CLYBL_HUMAN
ID CLYBL_HUMAN Reviewed; 340 AA.
AC Q8N0X4; Q5W0F7; Q8TDH8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Citramalyl-CoA lyase, mitochondrial {ECO:0000303|PubMed:29056341};
DE EC=4.1.3.25 {ECO:0000269|PubMed:29056341};
DE AltName: Full=(3S)-malyl-CoA thioesterase {ECO:0000305|PubMed:29056341};
DE EC=3.1.2.30 {ECO:0000269|PubMed:29056341};
DE AltName: Full=Beta-methylmalate synthase;
DE EC=2.3.3.- {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341};
DE AltName: Full=Citrate lyase subunit beta-like protein {ECO:0000305};
DE Short=Citrate lyase beta-like {ECO:0000305};
DE AltName: Full=Malate synthase;
DE EC=2.3.3.9 {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341};
DE Flags: Precursor;
GN Name=CLYBL {ECO:0000312|HGNC:HGNC:18355}; Synonyms=CLB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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] (ISOFORM 1), AND VARIANT VAL-241.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-241.
RC TISSUE=Skin;
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 [5]
RP POLYMORPHISM, VARIANT 259-ARG--LYS-340 DEL, AND CHARACTERIZATION OF VARIANT
RP 259-ARG--LYS-340 DEL.
RX PubMed=23754956; DOI=10.1371/journal.pgen.1003530;
RA Grarup N., Sulem P., Sandholt C.H., Thorleifsson G., Ahluwalia T.S.,
RA Steinthorsdottir V., Bjarnason H., Gudbjartsson D.F., Magnusson O.T.,
RA Sparsoe T., Albrechtsen A., Kong A., Masson G., Tian G., Cao H., Nie C.,
RA Kristiansen K., Husemoen L.L., Thuesen B., Li Y., Nielsen R., Linneberg A.,
RA Olafsson I., Eyjolfsson G.I., Joergensen T., Wang J., Hansen T.,
RA Thorsteinsdottir U., Stefansson K., Pedersen O.;
RT "Genetic architecture of vitamin B12 and folate levels uncovered applying
RT deeply sequenced large datasets.";
RL PLoS Genet. 9:E1003530-E1003530(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP POLYMORPHISM, VARIANT 259-ARG--LYS-340 DEL, AND CHARACTERIZATION OF VARIANT
RP 259-ARG--LYS-340 DEL.
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 23-340 IN COMPLEX WITH MAGNESIUM;
RP COENZYME A AND PROPIONYL-COA, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBUNIT, POLYMORPHISM, ACTIVE SITE, AND MUTAGENESIS OF ASP-320.
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
CC (PubMed:29056341). The C5-dicarboxylate catabolism pathway is required
CC to 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 (PubMed:29056341, PubMed:24334609).
CC Also displays malyl-CoA thioesterase activity (PubMed:29056341). Also
CC acts as a beta-methylmalate synthase in vitro, by mediating conversion
CC of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609,
CC PubMed:29056341). Also has very weak citramalate synthase activity in
CC vitro (PubMed:24334609, PubMed:29056341). {ECO:0000269|PubMed:24334609,
CC 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; Evidence={ECO:0000269|PubMed:24334609,
CC ECO:0000269|PubMed:29056341};
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:0000269|PubMed:24334609,
CC ECO:0000269|PubMed:29056341};
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:0000269|PubMed:29056341};
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:0000269|PubMed:29056341};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38292;
CC Evidence={ECO:0000305|PubMed:29056341};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:29056341};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.6 mM for glyoxylate (with acetyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:24334609};
CC KM=1.2 mM for glyoxylate (with propionyl-CoA as cosubstrate)
CC {ECO:0000269|PubMed:24334609};
CC KM=28.7 uM for propionyl-CoA (for beta-methylmalate synthase)
CC {ECO:0000269|PubMed:29056341};
CC KM=57.3 uM for acetyl-CoA (for malate synthase)
CC {ECO:0000269|PubMed:29056341};
CC KM=25 uM for acetyl-CoA (for citramalate synthase)
CC {ECO:0000269|PubMed:29056341};
CC KM=23 uM for (3S)-citramalyl-CoA (for citramalyl-CoA lyase)
CC {ECO:0000269|PubMed:29056341};
CC KM=74 uM for acetyl-CoA {ECO:0000269|PubMed:24334609};
CC KM=23 uM for propionyl-CoA {ECO:0000269|PubMed:24334609};
CC Note=kcat is 0.12 sec(-1) for malate synthase reaction
CC (PubMed:24334609). kcat is 0.09 sec(-1) for beta-methylmalate
CC synthase reaction (PubMed:24334609). kcat is 0.135 sec(-1) for beta-
CC methylmalate synthase reaction (PubMed:29056341). kcat is 0.146 sec(-
CC 1) for malate synthase reaction (PubMed:29056341). kcat is 0.08 sec(-
CC 1) for citramalate synthase reaction (PubMed:29056341). kcat is 14.1
CC sec(-1) for citramalyl-CoA lyase reaction (PubMed:29056341).
CC {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341};
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:29056341}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8R4N0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N0X4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N0X4-2; Sequence=VSP_034643;
CC -!- POLYMORPHISM: The protein is absent in 2.7% of the human population due
CC to a loss-of-function polymorphism (rs41281112) that changes Arg-259 to
CC a premature stop codon, leading to loss of the protein product
CC (PubMed:23754956, PubMed:24334609). This polymorphism is associated
CC with reduction of circulating vitamin B12 (PubMed:23754956,
CC PubMed:24334609). The reduction of circulating vitamin B12 is caused by
CC accumulation of citramalyl-CoA, an intermediate in the C5-dicarboxylate
CC metabolic pathway that includes itaconate (PubMed:29056341). Itaconate
CC acting as a vitamin B12-poisoning metabolite that inactivates the
CC mitochondrial methylglutaconyl-CoA hydratase (AUH) enzyme
CC (PubMed:29056341). {ECO:0000269|PubMed:23754956,
CC ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341}.
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; AF428253; AAL84703.1; -; mRNA.
DR EMBL; AK095506; BAC04561.1; -; mRNA.
DR EMBL; AL137139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034360; AAH34360.1; -; mRNA.
DR CCDS; CCDS32002.1; -. [Q8N0X4-1]
DR RefSeq; NP_996531.1; NM_206808.3. [Q8N0X4-1]
DR RefSeq; XP_005254087.1; XM_005254030.2.
DR RefSeq; XP_005254088.1; XM_005254031.2.
DR RefSeq; XP_006719978.1; XM_006719915.3.
DR RefSeq; XP_011519353.1; XM_011521051.2.
DR RefSeq; XP_011519354.1; XM_011521052.2.
DR RefSeq; XP_016875891.1; XM_017020402.1.
DR PDB; 5VXC; X-ray; 1.87 A; A=30-340.
DR PDB; 5VXO; X-ray; 2.27 A; A/B/C=30-340.
DR PDB; 5VXS; X-ray; 2.95 A; A/B/C/D/E/F=30-340.
DR PDBsum; 5VXC; -.
DR PDBsum; 5VXO; -.
DR PDBsum; 5VXS; -.
DR AlphaFoldDB; Q8N0X4; -.
DR SMR; Q8N0X4; -.
DR BioGRID; 128126; 11.
DR STRING; 9606.ENSP00000365533; -.
DR SwissLipids; SLP:000001839; -.
DR iPTMnet; Q8N0X4; -.
DR PhosphoSitePlus; Q8N0X4; -.
DR BioMuta; CLYBL; -.
DR DMDM; 146286073; -.
DR EPD; Q8N0X4; -.
DR jPOST; Q8N0X4; -.
DR MassIVE; Q8N0X4; -.
DR MaxQB; Q8N0X4; -.
DR PaxDb; Q8N0X4; -.
DR PeptideAtlas; Q8N0X4; -.
DR PRIDE; Q8N0X4; -.
DR ProteomicsDB; 71483; -. [Q8N0X4-1]
DR ProteomicsDB; 71484; -. [Q8N0X4-2]
DR Antibodypedia; 25197; 61 antibodies from 16 providers.
DR DNASU; 171425; -.
DR Ensembl; ENST00000339105.9; ENSP00000342991.4; ENSG00000125246.16. [Q8N0X4-1]
DR Ensembl; ENST00000376354.5; ENSP00000365532.1; ENSG00000125246.16. [Q8N0X4-2]
DR Ensembl; ENST00000376355.7; ENSP00000365533.4; ENSG00000125246.16. [Q8N0X4-1]
DR Ensembl; ENST00000689673.1; ENSP00000509937.1; ENSG00000125246.16. [Q8N0X4-1]
DR Ensembl; ENST00000693071.1; ENSP00000508871.1; ENSG00000125246.16. [Q8N0X4-2]
DR GeneID; 171425; -.
DR KEGG; hsa:171425; -.
DR MANE-Select; ENST00000339105.9; ENSP00000342991.4; NM_206808.5; NP_996531.1.
DR UCSC; uc001vok.5; human. [Q8N0X4-1]
DR CTD; 171425; -.
DR DisGeNET; 171425; -.
DR GeneCards; CLYBL; -.
DR HGNC; HGNC:18355; CLYBL.
DR HPA; ENSG00000125246; Tissue enhanced (liver).
DR MIM; 609686; gene.
DR neXtProt; NX_Q8N0X4; -.
DR OpenTargets; ENSG00000125246; -.
DR PharmGKB; PA26622; -.
DR VEuPathDB; HostDB:ENSG00000125246; -.
DR eggNOG; ENOG502QQPK; Eukaryota.
DR GeneTree; ENSGT00390000017163; -.
DR HOGENOM; CLU_044864_1_0_1; -.
DR InParanoid; Q8N0X4; -.
DR OMA; AWLFCPA; -.
DR OrthoDB; 1527380at2759; -.
DR PhylomeDB; Q8N0X4; -.
DR TreeFam; TF313596; -.
DR BioCyc; MetaCyc:HS04862-MON; -.
DR BRENDA; 4.1.3.6; 2681.
DR PathwayCommons; Q8N0X4; -.
DR BioGRID-ORCS; 171425; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; CLYBL; human.
DR GenomeRNAi; 171425; -.
DR Pharos; Q8N0X4; Tbio.
DR PRO; PR:Q8N0X4; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q8N0X4; protein.
DR Bgee; ENSG00000125246; Expressed in kidney epithelium and 166 other tissues.
DR ExpressionAtlas; Q8N0X4; baseline and differential.
DR Genevisible; Q8N0X4; HS.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR GO; GO:0004474; F:malate synthase activity; IDA:UniProtKB.
DR GO; GO:0106121; P:positive regulation of cobalamin metabolic process; IEA:Ensembl.
DR GO; GO:0070207; P:protein homotrimerization; IDA: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 3D-structure; Acetylation; Alternative splicing; Hydrolase; Lyase;
KW Magnesium; Metal-binding; Mitochondrion; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..340
FT /note="Citramalyl-CoA lyase, mitochondrial"
FT /id="PRO_0000286389"
FT ACT_SITE 320
FT /evidence="ECO:0000269|PubMed:29056341"
FT BINDING 50
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC, ECO:0007744|PDB:5VXO"
FT BINDING 57
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC, ECO:0007744|PDB:5VXO"
FT BINDING 61
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC, ECO:0007744|PDB:5VXO"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC, ECO:0007744|PDB:5VXO"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC"
FT BINDING 206
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC"
FT BINDING 272..273
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29056341,
FT ECO:0007744|PDB:5VXC, ECO:0007744|PDB:5VXO"
FT MOD_RES 57
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 61
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 82
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 82
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 92
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 92
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT MOD_RES 309
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8R4N0"
FT VAR_SEQ 147..180
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034643"
FT VARIANT 28
FT /note="D -> Y (in dbSNP:rs17577293)"
FT /id="VAR_032099"
FT VARIANT 128
FT /note="V -> I (in dbSNP:rs35680839)"
FT /id="VAR_032100"
FT VARIANT 241
FT /note="I -> V (in dbSNP:rs3783185)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_032101"
FT VARIANT 259..340
FT /note="Missing (loss of the protein product; reduction of
FT circulating vitamin B12; dbSNP:rs41281112)"
FT /evidence="ECO:0000269|PubMed:23754956,
FT ECO:0000269|PubMed:24334609"
FT /id="VAR_073420"
FT MUTAGEN 320
FT /note="D->A,N: Abolishes citramalyl-CoA lyase activity."
FT /evidence="ECO:0000269|PubMed:29056341"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 56..61
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 83..96
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 101..107
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 116..123
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 141..154
FT /evidence="ECO:0007829|PDB:5VXC"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 179..189
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 223..235
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 251..264
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 268..273
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 288..306
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:5VXC"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:5VXC"
FT HELIX 321..336
FT /evidence="ECO:0007829|PDB:5VXC"
SQ SEQUENCE 340 AA; 37359 MW; 0C99A5A4F09E03E2 CRC64;
MALRLLRRAA RGAAAAALLR LKASLAADIP RLGYSSSSHH KYIPRRAVLY VPGNDEKKIK
KIPSLNVDCA VLDCEDGVAA NKKNEARLRI VKTLEDIDLG PTEKCVRVNS VSSGLAEEDL
ETLLQSRVLP SSLMLPKVES PEEIQWFADK FSFHLKGRKL EQPMNLIPFV ETAMGLLNFK
AVCEETLKVG PQVGLFLDAV VFGGEDFRAS IGATSSKETL DILYARQKIV VIAKAFGLQA
IDLVYIDFRD GAGLLRQSRE GAAMGFTGKQ VIHPNQIAVV QEQFSPSPEK IKWAEELIAA
FKEHQQLGKG AFTFQGSMID MPLLKQAQNT VTLATSIKEK
