MACD1_RAT
ID MACD1_RAT Reviewed; 258 AA.
AC Q8K4G6;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 102.
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};
DE Flags: Fragment;
GN Name=Macrod1; Synonyms=Lrp16;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Zhang X., Ip N.Y.;
RT "Rat mRNA sequence similar to LRP16 protein of humans.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
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=AAM45760.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF404762; AAM45760.1; ALT_INIT; mRNA.
DR RefSeq; NP_647553.1; NM_139337.1.
DR AlphaFoldDB; Q8K4G6; -.
DR SMR; Q8K4G6; -.
DR STRING; 10116.ENSRNOP00000028749; -.
DR iPTMnet; Q8K4G6; -.
DR PhosphoSitePlus; Q8K4G6; -.
DR PRIDE; Q8K4G6; -.
DR GeneID; 246233; -.
DR KEGG; rno:246233; -.
DR UCSC; RGD:628701; rat.
DR CTD; 28992; -.
DR RGD; 628701; Macrod1.
DR eggNOG; KOG2633; Eukaryota.
DR InParanoid; Q8K4G6; -.
DR OrthoDB; 937161at2759; -.
DR PhylomeDB; Q8K4G6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
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:RGD.
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:RGD.
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 2: Evidence at transcript level;
KW Acetylation; DNA damage; Hydrolase; Isopeptide bond; Nucleus;
KW Reference proteome; Ubl conjugation.
FT CHAIN <1..258
FT /note="ADP-ribose glycohydrolase MACROD1"
FT /id="PRO_0000084487"
FT DOMAIN 74..255
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT BINDING 92..94
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 105..107
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 112..117
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 200..206
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A1Z1Q3"
FT MOD_RES 29
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q922B1"
FT MOD_RES 36
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q922B1"
FT MOD_RES 62
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q922B1"
FT MOD_RES 96
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q922B1"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BQ69"
FT NON_TER 1
SQ SEQUENCE 258 AA; 28643 MW; FB430516A12D6B42 CRC64;
AAGRGAWVRT WAPLAMAAKV DLSTSTDWKE AKSFLKGLSD KQREEHYFCK DFIKLKKIPM
WKETAKGLAG KVENPKYKKD KQLNEKISLF RGDITKLEVD AIVNAANNSL LGGGGVDGCI
HRAAGSLLTD ECRTLQNCET GKAKITCGYR LPAKHVIHTV GPIAVGQPTA SQAAELRSCY
LSSLDLLLEH RLRSVAFPCI STGVFGYPNE EAAEVVLATL REWLEQHKDK VDRLIICVFL
EKDEGIYQER LPHYFPVA
