ID   HOGA1_BOVIN             Reviewed;         327 AA.
AC   Q0P5I5; Q0V7M3;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   19-SEP-2006, sequence version 1.
DT   27-MAR-2024, entry version 100.
DE   RecName: Full=4-hydroxy-2-oxoglutarate aldolase, mitochondrial;
DE            EC=4.1.3.16 {ECO:0000269|PubMed:1587831};
DE   AltName: Full=Dihydrodipicolinate synthase-like;
DE            Short=DHDPS-like protein;
DE   AltName: Full=Probable 2-keto-4-hydroxyglutarate aldolase;
DE            Short=Probable KHG-aldolase;
DE   Flags: Precursor;
GN   Name=HOGA1; Synonyms=DHDPSL;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 26-30, TRANSIT PEPTIDE CLEAVAGE SITE, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=21998747; DOI=10.1371/journal.pone.0026021;
RA   Riedel T.J., Johnson L.C., Knight J., Hantgan R.R., Holmes R.P.,
RA   Lowther W.T.;
RT   "Structural and biochemical studies of human 4-hydroxy-2-oxoglutarate
RT   aldolase: implications for hydroxyproline metabolism in primary
RT   hyperoxaluria.";
RL   PLoS ONE 6:E26021-E26021(2011).
RN   [4]
RP   SUBUNIT, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=1587831; DOI=10.1016/s0021-9258(19)50046-1;
RA   Dekker E.E., Kitson R.P.;
RT   "2-Keto-4-hydroxyglutarate aldolase: purification and characterization of
RT   the homogeneous enzyme from bovine kidney.";
RL   J. Biol. Chem. 267:10507-10514(1992).
RN   [5]
RP   IDENTIFICATION.
RX   PubMed=20797690; DOI=10.1016/j.ajhg.2010.07.023;
RA   Belostotsky R., Seboun E., Idelson G.H., Milliner D.S., Becker-Cohen R.,
RA   Rinat C., Monico C.G., Feinstein S., Ben-Shalom E., Magen D., Weissman I.,
RA   Charon C., Frishberg Y.;
RT   "Mutations in DHDPSL are responsible for primary hyperoxaluria type III.";
RL   Am. J. Hum. Genet. 87:392-399(2010).
CC   -!- FUNCTION: Catalyzes the final step in the metabolic pathway of
CC       hydroxyproline. {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4S)-4-hydroxy-2-oxoglutarate = glyoxylate + pyruvate;
CC         Xref=Rhea:RHEA:35639, ChEBI:CHEBI:15361, ChEBI:CHEBI:36655,
CC         ChEBI:CHEBI:71685; EC=4.1.3.16;
CC         Evidence={ECO:0000269|PubMed:1587831};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(4R)-4-hydroxy-2-oxoglutarate = glyoxylate + pyruvate;
CC         Xref=Rhea:RHEA:30687, ChEBI:CHEBI:15361, ChEBI:CHEBI:36655,
CC         ChEBI:CHEBI:62213; EC=4.1.3.16;
CC         Evidence={ECO:0000269|PubMed:1587831};
CC   -!- ACTIVITY REGULATION: Inhibited by divalent cations.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=26 uM for DL-4-hydroxy-2-oxoglutarate
CC         {ECO:0000269|PubMed:1587831};
CC         Vmax=10.7 umol/min/mg enzyme {ECO:0000269|PubMed:1587831};
CC       pH dependence:
CC         Optimum pH is 8.8. {ECO:0000269|PubMed:1587831};
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:1587831}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21998747}.
CC   -!- SIMILARITY: Belongs to the DapA family. {ECO:0000305}.
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DR   EMBL; BT026547; ABH06334.1; -; mRNA.
DR   EMBL; BC119998; AAI19999.1; -; mRNA.
DR   RefSeq; NP_001068705.1; NM_001075237.1.
DR   AlphaFoldDB; Q0P5I5; -.
DR   SMR; Q0P5I5; -.
DR   STRING; 9913.ENSBTAP00000060890; -.
DR   PaxDb; 9913-ENSBTAP00000016909; -.
DR   Ensembl; ENSBTAT00000016909.5; ENSBTAP00000016909.4; ENSBTAG00000012721.5.
DR   GeneID; 506001; -.
DR   KEGG; bta:506001; -.
DR   CTD; 112817; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012721; -.
DR   VGNC; VGNC:29900; HOGA1.
DR   eggNOG; ENOG502QWNS; Eukaryota.
DR   GeneTree; ENSGT00530000063604; -.
DR   HOGENOM; CLU_049343_0_1_1; -.
DR   InParanoid; Q0P5I5; -.
DR   OMA; GMDACVP; -.
DR   OrthoDB; 1780992at2759; -.
DR   TreeFam; TF324600; -.
DR   BRENDA; 4.1.3.16; 908.
DR   Reactome; R-BTA-389661; Glyoxylate metabolism and glycine degradation.
DR   SABIO-RK; Q0P5I5; -.
DR   Proteomes; UP000009136; Chromosome 26.
DR   Bgee; ENSBTAG00000012721; Expressed in cortex of kidney and 86 other cell types or tissues.
DR   ExpressionAtlas; Q0P5I5; baseline.
DR   GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR   GO; GO:0106009; F:(4S)-4-hydroxy-2-oxoglutarate aldolase activity; IEA:RHEA.
DR   GO; GO:0008700; F:4-hydroxy-2-oxoglutarate aldolase activity; IDA:UniProtKB.
DR   GO; GO:0008747; F:N-acetylneuraminate lyase activity; IBA:GO_Central.
DR   GO; GO:0009436; P:glyoxylate catabolic process; IDA:UniProtKB.
DR   GO; GO:0019262; P:N-acetylneuraminate catabolic process; IBA:GO_Central.
DR   CDD; cd00408; DHDPS-like; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR002220; DapA-like.
DR   InterPro; IPR020625; Schiff_base-form_aldolases_AS.
DR   PANTHER; PTHR12128:SF72; 4-HYDROXY-2-OXOGLUTARATE ALDOLASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR12128; DIHYDRODIPICOLINATE SYNTHASE; 1.
DR   Pfam; PF00701; DHDPS; 1.
DR   PIRSF; PIRSF001365; DHDPS; 1.
DR   PRINTS; PR00146; DHPICSNTHASE.
DR   SMART; SM01130; DHDPS; 1.
DR   SUPFAM; SSF51569; Aldolase; 1.
DR   PROSITE; PS00666; DHDPS_2; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Lyase; Mitochondrion; Reference proteome;
KW   Schiff base; Transit peptide.
FT   TRANSIT         1..25
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:21998747"
FT   CHAIN           26..327
FT                   /note="4-hydroxy-2-oxoglutarate aldolase, mitochondrial"
FT                   /id="PRO_0000273345"
FT   ACT_SITE        196
FT                   /note="Schiff-base intermediate with substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         77..78
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         198
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         222
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            168
FT                   /note="Involved in proton transfer during cleavage"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        327
FT                   /note="L -> F (in Ref. 1; ABH06334)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   327 AA;  35217 MW;  153314DCD1F0D587 CRC64;
     MLVPRVWSSV RLGLSRVLSR TLRGWPSGEG RGMDLSGIYP PVTTPFTATA EVDYGKLEEN
     LHKLGTLPFR GFVVQGSNGE FPFLTSSERL EVVSRARQAL PKDKLLLAGS GCESTQATVE
     MTVSMAQVGA DAAMVVTPCY YRGRMSSAAL IHHYTKVADL SPVPVVLYSV PANTGLDLPV
     DAVVTLSQHP NIVGIKDSGG DVTRIGLIVH KTRSQDFQVL AGSAGFLLAS YAIGAVGGVC
     ALANVLGSQV CQLERLCLTG QWEDAQKLQH RLIEPNTAVT RRFGIPGLKK TMDWFGYYGG
     PCRSPLQELS PAQEEALRLD FASNGWL
//