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   27-MAR-2024, entry version 186.
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; 23.
DR   IntAct; Q9UJ83; 10.
DR   MINT; Q9UJ83; -.
DR   STRING; 9606.ENSP00000323811; -.
DR   SwissLipids; SLP:000001015; -.
DR   GlyGen; Q9UJ83; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9UJ83; -.
DR   MetOSite; Q9UJ83; -.
DR   PhosphoSitePlus; Q9UJ83; -.
DR   SwissPalm; Q9UJ83; -.
DR   BioMuta; HACL1; -.
DR   DMDM; 20455027; -.
DR   EPD; Q9UJ83; -.
DR   jPOST; Q9UJ83; -.
DR   MassIVE; Q9UJ83; -.
DR   MaxQB; Q9UJ83; -.
DR   PaxDb; 9606-ENSP00000323811; -.
DR   PeptideAtlas; Q9UJ83; -.
DR   ProteomicsDB; 19929; -.
DR   ProteomicsDB; 5341; -.
DR   ProteomicsDB; 5439; -.
DR   ProteomicsDB; 84601; -. [Q9UJ83-1]
DR   Pumba; Q9UJ83; -.
DR   Antibodypedia; 26826; 211 antibodies from 28 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   AGR; HGNC:17856; -.
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; YMGMIGM; -.
DR   OrthoDB; 1966690at2759; -.
DR   PhylomeDB; Q9UJ83; -.
DR   TreeFam; TF105690; -.
DR   BioCyc; MetaCyc:HS05516-MONOMER; -.
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 1151 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 175 other cell types or 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:0106359; F:2-hydroxyacyl-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   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   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
//