MACD1_MOUSE
ID MACD1_MOUSE Reviewed; 323 AA.
AC Q922B1;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=ADP-ribose glycohydrolase MACROD1 {ECO:0000305};
DE AltName: Full=MACRO domain-containing protein 1;
DE AltName: Full=O-acetyl-ADP-ribose deacetylase MACROD1;
DE EC=3.1.1.106 {ECO:0000250|UniProtKB:Q9BQ69};
DE AltName: Full=Protein LRP16;
DE AltName: Full=[Protein ADP-ribosylaspartate] hydrolase MACROD1 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000250|UniProtKB:Q9BQ69};
DE AltName: Full=[Protein ADP-ribosylglutamate] hydrolase MACROD1 {ECO:0000305};
DE EC=3.2.2.- {ECO:0000250|UniProtKB:Q9BQ69};
GN Name=Macrod1 {ECO:0000312|MGI:MGI:2147583}; Synonyms=Lrp16;
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=Head;
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 MRNA] OF 52-323.
RC TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Testis;
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).
RN [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-94; LYS-101 AND LYS-127, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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. Plays a role in estrogen signaling.
CC Binds to androgen receptor (AR) and amplifies the transactivation
CC function of AR in response to androgen. May play an important role in
CC carcinogenesis and/or progression of hormone-dependent cancers by feed-
CC forward mechanism that activates ESR1 transactivation. Could be an ESR1
CC coactivator, providing a positive feedback regulatory loop for ESR1
CC signal transduction. Could be involved in invasive growth by down-
CC regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated
CC transcription activity. {ECO:0000250|UniProtKB:Q9BQ69}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3''-O-acetyl-ADP-D-ribose + H2O = acetate + ADP-D-ribose +
CC H(+); Xref=Rhea:RHEA:59244, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:57967, ChEBI:CHEBI:142723;
CC EC=3.1.1.106; Evidence={ECO:0000250|UniProtKB:Q9BQ69};
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 EC=3.1.1.106; Evidence={ECO:0000250|UniProtKB:Q9BQ69};
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:Q9BQ69};
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:Q9BQ69};
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:Q9BQ69};
CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by the product
CC ADP-ribose. {ECO:0000250|UniProtKB:Q9BQ69}.
CC -!- SUBUNIT: Interacts with ESR1; Interacts in a manner that is estrogen
CC independent but is enhanced by estrogen. Interacts (via macro domain)
CC with AR. {ECO:0000250|UniProtKB:Q9BQ69}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9BQ69}.
CC Note=Recruited to DNA lesions, probably via mono-APD-ribosylated
CC proteins. {ECO:0000250|UniProtKB:Q9BQ69}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH08653.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC35234.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK052998; BAC35234.1; ALT_INIT; mRNA.
DR EMBL; BC008653; AAH08653.1; ALT_INIT; mRNA.
DR CCDS; CCDS50376.1; -.
DR RefSeq; NP_598908.2; NM_134147.4.
DR AlphaFoldDB; Q922B1; -.
DR SMR; Q922B1; -.
DR BioGRID; 223219; 5.
DR IntAct; Q922B1; 1.
DR MINT; Q922B1; -.
DR STRING; 10090.ENSMUSP00000039507; -.
DR iPTMnet; Q922B1; -.
DR PhosphoSitePlus; Q922B1; -.
DR SwissPalm; Q922B1; -.
DR EPD; Q922B1; -.
DR jPOST; Q922B1; -.
DR MaxQB; Q922B1; -.
DR PaxDb; Q922B1; -.
DR PeptideAtlas; Q922B1; -.
DR PRIDE; Q922B1; -.
DR ProteomicsDB; 291993; -.
DR Antibodypedia; 51757; 58 antibodies from 12 providers.
DR DNASU; 107227; -.
DR Ensembl; ENSMUST00000040261; ENSMUSP00000039507; ENSMUSG00000036278.
DR GeneID; 107227; -.
DR KEGG; mmu:107227; -.
DR UCSC; uc008gkg.2; mouse.
DR CTD; 28992; -.
DR MGI; MGI:2147583; Macrod1.
DR VEuPathDB; HostDB:ENSMUSG00000036278; -.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000161450; -.
DR HOGENOM; CLU_046550_4_1_1; -.
DR InParanoid; Q922B1; -.
DR OMA; DSAERDW; -.
DR OrthoDB; 937161at2759; -.
DR PhylomeDB; Q922B1; -.
DR TreeFam; TF341440; -.
DR BRENDA; 3.1.1.106; 3474.
DR BioGRID-ORCS; 107227; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Macrod1; mouse.
DR PRO; PR:Q922B1; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q922B1; protein.
DR Bgee; ENSMUSG00000036278; Expressed in interventricular septum and 222 other tissues.
DR Genevisible; Q922B1; MM.
DR GO; GO:0005739; C:mitochondrion; HDA: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: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 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 Acetylation; DNA damage; Hydrolase; Isopeptide bond; Nucleus;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..323
FT /note="ADP-ribose glycohydrolase MACROD1"
FT /id="PRO_0000084486"
FT DOMAIN 139..320
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT BINDING 157..159
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 170..172
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 177..182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 265..271
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT MOD_RES 94
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 101
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 127
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 161
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CROSSLNK 136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BQ69"
SQ SEQUENCE 323 AA; 35295 MW; 57842C4F20833A33 CRC64;
MSLQSQVSGR LAQLRAAGQL LVSLRPWPGR SAGGPRPRGS ACGPLVALGE HGYCAWLSAG
VGAWGAAGRG AWVRTWAPLA MAAKVDLSTS TDWKEAKSFL KGLSDKQREE HYFCKDFIKL
KKIPTWKETA KGLAVKVEDP KYKKDKQLNE KISLYRGDIT KLEVDAIVNA ANSSLLGGGG
VDGCIHRAAG SLLTDECRTL QNCETGKAKI TCGYRLPAKY VIHTVGPIAV GQPTASQAAE
LRSCYLSSLD LLLEHRLRSV AFPCISTGVF GYPNEEAAEV VLASLREWLE QHKDKVDRLI
ICVFLEKDEG IYRERLPHYF PVA
