DUFMech

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

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

UniProtProtein / organismSequenceProvenance
A1Z1Q3ADP-ribose glycohydrolase MACROD2
Homo sapiens
425 aa; version 2
UniProt 2026_03
PTM REGISTRY MIRROR
13 sibling references
K2PFJ6DNA ADP-ribosyl transferase-DNA ADP-ribosyl glycohydrolase fusion protein
Thermosipho africanus (strain H17ap60334)
388 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
K9N7C7Replicase polyprotein 1ab
Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
7078 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
O75367Core histone macro-H2A.1
Homo sapiens
369 aa; version 5
UniProt 2026_03
PTM REGISTRY MIRROR
3 sibling references
P0A8D6O-acetyl-ADP-ribose deacetylase
Escherichia coli (strain K12)
177 aa; version 1
UniProt 2026_03
PTM REGISTRY MIRROR
11 sibling references
P0C6F3Replicase polyprotein 1a
Berne virus
4569 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
P0C6F5Replicase polyprotein 1a
Bat coronavirus 279/2005
4388 aa; version 1
UniProt 2026_03
UNIPROT FETCH
5 sibling references
P0C6F6Replicase polyprotein 1a
Bat coronavirus 512/2005
4128 aa; version 1
UniProt 2026_03
UNIPROT FETCH
9 sibling references
P0C6F7Replicase polyprotein 1a
Bat coronavirus 133/2005
4441 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
P0C6F8Replicase polyprotein 1a
Bat coronavirus HKU3
4376 aa; version 1
UniProt 2026_03
UNIPROT FETCH
11 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

data/families/PF01661.yaml
Family YAML in this build

Download this family (JSON)

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.