P20D2_MOUSE
ID P20D2_MOUSE Reviewed; 431 AA.
AC A3KG59; Q3ULU7;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Xaa-Arg dipeptidase;
DE EC=3.4.13.4 {ECO:0000269|PubMed:24891507};
GN Name=Pm20d2 {ECO:0000303|PubMed:24891507, ECO:0000312|MGI:MGI:2685270};
GN Synonyms=Acy1l2, Gm424;
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] (ISOFORM 2).
RC TISSUE=Mammary gland;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, and Pancreas;
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 FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24891507; DOI=10.1074/jbc.m114.576579;
RA Veiga-da-Cunha M., Chevalier N., Stroobant V., Vertommen D.,
RA Van Schaftingen E.;
RT "Metabolite proofreading in carnosine and homocarnosine synthesis:
RT molecular identification of PM20D2 as beta-alanyl-lysine dipeptidase.";
RL J. Biol. Chem. 289:19726-19736(2014).
CC -!- FUNCTION: Catalyzes the peptide bond hydrolysis in dipeptides having
CC basic amino acids lysine, ornithine or arginine at C-terminus.
CC Postulated to function in a metabolite repair mechanism by eliminating
CC alternate dipeptide by-products formed during carnosine synthesis.
CC {ECO:0000269|PubMed:24891507}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanyl-L-lysine + H2O = beta-alanine + L-lysine;
CC Xref=Rhea:RHEA:59608, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:57966, ChEBI:CHEBI:143161; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59609;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanyl-L-arginine + H2O = beta-alanine + L-arginine;
CC Xref=Rhea:RHEA:59616, ChEBI:CHEBI:15377, ChEBI:CHEBI:32682,
CC ChEBI:CHEBI:57966, ChEBI:CHEBI:143157; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59617;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanyl-L-ornithine + H2O = beta-alanine + L-ornithine;
CC Xref=Rhea:RHEA:59612, ChEBI:CHEBI:15377, ChEBI:CHEBI:46911,
CC ChEBI:CHEBI:57966, ChEBI:CHEBI:143162; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59613;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-lysine = 4-aminobutanoate + L-
CC lysine; Xref=Rhea:RHEA:59620, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:59888, ChEBI:CHEBI:143159; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59621;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-arginine = 4-aminobutanoate +
CC L-arginine; Xref=Rhea:RHEA:59628, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32682, ChEBI:CHEBI:59888, ChEBI:CHEBI:143158;
CC EC=3.4.13.4; Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59629;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-ornithine = 4-aminobutanoate +
CC L-ornithine; Xref=Rhea:RHEA:59624, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:46911, ChEBI:CHEBI:59888, ChEBI:CHEBI:143160;
CC EC=3.4.13.4; Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59625;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.9 mM for beta-alanyl-L-lysine {ECO:0000269|PubMed:24891507};
CC KM=1.9 mM for beta-alanyl-L-ornithine {ECO:0000269|PubMed:24891507};
CC KM=6.8 mM for beta-alanyl-L-arginine {ECO:0000269|PubMed:24891507};
CC KM=2.6 mM for N(2)-(4-aminobutanoyl)-L-lysine
CC {ECO:0000269|PubMed:24891507};
CC KM=1.35 mM for N(2)-(4-aminobutanoyl)-L-ornithine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=17.4 umol/min/mg enzyme toward beta-alanyl-L-lysine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=30.7 umol/min/mg enzyme toward beta-alanyl-L-ornithine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=27 umol/min/mg enzyme toward N(2)-(4-aminobutanoyl)-L-lysine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=12.5 umol/min/mg enzyme toward N(2)-(4-aminobutanoyl)-L-
CC ornithine {ECO:0000269|PubMed:24891507};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A3KG59-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A3KG59-2; Sequence=VSP_025030, VSP_025031;
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK145296; BAE26351.1; -; mRNA.
DR EMBL; AL670464; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51136.1; -. [A3KG59-1]
DR RefSeq; NP_001030039.2; NM_001034867.2. [A3KG59-1]
DR AlphaFoldDB; A3KG59; -.
DR SMR; A3KG59; -.
DR STRING; 10090.ENSMUSP00000095783; -.
DR iPTMnet; A3KG59; -.
DR PhosphoSitePlus; A3KG59; -.
DR MaxQB; A3KG59; -.
DR PaxDb; A3KG59; -.
DR PeptideAtlas; A3KG59; -.
DR PRIDE; A3KG59; -.
DR ProteomicsDB; 294278; -. [A3KG59-1]
DR ProteomicsDB; 294279; -. [A3KG59-2]
DR Antibodypedia; 31855; 108 antibodies from 22 providers.
DR Ensembl; ENSMUST00000098181; ENSMUSP00000095783; ENSMUSG00000054659. [A3KG59-1]
DR Ensembl; ENSMUST00000119167; ENSMUSP00000113669; ENSMUSG00000054659. [A3KG59-2]
DR GeneID; 242377; -.
DR KEGG; mmu:242377; -.
DR UCSC; uc008sfs.1; mouse. [A3KG59-2]
DR UCSC; uc012dbj.2; mouse. [A3KG59-1]
DR CTD; 135293; -.
DR MGI; MGI:2685270; Pm20d2.
DR VEuPathDB; HostDB:ENSMUSG00000054659; -.
DR eggNOG; ENOG502QQPD; Eukaryota.
DR GeneTree; ENSGT00390000003365; -.
DR HOGENOM; CLU_031812_1_1_1; -.
DR InParanoid; A3KG59; -.
DR OMA; EHHAHGV; -.
DR OrthoDB; 455218at2759; -.
DR PhylomeDB; A3KG59; -.
DR TreeFam; TF332656; -.
DR BioGRID-ORCS; 242377; 1 hit in 72 CRISPR screens.
DR PRO; PR:A3KG59; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A3KG59; protein.
DR Bgee; ENSMUSG00000054659; Expressed in hindlimb stylopod muscle and 49 other tissues.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016805; F:dipeptidase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IDA:MGI.
DR InterPro; IPR017439; Amidohydrolase.
DR InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR InterPro; IPR017144; Xaa-Arg_dipeptidase.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF037226; Amidohydrolase_ACY1L2_prd; 1.
DR SUPFAM; SSF55031; SSF55031; 1.
DR TIGRFAMs; TIGR01891; amidohydrolases; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Carboxypeptidase; Hydrolase; Protease;
KW Reference proteome.
FT CHAIN 1..431
FT /note="Xaa-Arg dipeptidase"
FT /id="PRO_0000286341"
FT VAR_SEQ 301..305
FT /note="DIESE -> RAFQN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025030"
FT VAR_SEQ 306..431
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025031"
FT CONFLICT 175
FT /note="E -> K (in Ref. 1; BAE26351)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 431 AA; 46482 MW; AF2AD1380593F283 CRC64;
MGPVVERPAE PGTSSAAELE LLKRRAAERI DEAAERLGAL SRAIWSAPEL AYEEHRAHGE
LTRFFECEPP AASWAVQPHF GLPTAFRAEW APPESAAGPR ALQVAFLCEY DALPALGHAC
GHNLIAEVGV AAALGLRAAL ESIAAPPPVK VIVLGTPAEE DGGGKIDLIE AGAFENLDVV
FMAHPSQENA AYLPDVAEHD VTVKYYGKAS HAAAYPWEGV NALDAAVLAY TNLSVLRQQM
KPTWRVHGII KNGGVKPNII PSYSELVYYF RAPSMKELQV LTKKAEDCFR AAALATGCTV
DIESEAHDYY NVIPNKTLCS AYTENGKKLG MEFISEDAVL NGPSGSTDFG NVSFVVPGIH
PYFYIGTDAL NHTEQYTEAA GSQAAQLYTL RTAKALAMTA LDVIFKPALL EGVRKEFKCK
LQEEQLLNTA A
