HACD2_MOUSE
ID HACD2_MOUSE Reviewed; 254 AA.
AC Q9D3B1; Q3UG38; Q9JLK1;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2 {ECO:0000305};
DE EC=4.2.1.134 {ECO:0000250|UniProtKB:Q6Y1H2};
DE AltName: Full=3-hydroxyacyl-CoA dehydratase 2 {ECO:0000305};
DE Short=HACD2 {ECO:0000305};
DE AltName: Full=Protein-tyrosine phosphatase-like member B {ECO:0000312|MGI:MGI:1918007};
GN Name=Hacd2 {ECO:0000312|MGI:MGI:1918007}; Synonyms=Ptplb {ECO:0000305};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10644438; DOI=10.1006/geno.1999.5950;
RA Uwanogho D.A., Hardcastle Z., Balogh P., Mirza G., Thornburg K.L.,
RA Ragoussis J., Sharpe P.T.;
RT "Molecular cloning, chromosomal mapping, and developmental expression of a
RT novel protein tyrosine phosphatase-like gene.";
RL Genomics 62:406-416(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Brain, and Mammary tumor;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the third of the very long-chain fatty acids
CC (VLCFA) elongation four-step cycle (condensation, reduction,
CC dehydration, and reduction). This endoplasmic reticulum-elongation
CC process is characterized by the addition of two carbons to the lipid
CC chain through each cycle. This enzyme catalyzes the dehydration of the
CC 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each
CC cycle of elongation. Therefore, it participates in the production of
CC various VLCFAs involved in multiple biological processes as precursors
CC of membrane lipids and lipid mediators. {ECO:0000250|UniProtKB:Q6Y1H2}.
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45813;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39160;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39156;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39176;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39188;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39200;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
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:Q6Y1H2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39212;
CC Evidence={ECO:0000250|UniProtKB:Q6Y1H2};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q6Y1H2}.
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 Interacts with BCAP31. {ECO:0000250|UniProtKB:Q6Y1H2}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6Y1H2}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q6Y1H2}.
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 probably no phosphatase activity.
CC {ECO:0000250|UniProtKB:Q6Y1H2}.
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DR EMBL; AF169286; AAF29489.1; -; mRNA.
DR EMBL; AK148143; BAE28371.1; -; mRNA.
DR EMBL; AK018144; BAB31092.1; -; mRNA.
DR EMBL; BC027289; AAH27289.1; -; mRNA.
DR EMBL; BC131899; AAI31900.1; -; mRNA.
DR EMBL; BC131901; AAI31902.1; -; mRNA.
DR CCDS; CCDS37321.1; -.
DR RefSeq; NP_076076.2; NM_023587.2.
DR AlphaFoldDB; Q9D3B1; -.
DR BioGRID; 214237; 4.
DR STRING; 10090.ENSMUSP00000060462; -.
DR GlyGen; Q9D3B1; 1 site.
DR PhosphoSitePlus; Q9D3B1; -.
DR EPD; Q9D3B1; -.
DR jPOST; Q9D3B1; -.
DR MaxQB; Q9D3B1; -.
DR PaxDb; Q9D3B1; -.
DR PeptideAtlas; Q9D3B1; -.
DR PRIDE; Q9D3B1; -.
DR ProteomicsDB; 270931; -.
DR Antibodypedia; 32955; 93 antibodies from 16 providers.
DR DNASU; 70757; -.
DR Ensembl; ENSMUST00000061156; ENSMUSP00000060462; ENSMUSG00000035376.
DR GeneID; 70757; -.
DR KEGG; mmu:70757; -.
DR UCSC; uc007zbi.1; mouse.
DR CTD; 201562; -.
DR MGI; MGI:1918007; Hacd2.
DR VEuPathDB; HostDB:ENSMUSG00000035376; -.
DR eggNOG; KOG3187; Eukaryota.
DR GeneTree; ENSGT00530000062962; -.
DR HOGENOM; CLU_034302_2_0_1; -.
DR InParanoid; Q9D3B1; -.
DR OMA; RADNGYG; -.
DR OrthoDB; 1458293at2759; -.
DR PhylomeDB; Q9D3B1; -.
DR TreeFam; TF313326; -.
DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 70757; 9 hits in 73 CRISPR screens.
DR ChiTaRS; Hacd2; mouse.
DR PRO; PR:Q9D3B1; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9D3B1; protein.
DR Bgee; ENSMUSG00000035376; Expressed in right kidney and 204 other tissues.
DR Genevisible; Q9D3B1; MM.
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:0080023; F:3R-hydroxyacyl-CoA dehydratase activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Lyase; Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6Y1H2"
FT CHAIN 2..254
FT /note="Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
FT 2"
FT /id="PRO_0000349320"
FT TOPO_DOM 2..41
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..79
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..130
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..217
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT ACT_SITE 183
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q6Y1H2"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 130
FT /note="S -> A (in Ref. 1; AAF29489)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="I -> ITEII (in Ref. 1; AAF29489)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="Q -> R (in Ref. 2; BAE28371)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 254 AA; 28402 MW; 7DB21BB52473EB0C CRC64;
MAAAAATAAT KGNGGGSGRV GAGDSSGARK KKGPGPVATA YLVIYNVVMT AGWLVIAVGL
VRAYLAKGSY HSLYYSIERP LKFFQTGALL EILHCAIGIV PSSVVLTSFQ VMSRVFLIWA
VTHSVKEVQS EDSVLLFVIA WTITEIIRYS FYTFSLLNHL PYIIKWARYT LFIVLYPMGV
TGELLTIYAA LPFVRQAGLY SISLPNKYNF SFDYHAFLIL IMISYIPLFP QLYFHMIHQR
RKVLSHTEEH KKFE
