CLYBL_RAT
ID CLYBL_RAT Reviewed; 338 AA.
AC Q5I0K3;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Citramalyl-CoA lyase, mitochondrial {ECO:0000250|UniProtKB:Q8N0X4};
DE EC=4.1.3.25 {ECO:0000250|UniProtKB:Q8N0X4};
DE AltName: Full=(3S)-malyl-CoA thioesterase {ECO:0000250|UniProtKB:Q8N0X4};
DE EC=3.1.2.30 {ECO:0000250|UniProtKB:Q8N0X4};
DE AltName: Full=Beta-methylmalate synthase;
DE EC=2.3.3.- {ECO:0000250|UniProtKB:Q8N0X4};
DE AltName: Full=Citrate lyase subunit beta-like protein, mitochondrial;
DE Short=Citrate lyase beta-like;
DE AltName: Full=Malate synthase;
DE EC=2.3.3.9 {ECO:0000250|UniProtKB:Q8N0X4};
DE Flags: Precursor;
GN Name=Clybl;
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 [LARGE SCALE MRNA] OF 1-205 (ISOFORM 2).
RA Bonaldo M.F., Lennon G., Soares M.B.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-338 (ISOFORM 1).
RC TISSUE=Spleen;
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).
CC -!- FUNCTION: Mitochondrial citramalyl-CoA lyase indirectly involved in the
CC vitamin B12 metabolism. Converts citramalyl-CoA into acetyl-CoA and
CC pyruvate in the C5-dicarboxylate catabolism pathway. The C5-
CC dicarboxylate catabolism pathway is required to detoxify itaconate, a
CC vitamin B12-poisoning metabolite. Also acts as a malate synthase in
CC vitro, converting glyoxylate and acetyl-CoA to malate. Also displays
CC malyl-CoA thioesterase activity. Also acts as a beta-methylmalate
CC synthase in vitro, by mediating conversion of glyoxylate and propionyl-
CC CoA to beta-methylmalate. Also has very weak citramalate synthase
CC activity in vitro. {ECO:0000250|UniProtKB:Q8N0X4}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + glyoxylate + H2O = (S)-malate + CoA + H(+);
CC Xref=Rhea:RHEA:18181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15589, ChEBI:CHEBI:36655, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288; EC=2.3.3.9;
CC Evidence={ECO:0000250|UniProtKB:Q8N0X4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glyoxylate + H2O + propanoyl-CoA = 3-methylmalate + CoA +
CC H(+); Xref=Rhea:RHEA:47628, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:36655, ChEBI:CHEBI:57287, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:87810; Evidence={ECO:0000250|UniProtKB:Q8N0X4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-citramalyl-CoA = acetyl-CoA + pyruvate;
CC Xref=Rhea:RHEA:22612, ChEBI:CHEBI:15361, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58668; EC=4.1.3.25;
CC Evidence={ECO:0000250|UniProtKB:Q8N0X4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malyl-CoA + H2O = (S)-malate + CoA + H(+);
CC Xref=Rhea:RHEA:38291, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15589, ChEBI:CHEBI:57287, ChEBI:CHEBI:57317; EC=3.1.2.30;
CC Evidence={ECO:0000250|UniProtKB:Q8N0X4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8N0X4};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9RUZ0};
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q8N0X4}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8R4N0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5I0K3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5I0K3-2; Sequence=VSP_025044;
CC -!- SIMILARITY: Belongs to the HpcH/HpaI aldolase family. Citrate lyase
CC beta subunit-like subfamily. {ECO:0000305}.
CC -!- CAUTION: This organism lacks the other subunits that are necessary for
CC ATP-independent citrate lyase activity. Even though this protein has
CC clear similarity to citrate lyase beta subunit, it is expected to have
CC a somewhat different enzyme activity. {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; BF567092; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC088243; AAH88243.1; -; mRNA.
DR RefSeq; NP_001094155.1; NM_001100685.1. [Q5I0K3-1]
DR AlphaFoldDB; Q5I0K3; -.
DR SMR; Q5I0K3; -.
DR STRING; 10116.ENSRNOP00000018918; -.
DR iPTMnet; Q5I0K3; -.
DR PhosphoSitePlus; Q5I0K3; -.
DR PaxDb; Q5I0K3; -.
DR PRIDE; Q5I0K3; -.
DR Ensembl; ENSRNOT00000018918; ENSRNOP00000018918; ENSRNOG00000014075. [Q5I0K3-1]
DR GeneID; 306198; -.
DR KEGG; rno:306198; -.
DR CTD; 171425; -.
DR RGD; 1304615; Clybl.
DR eggNOG; ENOG502QQPK; Eukaryota.
DR GeneTree; ENSGT00390000017163; -.
DR HOGENOM; CLU_044864_1_0_1; -.
DR InParanoid; Q5I0K3; -.
DR OMA; AWLFCPA; -.
DR OrthoDB; 1527380at2759; -.
DR PhylomeDB; Q5I0K3; -.
DR TreeFam; TF313596; -.
DR ChiTaRS; Clybl; rat.
DR PRO; PR:Q5I0K3; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000014075; Expressed in heart and 20 other tissues.
DR Genevisible; Q5I0K3; RN.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0047777; F:(S)-citramalyl-CoA lyase activity; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004474; F:malate synthase activity; ISS:UniProtKB.
DR GO; GO:0106121; P:positive regulation of cobalamin metabolic process; ISO:RGD.
DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR GO; GO:0106064; P:regulation of cobalamin metabolic process; ISS:UniProtKB.
DR Gene3D; 3.20.20.60; -; 1.
DR InterPro; IPR005000; Aldolase/citrate-lyase_domain.
DR InterPro; IPR040186; Citramalyl-CoA_lyase.
DR InterPro; IPR011206; Citrate_lyase_beta/mcl1/mcl2.
DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR PANTHER; PTHR11105; PTHR11105; 1.
DR Pfam; PF03328; HpcH_HpaI; 1.
DR PIRSF; PIRSF015582; Cit_lyase_B; 1.
DR SUPFAM; SSF51621; SSF51621; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Hydrolase; Lyase; Magnesium;
KW Metal-binding; Mitochondrion; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 21..338
FT /note="Citramalyl-CoA lyase, mitochondrial"
FT /id="PRO_0000286391"
FT ACT_SITE 318
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 48
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 55
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 59
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 169
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 204
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT BINDING 270..271
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8N0X4"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 59
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 64
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 80
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 80
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 90
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 90
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 307
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT VAR_SEQ 82..144
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_025044"
SQ SEQUENCE 338 AA; 37321 MW; 09585D2C6CE1A3DE CRC64;
MALCVLQNAV RGAAALPRLK ASLVASVCRP GYSSLSNHKY VPRRAVLYVP GNDEKKIRKI
PSLKVDCAVL DCEDGVAENK KNEARLRIAK TLEDFDLGTT EKCVRINSVS SGLAEADLET
FLQARVLPSS LMLPKVEGPE EIQWFSDKFS LHLKGRKLEQ PMNLIPFVET AMGLLNFKAV
CEETLKIGPQ VGLFLDAVVF GGEDFRASIG ATSNKDTQDI LYARQKIVVT AKAFGLQAID
LVYIDFRDED GLLRQSREAA AMGFTGKQVI HPNQIAVVQE QFTPTPEKIR WAEELIAAFK
EHQQLGKGAF TFQGSMIDMP LLKQAQNIVT LATSIKEK
