HACD1_CANLF
ID HACD1_CANLF Reviewed; 249 AA.
AC Q4W1W1; Q4W1W0;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 81.
DE RecName: Full=Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1 {ECO:0000305};
DE EC=4.2.1.134 {ECO:0000250|UniProtKB:B0YJ81};
DE AltName: Full=3-hydroxyacyl-CoA dehydratase 1 {ECO:0000305};
DE Short=HACD1 {ECO:0000305};
DE AltName: Full=Protein-tyrosine phosphatase-like member A {ECO:0000305};
GN Name=HACD1; Synonyms=PTPLA {ECO:0000305};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), DISEASE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=15829503; DOI=10.1093/hmg/ddi151;
RA Pele M., Tiret L., Kessler J.-L., Blot S., Panthier J.-J.;
RT "SINE exonic insertion in the PTPLA gene leads to multiple splicing defects
RT and segregates with the autosomal recessive centronuclear myopathy in
RT dogs.";
RL Hum. Mol. Genet. 14:1417-1427(2005).
CC -!- FUNCTION: Catalyzes the third of the four reactions of the long-chain
CC fatty acids elongation cycle. This endoplasmic reticulum-bound
CC enzymatic process, allows the addition of two carbons to the chain of
CC long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme
CC catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into
CC trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation.
CC Thereby, it participates in the production of VLCFAs of different chain
CC lengths that are involved in multiple biological processes as
CC precursors of membrane lipids and lipid mediators.
CC {ECO:0000250|UniProtKB:B0YJ81}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA = a very-long-chain
CC (2E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:45812, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:83728, ChEBI:CHEBI:85440; EC=4.2.1.134;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45813;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39159, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:74278; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39160;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyoctadecanoyl-CoA = (2E)-octadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39155, ChEBI:CHEBI:15377, ChEBI:CHEBI:71412,
CC ChEBI:CHEBI:76374; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39156;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyeicosanoyl-CoA = (2E)-eicosenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39175, ChEBI:CHEBI:15377, ChEBI:CHEBI:74691,
CC ChEBI:CHEBI:76373; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39176;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxydocosanoyl-CoA = (2E)-docosenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39187, ChEBI:CHEBI:15377, ChEBI:CHEBI:74692,
CC ChEBI:CHEBI:76375; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39188;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxytetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39199, ChEBI:CHEBI:15377, ChEBI:CHEBI:74693,
CC ChEBI:CHEBI:76377; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39200;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexacosanoyl-CoA = (2E)-hexacosenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:39211, ChEBI:CHEBI:15377, ChEBI:CHEBI:74281,
CC ChEBI:CHEBI:76378; Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39212;
CC Evidence={ECO:0000250|UniProtKB:B0YJ81};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:B0YJ81}.
CC -!- SUBUNIT: May interact with enzymes of the ELO family (including
CC ELOVL1); with those enzymes that mediate condensation, the first of the
CC four steps of the reaction cycle responsible for fatty acids
CC elongation, may be part of a larger fatty acids elongase complex.
CC {ECO:0000250|UniProtKB:B0YJ81}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:B0YJ81}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:B0YJ81}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PTPLAfl;
CC IsoId=Q4W1W1-1; Sequence=Displayed;
CC Name=2; Synonyms=PTPLAd5;
CC IsoId=Q4W1W1-2; Sequence=VSP_035362;
CC -!- TISSUE SPECIFICITY: Skeletal muscle. {ECO:0000269|PubMed:15829503}.
CC -!- DISEASE: Note=Defects in HACD1 may be the cause of autosomal recessive
CC centronuclear myopathy in Labradors. {ECO:0000269|PubMed:15829503}.
CC -!- SIMILARITY: Belongs to the very long-chain fatty acids dehydratase HACD
CC family. {ECO:0000305}.
CC -!- CAUTION: Shares some similarity with tyrosine phosphatase proteins but
CC it has no phosphatase activity. {ECO:0000250|UniProtKB:B0YJ81}.
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DR EMBL; AJ876905; CAI46276.1; -; mRNA.
DR EMBL; AJ876904; CAI46275.1; -; mRNA.
DR RefSeq; NP_001020440.1; NM_001025269.1. [Q4W1W1-1]
DR AlphaFoldDB; Q4W1W1; -.
DR STRING; 9612.ENSCAFP00000032576; -.
DR PaxDb; Q4W1W1; -.
DR GeneID; 574011; -.
DR KEGG; cfa:574011; -.
DR CTD; 9200; -.
DR eggNOG; KOG3187; Eukaryota.
DR InParanoid; Q4W1W1; -.
DR OrthoDB; 1458293at2759; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0102343; F:3-hydroxy-arachidoyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0102344; F:3-hydroxy-behenoyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0102345; F:3-hydroxy-lignoceroyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0018812; F:3-hydroxyacyl-CoA dehydratase activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0102158; F:very-long-chain 3-hydroxyacyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0030497; P:fatty acid elongation; ISS:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR007482; Tyr_Pase-like_PTPLA.
DR PANTHER; PTHR11035; PTHR11035; 1.
DR Pfam; PF04387; PTPLA; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Lyase; Membrane; Protein phosphatase inhibitor; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..249
FT /note="Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
FT 1"
FT /id="PRO_0000349314"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 37..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..75
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..126
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..212
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 171
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT ACT_SITE 178
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 125..136
FT /note="NEESVVLFLVAW -> FFYHLISCRGCW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15829503"
FT /id="VSP_035362"
SQ SEQUENCE 249 AA; 28731 MW; F8CCC6D103C8A906 CRC64;
MASSEEDGTN GGASEAGEEK EAPGRRRRLG LLATVWLTFY NIAMTAGWLV LAIAMVRFYM
EKGTHKGLYK SIQKTLKFFQ TFALLEIVHC LIGIVPTSVI VAGVQVSSRI FMVWLITHSI
KPIQNEESVV LFLVAWTVTE ITRYSFYTFS LLDHLPYFIK WARYNFFIIL YPVGVVGELL
TIYAALPYVK KTGMFSIRLP NKYNVSFDYY YFLLITMASY IPLFPQLYFH MLRQRRKVLH
GEVIVEKDD
