ID HACL1_RAT Reviewed; 581 AA.
AC Q8CHM7;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 24-JAN-2024, entry version 133.
DE RecName: Full=2-hydroxyacyl-CoA lyase 1;
DE EC=4.1.2.63 {ECO:0000269|PubMed:10468558};
DE AltName: Full=2-hydroxyphytanoyl-CoA lyase {ECO:0000303|PubMed:10468558};
DE Short=2-HPCL {ECO:0000303|PubMed:10468558};
DE AltName: Full=Phytanoyl-CoA 2-hydroxylase 2;
GN Name=Hacl1; Synonyms=2hpcl, Hpcl2, Phyh2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar;
RA Van Veldhoven P.P., Foulon V., Casteels M.;
RT "Cloning of 2-hydroxyphytanoyl-CoA lyase of rodents.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [3]
RP PROTEIN SEQUENCE OF 28-44; 225-237 AND 341-351, SUBCELLULAR LOCATION,
RP COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RC STRAIN=Wistar;
RX PubMed=10468558; DOI=10.1073/pnas.96.18.10039;
RA Foulon V., Antonenkov V.D., Croes K., Waelkens E., Mannaerts G.P.,
RA Van Veldhoven P.P., Casteels M.;
RT "Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA
RT lyase, a peroxisomal thiamine hydrophosphate-dependent enzyme that
RT catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-
RT methyl-branched fatty acids.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:10039-10044(1999).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-4 AND SER-6, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes a carbon-carbon cleavage reaction; cleaves a 2-
CC hydroxy-3-methylacyl-CoA into formyl-CoA and a 2-methyl-branched fatty
CC aldehyde.
CC -!- FUNCTION: Peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1
CC removal) reaction in the fatty acid alpha-oxydation in a thiamine
CC pyrophosphate (TPP)-dependent manner. Involved in the degradation of 3-
CC methyl-branched fatty acids like phytanic acid (PubMed:10468558).
CC Involved also in the shortening of 2-hydroxy long-chain fatty acids (By
CC similarity). Plays a significant role in the biosynthesis of
CC heptadecanal in the liver (By similarity).
CC {ECO:0000250|UniProtKB:Q9QXE0, ECO:0000250|UniProtKB:Q9UJ83,
CC ECO:0000269|PubMed:10468558}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2-hydroxy-3-methyl fatty acyl-CoA = a 2-methyl-branched
CC fatty aldehyde + formyl-CoA; Xref=Rhea:RHEA:25375, ChEBI:CHEBI:49188,
CC ChEBI:CHEBI:57376, ChEBI:CHEBI:58783; EC=4.1.2.63;
CC Evidence={ECO:0000269|PubMed:10468558};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25376;
CC Evidence={ECO:0000305|PubMed:10468558};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an (R)-2-hydroxy-long-chain-fatty acyl-CoA = a long-chain
CC fatty aldehyde + formyl-CoA; Xref=Rhea:RHEA:67444, ChEBI:CHEBI:17176,
CC ChEBI:CHEBI:57376, ChEBI:CHEBI:170012; EC=4.1.2.63;
CC Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67445;
CC Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-3-methylhexadecanoyl-CoA = 2-methylpentadecanal +
CC formyl-CoA; Xref=Rhea:RHEA:25379, ChEBI:CHEBI:49190,
CC ChEBI:CHEBI:57376, ChEBI:CHEBI:58784;
CC Evidence={ECO:0000269|PubMed:10468558};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25380;
CC Evidence={ECO:0000305|PubMed:10468558};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyoctadecanoyl-CoA = formyl-CoA + heptadecanal;
CC Xref=Rhea:RHEA:55196, ChEBI:CHEBI:57376, ChEBI:CHEBI:74116,
CC ChEBI:CHEBI:138631; Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55197;
CC Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyphytanoyl-CoA = 2,6,10,14-tetramethylpentadecanal +
CC formyl-CoA; Xref=Rhea:RHEA:25355, ChEBI:CHEBI:49189,
CC ChEBI:CHEBI:57334, ChEBI:CHEBI:57376;
CC Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25356;
CC Evidence={ECO:0000250|UniProtKB:Q9UJ83};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10468558};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:10468558};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000269|PubMed:10468558};
CC Note=Binds 1 thiamine pyrophosphate per subunit.
CC {ECO:0000269|PubMed:10468558};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for 2-hydroxy-3-methylhexadecanoyl-CoA
CC {ECO:0000269|PubMed:10468558};
CC pH dependence:
CC Optimum pH is 7.5-8. {ECO:0000269|PubMed:10468558};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10468558}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:10468558}.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
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DR EMBL; BC078697; AAH78697.1; -; mRNA.
DR EMBL; AJ517469; CAD56981.1; -; mRNA.
DR RefSeq; NP_445945.1; NM_053493.1.
DR AlphaFoldDB; Q8CHM7; -.
DR SMR; Q8CHM7; -.
DR STRING; 10116.ENSRNOP00000026588; -.
DR SwissLipids; SLP:000001016; -.
DR iPTMnet; Q8CHM7; -.
DR PhosphoSitePlus; Q8CHM7; -.
DR jPOST; Q8CHM7; -.
DR PaxDb; 10116-ENSRNOP00000026588; -.
DR Ensembl; ENSRNOT00000026588.4; ENSRNOP00000026588.2; ENSRNOG00000019630.8.
DR GeneID; 85255; -.
DR KEGG; rno:85255; -.
DR UCSC; RGD:619849; rat.
DR AGR; RGD:619849; -.
DR CTD; 26061; -.
DR RGD; 619849; Hacl1.
DR eggNOG; KOG1185; Eukaryota.
DR GeneTree; ENSGT00940000156802; -.
DR HOGENOM; CLU_013748_3_3_1; -.
DR InParanoid; Q8CHM7; -.
DR OrthoDB; 1966690at2759; -.
DR PhylomeDB; Q8CHM7; -.
DR TreeFam; TF105690; -.
DR BioCyc; MetaCyc:MONOMER-17701; -.
DR BRENDA; 4.1.2.63; 5301.
DR Reactome; R-RNO-389599; Alpha-oxidation of phytanate.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR SABIO-RK; Q8CHM7; -.
DR UniPathway; UPA00199; -.
DR PRO; PR:Q8CHM7; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000019630; Expressed in liver and 20 other cell types or tissues.
DR Genevisible; Q8CHM7; RN.
DR GO; GO:0005777; C:peroxisome; IDA:HGNC-UCL.
DR GO; GO:0106359; F:2-hydroxyacyl-CoA lyase activity; ISO:RGD.
DR GO; GO:0106376; F:2-hydroxyphytanoyl-CoA lyase activity; IEA:RHEA.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0016830; F:carbon-carbon lyase activity; IDA:HGNC-UCL.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0016829; F:lyase activity; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISO:RGD.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IDA:HGNC-UCL.
DR GO; GO:0001561; P:fatty acid alpha-oxidation; IDA:HGNC-UCL.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0097089; P:methyl-branched fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:1903512; P:phytanic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006625; P:protein targeting to peroxisome; ISS:UniProtKB.
DR CDD; cd02004; TPP_BZL_OCoD_HPCL; 1.
DR CDD; cd07035; TPP_PYR_POX_like; 1.
DR Gene3D; 3.40.50.970; -; 2.
DR Gene3D; 3.40.50.1220; TPP-binding domain; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR045025; HACL1-like.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR011766; TPP_enzyme_TPP-bd.
DR PANTHER; PTHR43710; 2-HYDROXYACYL-COA LYASE; 1.
DR PANTHER; PTHR43710:SF2; 2-HYDROXYACYL-COA LYASE 1; 1.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF00205; TPP_enzyme_M; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1.
DR SUPFAM; SSF52518; Thiamin diphosphate-binding fold (THDP-binding); 2.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Magnesium; Metal-binding; Peroxisome; Phosphoprotein; Reference proteome;
KW Thiamine pyrophosphate.
FT CHAIN 1..581
FT /note="2-hydroxyacyl-CoA lyase 1"
FT /id="PRO_0000337675"
FT REGION 404..489
FT /note="Thiamine pyrophosphate binding"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT MOTIF 579..581
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250|UniProtKB:Q9UJ83"
FT BINDING 63
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 458
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 485
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 361
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXE0"
FT MOD_RES 368
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXE0"
SQ SEQUENCE 581 AA; 63616 MW; 007F0738173A8BA9 CRC64;
MSESNSAEGS DRSEEQVSGA KVIAQALKTQ DVEYMFGVVG IPVTEIALAA QELGIKYIGM
RNEQAACYAA SAVGYLTGRP GVCLVVSGPG LIHALGGMAN ANMNCWPLIV IGGSSERNQE
AMGAFQEFPQ VEACRLYSKF SARPSSIQHI PFVIEKAVRS SIYGRPGACY IDVPADLVTL
QESTTSIKYK ECCMPPPLSL AETSAVRAAA SVLRSAKQPL LIIGKGAAYS HAEDSIRKLV
ELCNLPFLPT PMGKGVVPDN HPNCVGAARS RALQFADVIV LFGARLNWIL HFGLPPRYQA
DVKFIQIDIC AEELGNNVRP SVTLLGDVNA VSKQLLEQFV KNPWQYPTDS KWWETLREKR
KNNEAVSKEL ASKKSLPMNY YTVFYHVQEQ LPRNCFIVSE GANTMDIGRT VLQNYLPRHR
LDAGSFGTMG VGLGFAIAAA VVAKERSPGQ RVICVEGDSA FGFSGMEVET ICRYNLPIII
LVVNNNGIYQ GFDADTWGKI LNFQGTATTI PPMCLLPNSH YEQVMTAFGG KGYFVQTPEE
LQDSLRQALK DTSKPCLINI MIEPQSTRKA QDFHWLTRSN I
//
