HACL1_HUMAN
ID HACL1_HUMAN Reviewed; 578 AA.
AC Q9UJ83; B4DWI1; B4DXI5; E9PEN4; Q9BV42; Q9P0A2;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=2-hydroxyacyl-CoA lyase 1;
DE EC=4.1.2.63 {ECO:0000269|PubMed:10468558, ECO:0000269|PubMed:21708296, ECO:0000269|PubMed:28289220};
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 {ECO:0000312|HGNC:HGNC:17856}; Synonyms=HPCL, HPCL2, PHYH2;
GN ORFNames=HSPC279;
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), TISSUE SPECIFICITY, CATALYTIC
RP ACTIVITY, FUNCTION, AND SUBCELLULAR LOCATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Mammary gland, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-455 AND SER-456, SUBUNIT, AND
RP CATALYTIC ACTIVITY.
RX PubMed=21708296; DOI=10.1016/j.bbapap.2011.06.007;
RA Fraccascia P., Casteels M., De Schryver E., Van Veldhoven P.P.;
RT "Role of thiamine pyrophosphate in oligomerisation, functioning and import
RT of peroxisomal 2-hydroxyacyl-CoA lyase.";
RL Biochim. Biophys. Acta 1814:1226-1233(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
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 [12]
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 [13]
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28289220; DOI=10.1073/pnas.1700138114;
RA Kitamura T., Seki N., Kihara A.;
RT "Phytosphingosine degradation pathway includes fatty acid alpha-oxidation
RT reactions in the endoplasmic reticulum.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E2616-E2623(2017).
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 (PubMed:28289220, PubMed:21708296,
CC PubMed:10468558). Involved in the degradation of 3-methyl-branched
CC fatty acids like phytanic acid and the shortening of 2-hydroxy long-
CC chain fatty acids (PubMed:28289220, PubMed:21708296, PubMed:10468558).
CC Plays a significant role in the biosynthesis of heptadecanal in the
CC liver (By similarity). {ECO:0000250|UniProtKB:Q9QXE0,
CC ECO:0000269|PubMed:10468558, ECO:0000269|PubMed:21708296,
CC ECO:0000269|PubMed:28289220}.
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, ECO:0000269|PubMed:21708296};
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:0000269|PubMed:28289220};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67445;
CC Evidence={ECO:0000305|PubMed:28289220};
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, ECO:0000269|PubMed:21708296};
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:0000269|PubMed:28289220};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55197;
CC Evidence={ECO:0000305|PubMed:28289220};
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:0000269|PubMed:28289220};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25356;
CC Evidence={ECO:0000305|PubMed:28289220};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8CHM7};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8CHM7};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000250|UniProtKB:Q8CHM7};
CC Note=Binds 1 thiamine pyrophosphate per subunit.
CC {ECO:0000250|UniProtKB:Q8CHM7};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:21708296}.
CC -!- INTERACTION:
CC Q9UJ83; Q9UJ83: HACL1; NbExp=3; IntAct=EBI-746580, EBI-746580;
CC Q9UJ83; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-746580, EBI-6447163;
CC Q9UJ83; Q96E35: ZMYND19; NbExp=7; IntAct=EBI-746580, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:10468558,
CC ECO:0000269|PubMed:21708296, ECO:0000269|PubMed:28289220}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UJ83-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJ83-2; Sequence=VSP_054191;
CC Name=4;
CC IsoId=Q9UJ83-4; Sequence=VSP_054749, VSP_054750;
CC Name=3;
CC IsoId=Q9UJ83-3; Sequence=VSP_054192;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10468558,
CC ECO:0000269|PubMed:28289220}.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF28957.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ131753; CAB60200.1; -; mRNA.
DR EMBL; AF161397; AAF28957.1; ALT_INIT; mRNA.
DR EMBL; AK301546; BAG63043.1; -; mRNA.
DR EMBL; AK301990; BAG63397.1; -; mRNA.
DR EMBL; AC027129; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001627; AAH01627.1; -; mRNA.
DR CCDS; CCDS2627.1; -. [Q9UJ83-1]
DR CCDS; CCDS68360.1; -. [Q9UJ83-2]
DR CCDS; CCDS68361.1; -. [Q9UJ83-3]
DR CCDS; CCDS68362.1; -. [Q9UJ83-4]
DR RefSeq; NP_001271342.1; NM_001284413.1. [Q9UJ83-2]
DR RefSeq; NP_001271344.1; NM_001284415.1. [Q9UJ83-4]
DR RefSeq; NP_001271345.1; NM_001284416.1. [Q9UJ83-3]
DR RefSeq; NP_036392.2; NM_012260.3. [Q9UJ83-1]
DR AlphaFoldDB; Q9UJ83; -.
DR SMR; Q9UJ83; -.
DR BioGRID; 117523; 21.
DR IntAct; Q9UJ83; 9.
DR MINT; Q9UJ83; -.
DR STRING; 9606.ENSP00000323811; -.
DR SwissLipids; SLP:000001015; -.
DR iPTMnet; Q9UJ83; -.
DR MetOSite; Q9UJ83; -.
DR PhosphoSitePlus; Q9UJ83; -.
DR BioMuta; HACL1; -.
DR DMDM; 20455027; -.
DR EPD; Q9UJ83; -.
DR jPOST; Q9UJ83; -.
DR MassIVE; Q9UJ83; -.
DR MaxQB; Q9UJ83; -.
DR PaxDb; Q9UJ83; -.
DR PeptideAtlas; Q9UJ83; -.
DR PRIDE; Q9UJ83; -.
DR ProteomicsDB; 19929; -.
DR ProteomicsDB; 5341; -.
DR ProteomicsDB; 5439; -.
DR ProteomicsDB; 84601; -. [Q9UJ83-1]
DR Antibodypedia; 26826; 199 antibodies from 27 providers.
DR DNASU; 26061; -.
DR Ensembl; ENST00000321169.10; ENSP00000323811.5; ENSG00000131373.15. [Q9UJ83-1]
DR Ensembl; ENST00000451445.6; ENSP00000403656.2; ENSG00000131373.15. [Q9UJ83-3]
DR Ensembl; ENST00000456194.6; ENSP00000390699.2; ENSG00000131373.15. [Q9UJ83-2]
DR Ensembl; ENST00000457447.6; ENSP00000404883.2; ENSG00000131373.15. [Q9UJ83-4]
DR GeneID; 26061; -.
DR KEGG; hsa:26061; -.
DR MANE-Select; ENST00000321169.10; ENSP00000323811.5; NM_012260.4; NP_036392.2.
DR UCSC; uc003caf.5; human. [Q9UJ83-1]
DR CTD; 26061; -.
DR DisGeNET; 26061; -.
DR GeneCards; HACL1; -.
DR HGNC; HGNC:17856; HACL1.
DR HPA; ENSG00000131373; Low tissue specificity.
DR MIM; 604300; gene.
DR neXtProt; NX_Q9UJ83; -.
DR OpenTargets; ENSG00000131373; -.
DR PharmGKB; PA142671172; -.
DR VEuPathDB; HostDB:ENSG00000131373; -.
DR eggNOG; KOG1185; Eukaryota.
DR GeneTree; ENSGT00940000156802; -.
DR HOGENOM; CLU_013748_3_3_1; -.
DR InParanoid; Q9UJ83; -.
DR OMA; FQEWPQV; -.
DR OrthoDB; 330201at2759; -.
DR PhylomeDB; Q9UJ83; -.
DR TreeFam; TF105690; -.
DR BioCyc; MetaCyc:HS05516-MON; -.
DR BRENDA; 4.1.2.63; 2681.
DR PathwayCommons; Q9UJ83; -.
DR Reactome; R-HSA-389599; Alpha-oxidation of phytanate.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SignaLink; Q9UJ83; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 26061; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; HACL1; human.
DR GenomeRNAi; 26061; -.
DR Pharos; Q9UJ83; Tbio.
DR PRO; PR:Q9UJ83; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UJ83; protein.
DR Bgee; ENSG00000131373; Expressed in jejunal mucosa and 173 other tissues.
DR ExpressionAtlas; Q9UJ83; baseline and differential.
DR Genevisible; Q9UJ83; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0106360; F:2-hydroxy-3-methylhexadecanoyl-CoA lyase activity; IMP:UniProtKB.
DR GO; GO:0106376; F:2-hydroxyphytanoyl-CoA lyase activity; IEA:RHEA.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016830; F:carbon-carbon lyase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IDA:HGNC-UCL.
DR GO; GO:0001561; P:fatty acid alpha-oxidation; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0097089; P:methyl-branched fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:1903512; P:phytanic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006625; P:protein targeting to peroxisome; IMP:UniProtKB.
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-bd_C.
DR PANTHER; PTHR43710; PTHR43710; 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; SSF52467; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Magnesium; Metal-binding; Peroxisome; Phosphoprotein; Reference proteome;
KW Thiamine pyrophosphate.
FT CHAIN 1..578
FT /note="2-hydroxyacyl-CoA lyase 1"
FT /id="PRO_0000090816"
FT REGION 401..486
FT /note="Thiamine pyrophosphate binding"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT MOTIF 576..578
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000269|PubMed:10468558"
FT BINDING 60
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 455
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 482
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 351
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXE0"
FT MOD_RES 358
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXE0"
FT MOD_RES 365
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXE0"
FT VAR_SEQ 77..103
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054191"
FT VAR_SEQ 104..185
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054192"
FT VAR_SEQ 128..153
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054749"
FT VAR_SEQ 332..365
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_054750"
FT MUTAGEN 455
FT /note="D->S,R: Does not affect subcellular localization.
FT Abolishes lyase activity. Does not affect subcellular
FT localization, abolishes lyase activity, does not affect
FT oligomerisation and does not bind TTP; when associated with
FT S-456."
FT /evidence="ECO:0000269|PubMed:21708296"
FT MUTAGEN 456
FT /note="S->R: Does not affect subcellular localization.
FT Abolishes lyase activity. Does not affect subcellular
FT localization, abolishes lyase activity, does not affect
FT oligomerisation and does not bind TTP; when associated with
FT S-455."
FT /evidence="ECO:0000269|PubMed:21708296"
FT CONFLICT 447
FT /note="Q -> H (in Ref. 1; CAB60200)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="R -> E (in Ref. 1; CAB60200)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 63729 MW; CF4F4B1A97025140 CRC64;
MPDSNFAERS EEQVSGAKVI AQALKTQDVE YIFGIVGIPV TEIAIAAQQL GIKYIGMRNE
QAACYAASAI GYLTSRPGVC LVVSGPGLIH ALGGMANANM NCWPLLVIGG SSERNQETMG
AFQEFPQVEA CRLYTKFSAR PSSIEAIPFV IEKAVRSSIY GRPGACYVDI PADFVNLQVN
VNSIKYMERC MSPPISMAET SAVCTAASVI RNAKQPLLII GKGAAYAHAE ESIKKLVEQY
KLPFLPTPMG KGVVPDNHPY CVGAARSRAL QFADVIVLFG ARLNWILHFG LPPRYQPDVK
FIQVDICAEE LGNNVKPAVT LLGNIHAVTK QLLEELDKTP WQYPPESKWW KTLREKMKSN
EAASKELASK KSLPMNYYTV FYHVQEQLPR DCFVVSEGAN TMDIGRTVLQ NYLPRHRLDA
GTFGTMGVGL GFAIAAAVVA KDRSPGQWII CVEGDSAFGF SGMEVETICR YNLPIILLVV
NNNGIYQGFD TDTWKEMLKF QDATAVVPPM CLLPNSHYEQ VMTAFGGKGY FVQTPEELQK
SLRQSLADTT KPSLINIMIE PQATRKAQDF HWLTRSNM
