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 13-SEP-2023, entry version 194. 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}. 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; 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 ProteomicsDB; 294399; -. DR Antibodypedia; 336; 806 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 AGR; MGI:97448; -. 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; 2782890at2759; -. 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; 2 hits in 77 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: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: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:0055081; P:monoatomic anion homeostasis; ISO:MGI. 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; Aspartate/ornithine carbamoyltransferase; 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 NCBIfam; TIGR00658; orni_carb_tr; 1. DR PANTHER; PTHR45753; ORNITHINE CARBAMOYLTRANSFERASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR45753:SF3; ORNITHINE TRANSCARBAMYLASE, MITOCHONDRIAL; 1. DR Pfam; PF00185; OTCace; 1. DR Pfam; PF02729; OTCace_N; 1. DR PRINTS; PR00100; AOTCASE. DR PRINTS; PR00102; OTCASE. DR SUPFAM; SSF53671; Aspartate/ornithine carbamoyltransferase; 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 //