All families / PF01661
PF01661: Macro
Macro domain
- Curation status
- SEEDED
- Seed status
- EX DUF
- Characterization
- UNSCORED
Grounding
PF01661: Macro domain
IPR002589: integrated entry for Macro domain
Source description
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 [InterPro reference PUB00052327]: in certain cases it is believed to bind non-covalently [InterPro reference PUB00052325]; 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 [InterPro reference PUB00052328]. 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 [InterPro reference PUB00043976]. 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 [InterPro reference PUB00021744].
Evidence and references
- InterPro entry and its literature references. PUB identifiers are internal InterPro references, not PubMed identifiers. Unresolved citations link to the originating entry.
- Frozen description source: InterPro/Pfam API
Source descriptions and links are provenance, not independent functional validation.
Evidence counts: not scored.
Curated functional assertions
No curated functional assertions supplied.
Protein sequence examples
46 verified sequence examples. FASTA
| UniProt | Protein / organism | Sequence | Provenance |
|---|---|---|---|
| A1Z1Q3 | ADP-ribose glycohydrolase MACROD2 Homo sapiens | 425 aa; version 2 UniProt 2026_03 | PTM REGISTRY MIRROR13 sibling references
|
| K2PFJ6 | DNA ADP-ribosyl transferase-DNA ADP-ribosyl glycohydrolase fusion protein Thermosipho africanus (strain H17ap60334) | 388 aa; version 1 UniProt 2026_03 | UNIPROT FETCH1 sibling references |
| K9N7C7 | Replicase polyprotein 1ab Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012) | 7078 aa; version 1 UniProt 2026_03 | UNIPROT FETCH1 sibling references |
| O75367 | Core histone macro-H2A.1 Homo sapiens | 369 aa; version 5 UniProt 2026_03 | PTM REGISTRY MIRROR |
| P0A8D6 | O-acetyl-ADP-ribose deacetylase Escherichia coli (strain K12) | 177 aa; version 1 UniProt 2026_03 | PTM REGISTRY MIRROR11 sibling references
|
| P0C6F3 | Replicase polyprotein 1a Berne virus | 4569 aa; version 1 UniProt 2026_03 | UNIPROT FETCH1 sibling references |
| P0C6F5 | Replicase polyprotein 1a Bat coronavirus 279/2005 | 4388 aa; version 1 UniProt 2026_03 | UNIPROT FETCH |
| P0C6F6 | Replicase polyprotein 1a Bat coronavirus 512/2005 | 4128 aa; version 1 UniProt 2026_03 | UNIPROT FETCH |
| P0C6F7 | Replicase polyprotein 1a Bat coronavirus 133/2005 | 4441 aa; version 1 UniProt 2026_03 | UNIPROT FETCH1 sibling references |
| P0C6F8 | Replicase polyprotein 1a Bat coronavirus HKU3 | 4376 aa; version 1 UniProt 2026_03 | UNIPROT FETCH11 sibling references
|
First 10 shown; the FASTA and family JSON contain all examples.
Pfam membership is not functional evidence. Whole-protein sequences do not establish domain boundaries. A coverage gap here is not absence from UniProt.
Sequences and metadata: UniProt Consortium, CC BY 4.0.
Domain matches
No residue-level domain match evidence is available in this build. Structure and AlphaFold counters do not supply coordinates or establish function.
Snapshot counters
- proteins
- 32,372
- matches
- 38,291
- proteomes
- 12,852
- taxa
- 24,044
- structures
- 1,152
- alphafold models
- 21,017
- domain architectures
- 1,119
Classification basis
pfam previous unknown name
No scoring reasons supplied.
Related Mech records
This family joined the worklist after the frozen cross-Mech scan, so other Mechs were not searched for it. Missing links here are not evidence that other Mechs lack it; rows shown come from mentions of a former DUF/UPF name.
No cross-Mech examples are present in the supplied snapshot.
Curation history and reviews
No retained curation events supplied.
No retained review supplied.
Record source
Status and evidence
- Seed status
- A name-based classification of frozen InterPro/Pfam metadata. UNKNOWN CANDIDATE means the metadata explicitly says the function is unknown. KNOWN HISTORICAL DUF means a DUF name matched without that wording; this heuristic is not proof of a known function and does not establish experimental characterization. EX DUF means Pfam renamed the family away from a DUF/UPF name, as recorded in Pfam's previous identifiers; a rename usually follows published work on some members but is naming history, not proof of function for every member. Some EX DUF families' current names or descriptions still say the function is unknown; their classification basis lists this, and scoring does not treat them as characterized. FALSE POSITIVE TEXT HIT means the naming rules did not match.
- Characterization
- A separate evidence-scoring result. UNSCORED means no score has been calculated; it is not evidence that the family lacks a known function. Missing scores are not negative evidence. PARTIALLY CHARACTERIZED has partial support; KNOWN HISTORICAL DUF can inherit the seed label or reflect a known-function signal. Neither label implies experimental validation.
- Evidence counts
- Source-specific signals, not unique proteins, publications, or confidence scores. Known counts Rhea reactions and experimentally supported GO molecular-function annotations. Partial counts functional/domain assignments. Context counts structural, environmental, orthology, interaction and neighborhood signals; context alone does not assign function. Repeated annotations may not be independent.
- Curation status
- Reported separately from seed classification and characterization. SNAPSHOT ONLY means no curated metadata was supplied for this build. SEEDED denotes a source-derived record, not an expert-reviewed functional claim.
- Missing counts
- Not available means the source did not supply that counter. A zero is a reported count. Not scored means evidence counts are unavailable.