BUP1_RAT
ID BUP1_RAT Reviewed; 393 AA.
AC Q03248;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Beta-ureidopropionase;
DE EC=3.5.1.6 {ECO:0000269|PubMed:1536562, ECO:0000269|PubMed:8449931};
DE AltName: Full=Beta-alanine synthase {ECO:0000303|PubMed:8449931};
DE AltName: Full=N-carbamoyl-beta-alanine amidohydrolase;
GN Name=Upb1; Synonyms=Bup1;
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], PROTEIN SEQUENCE OF 202-212, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, PREDICTED ZINC-BINDING SITES, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8449931; DOI=10.1016/s0021-9258(18)53373-1;
RA Kvalnes-Krick K.L., Traut T.W.;
RT "Cloning, sequencing, and expression of a cDNA encoding beta-alanine
RT synthase from rat liver.";
RL J. Biol. Chem. 268:5686-5693(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, PATHWAY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=1536562; DOI=10.1016/0003-9861(92)90393-b;
RA Matthews M.M., Liao W., Kvalnes-Krick K.L., Traut T.W.;
RT "beta-Alanine synthase: purification and allosteric properties.";
RL Arch. Biochem. Biophys. 293:254-263(1992).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-378, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes a late step in pyrimidine degradation. Converts N-
CC carbamoyl-beta-alanine (3-ureidopropanoate) into beta-alanine, ammonia
CC and carbon dioxide. Likewise, converts N-carbamoyl-beta-
CC aminoisobutyrate (3-ureidoisobutyrate) into beta-aminoisobutyrate,
CC ammonia and carbon dioxide. {ECO:0000250|UniProtKB:Q9UBR1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(carbamoylamino)propanoate + 2 H(+) + H2O = beta-alanine +
CC CO2 + NH4(+); Xref=Rhea:RHEA:11184, ChEBI:CHEBI:11892,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:57966; EC=3.5.1.6;
CC Evidence={ECO:0000269|PubMed:1536562, ECO:0000269|PubMed:8449931};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(carbamoylamino)-2-methylpropanoate + 2 H(+) + H2O = (R)-3-
CC amino-2-methylpropanoate + CO2 + NH4(+); Xref=Rhea:RHEA:37339,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:57731, ChEBI:CHEBI:74414; EC=3.5.1.6;
CC Evidence={ECO:0000250|UniProtKB:Q9UBR1};
CC -!- ACTIVITY REGULATION: Allosteric enzyme with positive cooperativity
CC toward the substrate N-carbamoyl-beta-alanine at low substrate
CC concentrations (below 12 nM). Displays no cooperativity at substrate
CC levels above 12 nM. {ECO:0000269|PubMed:1536562}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.5 uM for N-carbamoyl-beta-alanine {ECO:0000269|PubMed:1536562};
CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis.
CC {ECO:0000269|PubMed:1536562, ECO:0000269|PubMed:8449931}.
CC -!- SUBUNIT: Homodimer, homotetramer, homooctamer; can also form higher
CC homooligomers. {ECO:0000269|PubMed:1536562}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level).
CC {ECO:0000269|PubMed:8449931}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000305|PubMed:8449931}.
CC -!- SIMILARITY: Belongs to the carbon-nitrogen hydrolase superfamily. BUP
CC family. {ECO:0000305}.
CC -!- CAUTION: The purified enzyme was shown to contain 1.8 zinc atoms per
CC subunit, and sequence analysis was used to predict the zinc binding
CC site (PubMed:8449931). The crystal structure of the human ortholog
CC indicates a lack of bound zinc ions, and shows that the residues that
CC were predicted to bind zinc are too far apart in space to form a zinc
CC binding site (By similarity). {ECO:0000250|UniProtKB:Q9UBR1,
CC ECO:0000269|PubMed:8449931}.
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DR EMBL; M97662; AAA40804.1; -; mRNA.
DR EMBL; BC078767; AAH78767.1; -; mRNA.
DR PIR; A46624; S27881.
DR RefSeq; NP_446297.1; NM_053845.1.
DR AlphaFoldDB; Q03248; -.
DR SMR; Q03248; -.
DR BioGRID; 250508; 1.
DR STRING; 10116.ENSRNOP00000055035; -.
DR iPTMnet; Q03248; -.
DR PhosphoSitePlus; Q03248; -.
DR PRIDE; Q03248; -.
DR Ensembl; ENSRNOT00000115726; ENSRNOP00000092718; ENSRNOG00000038258.
DR GeneID; 116593; -.
DR KEGG; rno:116593; -.
DR CTD; 51733; -.
DR RGD; 620091; Upb1.
DR GeneTree; ENSGT00390000004906; -.
DR InParanoid; Q03248; -.
DR OrthoDB; 996578at2759; -.
DR PhylomeDB; Q03248; -.
DR BioCyc; MetaCyc:MON-15401; -.
DR Reactome; R-RNO-73621; Pyrimidine catabolism.
DR SABIO-RK; Q03248; -.
DR UniPathway; UPA00131; -.
DR PRO; PR:Q03248; -.
DR Proteomes; UP000002494; Chromosome 20.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0003837; F:beta-ureidopropionase activity; IDA:RGD.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0019483; P:beta-alanine biosynthetic process; TAS:RGD.
DR GO; GO:0033396; P:beta-alanine biosynthetic process via 3-ureidopropionate; ISS:UniProtKB.
DR GO; GO:0019482; P:beta-alanine metabolic process; IDA:RGD.
DR GO; GO:0006248; P:CMP catabolic process; ISO:RGD.
DR GO; GO:0006249; P:dCMP catabolic process; ISO:RGD.
DR GO; GO:0046079; P:dUMP catabolic process; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; IEP:RGD.
DR GO; GO:0001889; P:liver development; IDA:RGD.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISO:RGD.
DR GO; GO:0046135; P:pyrimidine nucleoside catabolic process; ISS:UniProtKB.
DR GO; GO:0046050; P:UMP catabolic process; ISO:RGD.
DR Gene3D; 3.60.110.10; -; 1.
DR InterPro; IPR003010; C-N_Hydrolase.
DR InterPro; IPR036526; C-N_Hydrolase_sf.
DR Pfam; PF00795; CN_hydrolase; 1.
DR SUPFAM; SSF56317; SSF56317; 1.
DR PROSITE; PS50263; CN_HYDROLASE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Metal-binding; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..393
FT /note="Beta-ureidopropionase"
FT /id="PRO_0000204054"
FT DOMAIN 72..344
FT /note="CN hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 119
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 196
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 233
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 393 AA; 44042 MW; 723E5AF5B01E3AAD CRC64;
MAGPEWQSLE QCLEKHLPPD DLSQVKRILY GKQTRNLDLP RKALEAASER NFELKGYAFG
AAKEQQRCPQ IVRVGLVQNR IPLPTSAPVA EQVSALHKRI EEIAEVAAMC GVNIICFQEA
WNMPFAFCTR EKLPWTEFAE SAEDGLTTRF CQKLAKKHNM VVISPILERD RDHGGVLWNT
AVVISNSGLV MGKTRKNHIP RVGDFNESTY YMEGNLGHPV FQTQFGRIAV NICYGRHHPL
NWLMYSVNGA EIIFNPSATI GELSESMWPI EARNAAIANH CFTCALNRVG QEHYPNEFTS
GDGKKAHHDL GYFYGSSYVA APDGSRTPGL SRNQDGLLVT ELNLNLCQQI NDFWTFKMTG
RLEMYARELA EAVKPNYSPN IVKEDLVLAP SSG
