MACD2_MOUSE
ID MACD2_MOUSE Reviewed; 475 AA.
AC Q3UYG8;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=ADP-ribose glycohydrolase MACROD2 {ECO:0000305};
DE AltName: Full=MACRO domain-containing protein 2;
DE AltName: Full=O-acetyl-ADP-ribose deacetylase MACROD2 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000250|UniProtKB:A1Z1Q3};
DE AltName: Full=[Protein ADP-ribosylaspartate] hydrolase MACROD2 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000250|UniProtKB:A1Z1Q3};
DE AltName: Full=[Protein ADP-ribosylglutamate] hydrolase MACROD2 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000250|UniProtKB:A1Z1Q3};
GN Name=Macrod2 {ECO:0000312|MGI:MGI:1920149};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=17586838; DOI=10.1136/jmg.2007.049510;
RA Maas N.M.C., Van de Putte T., Melotte C., Francis A.,
RA Schrander-Stumpel C.T.R.M., Sanlaville D., Genevieve D., Lyonnet S.,
RA Dimitrov B., Devriendt K., Fryns J.-P., Vermeesch J.R.;
RT "The C20orf133 gene is disrupted in a patient with Kabuki syndrome.";
RL J. Med. Genet. 44:562-569(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Removes ADP-ribose from aspartate and glutamate residues in
CC proteins bearing a single ADP-ribose moiety. Inactive towards proteins
CC bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling
CC molecule generated by the deacetylation of acetylated lysine residues
CC in histones and other proteins. {ECO:0000250|UniProtKB:A1Z1Q3}.
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:0000250|UniProtKB:A1Z1Q3};
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:0000250|UniProtKB:A1Z1Q3};
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:0000250|UniProtKB:A1Z1Q3};
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:0000250|UniProtKB:A1Z1Q3};
CC -!- ACTIVITY REGULATION: Subject to product inhibition by ADP-ribose.
CC {ECO:0000250|UniProtKB:A1Z1Q3}.
CC -!- SUBUNIT: Interacts with ADP-ribosylated PARP1.
CC {ECO:0000250|UniProtKB:A1Z1Q3}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:A1Z1Q3}.
CC Note=Recruited to DNA lesions, probably via mono-APD-ribosylated
CC proteins. {ECO:0000250|UniProtKB:A1Z1Q3}.
CC -!- TISSUE SPECIFICITY: Expressed in the kidney.
CC {ECO:0000269|PubMed:17586838}.
CC -!- DEVELOPMENTAL STAGE: At 12.5 dpc, expressed in the neural tube and in
CC the dorsal root and cranial ganglia. At 14.5 dpc, expressed in
CC metanephric glomeruli, but not in the medullary region of the kidney,
CC in the epithelium lining the gut, the stomach and the seminiferous
CC tubules, as well as in lung. Expression is maintained in the dorsal
CC root and cranial ganglia. In the cranial region, up-regulated in the
CC epithelial and mesenchymal components of the tooth bud, in the
CC epithelium lining the primitive nasal cavity, the vestibulocochlear and
CC cochlear ducts and in the cranial ganglia. At 16.5 dpc, expression is
CC maintained in kidney and lung. Detected in the papilla of the whisker
CC follicle. In the eye, highly expressed in the cuboid epithelium of the
CC lens and the inner nuclear (neuroblastic) layer of the retina.
CC Expression begins in the brain, in particular the ventricular zone, and
CC in the heart. At 18.5 dpc, expression is maintained in the brain,
CC including the subventricular zone of striatum and olfactory lobe, the
CC cortical plate, the cerebellar primordium and the inferior colliculus
CC of the tectum. At this stage, the expression in the heart is 45 times
CC lower than in the brain. At birth, still detectable in the metanephric
CC glomeruli, but not in the adrenal gland. {ECO:0000269|PubMed:17586838}.
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DR EMBL; AK134694; BAE22244.1; -; mRNA.
DR EMBL; AL731795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL837516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL845530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928823; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929027; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS50733.1; -.
DR RefSeq; NP_001013824.2; NM_001013802.3.
DR AlphaFoldDB; Q3UYG8; -.
DR SMR; Q3UYG8; -.
DR STRING; 10090.ENSMUSP00000105691; -.
DR iPTMnet; Q3UYG8; -.
DR PhosphoSitePlus; Q3UYG8; -.
DR MaxQB; Q3UYG8; -.
DR PaxDb; Q3UYG8; -.
DR PeptideAtlas; Q3UYG8; -.
DR PRIDE; Q3UYG8; -.
DR ProteomicsDB; 295759; -.
DR Antibodypedia; 62792; 23 antibodies from 8 providers.
DR DNASU; 72899; -.
DR Ensembl; ENSMUST00000078027; ENSMUSP00000077174; ENSMUSG00000068205.
DR Ensembl; ENSMUST00000110064; ENSMUSP00000105691; ENSMUSG00000068205.
DR GeneID; 72899; -.
DR KEGG; mmu:72899; -.
DR UCSC; uc008mpv.1; mouse.
DR CTD; 140733; -.
DR MGI; MGI:1920149; Macrod2.
DR VEuPathDB; HostDB:ENSMUSG00000068205; -.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000157404; -.
DR InParanoid; Q3UYG8; -.
DR OMA; XAFPCIS; -.
DR OrthoDB; 937161at2759; -.
DR PhylomeDB; Q3UYG8; -.
DR TreeFam; TF341440; -.
DR BioGRID-ORCS; 72899; 3 hits in 69 CRISPR screens.
DR ChiTaRS; Macrod2; mouse.
DR PRO; PR:Q3UYG8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q3UYG8; protein.
DR Bgee; ENSMUSG00000068205; Expressed in primary oocyte and 233 other tissues.
DR ExpressionAtlas; Q3UYG8; baseline and differential.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0140293; F:ADP-ribosylglutamate hydrolase activity; ISS:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; ISO:MGI.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0140291; P:peptidyl-glutamate ADP-deribosylation; ISS:UniProtKB.
DR GO; GO:0051725; P:protein de-ADP-ribosylation; ISS:UniProtKB.
DR GO; GO:0042278; P:purine nucleoside metabolic process; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
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 DNA damage; Hydrolase; Isopeptide bond; Nucleus; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..475
FT /note="ADP-ribose glycohydrolase MACROD2"
FT /id="PRO_0000300462"
FT DOMAIN 59..240
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT REGION 241..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..299
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..357
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 358..377
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..399
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 77..79
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 90..92
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 97..102
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 185..191
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT CROSSLNK 170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
SQ SEQUENCE 475 AA; 52145 MW; 47D6AE85DF7FF08A CRC64;
MYPSNKKKKV WREEKERLLK MTLEERRKEY IRDYVSLSTI LSWKEEMKSK GQNDEENTQE
APQMKKSLSE KVSLYRGDIT LLEVDAIVNA ANASLLGGGG VDGCIHRAAG PCLLAECRNL
NGCETGHAKI TCGYDLPAKY VIHTVGPIAR GHINGSHKED LANCYQSSLK LVKENNLRSV
AFPCISTGIY GFPNEPAAVI ALGTIKEWLA KNHQEVDRII FCVFLEVDFK IYKKKMNEFF
PVDDNNEGTD ADMKEDSEGP EPKGLSPPHK KSKAKKPESS KDSSEDESGP EEKQTAEEME
GQSQEAGGLR FLLRNLLGLI HRDGVNTTPV PSPASEDKAE VHKDEDSAKD DNTVKDSDMT
NHSVCDQELP NGQENDSAKS EGKTEAESPS SSMETEDLSP NQEDAAIVEQ PEVIPLIDDQ
EAQEGGEAQG KDAPAVFAES QGSSEAENTS GPDVDMNSQV DGVNEPTESL QEDLQ
