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Protein

Citrate lyase subunit beta-like protein, mitochondrial

Gene

CLYBL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mitochondrial malate and beta-methylmalate synthase, which may be involved in vitamin B12 metabolism (Probable). Acts both as a malate synthase, converting glyoxylate and acetyl-CoA to malate. Also acts as a beta-methylmalate synthase by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609).1 Publication

Catalytic activityi

Acetyl-CoA + H2O + glyoxylate = (S)-malate + CoA.1 Publication
Propionyl-CoA + H2O + glyoxylate = beta-methylmalate + CoA.1 Publication

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.By similarity

Kineticsi

kcat is 0.12 sec(-1) for malate synthase reaction. kcat is 0.09 sec(-1) for beta-methylmalate synthase reaction.1 Publication

  1. KM=3.6 mM for glyoxylate (with acetyl-CoA as cosubstrate)1 Publication
  2. KM=1.2 mM for glyoxylate (with propionyl-CoA as cosubstrate)1 Publication
  3. KM=74 µM for acetyl-CoA1 Publication
  4. KM=23 µM for propionyl-CoA1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei107 – 1071SubstrateBy similarity
    Metal bindingi171 – 1711MagnesiumBy similarity
    Binding sitei171 – 1711SubstrateBy similarity
    Metal bindingi206 – 2061MagnesiumBy similarity

    GO - Molecular functioni

    • magnesium ion binding Source: UniProtKB
    • malate synthase activity Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BRENDAi4.1.3.6. 2681.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Citrate lyase subunit beta-like protein, mitochondrial
    Short name:
    Citrate lyase beta-like
    Alternative name(s):
    Beta-methylmalate synthase (EC:2.3.3.-1 Publication)
    Malate synthase (EC:2.3.3.91 Publication)
    Gene namesi
    Name:CLYBL
    Synonyms:CLB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:18355. CLYBL.

    Subcellular locationi

    • Mitochondrion By similarity

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26622.

    Polymorphism and mutation databases

    BioMutaiCLYBL.
    DMDMi146286073.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2222MitochondrionSequence analysisAdd
    BLAST
    Chaini23 – 340318Citrate lyase subunit beta-like protein, mitochondrialPRO_0000286389Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei57 – 571N6-acetyllysineBy similarity
    Modified residuei61 – 611N6-acetyllysineBy similarity
    Modified residuei82 – 821N6-acetyllysine; alternateBy similarity
    Modified residuei82 – 821N6-succinyllysine; alternateBy similarity
    Modified residuei92 – 921N6-acetyllysine; alternateBy similarity
    Modified residuei92 – 921N6-succinyllysine; alternateBy similarity
    Modified residuei309 – 3091N6-succinyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ8N0X4.
    MaxQBiQ8N0X4.
    PaxDbiQ8N0X4.
    PRIDEiQ8N0X4.

    PTM databases

    iPTMnetiQ8N0X4.
    PhosphoSiteiQ8N0X4.

    Expressioni

    Gene expression databases

    BgeeiQ8N0X4.
    CleanExiHS_CLYBL.
    ExpressionAtlasiQ8N0X4. baseline and differential.
    GenevisibleiQ8N0X4. HS.

    Organism-specific databases

    HPAiHPA039959.
    HPA040691.

    Interactioni

    Protein-protein interaction databases

    BioGridi128126. 2 interactions.
    STRINGi9606.ENSP00000342991.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8N0X4.
    SMRiQ8N0X4. Positions 44-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiENOG410IGUQ. Eukaryota.
    COG2301. LUCA.
    GeneTreeiENSGT00390000017163.
    HOGENOMiHOG000242281.
    HOVERGENiHBG059382.
    InParanoidiQ8N0X4.
    KOiK11390.
    OMAiKCESAAD.
    OrthoDBiEOG793B83.
    PhylomeDBiQ8N0X4.
    TreeFamiTF313596.

    Family and domain databases

    Gene3Di3.20.20.60. 1 hit.
    InterProiIPR005000. Aldolase/citrate-lyase_domain.
    IPR011206. Citrate_lyase_beta/mcl1/mcl2.
    IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
    [Graphical view]
    PfamiPF03328. HpcH_HpaI. 1 hit.
    [Graphical view]
    PIRSFiPIRSF015582. Cit_lyase_B. 1 hit.
    SUPFAMiSSF51621. SSF51621. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8N0X4-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MALRLLRRAA RGAAAAALLR LKASLAADIP RLGYSSSSHH KYIPRRAVLY
    60 70 80 90 100
    VPGNDEKKIK KIPSLNVDCA VLDCEDGVAA NKKNEARLRI VKTLEDIDLG
    110 120 130 140 150
    PTEKCVRVNS VSSGLAEEDL ETLLQSRVLP SSLMLPKVES PEEIQWFADK
    160 170 180 190 200
    FSFHLKGRKL EQPMNLIPFV ETAMGLLNFK AVCEETLKVG PQVGLFLDAV
    210 220 230 240 250
    VFGGEDFRAS IGATSSKETL DILYARQKIV VIAKAFGLQA IDLVYIDFRD
    260 270 280 290 300
    GAGLLRQSRE GAAMGFTGKQ VIHPNQIAVV QEQFSPSPEK IKWAEELIAA
    310 320 330 340
    FKEHQQLGKG AFTFQGSMID MPLLKQAQNT VTLATSIKEK
    Length:340
    Mass (Da):37,359
    Last modified:May 1, 2007 - v2
    Checksum:i0C99A5A4F09E03E2
    GO
    Isoform 2 (identifier: Q8N0X4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         147-180: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:306
    Mass (Da):33,409
    Checksum:iEDFEA04BA12E1934
    GO

    Polymorphismi

    The loss-of-function polymorphism (rs41281112) changes Arg-259 to a premature stop codon, leading to loss of the protein product, may be associated with reduction of circulating vitamin B12.1 Publication

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti28 – 281D → Y.
    Corresponds to variant rs17577293 [ dbSNP | Ensembl ].
    VAR_032099
    Natural varianti128 – 1281V → I.
    Corresponds to variant rs35680839 [ dbSNP | Ensembl ].
    VAR_032100
    Natural varianti241 – 2411I → V.2 Publications
    Corresponds to variant rs3783185 [ dbSNP | Ensembl ].
    VAR_032101
    Natural varianti259 – 34082Missing .
    Corresponds to variant rs41281112 [ dbSNP | Ensembl ].
    VAR_073420Add
    BLAST

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei147 – 18034Missing in isoform 2. CuratedVSP_034643Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF428253 mRNA. Translation: AAL84703.1.
    AK095506 mRNA. Translation: BAC04561.1.
    AL137139, AL139035 Genomic DNA. Translation: CAI39520.1.
    AL139035, AL137139 Genomic DNA. Translation: CAH71385.1.
    AL139035, AL137139 Genomic DNA. Translation: CAH71384.1.
    AL137139, AL139035 Genomic DNA. Translation: CAI39521.1.
    BC034360 mRNA. Translation: AAH34360.1.
    CCDSiCCDS32002.1. [Q8N0X4-1]
    RefSeqiNP_996531.1. NM_206808.3. [Q8N0X4-1]
    XP_005254087.1. XM_005254030.1. [Q8N0X4-1]
    XP_005254088.1. XM_005254031.1. [Q8N0X4-2]
    XP_006719978.1. XM_006719915.2. [Q8N0X4-1]
    XP_011519353.1. XM_011521051.1. [Q8N0X4-1]
    XP_011519354.1. XM_011521052.1. [Q8N0X4-1]
    UniGeneiHs.655642.

    Genome annotation databases

    EnsembliENST00000339105; ENSP00000342991; ENSG00000125246. [Q8N0X4-1]
    ENST00000376354; ENSP00000365532; ENSG00000125246. [Q8N0X4-2]
    ENST00000376355; ENSP00000365533; ENSG00000125246. [Q8N0X4-1]
    GeneIDi171425.
    KEGGihsa:171425.
    UCSCiuc001vok.5. human. [Q8N0X4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF428253 mRNA. Translation: AAL84703.1.
    AK095506 mRNA. Translation: BAC04561.1.
    AL137139, AL139035 Genomic DNA. Translation: CAI39520.1.
    AL139035, AL137139 Genomic DNA. Translation: CAH71385.1.
    AL139035, AL137139 Genomic DNA. Translation: CAH71384.1.
    AL137139, AL139035 Genomic DNA. Translation: CAI39521.1.
    BC034360 mRNA. Translation: AAH34360.1.
    CCDSiCCDS32002.1. [Q8N0X4-1]
    RefSeqiNP_996531.1. NM_206808.3. [Q8N0X4-1]
    XP_005254087.1. XM_005254030.1. [Q8N0X4-1]
    XP_005254088.1. XM_005254031.1. [Q8N0X4-2]
    XP_006719978.1. XM_006719915.2. [Q8N0X4-1]
    XP_011519353.1. XM_011521051.1. [Q8N0X4-1]
    XP_011519354.1. XM_011521052.1. [Q8N0X4-1]
    UniGeneiHs.655642.

    3D structure databases

    ProteinModelPortaliQ8N0X4.
    SMRiQ8N0X4. Positions 44-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi128126. 2 interactions.
    STRINGi9606.ENSP00000342991.

    PTM databases

    iPTMnetiQ8N0X4.
    PhosphoSiteiQ8N0X4.

    Polymorphism and mutation databases

    BioMutaiCLYBL.
    DMDMi146286073.

    Proteomic databases

    EPDiQ8N0X4.
    MaxQBiQ8N0X4.
    PaxDbiQ8N0X4.
    PRIDEiQ8N0X4.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000339105; ENSP00000342991; ENSG00000125246. [Q8N0X4-1]
    ENST00000376354; ENSP00000365532; ENSG00000125246. [Q8N0X4-2]
    ENST00000376355; ENSP00000365533; ENSG00000125246. [Q8N0X4-1]
    GeneIDi171425.
    KEGGihsa:171425.
    UCSCiuc001vok.5. human. [Q8N0X4-1]

    Organism-specific databases

    CTDi171425.
    GeneCardsiCLYBL.
    HGNCiHGNC:18355. CLYBL.
    HPAiHPA039959.
    HPA040691.
    MIMi609686. gene.
    neXtProtiNX_Q8N0X4.
    PharmGKBiPA26622.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410IGUQ. Eukaryota.
    COG2301. LUCA.
    GeneTreeiENSGT00390000017163.
    HOGENOMiHOG000242281.
    HOVERGENiHBG059382.
    InParanoidiQ8N0X4.
    KOiK11390.
    OMAiKCESAAD.
    OrthoDBiEOG793B83.
    PhylomeDBiQ8N0X4.
    TreeFamiTF313596.

    Enzyme and pathway databases

    BRENDAi4.1.3.6. 2681.

    Miscellaneous databases

    GenomeRNAii171425.
    NextBioi89246.
    PROiQ8N0X4.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ8N0X4.
    CleanExiHS_CLYBL.
    ExpressionAtlasiQ8N0X4. baseline and differential.
    GenevisibleiQ8N0X4. HS.

    Family and domain databases

    Gene3Di3.20.20.60. 1 hit.
    InterProiIPR005000. Aldolase/citrate-lyase_domain.
    IPR011206. Citrate_lyase_beta/mcl1/mcl2.
    IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
    [Graphical view]
    PfamiPF03328. HpcH_HpaI. 1 hit.
    [Graphical view]
    PIRSFiPIRSF015582. Cit_lyase_B. 1 hit.
    SUPFAMiSSF51621. SSF51621. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning of novel mouse and human putative citrate lyase beta-subunit."
      Morikawa J., Nishimura Y., Uchida A., Tanaka T.
      Biochem. Biophys. Res. Commun. 289:1282-1286(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-241.
      Tissue: Brain.
    3. "The DNA sequence and analysis of human chromosome 13."
      Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
      Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-241.
      Tissue: Skin.
    5. "CLYBL is a polymorphic human enzyme with malate synthase and beta-methylmalate synthase activity."
      Strittmatter L., Li Y., Nakatsuka N.J., Calvo S.E., Grabarek Z., Mootha V.K.
      Hum. Mol. Genet. 23:2313-2323(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, POLYMORPHISM, VARIANT 259-ARG--LYS-340 DEL.
    6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiCLYBL_HUMAN
    AccessioniPrimary (citable) accession number: Q8N0X4
    Secondary accession number(s): Q5W0F7, Q8TDH8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 2007
    Last sequence update: May 1, 2007
    Last modified: March 16, 2016
    This is version 112 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    This organism lacks the other subunits that are necessary for ATP-independent citrate lyase activity. Even though this protein has clear similarity to citrate lyase beta subunit, it is expected to have a somewhat different enzyme activity.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.