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MACROD2 mono-ADP ribosylhydrolase 2 [ Homo sapiens (human) ]

Gene ID: 140733, updated on 13-Apr-2024

Summary

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Official Symbol
MACROD2provided by HGNC
Official Full Name
mono-ADP ribosylhydrolase 2provided by HGNC
Primary source
HGNC:HGNC:16126
See related
Ensembl:ENSG00000172264 MIM:611567; AllianceGenome:HGNC:16126
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
C2orf133; C20orf133
Summary
The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]
Expression
Broad expression in lung (RPKM 4.7), brain (RPKM 4.0) and 20 other tissues See more
Orthologs
mouse all
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Genomic context

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See MACROD2 in Genome Data Viewer
Location:
20p12.1
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (13995516..16053197)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (14044768..16102640)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (13976162..16033842)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene tRNA-Glu (CTC) 10-1 Neighboring gene SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase Neighboring gene RNA, U6 small nuclear 278, pseudogene Neighboring gene ribosomal protein S3 pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:14200853-14201581 Neighboring gene aminoacyl tRNA synthetase complex interacting multifunctional protein 1 pseudogene 1 Neighboring gene RNA, 7SL, cytoplasmic 864, pseudogene Neighboring gene RNA, U6 small nuclear 228, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:14447417-14447918 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:14447919-14448418 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr20:14451799-14452358 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59600 Neighboring gene uncharacterized LOC124904873 Neighboring gene fibronectin leucine rich transmembrane protein 3 Neighboring gene MACROD2 intronic transcript 1 Neighboring gene ring finger protein 11 pseudogene 2 Neighboring gene NANOG hESC enhancer GRCh37_chr20:14695990-14696491 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12681 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17553 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:14840969-14841588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17554 Neighboring gene MACROD2 antisense RNA 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:14900087-14900936 Neighboring gene ribosomal protein S10 pseudogene 2 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59609 Neighboring gene RNA, U6 small nuclear 1159, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59643 Neighboring gene RNA, U6 small nuclear 115, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59649 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59671 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17555 Neighboring gene NANOG hESC enhancer GRCh37_chr20:15316554-15317055 Neighboring gene RNA, 5S ribosomal pseudogene 475 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17556 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:15542248-15542790 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:15608178-15608731 Neighboring gene endosulfine alpha pseudogene 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_59806 Neighboring gene NANOG hESC enhancer GRCh37_chr20:15869460-15869961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17558 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17559 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17560 Neighboring gene uncharacterized LOC613266 Neighboring gene uncharacterized LOC124904874 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:16187279-16187780 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:16187781-16188280 Neighboring gene peptidylprolyl isomerase A pseudogene 17

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Human papillomavirus (HPV) integration signature in cervical lesions: identification of MACROD2 gene as HPV hot spot integration site. Zhao J, et al. Arch Gynecol Obstet, 2023 Apr. PMID 36008642
  2. Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population. Yang J, et al. Immun Inflamm Dis, 2022 Jul. PMID 35759225, Free PMC Article
  3. Association of MACROD2 gene variants with obesity and physical activity in a Korean population. Kim HR, et al. Mol Genet Genomic Med, 2021 Apr. PMID 33624934, Free PMC Article
  4. Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site. Kamal M, et al. Br J Cancer, 2021 Feb. PMID 33191407, Free PMC Article
  5. Intragenic Deletion in MACROD2: A Family with Complex Phenotypes Including Microcephaly, Intellectual Disability, Polydactyly, Renal and Pancreatic Malformations. Lombardo B, et al. Cytogenet Genome Res, 2019. PMID 31055587

See all (44) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
    Title: Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
  2. Human papillomavirus (HPV) integration signature in cervical lesions: identification of MACROD2 gene as HPV hot spot integration site.
    Title: Human papillomavirus (HPV) integration signature in cervical lesions: identification of MACROD2 gene as HPV hot spot integration site.
  3. Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population.
    Title: Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population.
  4. Association of MACROD2 gene variants with obesity and physical activity in a Korean population.
    Title: Association of MACROD2 gene variants with obesity and physical activity in a Korean population.
  5. Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site.
    Title: Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site.
  6. Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome.
    Title: Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome.
  7. Study identifies MACROD2 deletion as a cause of chromosome instability (CIN) in human colorectal cancer. MACROD2 loss causes repression of PARP1 activity, impairing DNA repair. MACROD2 haploinsufficiency promotes CIN and intestinal tumor growth. These results reveal MACROD2 as a major caretaker tumor suppressor gene in intestinal neoplasm.
    Title: MACROD2 Haploinsufficiency Impairs Catalytic Activity of PARP1 and Promotes Chromosome Instability and Growth of Intestinal Tumors.
  8. A deletion of chromosome 20p12.1 involving the macrodomain containing 2/mono-ADP ribosylhydrolase 2 gene (MACROD2) was found in several members of the family with complex phenotypes, including microcephaly, intellectual disability, dysmorphic features, and polydactyly. This deletion may affect correct embryonic development. Associated epigenetic modifications at the MACROD2 locus, can influence the phenotype severity.
    Title: Intragenic Deletion in MACROD2: A Family with Complex Phenotypes Including Microcephaly, Intellectual Disability, Polydactyly, Renal and Pancreatic Malformations.
  9. In patients with Graves' disease, a common genetic variant in MACROD2 may increase susceptibility for thyroid-associated orbitopathy.
    Title: Association of Polymorphisms in MACRO Domain Containing 2 With Thyroid-Associated Orbitopathy.
  10. ATM induces MacroD2 nuclear export upon DNA damage.
    Title: ATM induces MacroD2 nuclear export upon DNA damage.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
EBI GWAS Catalog
A genome-wide scan for common alleles affecting risk for autism.
EBI GWAS Catalog
Common body mass index-associated variants confer risk of extreme obesity.
EBI GWAS Catalog
Genetic variants associated with disordered eating.
EBI GWAS Catalog
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
EBI GWAS Catalog
Genome-wide association study identifies candidate genes for male fertility traits in humans.
EBI GWAS Catalog
Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
EBI GWAS Catalog
Genome-wide association study of antiphospholipid antibodies.
EBI GWAS Catalog
Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog
Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ADP-ribosylglutamate hydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ADP-ribosylglutamate hydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables deacetylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables hydrolase activity, acting on glycosyl bonds IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in DNA damage response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in brain development IEA
Inferred from Electronic Annotation
more info
  
involved_in peptidyl-glutamate ADP-deribosylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in peptidyl-glutamate ADP-deribosylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein de-ADP-ribosylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in purine nucleoside metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in purine nucleoside metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to bacterium IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
is_active_in nucleoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
ADP-ribose glycohydrolase MACROD2
Names
MACRO domain containing 2
MACRO domain-containing protein 2
O-acetyl-ADP-ribose deacetylase MACROD2
[Protein ADP-ribosylaspartate] hydrolase MACROD2
[Protein ADP-ribosylglutamate] hydrolase
[Protein ADP-ribosylglutamate] hydrolase MACROD2
NP_001028259.1
NP_001338590.1
NP_001338592.1
NP_001338593.1
NP_542407.2
XP_016883164.1
XP_016883165.1
XP_024307602.1
XP_054178994.1
XP_054178995.1
XP_054178996.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_054905.1 RefSeqGene

    Range
    5017..2062698
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001033087.2 → NP_001028259.1  ADP-ribose glycohydrolase MACROD2 isoform 2

    See identical proteins and their annotated locations for NP_001028259.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 3. The resulting isoform (2) is shorter at the N-terminus compared to isoform 3.
    Source sequence(s)
    AL133462, AL136991, BC018687
    Consensus CDS
    CCDS33443.1
    UniProtKB/Swiss-Prot
    A1Z1Q3
    Related
    ENSP00000385290.1, ENST00000402914.5

  2. NM_001351661.2 → NP_001338590.1  ADP-ribose glycohydrolase MACROD2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
    Source sequence(s)
    AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654
    Consensus CDS
    CCDS93008.1
    UniProtKB/TrEMBL
    A0A2R8YFN3
    Related
    ENSP00000507484.1, ENST00000684519.1
    Conserved Domains (2) summary
    cd02908
    Location:71 → 237
    Macro_Appr_pase_like; Macro domain, Appr-1"-pase_like family. The macro domain is a high-affinity ADP-ribose binding module found in a variety of proteins as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose ...
    cl26761
    Location:263 → 448
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

  3. NM_001351663.2 → NP_001338592.1  ADP-ribose glycohydrolase MACROD2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice junction in the 3' end compared to variant 3. The resulting isoform (4) has the same N- and C-termini but is 1 aa shorter compared to isoform 4.
    Source sequence(s)
    AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654
    UniProtKB/TrEMBL
    A0A2R8YFN3
    Conserved Domains (2) summary
    cd02908
    Location:71 → 237
    Macro_Appr_pase_like; Macro domain, Appr-1"-pase_like family. The macro domain is a high-affinity ADP-ribose binding module found in a variety of proteins as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose ...
    cl26761
    Location:258 → 442
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

  4. NM_001351664.2 → NP_001338593.1  ADP-ribose glycohydrolase MACROD2 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence and contains an alternate in-frame exon compared to variant 3. The resulting isoform (5) is shorter at the N-terminus and contains an alternate internal segment compared to isoform 3.
    Source sequence(s)
    AL049633, AL079338, AL121584, AL133462, AL136991, AL158088, AL357654

  5. NM_080676.6 → NP_542407.2  ADP-ribose glycohydrolase MACROD2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) lacks an alternate in-frame exon in the 3' end compared to variant 3. The resulting isoform (1) has the same N- and C-termini but is shorter compared to isoform 3.
    Source sequence(s)
    AK125899, AL136991, DB125529, DB495787, DR001087
    Consensus CDS
    CCDS13120.2
    UniProtKB/Swiss-Prot
    A1Z1Q3, A6NFF7, B0QZ39, B3KWV0, Q0P6D5, Q495E0, Q5W199, Q6ZN71
    UniProtKB/TrEMBL
    A0A2R8YFN3
    Related
    ENSP00000217246.4, ENST00000217246.8
    Conserved Domains (2) summary
    cd02908
    Location:71 → 237
    Macro_Appr_pase_like; Macro domain, Appr-1"-pase_like family. The macro domain is a high-affinity ADP-ribose binding module found in a variety of proteins as a stand-alone domain or in combination with other domains like in histone macroH2A and some PARPs (poly ADP-ribose ...
    cl26761
    Location:263 → 420
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    13995516..16053197
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024451834.2 → XP_024307602.1  ADP-ribose glycohydrolase MACROD2 isoform X1

    Conserved Domains (1) summary
    COG5271
    Location:49 → 272
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

  2. XM_017027675.2 → XP_016883164.1  ADP-ribose glycohydrolase MACROD2 isoform X2

  3. XM_017027676.2 → XP_016883165.1  ADP-ribose glycohydrolase MACROD2 isoform X3

    Conserved Domains (1) summary
    COG5271
    Location:62 → 219
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_025791811.1 Reference GRCh38.p14 PATCHES

    Range
    209125..248432
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    14044768..16102640
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054323019.1 → XP_054178994.1  ADP-ribose glycohydrolase MACROD2 isoform X1

  2. XM_054323020.1 → XP_054178995.1  ADP-ribose glycohydrolase MACROD2 isoform X2

  3. XM_054323021.1 → XP_054178996.1  ADP-ribose glycohydrolase MACROD2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
A1Z1Q3.2 GenPept UniProtKB/Swiss-Prot:A1Z1Q3

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