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Protein

O-acetyl-ADP-ribose deacetylase MACROD2

Gene

MACROD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins.2 Publications

Enzyme regulationi

Subject to product inhibition by ADP-ribose.1 Publication

Kineticsi

  1. KM=107 µM for O-acetyl-ADP-ribose1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei224Substrate1

    GO - Molecular functioni

    • deacetylase activity Source: UniProtKB
    • hydrolase activity, acting on glycosyl bonds Source: UniProtKB

    GO - Biological processi

    • brain development Source: Ensembl
    • cellular response to DNA damage stimulus Source: UniProtKB
    • protein de-ADP-ribosylation Source: UniProtKB
    • purine nucleoside metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    DNA damage

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    O-acetyl-ADP-ribose deacetylase MACROD2 (EC:3.2.2.-, EC:3.5.1.-)
    Alternative name(s):
    MACRO domain-containing protein 2
    [Protein ADP-ribosylglutamate] hydrolase
    Gene namesi
    Name:MACROD2
    Synonyms:C20orf133
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:16126. MACROD2.

    Subcellular locationi

    • Nucleus

    • Note: Recruited to DNA lesions, probably via mono-APD-ribosylated proteins.

    GO - Cellular componenti

    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi92N → A: Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-102. 1 Publication1
    Mutagenesisi102D → A: Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-92. 1 Publication1
    Mutagenesisi188G → E: Abolishes interaction with ADP-ribosylated proteins. Strongly reduced ADP-ribosyl hydrolase activity. 1 Publication1

    Organism-specific databases

    DisGeNETi140733.
    OpenTargetsiENSG00000172264.
    PharmGKBiPA162394843.

    Polymorphism and mutation databases

    BioMutaiMACROD2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003004611 – 448O-acetyl-ADP-ribose deacetylase MACROD2Add BLAST448

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Cross-linki170Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    MaxQBiA1Z1Q3.
    PRIDEiA1Z1Q3.

    PTM databases

    iPTMnetiA1Z1Q3.
    PhosphoSitePlusiA1Z1Q3.

    Expressioni

    Gene expression databases

    BgeeiENSG00000172264.
    CleanExiHS_MACROD2.
    GenevisibleiA1Z1Q3. HS.

    Organism-specific databases

    HPAiHPA049076.

    Interactioni

    Subunit structurei

    Interacts with ADP-ribosylated PARP1.1 Publication

    Protein-protein interaction databases

    BioGridi126679. 2 interactors.

    Structurei

    Secondary structure

    1448
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi11 – 19Combined sources9
    Helixi23 – 26Combined sources4
    Turni27 – 29Combined sources3
    Helixi37 – 39Combined sources3
    Helixi43 – 46Combined sources4
    Turni47 – 49Combined sources3
    Beta strandi71 – 77Combined sources7
    Helixi79 – 81Combined sources3
    Beta strandi82 – 91Combined sources10
    Helixi100 – 109Combined sources10
    Helixi111 – 117Combined sources7
    Turni118 – 121Combined sources4
    Beta strandi128 – 132Combined sources5
    Beta strandi136 – 145Combined sources10
    Turni154 – 156Combined sources3
    Helixi157 – 174Combined sources18
    Beta strandi179 – 182Combined sources4
    Helixi194 – 212Combined sources19
    Helixi213 – 215Combined sources3
    Beta strandi217 – 223Combined sources7
    Helixi226 – 240Combined sources15

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IQYX-ray1.55A/B7-243[»]
    ProteinModelPortaliA1Z1Q3.
    SMRiA1Z1Q3.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini59 – 240MacroPROSITE-ProRule annotationAdd BLAST182

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni77 – 79Substrate binding3
    Regioni90 – 92Substrate binding3
    Regioni97 – 102Substrate binding6
    Regioni185 – 191Substrate binding7

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi6 – 9Poly-Lys4
    Compositional biasi247 – 388Glu-richAdd BLAST142

    Sequence similaritiesi

    Contains 1 Macro domain.PROSITE-ProRule annotation

    Phylogenomic databases

    GeneTreeiENSGT00520000055566.
    HOVERGENiHBG099716.
    InParanoidiA1Z1Q3.
    OMAiNGQEHDS.
    OrthoDBiEOG091G0NNH.
    PhylomeDBiA1Z1Q3.
    TreeFamiTF341440.

    Family and domain databases

    InterProiIPR002589. Macro_dom.
    [Graphical view]
    PfamiPF01661. Macro. 1 hit.
    [Graphical view]
    SMARTiSM00506. A1pp. 1 hit.
    [Graphical view]
    PROSITEiPS51154. MACRO. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: A1Z1Q3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MYPSNKKKKV WREEKERLLK MTLEERRKEY LRDYIPLNSI LSWKEEMKGK
    60 70 80 90 100
    GQNDEENTQE TSQVKKSLTE KVSLYRGDIT LLEVDAIVNA ANASLLGGGG
    110 120 130 140 150
    VDGCIHRAAG PCLLAECRNL NGCDTGHAKI TCGYDLPAKY VIHTVGPIAR
    160 170 180 190 200
    GHINGSHKED LANCYKSSLK LVKENNIRSV AFPCISTGIY GFPNEPAAVI
    210 220 230 240 250
    ALNTIKEWLA KNHHEVDRII FCVFLEVDFK IYKKKMNEFF SVDDNNEEEE
    260 270 280 290 300
    DVEMKEDSDE NGPEEKQSVE EMEEQSQDAD GVNTVTVPGP ASEEAVEDCK
    310 320 330 340 350
    DEDFAKDENI TKGGEVTDHS VRDQDHPDGQ ENDSTKNEIK IETESQSSYM
    360 370 380 390 400
    ETEELSSNQE DAVIVEQPEV IPLTEDQEEK EGEKAPGEDT PRMPGKSEGS
    410 420 430 440
    SDLENTPGPD VEMNSQVDKV NDPTESQQED QLIAGAQDEA KEQRNGTK
    Length:448
    Mass (Da):50,050
    Last modified:February 6, 2007 - v1
    Checksum:iA0E49D46E76161DB
    GO
    Isoform 2 (identifier: A1Z1Q3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         411-433: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:425
    Mass (Da):47,421
    Checksum:i2CB614734EDB6314
    GO
    Isoform 4 (identifier: A1Z1Q3-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-235: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:213
    Mass (Da):23,616
    Checksum:i6697DB0A302DA7DC
    GO
    Isoform 5 (identifier: A1Z1Q3-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-235: Missing.
         411-433: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:190
    Mass (Da):20,987
    Checksum:iB631FBC82B66F388
    GO
    Isoform 6 (identifier: A1Z1Q3-6) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-349: Missing.
         434-434: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:98
    Mass (Da):10,769
    Checksum:i797D03BFA265AC2C
    GO

    Sequence cautioni

    The sequence BAD18504 differs from that shown. Reason: Frameshift at position 151.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05693558T → I.1 PublicationCorresponds to variant rs2990505dbSNPEnsembl.1
    Natural variantiVAR_061681335T → M.Corresponds to variant rs41275442dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0357211 – 349Missing in isoform 6. 1 PublicationAdd BLAST349
    Alternative sequenceiVSP_0354781 – 235Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST235
    Alternative sequenceiVSP_027806411 – 433Missing in isoform 2 and isoform 5. 1 PublicationAdd BLAST23
    Alternative sequenceiVSP_035722434Missing in isoform 6. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    EF159161 mRNA. Translation: ABM46908.1.
    AK131348 mRNA. Translation: BAD18504.1. Frameshift.
    AK125899 mRNA. Translation: BAG54262.1.
    AC006198 Genomic DNA. No translation available.
    AL035073 Genomic DNA. No translation available.
    AL049867 Genomic DNA. No translation available.
    AL050324 Genomic DNA. No translation available.
    AL118503 Genomic DNA. No translation available.
    AL118510 Genomic DNA. No translation available.
    AL132826 Genomic DNA. No translation available.
    AL133462 Genomic DNA. No translation available.
    AL136992 Genomic DNA. No translation available.
    AL138808 Genomic DNA. No translation available.
    AL139825 Genomic DNA. No translation available.
    AL161800 Genomic DNA. No translation available.
    AL355133 Genomic DNA. No translation available.
    AL121582
    , AL049633, AL079338, AL117333, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAH71976.2.
    AL353798
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL354773, AL357654 Genomic DNA. Translation: CAI16368.2.
    AL136991
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM14046.1.
    AL121584
    , AL049633, AL079338, AL117333, AL121582, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM18337.1.
    AL158088
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM26942.1.
    AL357654
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773 Genomic DNA. Translation: CAM27056.1.
    AL049633
    , AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM27329.1.
    AL117333
    , AL049633, AL079338, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM28281.1.
    AL079338
    , AL049633, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM28328.1.
    AL354773
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL357654 Genomic DNA. Translation: CAM28330.1.
    AL357654, AL079338, AL136991 Genomic DNA. Translation: CAQ06880.1.
    AL357654, AL136991 Genomic DNA. Translation: CAQ06881.1.
    AL079338, AL136991, AL357654 Genomic DNA. Translation: CAQ07295.1.
    AL136991, AL079338, AL357654 Genomic DNA. Translation: CAQ08720.1.
    AL136991, AL357654 Genomic DNA. Translation: CAQ08721.1.
    CH471133 Genomic DNA. Translation: EAX10293.1.
    CH471133 Genomic DNA. Translation: EAX10302.1.
    BC018687 mRNA. Translation: AAH18687.1.
    BC101216 mRNA. No translation available.
    BC101217 mRNA. No translation available.
    BC101218 mRNA. No translation available.
    BC101219 mRNA. No translation available.
    BC126936 mRNA. No translation available.
    BC035876 mRNA. No translation available.
    CCDSiCCDS13120.2. [A1Z1Q3-2]
    CCDS33443.1. [A1Z1Q3-4]
    RefSeqiNP_001028259.1. NM_001033087.1. [A1Z1Q3-4]
    NP_542407.2. NM_080676.5.
    XP_016883166.1. XM_017027677.1. [A1Z1Q3-1]
    UniGeneiHs.661576.

    Genome annotation databases

    EnsembliENST00000217246; ENSP00000217246; ENSG00000172264. [A1Z1Q3-2]
    ENST00000378058; ENSP00000367297; ENSG00000172264. [A1Z1Q3-4]
    ENST00000402914; ENSP00000385290; ENSG00000172264. [A1Z1Q3-4]
    ENST00000407045; ENSP00000385516; ENSG00000172264. [A1Z1Q3-6]
    GeneIDi140733.
    KEGGihsa:140733.
    UCSCiuc002wot.4. human. [A1Z1Q3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    EF159161 mRNA. Translation: ABM46908.1.
    AK131348 mRNA. Translation: BAD18504.1. Frameshift.
    AK125899 mRNA. Translation: BAG54262.1.
    AC006198 Genomic DNA. No translation available.
    AL035073 Genomic DNA. No translation available.
    AL049867 Genomic DNA. No translation available.
    AL050324 Genomic DNA. No translation available.
    AL118503 Genomic DNA. No translation available.
    AL118510 Genomic DNA. No translation available.
    AL132826 Genomic DNA. No translation available.
    AL133462 Genomic DNA. No translation available.
    AL136992 Genomic DNA. No translation available.
    AL138808 Genomic DNA. No translation available.
    AL139825 Genomic DNA. No translation available.
    AL161800 Genomic DNA. No translation available.
    AL355133 Genomic DNA. No translation available.
    AL121582
    , AL049633, AL079338, AL117333, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAH71976.2.
    AL353798
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL354773, AL357654 Genomic DNA. Translation: CAI16368.2.
    AL136991
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM14046.1.
    AL121584
    , AL049633, AL079338, AL117333, AL121582, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM18337.1.
    AL158088
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM26942.1.
    AL357654
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773 Genomic DNA. Translation: CAM27056.1.
    AL049633
    , AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM27329.1.
    AL117333
    , AL049633, AL079338, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM28281.1.
    AL079338
    , AL049633, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL354773, AL357654 Genomic DNA. Translation: CAM28328.1.
    AL354773
    , AL049633, AL079338, AL117333, AL121582, AL121584, AL136991, AL158088, AL353798, AL357654 Genomic DNA. Translation: CAM28330.1.
    AL357654, AL079338, AL136991 Genomic DNA. Translation: CAQ06880.1.
    AL357654, AL136991 Genomic DNA. Translation: CAQ06881.1.
    AL079338, AL136991, AL357654 Genomic DNA. Translation: CAQ07295.1.
    AL136991, AL079338, AL357654 Genomic DNA. Translation: CAQ08720.1.
    AL136991, AL357654 Genomic DNA. Translation: CAQ08721.1.
    CH471133 Genomic DNA. Translation: EAX10293.1.
    CH471133 Genomic DNA. Translation: EAX10302.1.
    BC018687 mRNA. Translation: AAH18687.1.
    BC101216 mRNA. No translation available.
    BC101217 mRNA. No translation available.
    BC101218 mRNA. No translation available.
    BC101219 mRNA. No translation available.
    BC126936 mRNA. No translation available.
    BC035876 mRNA. No translation available.
    CCDSiCCDS13120.2. [A1Z1Q3-2]
    CCDS33443.1. [A1Z1Q3-4]
    RefSeqiNP_001028259.1. NM_001033087.1. [A1Z1Q3-4]
    NP_542407.2. NM_080676.5.
    XP_016883166.1. XM_017027677.1. [A1Z1Q3-1]
    UniGeneiHs.661576.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4IQYX-ray1.55A/B7-243[»]
    ProteinModelPortaliA1Z1Q3.
    SMRiA1Z1Q3.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi126679. 2 interactors.

    PTM databases

    iPTMnetiA1Z1Q3.
    PhosphoSitePlusiA1Z1Q3.

    Polymorphism and mutation databases

    BioMutaiMACROD2.

    Proteomic databases

    MaxQBiA1Z1Q3.
    PRIDEiA1Z1Q3.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000217246; ENSP00000217246; ENSG00000172264. [A1Z1Q3-2]
    ENST00000378058; ENSP00000367297; ENSG00000172264. [A1Z1Q3-4]
    ENST00000402914; ENSP00000385290; ENSG00000172264. [A1Z1Q3-4]
    ENST00000407045; ENSP00000385516; ENSG00000172264. [A1Z1Q3-6]
    GeneIDi140733.
    KEGGihsa:140733.
    UCSCiuc002wot.4. human. [A1Z1Q3-1]

    Organism-specific databases

    CTDi140733.
    DisGeNETi140733.
    GeneCardsiMACROD2.
    HGNCiHGNC:16126. MACROD2.
    HPAiHPA049076.
    MIMi611567. gene.
    neXtProtiNX_A1Z1Q3.
    OpenTargetsiENSG00000172264.
    PharmGKBiPA162394843.
    GenAtlasiSearch...

    Phylogenomic databases

    GeneTreeiENSGT00520000055566.
    HOVERGENiHBG099716.
    InParanoidiA1Z1Q3.
    OMAiNGQEHDS.
    OrthoDBiEOG091G0NNH.
    PhylomeDBiA1Z1Q3.
    TreeFamiTF341440.

    Miscellaneous databases

    ChiTaRSiMACROD2. human.
    GenomeRNAii140733.
    PROiA1Z1Q3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000172264.
    CleanExiHS_MACROD2.
    GenevisibleiA1Z1Q3. HS.

    Family and domain databases

    InterProiIPR002589. Macro_dom.
    [Graphical view]
    PfamiPF01661. Macro. 1 hit.
    [Graphical view]
    SMARTiSM00506. A1pp. 1 hit.
    [Graphical view]
    PROSITEiPS51154. MACRO. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMACD2_HUMAN
    AccessioniPrimary (citable) accession number: A1Z1Q3
    Secondary accession number(s): A6NFF7
    , B0QZ39, B3KWV0, Q0P6D5, Q495E0, Q5W199, Q6ZN71
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 11, 2007
    Last sequence update: February 6, 2007
    Last modified: November 2, 2016
    This is version 79 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.