OTC_MOUSE
ID OTC_MOUSE Reviewed; 354 AA.
AC P11725;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Ornithine transcarbamylase, mitochondrial {ECO:0000305|PubMed:3011788};
DE Short=OTCase {ECO:0000305};
DE EC=2.1.3.3 {ECO:0000250|UniProtKB:P00480};
DE AltName: Full=Ornithine carbamoyltransferase, mitochondrial;
DE Flags: Precursor;
GN Name=Otc {ECO:0000312|MGI:MGI:97448};
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 [MRNA], VARIANT SPF ASN-117, AND DISEASE.
RC STRAIN=C57BL/6J;
RX PubMed=3603027; DOI=10.1126/science.3603027;
RA Veres G., Gibbs R.A., Scherer S.E., Caskey C.T.;
RT "The molecular basis of the sparse fur mouse mutation.";
RL Science 237:415-417(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2831503; DOI=10.1093/nar/16.4.1593;
RA Scherer S.E., Veres G., Caskey C.T.;
RT "The genetic structure of mouse ornithine transcarbamylase.";
RL Nucleic Acids Res. 16:1593-1601(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26.
RC STRAIN=C57BL/6J;
RX PubMed=3011788; DOI=10.1016/s0021-9258(19)57435-x;
RA Veres G., Craigen W.J., Caskey C.T.;
RT "The 5' flanking region of the ornithine transcarbamylase gene contains DNA
RT sequences regulating tissue-specific expression.";
RL J. Biol. Chem. 261:7588-7591(1986).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
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 [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-70; LYS-80; LYS-88; LYS-144;
RP LYS-221; LYS-231; LYS-238; LYS-274; LYS-289; LYS-292 AND LYS-307, 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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70; LYS-88; LYS-144; LYS-221;
RP LYS-231; LYS-238; LYS-243; LYS-292 AND LYS-307, 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: Catalyzes the second step of the urea cycle, the condensation
CC of carbamoyl phosphate with L-ornithine to form L-citrulline. The urea
CC cycle ensures the detoxification of ammonia by converting it to urea
CC for excretion. {ECO:0000250|UniProtKB:P00480}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=carbamoyl phosphate + L-ornithine = H(+) + L-citrulline +
CC phosphate; Xref=Rhea:RHEA:19513, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:46911, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:58228; EC=2.1.3.3;
CC Evidence={ECO:0000250|UniProtKB:P00480};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19515;
CC Evidence={ECO:0000250|UniProtKB:P00480};
CC -!- ACTIVITY REGULATION: Negatively regulated by lysine acetylation.
CC {ECO:0000250|UniProtKB:P00480}.
CC -!- PATHWAY: Nitrogen metabolism; urea cycle; L-citrulline from L-ornithine
CC and carbamoyl phosphate: step 1/1. {ECO:0000250|UniProtKB:P00480}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:P00480}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P00480}.
CC -!- PTM: Acetylation at Lys-88 negatively regulates ornithine
CC carbamoyltransferase activity in response to nutrient signals.
CC {ECO:0000250|UniProtKB:P00480}.
CC -!- DISEASE: Note=Defects in Otc are the cause of the Sparse fur (spf)
CC phenotype. Spf mouse have an OTCase with an overall decrease in
CC activity, and altered substrate affinity. {ECO:0000269|PubMed:3603027}.
CC -!- SIMILARITY: Belongs to the aspartate/ornithine carbamoyltransferase
CC superfamily. OTCase family. {ECO:0000305}.
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DR EMBL; M17030; AAA39865.1; -; mRNA.
DR EMBL; M12716; AAA39864.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X07092; CAA30121.1; -; Genomic_DNA.
DR EMBL; X07093; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07094; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07095; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07096; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07097; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07098; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07099; CAA30121.1; JOINED; Genomic_DNA.
DR EMBL; X07100; CAA30121.1; JOINED; Genomic_DNA.
DR CCDS; CCDS30015.1; -.
DR PIR; A43609; OWMS.
DR RefSeq; NP_032795.1; NM_008769.4.
DR AlphaFoldDB; P11725; -.
DR SMR; P11725; -.
DR BioGRID; 201986; 1.
DR STRING; 10090.ENSMUSP00000056152; -.
DR iPTMnet; P11725; -.
DR PhosphoSitePlus; P11725; -.
DR SwissPalm; P11725; -.
DR SWISS-2DPAGE; P11725; -.
DR jPOST; P11725; -.
DR PaxDb; P11725; -.
DR PeptideAtlas; P11725; -.
DR PRIDE; P11725; -.
DR ProteomicsDB; 294399; -.
DR Antibodypedia; 336; 736 antibodies from 30 providers.
DR DNASU; 18416; -.
DR Ensembl; ENSMUST00000049910; ENSMUSP00000056152; ENSMUSG00000031173.
DR GeneID; 18416; -.
DR KEGG; mmu:18416; -.
DR UCSC; uc009sqk.1; mouse.
DR CTD; 5009; -.
DR MGI; MGI:97448; Otc.
DR VEuPathDB; HostDB:ENSMUSG00000031173; -.
DR eggNOG; KOG1504; Eukaryota.
DR GeneTree; ENSGT00510000047417; -.
DR HOGENOM; CLU_043846_3_0_1; -.
DR InParanoid; P11725; -.
DR OMA; DGNNVCN; -.
DR OrthoDB; 1404554at2759; -.
DR PhylomeDB; P11725; -.
DR TreeFam; TF352580; -.
DR Reactome; R-MMU-1268020; Mitochondrial protein import.
DR Reactome; R-MMU-70635; Urea cycle.
DR UniPathway; UPA00158; UER00271.
DR BioGRID-ORCS; 18416; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Otc; mouse.
DR PRO; PR:P11725; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P11725; protein.
DR Bgee; ENSMUSG00000031173; Expressed in left lobe of liver and 41 other tissues.
DR ExpressionAtlas; P11725; baseline and differential.
DR Genevisible; P11725; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004585; F:ornithine carbamoyltransferase activity; ISO:MGI.
DR GO; GO:0042301; F:phosphate ion binding; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; ISO:MGI.
DR GO; GO:0097272; P:ammonium homeostasis; ISO:MGI.
DR GO; GO:0055081; P:anion homeostasis; ISO:MGI.
DR GO; GO:0042450; P:arginine biosynthetic process via ornithine; IBA:GO_Central.
DR GO; GO:0019240; P:citrulline biosynthetic process; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0007494; P:midgut development; IEA:Ensembl.
DR GO; GO:0006593; P:ornithine catabolic process; ISO:MGI.
DR GO; GO:0006591; P:ornithine metabolic process; ISO:MGI.
DR GO; GO:0070781; P:response to biotin; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0000050; P:urea cycle; ISO:MGI.
DR Gene3D; 3.40.50.1370; -; 2.
DR InterPro; IPR006132; Asp/Orn_carbamoyltranf_P-bd.
DR InterPro; IPR006130; Asp/Orn_carbamoylTrfase.
DR InterPro; IPR036901; Asp/Orn_carbamoylTrfase_sf.
DR InterPro; IPR006131; Asp_carbamoyltransf_Asp/Orn-bd.
DR InterPro; IPR002292; Orn/put_carbamltrans.
DR Pfam; PF00185; OTCace; 1.
DR Pfam; PF02729; OTCace_N; 1.
DR PRINTS; PR00100; AOTCASE.
DR PRINTS; PR00102; OTCASE.
DR SUPFAM; SSF53671; SSF53671; 1.
DR TIGRFAMs; TIGR00658; orni_carb_tr; 1.
DR PROSITE; PS00097; CARBAMOYLTRANSFERASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Amino-acid biosynthesis; Arginine biosynthesis;
KW Disease variant; Mitochondrion; Phosphoprotein; Reference proteome;
KW Transferase; Transit peptide; Urea cycle.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT CHAIN 33..354
FT /note="Ornithine transcarbamylase, mitochondrial"
FT /id="PRO_0000020335"
FT ACT_SITE 303
FT /evidence="ECO:0000250"
FT BINDING 90..94
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250"
FT BINDING 141
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250"
FT BINDING 141
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250"
FT BINDING 263..267
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250"
FT BINDING 302..305
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 70
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 80
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 88
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 88
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT MOD_RES 144
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 144
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 221
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 221
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 231
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 231
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 238
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 238
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 274
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 289
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 292
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 292
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 307
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 307
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VARIANT 117
FT /note="H -> N (in spf)"
FT /evidence="ECO:0000269|PubMed:3603027"
FT CONFLICT 195
FT /note="G -> R (in Ref. 2; CAA30121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 39765 MW; 33BBE5D1E88AA196 CRC64;
MLSNLRILLN NAALRKGHTS VVRHFWCGKP VQSQVQLKGR DLLTLKNFTG EEIQYMLWLS
ADLKFRIKQK GEYLPLLQGK SLGMIFEKRS TRTRLSTETG FALLGGHPSF LTTQDIHLGV
NESLTDTARV LSSMTDAVLA RVYKQSDLDT LAKEASIPIV NGLSDLYHPI QILADYLTLQ
EHYGSLKGLT LSWIGDGNNI LHSIMMSAAK FGMHLQAATP KGYEPDPNIV KLAEQYAKEN
GTKLSMTNDP LEAARGGNVL ITDTWISMGQ EDEKKKRLQA FQGYQVTMKT AKVAASDWTF
LHCLPRKPEE VDDEVFYSPR SLVFPEAENR KWTIMAVMVS LLTDYSPVLQ KPKF
