HACL2_HUMAN
ID HACL2_HUMAN Reviewed; 632 AA.
AC A1L0T0; O43341; Q96F08; Q99651; Q9BWN5; Q9UEB2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=2-hydroxyacyl-CoA lyase 2 {ECO:0000303|PubMed:28289220};
DE EC=4.1.2.- {ECO:0000269|PubMed:28289220};
DE AltName: Full=Acetolactate synthase-like protein;
DE AltName: Full=IlvB-like protein;
GN Name=ILVBL {ECO:0000312|HGNC:HGNC:6041};
GN Synonyms=AHAS, HACL2 {ECO:0000303|PubMed:28289220};
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], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=8954801; DOI=10.1006/geno.1996.0615;
RA Joutel A., Ducros A., Alamowitch S., Cruaud C., Domenga V., Marechal E.,
RA Vahedi K., Chabriat H., Bousser M.G., Tournier-Lasserve E.;
RT "A human homolog of bacterial acetolactate synthase genes maps within the
RT CADASIL critical region.";
RL Genomics 38:192-198(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-374.
RC TISSUE=Pancreas, and Placenta;
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 [5]
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 [6]
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 [7]
RP SUBCELLULAR LOCATION, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND TISSUE
RP 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: Endoplasmic reticulum 2-OH acyl-CoA lyase involved in the
CC cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a
CC thiamine pyrophosphate (TPP)-dependent manner. Involved in the
CC phytosphingosine degradation pathway. {ECO:0000269|PubMed:28289220}.
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=(2R)-hydroxyhexadecanoyl-CoA = formyl-CoA + pentadecanal;
CC Xref=Rhea:RHEA:55212, ChEBI:CHEBI:17302, ChEBI:CHEBI:57376,
CC ChEBI:CHEBI:138654; Evidence={ECO:0000269|PubMed:28289220};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55213;
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:0000269|PubMed:28289220};
CC Note=Binds 1 thiamine pyrophosphate per subunit.
CC {ECO:0000250|UniProtKB:Q8CHM7};
CC -!- INTERACTION:
CC A1L0T0; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-720553, EBI-742887;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:28289220}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, with highest
CC expression in heart, pancreas and placenta.
CC {ECO:0000269|PubMed:28289220, ECO:0000269|PubMed:8954801}.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC18916.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAH00109.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=AAI26914.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI26914.1; Type=Miscellaneous discrepancy; Note=Sequence of unknown origin at the C-terminus.; Evidence={ECO:0000305};
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DR EMBL; U61263; AAC50934.1; -; mRNA.
DR EMBL; AC003956; AAB94632.1; -; Genomic_DNA.
DR EMBL; AC004794; AAC18916.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471106; EAW84464.1; -; Genomic_DNA.
DR EMBL; BC000109; AAH00109.1; ALT_SEQ; mRNA.
DR EMBL; BC011722; AAH11722.1; -; mRNA.
DR EMBL; BC011761; AAH11761.1; -; mRNA.
DR EMBL; BC126913; AAI26914.1; ALT_SEQ; mRNA.
DR CCDS; CCDS12325.1; -.
DR RefSeq; NP_006835.2; NM_006844.4.
DR RefSeq; XP_005259774.1; XM_005259717.4.
DR AlphaFoldDB; A1L0T0; -.
DR SMR; A1L0T0; -.
DR BioGRID; 116190; 174.
DR IntAct; A1L0T0; 52.
DR MINT; A1L0T0; -.
DR STRING; 9606.ENSP00000263383; -.
DR SwissLipids; SLP:000001821; -.
DR GlyGen; A1L0T0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A1L0T0; -.
DR PhosphoSitePlus; A1L0T0; -.
DR SwissPalm; A1L0T0; -.
DR BioMuta; ILVBL; -.
DR EPD; A1L0T0; -.
DR jPOST; A1L0T0; -.
DR MassIVE; A1L0T0; -.
DR MaxQB; A1L0T0; -.
DR PaxDb; A1L0T0; -.
DR PeptideAtlas; A1L0T0; -.
DR PRIDE; A1L0T0; -.
DR ProteomicsDB; 129; -.
DR TopDownProteomics; A1L0T0; -.
DR Antibodypedia; 26957; 334 antibodies from 22 providers.
DR DNASU; 10994; -.
DR Ensembl; ENST00000263383.8; ENSP00000263383.3; ENSG00000105135.16.
DR GeneID; 10994; -.
DR KEGG; hsa:10994; -.
DR MANE-Select; ENST00000263383.8; ENSP00000263383.3; NM_006844.5; NP_006835.2.
DR UCSC; uc002nam.5; human.
DR CTD; 10994; -.
DR DisGeNET; 10994; -.
DR GeneCards; ILVBL; -.
DR HGNC; HGNC:6041; ILVBL.
DR HPA; ENSG00000105135; Low tissue specificity.
DR MIM; 605770; gene.
DR neXtProt; NX_A1L0T0; -.
DR OpenTargets; ENSG00000105135; -.
DR PharmGKB; PA29857; -.
DR VEuPathDB; HostDB:ENSG00000105135; -.
DR eggNOG; KOG1185; Eukaryota.
DR GeneTree; ENSGT00940000158035; -.
DR HOGENOM; CLU_013748_3_3_1; -.
DR InParanoid; A1L0T0; -.
DR OMA; CFGTSGP; -.
DR OrthoDB; 1132247at2759; -.
DR PhylomeDB; A1L0T0; -.
DR TreeFam; TF354221; -.
DR PathwayCommons; A1L0T0; -.
DR SignaLink; A1L0T0; -.
DR BioGRID-ORCS; 10994; 15 hits in 1079 CRISPR screens.
DR ChiTaRS; ILVBL; human.
DR GenomeRNAi; 10994; -.
DR Pharos; A1L0T0; Tbio.
DR PRO; PR:A1L0T0; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; A1L0T0; protein.
DR Bgee; ENSG00000105135; Expressed in apex of heart and 191 other tissues.
DR ExpressionAtlas; A1L0T0; baseline and differential.
DR Genevisible; A1L0T0; HS.
DR GO; GO:0005948; C:acetolactate synthase complex; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0003984; F:acetolactate synthase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:InterPro.
DR GO; GO:0001561; P:fatty acid alpha-oxidation; IDA:UniProtKB.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009099; P:valine biosynthetic process; IBA:GO_Central.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR000399; TPP-bd_CS.
DR InterPro; IPR045229; TPP_enz.
DR InterPro; IPR011766; TPP_enzyme-bd_C.
DR PANTHER; PTHR18968; PTHR18968; 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.
DR PROSITE; PS00187; TPP_ENZYMES; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid metabolism; Lipid metabolism; Lyase;
KW Magnesium; Membrane; Metal-binding; Reference proteome;
KW Thiamine pyrophosphate; Transmembrane; Transmembrane helix.
FT CHAIN 1..632
FT /note="2-hydroxyacyl-CoA lyase 2"
FT /id="PRO_0000314825"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 470..550
FT /note="Thiamine pyrophosphate binding"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 98
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 521
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT BINDING 547
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P40149"
FT VARIANT 374
FT /note="N -> D (in dbSNP:rs17856373)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038064"
FT VARIANT 510
FT /note="R -> Q (in dbSNP:rs35548653)"
FT /id="VAR_061901"
SQ SEQUENCE 632 AA; 67868 MW; 893F539FC5F1B2EC CRC64;
METPAAAAPA GSLFPSFLLL ACGTLVAALL GAAHRLGLFY QLLHKVDKAS VRHGGENVAA
VLRAHGVRFI FTLVGGHISP LLVACEKLGI RVVDTRHEVT AVFAADAMAR LSGTVGVAAV
TAGPGLTNTV TAVKNAQMAQ SPILLLGGAA STLLQNRGAL QAVDQLSLFR PLCKFCVSVR
RVRDIVPTLR AAMAAAQSGT PGPVFVELPV DVLYPYFMVQ KEMVPAKPPK GLVGRVVSWY
LENYLANLFA GAWEPQPEGP LPLDIPQASP QQVQRCVEIL SRAKRPLMVL GSQALLTPTS
ADKLRAAVET LGVPCFLGGM ARGLLGRNHP LHIRENRSAA LKKADVIVLA GTVCDFRLSY
GRVLSHSSKI IIVNRNREEM LLNSDIFWKP QEAVQGDVGS FVLKLVEGLQ GQTWAPDWVE
ELREADRQKE QTFREKAAMP VAQHLNPVQV LQLVEETLPD NSILVVDGGD FVGTAAHLVQ
PRGPLRWLDP GAFGTLGVGA GFALGAKLCR PDAEVWCLFG DGAFGYSLIE FDTFVRHKIP
VMALVGNDAG WTQISREQVP SLGSNVACGL AYTDYHKAAM GLGARGLLLS RENEDQVVKV
LHDAQQQCRD GHPVVVNILI GRTDFRDGSI AV
