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 11-NOV-2015, entry version 110. DE RecName: Full=Citrate lyase subunit beta-like protein, mitochondrial; DE Short=Citrate lyase beta-like; DE AltName: Full=Beta-methylmalate synthase; DE EC=2.3.3.- {ECO:0000269|PubMed:24334609}; DE AltName: Full=Malate synthase; DE EC=2.3.3.9 {ECO:0000269|PubMed:24334609}; DE Flags: Precursor; GN Name=CLYBL; Synonyms=CLB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT beta-subunit."; RL Biochem. Biophys. Res. Commun. 289:1282-1286(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA 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., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA 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., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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 RP 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, RP POLYMORPHISM, AND VARIANT 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 [6] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [7] 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., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). CC -!- FUNCTION: Mitochondrial malate and beta-methylmalate synthase, CC which may be involved in vitamin B12 metabolism (Probable). Acts CC both as a malate synthase, converting glyoxylate and acetyl-CoA to CC malate. Also acts as a beta-methylmalate synthase by mediating CC conversion of glyoxylate and propionyl-CoA to beta-methylmalate CC (PubMed:24334609). {ECO:0000269|PubMed:24334609}. CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + H(2)O + glyoxylate = (S)-malate + CC CoA. {ECO:0000269|PubMed:24334609}. CC -!- CATALYTIC ACTIVITY: Propionyl-CoA + H(2)O + glyoxylate = beta- CC methylmalate + CoA. {ECO:0000269|PubMed:24334609}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:24334609}; CC Note=Binds 1 Mg(2+) ion per subunit. CC {ECO:0000250|UniProtKB:Q9RUZ0}; 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=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. kcat is CC 0.09 sec(-1) for beta-methylmalate synthase reaction. CC {ECO:0000269|PubMed:24334609}; CC -!- SUBCELLULAR LOCATION: Mitochondrion CC {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 Note=No experimental confirmation available.; CC -!- POLYMORPHISM: The loss-of-function polymorphism (rs41281112) CC changes Arg-259 to a premature stop codon, leading to loss of the CC protein product, may be associated with reduction of circulating CC vitamin B12. {ECO:0000305|PubMed:24334609}. CC -!- SIMILARITY: Belongs to the HpcH/HpaI aldolase family. Citrate CC lyase beta subunit-like subfamily. {ECO:0000305}. CC -!- CAUTION: This organism lacks the other subunits that are necessary CC for ATP-independent citrate lyase activity. Even though this CC protein has clear similarity to citrate lyase beta subunit, it is CC expected to have a somewhat different enzyme activity. CC {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; CAI39520.1; -; Genomic_DNA. DR EMBL; AL139035; CAI39520.1; JOINED; Genomic_DNA. DR EMBL; AL139035; CAH71385.1; -; Genomic_DNA. DR EMBL; AL137139; CAH71385.1; JOINED; Genomic_DNA. DR EMBL; AL139035; CAH71384.1; -; Genomic_DNA. DR EMBL; AL137139; CAH71384.1; JOINED; Genomic_DNA. DR EMBL; AL137139; CAI39521.1; -; Genomic_DNA. DR EMBL; AL139035; CAI39521.1; JOINED; 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_005254030.1. [Q8N0X4-1] DR RefSeq; XP_005254088.1; XM_005254031.1. [Q8N0X4-2] DR RefSeq; XP_006719978.1; XM_006719915.2. [Q8N0X4-1] DR RefSeq; XP_011519353.1; XM_011521051.1. [Q8N0X4-1] DR RefSeq; XP_011519354.1; XM_011521052.1. [Q8N0X4-1] DR UniGene; Hs.655642; -. DR ProteinModelPortal; Q8N0X4; -. DR SMR; Q8N0X4; 44-334. DR BioGrid; 128126; 3. DR STRING; 9606.ENSP00000342991; -. DR PhosphoSite; Q8N0X4; -. DR BioMuta; CLYBL; -. DR DMDM; 146286073; -. DR MaxQB; Q8N0X4; -. DR PaxDb; Q8N0X4; -. DR PRIDE; Q8N0X4; -. DR Ensembl; ENST00000339105; ENSP00000342991; ENSG00000125246. [Q8N0X4-1] DR Ensembl; ENST00000376354; ENSP00000365532; ENSG00000125246. [Q8N0X4-2] DR Ensembl; ENST00000376355; ENSP00000365533; ENSG00000125246. [Q8N0X4-1] DR GeneID; 171425; -. DR KEGG; hsa:171425; -. DR UCSC; uc001vok.3; human. [Q8N0X4-1] DR CTD; 171425; -. DR GeneCards; CLYBL; -. DR HGNC; HGNC:18355; CLYBL. DR HPA; HPA039959; -. DR HPA; HPA040691; -. DR MIM; 609686; gene. DR neXtProt; NX_Q8N0X4; -. DR PharmGKB; PA26622; -. DR eggNOG; ENOG410IGUQ; Eukaryota. DR eggNOG; COG2301; LUCA. DR GeneTree; ENSGT00390000017163; -. DR HOGENOM; HOG000242281; -. DR HOVERGEN; HBG059382; -. DR InParanoid; Q8N0X4; -. DR KO; K11390; -. DR OMA; KCESAAD; -. DR OrthoDB; EOG793B83; -. DR PhylomeDB; Q8N0X4; -. DR TreeFam; TF313596; -. DR BRENDA; 4.1.3.6; 2681. DR GenomeRNAi; 171425; -. DR NextBio; 89246; -. DR PRO; PR:Q8N0X4; -. DR Proteomes; UP000005640; Chromosome 13. DR Bgee; Q8N0X4; -. DR CleanEx; HS_CLYBL; -. DR ExpressionAtlas; Q8N0X4; baseline and differential. DR Genevisible; Q8N0X4; HS. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0004474; F:malate synthase activity; IDA:UniProtKB. DR Gene3D; 3.20.20.60; -; 1. DR InterPro; IPR005000; Aldolase/citrate-lyase_domain. DR InterPro; IPR011206; Citrate_lyase_beta/mcl1/mcl2. DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom. 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; Alternative splicing; Complete proteome; Magnesium; KW Metal-binding; Mitochondrion; Polymorphism; Reference proteome; KW Transferase; Transit peptide. FT TRANSIT 1 22 Mitochondrion. {ECO:0000255}. FT CHAIN 23 340 Citrate lyase subunit beta-like protein, FT mitochondrial. FT /FTId=PRO_0000286389. FT METAL 171 171 Magnesium. FT {ECO:0000250|UniProtKB:Q9RUZ0}. FT METAL 206 206 Magnesium. FT {ECO:0000250|UniProtKB:Q9RUZ0}. FT BINDING 107 107 Substrate. FT {ECO:0000250|UniProtKB:Q9RUZ0}. FT BINDING 171 171 Substrate. FT {ECO:0000250|UniProtKB:Q9RUZ0}. FT MOD_RES 57 57 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 61 61 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 82 82 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 82 82 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 92 92 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 92 92 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT MOD_RES 309 309 N6-succinyllysine. FT {ECO:0000250|UniProtKB:Q8R4N0}. FT VAR_SEQ 147 180 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_034643. FT VARIANT 28 28 D -> Y (in dbSNP:rs17577293). FT /FTId=VAR_032099. FT VARIANT 128 128 V -> I (in dbSNP:rs35680839). FT /FTId=VAR_032100. FT VARIANT 241 241 I -> V (in dbSNP:rs3783185). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334}. FT /FTId=VAR_032101. FT VARIANT 259 340 Missing (in dbSNP:rs41281112). FT /FTId=VAR_073420. 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 //