OTC_RAT
ID OTC_RAT Reviewed; 354 AA.
AC P00481; Q63407;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Ornithine transcarbamylase, mitochondrial {ECO:0000305|PubMed:3839075};
DE Short=OTCase {ECO:0000303|PubMed:3839075};
DE EC=2.1.3.3 {ECO:0000269|PubMed:2290837};
DE AltName: Full=Ornithine carbamoyltransferase, mitochondrial;
DE Flags: Precursor;
GN Name=Otc {ECO:0000312|RGD:3236};
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].
RX PubMed=6095294; DOI=10.1073/pnas.81.23.7412;
RA Takiguchi M., Miura S., Mori M., Tatibana M., Nagata S., Kaziro Y.;
RT "Molecular cloning and nucleotide sequence of cDNA for rat ornithine
RT carbamoyltransferase precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:7412-7416(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=3476935; DOI=10.1073/pnas.84.17.6136;
RA Takiguchi M., Murakami T., Miura S., Mori M.;
RT "Structure of the rat ornithine carbamoyltransferase gene, a large, X
RT chromosome-linked gene with an atypical promoter.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6136-6140(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3839075; DOI=10.1093/nar/13.3.943;
RA Kraus J.P., Hodges P.E., Williamson C.L., Horwich A.L., Kalousek F.,
RA Williams K.R., Rosenberg L.E.;
RT "A cDNA clone for the precursor of rat mitochondrial ornithine
RT transcarbamylase: comparison of rat and human leader sequences and
RT conservation of catalytic sites.";
RL Nucleic Acids Res. 13:943-952(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3838931; DOI=10.1089/dna.1985.4.147;
RA McIntyre P., Graf L., Mercer J.F.B., Wake S.A., Hudson P.J., Hoogenraad N.;
RT "The primary structure of the imported mitochondrial protein, ornithine
RT transcarbamylase from rat liver: mRNA levels during ontogeny.";
RL DNA 4:147-156(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 1-102.
RX PubMed=6548714; DOI=10.1016/0014-5793(84)80977-1;
RA McIntyre P., Graf L., Mercer J., Peterson G., Hudson P.J., Hoogenraad N.;
RT "A highly basic N-terminal extension of the mitochondrial matrix enzyme
RT ornithine transcarbamylase from rat liver.";
RL FEBS Lett. 177:41-46(1984).
RN [6]
RP PROTEIN SEQUENCE OF 33-56; 293-302; 307-317 AND 321-329, AND TRANSIT
RP PEPTIDE.
RC TISSUE=Liver;
RX PubMed=3390141; DOI=10.1042/bj2500735;
RA Aoki Y., Sunaga H., Suzuki K.T.;
RT "A cadmium-binding protein in rat liver identified as ornithine
RT carbamoyltransferase.";
RL Biochem. J. 250:735-742(1988).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-92 AND CYS-303.
RX PubMed=2290837; DOI=10.1093/protein/4.1.73;
RA McDowall S., van Heeswijck R., Hoogenraad N.;
RT "Site-directed mutagenesis of Arg60 and Cys271 in ornithine
RT transcarbamylase from rat liver.";
RL Protein Eng. 4:73-77(1990).
CC -!- FUNCTION: Catalyzes the second step of the urea cycle, the condensation
CC of carbamoyl phosphate with L-ornithine to form L-citrulline
CC (PubMed:2290837). The urea cycle ensures the detoxification of ammonia
CC by converting it to urea for excretion (PubMed:2290837).
CC {ECO:0000269|PubMed:2290837}.
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; Evidence={ECO:0000269|PubMed:2290837};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19515;
CC Evidence={ECO:0000305|PubMed:2290837};
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:0000305|PubMed:2290837}.
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 -!- SIMILARITY: Belongs to the aspartate/ornithine carbamoyltransferase
CC superfamily. OTCase family. {ECO:0000305}.
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DR EMBL; K03040; AAA41768.1; -; mRNA.
DR EMBL; M16933; AAA41769.1; -; Genomic_DNA.
DR EMBL; M16924; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16925; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16926; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16928; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16929; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16930; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; M16932; AAA41769.1; JOINED; Genomic_DNA.
DR EMBL; X01976; CAA26007.1; -; mRNA.
DR EMBL; K00001; AAA41772.1; -; mRNA.
DR EMBL; M11266; AAA41767.1; -; mRNA.
DR EMBL; X01178; CAA25618.1; -; mRNA.
DR PIR; A00563; OWRT.
DR RefSeq; NP_037210.1; NM_013078.1.
DR AlphaFoldDB; P00481; -.
DR SMR; P00481; -.
DR STRING; 10116.ENSRNOP00000004686; -.
DR iPTMnet; P00481; -.
DR PhosphoSitePlus; P00481; -.
DR PaxDb; P00481; -.
DR Ensembl; ENSRNOT00000004686; ENSRNOP00000004686; ENSRNOG00000003370.
DR GeneID; 25611; -.
DR KEGG; rno:25611; -.
DR UCSC; RGD:3236; rat.
DR CTD; 5009; -.
DR RGD; 3236; Otc.
DR eggNOG; KOG1504; Eukaryota.
DR GeneTree; ENSGT00510000047417; -.
DR HOGENOM; CLU_043846_3_0_1; -.
DR InParanoid; P00481; -.
DR OMA; DGNNVCN; -.
DR OrthoDB; 1404554at2759; -.
DR PhylomeDB; P00481; -.
DR TreeFam; TF352580; -.
DR Reactome; R-RNO-1268020; Mitochondrial protein import.
DR Reactome; R-RNO-70635; Urea cycle.
DR SABIO-RK; P00481; -.
DR UniPathway; UPA00158; UER00271.
DR PRO; PR:P00481; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003370; Expressed in liver and 15 other tissues.
DR Genevisible; P00481; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0016597; F:amino acid binding; IMP:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0004585; F:ornithine carbamoyltransferase activity; IDA:RGD.
DR GO; GO:0042301; F:phosphate ion binding; IMP:RGD.
DR GO; GO:0005543; F:phospholipid binding; IDA:RGD.
DR GO; GO:0097272; P:ammonium homeostasis; ISO:RGD.
DR GO; GO:0055081; P:anion homeostasis; IDA:RGD.
DR GO; GO:0042450; P:arginine biosynthetic process via ornithine; IBA:GO_Central.
DR GO; GO:0019240; P:citrulline biosynthetic process; IDA:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0007494; P:midgut development; IEP:RGD.
DR GO; GO:0006593; P:ornithine catabolic process; ISO:RGD.
DR GO; GO:0006591; P:ornithine metabolic process; IDA:RGD.
DR GO; GO:0070781; P:response to biotin; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0000050; P:urea cycle; IDA:RGD.
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 Direct protein sequencing; Mitochondrion; Phosphoprotein;
KW Reference proteome; Transferase; Transit peptide; Urea cycle.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3390141"
FT CHAIN 33..354
FT /note="Ornithine transcarbamylase, mitochondrial"
FT /id="PRO_0000020339"
FT ACT_SITE 303
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 90..93
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 141
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 168
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 171
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 199
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 263
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 267
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 268
FT /ligand="L-ornithine"
FT /ligand_id="ChEBI:CHEBI:46911"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 303..304
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT BINDING 330
FT /ligand="carbamoyl phosphate"
FT /ligand_id="ChEBI:CHEBI:58228"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 70
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 80
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 88
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00480"
FT MOD_RES 88
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
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:0000250|UniProtKB:P11725"
FT MOD_RES 144
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 221
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 221
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 231
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 231
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 238
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 238
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 274
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 289
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 292
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 292
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 307
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MOD_RES 307
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11725"
FT MUTAGEN 92
FT /note="R->L: Strong decrease in ornithine
FT carbamoyltransferase activity."
FT /evidence="ECO:0000269|PubMed:2290837"
FT MUTAGEN 303
FT /note="C->S: Increases KM for ornithine 5-fold and
FT decreases kcat 20-fold."
FT /evidence="ECO:0000269|PubMed:2290837"
FT CONFLICT 39
FT /note="G -> P (in Ref. 3; AAA41772)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="G -> S (in Ref. 3; CAA26007/AAA41772)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 39886 MW; 156B511AF7063F0C CRC64;
MLSNLRILLN KAALRKAHTS MVRNFRYGKP VQSQVQLKGR DLLTLKNFTG EEIQYMLWLS
ADLKFRIKQK GEYLPLLQGK SLGMIFEKRS TRTRLSTETG FALLGGHPSF LTTQDIHLGV
NESLTDTARV LSSMTDAVLA RVYKQSDLDI LAKEATIPIV NGLSDLYHPI QILADYLTLQ
EHYGSLKGLT LSWIGDGNNI LHSIMMSAAK FGMHLQAATP KGYEPDPNIV KLAEQYAKEN
GTRLSMTNDP LEAARGGNVL ITDTWISMGQ EDEKKKRLQA FQGYQVTMKT AKVAASDWTF
LHCLPRKPEE VDDEVFYSPR SLVFPEAENR KWTIMAVMVS LLTDYSPVLQ KPKF
