CLYBL_MOUSE
ID CLYBL_MOUSE Reviewed; 338 AA.
AC Q8R4N0; Q9D7D0;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Citramalyl-CoA lyase, mitochondrial;
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 {ECO:0000312|MGI:MGI:1916884}; Synonyms=Clb;
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], AND TISSUE SPECIFICITY.
RX PubMed=11741334; DOI=10.1006/bbrc.2001.6125;
RA Morikawa J., Nishimura Y., Uchida A., Tanaka T.;
RT "Molecular cloning of novel mouse and human putative citrate lyase beta-
RT subunit.";
RL Biochem. Biophys. Res. Commun. 289:1282-1286(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [4]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=18614015; DOI=10.1016/j.cell.2008.06.016;
RA Pagliarini D.J., Calvo S.E., Chang B., Sheth S.A., Vafai S.B., Ong S.E.,
RA Walford G.A., Sugiana C., Boneh A., Chen W.K., Hill D.E., Vidal M.,
RA Evans J.G., Thorburn D.R., Carr S.A., Mootha V.K.;
RT "A mitochondrial protein compendium elucidates complex I disease biology.";
RL Cell 134:112-123(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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 [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-80; LYS-90 AND LYS-307, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55; LYS-59; LYS-64; LYS-80 AND
RP LYS-90, AND IDENTIFICATION BY MASS 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).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=24334609; DOI=10.1093/hmg/ddt624;
RA Strittmatter L., Li Y., Nakatsuka N.J., Calvo S.E., Grabarek Z.,
RA Mootha V.K.;
RT "CLYBL is a polymorphic human enzyme with malate synthase and beta-
RT methylmalate synthase activity.";
RL Hum. Mol. Genet. 23:2313-2323(2014).
RN [9]
RP FUNCTION.
RX PubMed=29056341; DOI=10.1016/j.cell.2017.09.051;
RA Shen H., Campanello G.C., Flicker D., Grabarek Z., Hu J., Luo C.,
RA Banerjee R., Mootha V.K.;
RT "The human knockout gene CLYBL connects itaconate to vitamin B12.";
RL Cell 171:771-782(2017).
CC -!- FUNCTION: Mitochondrial citramalyl-CoA lyase indirectly involved in the
CC vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into
CC acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (By
CC similarity). The C5-dicarboxylate catabolism pathway is required to
CC detoxify itaconate, a vitamin B12-poisoning metabolite
CC (PubMed:29056341). Also acts as a malate synthase in vitro, converting
CC glyoxylate and acetyl-CoA to malate (By similarity). 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 (By similarity). Also has very weak
CC citramalate synthase activity in vitro (By similarity).
CC {ECO:0000250|UniProtKB:Q8N0X4, ECO:0000269|PubMed:29056341}.
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:0000269|PubMed:18614015}.
CC -!- TISSUE SPECIFICITY: Detected in brown fat, brain, liver, kidney, heart,
CC skeletal muscle and ovary (at protein level).
CC {ECO:0000269|PubMed:11741334, ECO:0000269|PubMed:24334609}.
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}.
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DR EMBL; AF428254; AAL84704.1; -; mRNA.
DR EMBL; AK009345; BAB26232.1; -; mRNA.
DR EMBL; BC023398; AAH23398.1; -; mRNA.
DR CCDS; CCDS27346.1; -.
DR RefSeq; NP_083832.2; NM_029556.3.
DR AlphaFoldDB; Q8R4N0; -.
DR SMR; Q8R4N0; -.
DR BioGRID; 213580; 4.
DR STRING; 10090.ENSMUSP00000026625; -.
DR iPTMnet; Q8R4N0; -.
DR PhosphoSitePlus; Q8R4N0; -.
DR REPRODUCTION-2DPAGE; Q8R4N0; -.
DR EPD; Q8R4N0; -.
DR jPOST; Q8R4N0; -.
DR MaxQB; Q8R4N0; -.
DR PaxDb; Q8R4N0; -.
DR PeptideAtlas; Q8R4N0; -.
DR PRIDE; Q8R4N0; -.
DR ProteomicsDB; 283314; -.
DR Antibodypedia; 25197; 61 antibodies from 16 providers.
DR DNASU; 69634; -.
DR Ensembl; ENSMUST00000026625; ENSMUSP00000026625; ENSMUSG00000025545.
DR GeneID; 69634; -.
DR KEGG; mmu:69634; -.
DR UCSC; uc007vax.2; mouse.
DR CTD; 171425; -.
DR MGI; MGI:1916884; Clybl.
DR VEuPathDB; HostDB:ENSMUSG00000025545; -.
DR eggNOG; ENOG502QQPK; Eukaryota.
DR GeneTree; ENSGT00390000017163; -.
DR HOGENOM; CLU_044864_1_0_1; -.
DR InParanoid; Q8R4N0; -.
DR OMA; AWLFCPA; -.
DR OrthoDB; 1527380at2759; -.
DR PhylomeDB; Q8R4N0; -.
DR TreeFam; TF313596; -.
DR BRENDA; 4.1.3.6; 3474.
DR BioGRID-ORCS; 69634; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Clybl; mouse.
DR PRO; PR:Q8R4N0; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8R4N0; protein.
DR Bgee; ENSMUSG00000025545; Expressed in interventricular septum and 247 other tissues.
DR Genevisible; Q8R4N0; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047777; F:(S)-citramalyl-CoA lyase activity; IDA: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; IMP:CACAO.
DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR GO; GO:0106064; P:regulation of cobalamin metabolic process; IDA: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 1: Evidence at protein level;
KW Acetylation; Hydrolase; Lyase; Magnesium; Metal-binding; Mitochondrion;
KW Reference proteome; Transferase; 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_0000286390"
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:0007744|PubMed:23576753"
FT MOD_RES 59
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 64
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 80
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 80
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 90
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 90
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 307
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 9
FT /note="T -> A (in Ref. 1; AAL84704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 338 AA; 37549 MW; 6F8AA53D9EDC3958 CRC64;
MALCVLRNTV RGAAALPRLK ASHVVSVYKP RYSSLSNHKY VPRRAVLYVP GNDEKKIRKI
PSLKVDCAVL DCEDGVAENK KNEARLRIAK TLEDFDLGTT EKCVRINSVS SGLAEVDLET
FLQARVLPSS LMLPKVEGPE EIRWFSDKFS LHLKGRKLEQ PMNLIPFVET AMGLLNFKAV
CEETLKTGPQ VGLCLDAVVF GGEDFRASIG ATSNKDTQDI LYARQKVVVT AKAFGLQAID
LVYIDFRDED GLLRQSREAA AMGFTGKQVI HPNQIAVVQE QFTPTPEKIQ WAEELIAAFK
EHQQLGKGAF TFRGSMIDMP LLKQAQNIVT LATSIKEK
