MACD2_HUMAN
ID MACD2_HUMAN Reviewed; 425 AA.
AC A1Z1Q3; A6NFF7; B0QZ39; B3KWV0; Q0P6D5; Q495E0; Q5W199; Q6ZN71;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=ADP-ribose glycohydrolase MACROD2 {ECO:0000305};
DE AltName: Full=MACRO domain-containing protein 2 {ECO:0000303|PubMed:23474712};
DE AltName: Full=O-acetyl-ADP-ribose deacetylase MACROD2;
DE EC=3.5.1.- {ECO:0000305|PubMed:21257746};
DE AltName: Full=[Protein ADP-ribosylaspartate] hydrolase MACROD2 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000269|PubMed:23474714};
DE AltName: Full=[Protein ADP-ribosylglutamate] hydrolase MACROD2 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000269|PubMed:23474712, ECO:0000269|PubMed:23474714};
GN Name=MACROD2 {ECO:0000303|PubMed:23474712, ECO:0000312|HGNC:HGNC:16126};
GN Synonyms=C20orf133 {ECO:0000312|HGNC:HGNC:16126};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
RA Lin L.-J., Asaoka Y., Tada M., Muroyama R., Tanaka Y., Ohta M., Seto M.,
RA Kanai F., Zheng C.-Q., Omata M.;
RT "Homozygous deletions and chromosome amplifications in human pancreatic
RT cancer cell lines identified using a single nucleotide polymorphism
RT array.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5), AND VARIANT
RP ILE-58.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-170, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18655026; DOI=10.1002/pmic.200700887;
RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J.,
RA Luo Y., Qiang B., Yuan J., Sun X., Peng X.;
RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell
RT line Chang liver cells.";
RL Proteomics 8:2885-2896(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21257746; DOI=10.1074/jbc.m110.206771;
RA Chen D., Vollmar M., Rossi M.N., Phillips C., Kraehenbuehl R., Slade D.,
RA Mehrotra P.V., von Delft F., Crosthwaite S.K., Gileadi O., Denu J.M.,
RA Ahel I.;
RT "Identification of macrodomain proteins as novel O-acetyl-ADP-ribose
RT deacetylases.";
RL J. Biol. Chem. 286:13261-13271(2011).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-100; ASP-102 AND
RP HIS-106.
RX PubMed=23474714; DOI=10.1038/nsmb.2521;
RA Rosenthal F., Feijs K.L., Frugier E., Bonalli M., Forst A.H., Imhof R.,
RA Winkler H.C., Fischer D., Caflisch A., Hassa P.O., Luescher B.,
RA Hottiger M.O.;
RT "Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases.";
RL Nat. Struct. Mol. Biol. 20:502-507(2013).
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=31599159; DOI=10.1021/acschembio.9b00429;
RA Stevens L.A., Kato J., Kasamatsu A., Oda H., Lee D.Y., Moss J.;
RT "The ARH and Macrodomain Families of alpha-ADP-ribose-acceptor Hydrolases
RT Catalyze alpha-NAD+ Hydrolysis.";
RL ACS Chem. Biol. 14:2576-2584(2019).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 7-243 IN COMPLEX WITH ADP-RIBOSE,
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, INTERACTION WITH
RP PARP1, AND MUTAGENESIS OF ASN-92; ASP-102 AND GLY-188.
RX PubMed=23474712; DOI=10.1038/nsmb.2523;
RA Jankevicius G., Hassler M., Golia B., Rybin V., Zacharias M., Timinszky G.,
RA Ladurner A.G.;
RT "A family of macrodomain proteins reverses cellular mono-ADP-
RT ribosylation.";
RL Nat. Struct. Mol. Biol. 20:508-514(2013).
CC -!- FUNCTION: Removes ADP-ribose from aspartate and glutamate residues in
CC proteins bearing a single ADP-ribose moiety (PubMed:23474714,
CC PubMed:23474712). Inactive towards proteins bearing poly-ADP-ribose
CC (PubMed:23474714, PubMed:23474712). Deacetylates O-acetyl-ADP ribose, a
CC signaling molecule generated by the deacetylation of acetylated lysine
CC residues in histones and other proteins (PubMed:21257746).
CC {ECO:0000269|PubMed:21257746, ECO:0000269|PubMed:23474712,
CC ECO:0000269|PubMed:23474714}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2''-O-acetyl-ADP-D-ribose + H2O = acetate + ADP-D-ribose +
CC H(+); Xref=Rhea:RHEA:57060, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:57967, ChEBI:CHEBI:83767;
CC Evidence={ECO:0000305|PubMed:21257746};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57061;
CC Evidence={ECO:0000305|PubMed:21257746};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-
CC COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:138102; Evidence={ECO:0000269|PubMed:23474714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC Evidence={ECO:0000269|PubMed:23474714};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-
CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:142540; Evidence={ECO:0000269|PubMed:23474712,
CC ECO:0000269|PubMed:23474714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000269|PubMed:23474712, ECO:0000269|PubMed:23474714};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-NAD(+) + H2O = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:68792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57967, ChEBI:CHEBI:77017;
CC Evidence={ECO:0000269|PubMed:31599159};
CC -!- ACTIVITY REGULATION: Subject to product inhibition by ADP-ribose.
CC {ECO:0000269|PubMed:23474712}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=107 uM for O-acetyl-ADP-ribose {ECO:0000269|PubMed:21257746};
CC -!- SUBUNIT: Interacts with ADP-ribosylated PARP1.
CC {ECO:0000269|PubMed:23474712}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23474712}.
CC Note=Recruited to DNA lesions, probably via mono-APD-ribosylated
CC proteins. {ECO:0000269|PubMed:23474712}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2;
CC IsoId=A1Z1Q3-2; Sequence=Displayed;
CC Name=1;
CC IsoId=A1Z1Q3-1; Sequence=VSP_059643;
CC Name=4;
CC IsoId=A1Z1Q3-4; Sequence=VSP_059642, VSP_059643;
CC Name=5;
CC IsoId=A1Z1Q3-5; Sequence=VSP_059642;
CC Name=6;
CC IsoId=A1Z1Q3-6; Sequence=VSP_059641, VSP_059644;
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD18504.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; EF159161; ABM46908.1; -; mRNA.
DR EMBL; AK131348; BAD18504.1; ALT_FRAME; mRNA.
DR EMBL; AK125899; BAG54262.1; -; mRNA.
DR EMBL; AC006198; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL035073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049867; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL050324; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL118503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL118510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138808; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161800; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL079338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL117333; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10293.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10302.1; -; Genomic_DNA.
DR EMBL; BC018687; AAH18687.1; -; mRNA.
DR EMBL; BC101216; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC101217; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC101218; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC101219; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC126936; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC035876; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS13120.2; -. [A1Z1Q3-2]
DR CCDS; CCDS33443.1; -. [A1Z1Q3-4]
DR RefSeq; NP_001028259.1; NM_001033087.1. [A1Z1Q3-4]
DR RefSeq; NP_542407.2; NM_080676.5. [A1Z1Q3-2]
DR RefSeq; XP_016883166.1; XM_017027677.1.
DR PDB; 4IQY; X-ray; 1.55 A; A/B=7-243.
DR PDB; 6Y4Y; X-ray; 1.75 A; A/B/C/D=7-243.
DR PDB; 6Y4Z; X-ray; 1.90 A; A/B/C/D=7-243.
DR PDB; 6Y73; X-ray; 1.70 A; A/B/C/D/E/F/G/H=7-243.
DR PDBsum; 4IQY; -.
DR PDBsum; 6Y4Y; -.
DR PDBsum; 6Y4Z; -.
DR PDBsum; 6Y73; -.
DR AlphaFoldDB; A1Z1Q3; -.
DR SMR; A1Z1Q3; -.
DR BioGRID; 126679; 7.
DR IntAct; A1Z1Q3; 3.
DR STRING; 9606.ENSP00000217246; -.
DR BindingDB; A1Z1Q3; -.
DR ChEMBL; CHEMBL4295630; -.
DR iPTMnet; A1Z1Q3; -.
DR PhosphoSitePlus; A1Z1Q3; -.
DR BioMuta; MACROD2; -.
DR EPD; A1Z1Q3; -.
DR jPOST; A1Z1Q3; -.
DR MassIVE; A1Z1Q3; -.
DR MaxQB; A1Z1Q3; -.
DR PeptideAtlas; A1Z1Q3; -.
DR PRIDE; A1Z1Q3; -.
DR ProteomicsDB; 165; -. [A1Z1Q3-1]
DR ProteomicsDB; 166; -. [A1Z1Q3-2]
DR ProteomicsDB; 167; -. [A1Z1Q3-4]
DR ProteomicsDB; 168; -. [A1Z1Q3-5]
DR ProteomicsDB; 169; -. [A1Z1Q3-6]
DR Antibodypedia; 62792; 23 antibodies from 8 providers.
DR DNASU; 140733; -.
DR Ensembl; ENST00000217246.8; ENSP00000217246.4; ENSG00000172264.18. [A1Z1Q3-2]
DR Ensembl; ENST00000378058.7; ENSP00000367297.3; ENSG00000172264.18. [A1Z1Q3-4]
DR Ensembl; ENST00000402914.5; ENSP00000385290.1; ENSG00000172264.18. [A1Z1Q3-4]
DR Ensembl; ENST00000407045.3; ENSP00000385516.3; ENSG00000172264.18. [A1Z1Q3-6]
DR Ensembl; ENST00000684519.1; ENSP00000507484.1; ENSG00000172264.18. [A1Z1Q3-1]
DR GeneID; 140733; -.
DR KEGG; hsa:140733; -.
DR MANE-Select; ENST00000684519.1; ENSP00000507484.1; NM_001351661.2; NP_001338590.1. [A1Z1Q3-1]
DR UCSC; uc002wot.4; human. [A1Z1Q3-2]
DR CTD; 140733; -.
DR DisGeNET; 140733; -.
DR GeneCards; MACROD2; -.
DR HGNC; HGNC:16126; MACROD2.
DR HPA; ENSG00000172264; Low tissue specificity.
DR MalaCards; MACROD2; -.
DR MIM; 611567; gene.
DR neXtProt; NX_A1Z1Q3; -.
DR OpenTargets; ENSG00000172264; -.
DR PharmGKB; PA162394843; -.
DR VEuPathDB; HostDB:ENSG00000172264; -.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000157404; -.
DR HOGENOM; CLU_046550_10_3_1; -.
DR InParanoid; A1Z1Q3; -.
DR OMA; VEMNTQV; -.
DR OrthoDB; 937161at2759; -.
DR PhylomeDB; A1Z1Q3; -.
DR TreeFam; TF341440; -.
DR BRENDA; 3.1.1.106; 2681.
DR PathwayCommons; A1Z1Q3; -.
DR SignaLink; A1Z1Q3; -.
DR BioGRID-ORCS; 140733; 6 hits in 1067 CRISPR screens.
DR ChiTaRS; MACROD2; human.
DR GenomeRNAi; 140733; -.
DR Pharos; A1Z1Q3; Tchem.
DR PRO; PR:A1Z1Q3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; A1Z1Q3; protein.
DR Bgee; ENSG00000172264; Expressed in endothelial cell and 157 other tissues.
DR ExpressionAtlas; A1Z1Q3; baseline and differential.
DR Genevisible; A1Z1Q3; HS.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140293; F:ADP-ribosylglutamate hydrolase activity; IDA:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; IDA:UniProtKB.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0140291; P:peptidyl-glutamate ADP-deribosylation; IDA:UniProtKB.
DR GO; GO:0051725; P:protein de-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0042278; P:purine nucleoside metabolic process; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 3.40.220.10; -; 1.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR Pfam; PF01661; Macro; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR PROSITE; PS51154; MACRO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; DNA damage; Hydrolase; Isopeptide bond;
KW Nucleus; Reference proteome; Ubl conjugation.
FT CHAIN 1..425
FT /note="ADP-ribose glycohydrolase MACROD2"
FT /id="PRO_0000300461"
FT DOMAIN 59..240
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT REGION 243..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..267
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..340
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..391
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 77..79
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23474712"
FT BINDING 90..92
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23474712"
FT BINDING 97..102
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23474712"
FT BINDING 185..191
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23474712"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:23474712"
FT CROSSLNK 170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18655026"
FT VAR_SEQ 1..349
FT /note="Missing (in isoform 6)"
FT /id="VSP_059641"
FT VAR_SEQ 1..235
FT /note="Missing (in isoform 4 and isoform 5)"
FT /id="VSP_059642"
FT VAR_SEQ 410
FT /note="D -> DVEMNSQVDKVNDPTESQQEDQLI (in isoform 1 and
FT isoform 4)"
FT /id="VSP_059643"
FT VAR_SEQ 411
FT /note="A -> VEMNSQVDKVNDPTESQQEDQLI (in isoform 6)"
FT /id="VSP_059644"
FT VARIANT 58
FT /note="T -> I (in dbSNP:rs2990505)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_056935"
FT VARIANT 335
FT /note="T -> M (in dbSNP:rs41275442)"
FT /id="VAR_061681"
FT MUTAGEN 92
FT /note="N->A: Reduced ADP-ribosyl hydrolase activity; when
FT associated with A-102."
FT /evidence="ECO:0000269|PubMed:23474712"
FT MUTAGEN 100
FT /note="G->A: Abolished hydrolase activity and ability to
FT bind ADP-D-ribose."
FT /evidence="ECO:0000269|PubMed:23474714"
FT MUTAGEN 102
FT /note="D->A: Reduced ADP-ribosyl hydrolase activity.
FT Reduced ADP-ribosyl hydrolase activity; when associated
FT with A-92."
FT /evidence="ECO:0000269|PubMed:23474712,
FT ECO:0000269|PubMed:23474714"
FT MUTAGEN 106
FT /note="H->A: Reduced hydrolase activity."
FT /evidence="ECO:0000269|PubMed:23474714"
FT MUTAGEN 188
FT /note="G->E: Abolishes interaction with ADP-ribosylated
FT proteins. Strongly reduced ADP-ribosyl hydrolase activity."
FT /evidence="ECO:0000269|PubMed:23474712"
FT HELIX 11..19
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:4IQY"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:4IQY"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:6Y73"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 82..91
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 111..117
FT /evidence="ECO:0007829|PDB:4IQY"
FT TURN 118..121
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:6Y73"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 157..174
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6Y73"
FT HELIX 194..212
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:4IQY"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:4IQY"
FT HELIX 226..240
FT /evidence="ECO:0007829|PDB:4IQY"
SQ SEQUENCE 425 AA; 47421 MW; 2CB614734EDB6314 CRC64;
MYPSNKKKKV WREEKERLLK MTLEERRKEY LRDYIPLNSI LSWKEEMKGK GQNDEENTQE
TSQVKKSLTE KVSLYRGDIT LLEVDAIVNA ANASLLGGGG VDGCIHRAAG PCLLAECRNL
NGCDTGHAKI TCGYDLPAKY VIHTVGPIAR GHINGSHKED LANCYKSSLK LVKENNIRSV
AFPCISTGIY GFPNEPAAVI ALNTIKEWLA KNHHEVDRII FCVFLEVDFK IYKKKMNEFF
SVDDNNEEEE DVEMKEDSDE NGPEEKQSVE EMEEQSQDAD GVNTVTVPGP ASEEAVEDCK
DEDFAKDENI TKGGEVTDHS VRDQDHPDGQ ENDSTKNEIK IETESQSSYM ETEELSSNQE
DAVIVEQPEV IPLTEDQEEK EGEKAPGEDT PRMPGKSEGS SDLENTPGPD AGAQDEAKEQ
RNGTK
