journal}}:|access-date=requires|url=(help); Unknown parameter|month=ignored (help) - ^ Ji Y, Tulin AV (2010). "The roles of PARP1 in gene control and cell differentiation". Current Opinion in Genetics & Development. 20 (5): 512–8. doi:10.1016/j.gde.2010.06.001. PMID 20591646.
{{cite journal}}:|access-date=requires|url=(help); Unknown parameter|month=ignored (help) - ^ Han W, Li X, Fu X (2011). "The macro domain protein family: Structure, functions, and their potential therapeutic implications". Mutation Research. 727 (3): 86–103. doi:10.1016/j.mrrev.2011.03.001. PMID 21421074.
{{cite journal}}:|access-date=requires|url=(help)CS1 maint: multiple names: authors list (link) - ^ Schreiber V, Dantzer F, Ame JC, de Murcia G (2006). "Poly(ADP-ribose): novel functions for an old molecule". Nature Reviews. Molecular Cell Biology. 7 (7): 517–28. doi:10.1038/nrm1963. PMID 16829982.
{{cite journal}}:|access-date=requires|url=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b c Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG (2005). "The macro domain is an ADP-ribose binding module". EMBO J. 24 (11): 1911–20. doi:10.1038/sj.emboj.7600664. PMC 1142602. PMID 15902274.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Kustatscher G, Hothorn M, Pugieux C, Scheffzek K, Ladurner AG (2005). "Splicing regulates NAD metabolite binding to histone macroH2A". Nat. Struct. Mol. Biol. 12 (7): 624–5. doi:10.1038/nsmb956. PMID 15965484.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Egloff MP, Malet H, Putics A, Heinonen M, Dutartre H, Frangeul A, Gruez A, Campanacci V, Cambillau C, Ziebuhr J, Ahola T, Canard B (2006). "Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains". J. Virol. 80 (17): 8493–502. doi:10.1128/JVI.00713-06. PMC 1563857. PMID 16912299.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
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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
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 [1] in certain cases it is believed to bind non-covalently [2]; 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 [3]. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein [4]. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [5].
Literature references
-
Hassa PO, Haenni SS, Elser M, Hottiger MO;, Microbiol Mol Biol Rev. 2006;70:789-829.: Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?. PUBMED:16959969 EPMC:16959969
-
Neuvonen M, Ahola T;, J Mol Biol. 2009;385:212-225.: Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites. PUBMED:18983849 EPMC:18983849
-
Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC;, Nature. 2008;451:81-85.: Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. PUBMED:18172500 EPMC:18172500
-
Egloff MP, Malet H, Putics A, Heinonen M, Dutartre H, Frangeul A, Gruez A, Campanacci V, Cambillau C, Ziebuhr J, Ahola T, Canard B;, J Virol. 2006;80:8493-8502.: Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. PUBMED:16912299 EPMC:16912299
-
Allen MD, Buckle AM, Cordell SC, Lowe J, Bycroft M;, J Mol Biol. 2003;330:503-511.: The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A. PUBMED:12842467 EPMC:12842467
Internal database links
| SCOOP: | Macro_2 |
| Similarity to PfamA using HHSearch: | Macro_2 |
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 [ PUBMED:21525212 , PUBMED:31095648 ], 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 SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein [ PUBMED:16912299 ]. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the beta-sheet 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 8 members:
bCoV_SUD_M DUF2263 DUF2362 Macro Macro_2 PARG_cat Pdase_M17_N2 Peptidase_M17_NAlignments
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| Seed (85) |
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Representative proteomes | UniProt (91959) |
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| RP15 (3042) |
RP35 (6919) |
RP55 (12821) |
RP75 (19013) |
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| PP/heatmap | 1 | ||||||
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| Seed (85) |
Full (14562) |
Representative proteomes | UniProt (91959) |
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| RP15 (3042) |
RP35 (6919) |
RP55 (12821) |
RP75 (19013) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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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
| Seed source: | Pfam-B_434 (release 4.1) |
| Previous IDs: | DUF27;A1pp; |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Bateman A  , Mistry J , Wood V , Williams LS
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| Number in seed: | 85 |
| Number in full: | 14562 |
| Average length of the domain: | 112.7 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 26.77 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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| Model length: | 118 | ||||||||||||
| Family (HMM) version: | 24 | ||||||||||||
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Species distribution
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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 829 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 sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
