HACD4_MOUSE
ID HACD4_MOUSE Reviewed; 232 AA.
AC A2AKM2; A2AKM1; Q8BG85; Q9CPS2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4 {ECO:0000305};
DE EC=4.2.1.134 {ECO:0000250|UniProtKB:Q9P035};
DE AltName: Full=3-hydroxyacyl-CoA dehydratase 4 {ECO:0000305};
DE Short=HACD4 {ECO:0000305};
DE AltName: Full=Protein-tyrosine phosphatase-like A domain-containing protein 2 {ECO:0000305};
GN Name=Hacd4 {ECO:0000312|MGI:MGI:1914025}; Synonyms=Ptplad2 {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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Head, Spinal cord, and Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=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).
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:Q5VWC8}.
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:Q5VWC8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45813;
CC Evidence={ECO:0000250|UniProtKB:Q5VWC8};
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:Q5VWC8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39160;
CC Evidence={ECO:0000250|UniProtKB:Q5VWC8};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q5VWC8}.
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:Q5VWC8}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5VWC8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5VWC8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2AKM2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2AKM2-2; Sequence=VSP_030124;
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:Q5VWC8}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK016968; BAB30529.1; -; mRNA.
DR EMBL; AK017257; BAB30656.1; -; mRNA.
DR EMBL; AK039344; BAC30324.1; -; mRNA.
DR EMBL; AK039602; BAC30396.1; -; mRNA.
DR EMBL; AK048282; BAC33294.1; -; mRNA.
DR EMBL; AK050927; BAC34463.1; -; mRNA.
DR EMBL; AL772316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020155; AAH20155.1; -; mRNA.
DR CCDS; CCDS18317.1; -. [A2AKM2-1]
DR RefSeq; NP_080036.1; NM_025760.4. [A2AKM2-1]
DR RefSeq; XP_006538252.1; XM_006538189.3.
DR RefSeq; XP_006538253.1; XM_006538190.3. [A2AKM2-1]
DR RefSeq; XP_006538254.1; XM_006538191.3.
DR AlphaFoldDB; A2AKM2; -.
DR STRING; 10090.ENSMUSP00000119411; -.
DR iPTMnet; A2AKM2; -.
DR PhosphoSitePlus; A2AKM2; -.
DR MaxQB; A2AKM2; -.
DR PaxDb; A2AKM2; -.
DR PRIDE; A2AKM2; -.
DR ProteomicsDB; 269809; -. [A2AKM2-1]
DR ProteomicsDB; 269810; -. [A2AKM2-2]
DR Antibodypedia; 24843; 31 antibodies from 14 providers.
DR DNASU; 66775; -.
DR Ensembl; ENSMUST00000030221; ENSMUSP00000030221; ENSMUSG00000028497. [A2AKM2-1]
DR GeneID; 66775; -.
DR KEGG; mmu:66775; -.
DR UCSC; uc008tmx.2; mouse. [A2AKM2-2]
DR UCSC; uc008tmy.2; mouse. [A2AKM2-1]
DR CTD; 401494; -.
DR MGI; MGI:1914025; Hacd4.
DR VEuPathDB; HostDB:ENSMUSG00000028497; -.
DR eggNOG; KOG3187; Eukaryota.
DR GeneTree; ENSGT00530000062962; -.
DR HOGENOM; CLU_034302_3_0_1; -.
DR InParanoid; A2AKM2; -.
DR OrthoDB; 1458293at2759; -.
DR PhylomeDB; A2AKM2; -.
DR TreeFam; TF313326; -.
DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 66775; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Hacd4; mouse.
DR PRO; PR:A2AKM2; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; A2AKM2; protein.
DR Bgee; ENSMUSG00000028497; Expressed in granulocyte and 186 other tissues.
DR ExpressionAtlas; A2AKM2; baseline and differential.
DR Genevisible; A2AKM2; 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: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; IBA:GO_Central.
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; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..232
FT /note="Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
FT 4"
FT /id="PRO_0000313731"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..56
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..112
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..135
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..189
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 156
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT ACT_SITE 163
FT /evidence="ECO:0000250|UniProtKB:P40857"
FT VAR_SEQ 207..232
FT /note="MYFTYSHLYTERKDFLRVFSVKQKNV -> NAKMFLIKCKKLCLKVFHSPIH
FT LLHVLNTGHTTRPTTRPDI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030124"
SQ SEQUENCE 232 AA; 27235 MW; FD0C8A2AC573F6E4 CRC64;
MGPSVLPAWL QPRYRKNVYL FIYYLIQFCG HSWILANMTV RFFSFGKDSM ADTFYAIGLV
MRVCQSISLL ELLHIYIGIE SNQLFPRFLQ LTERVIILFG VITSQEEVQE KCVVCVLFIL
WNLLDMVRYT YSMLSVIGTS YAALTWLSQT LWMPIYPLCV LAEAFTIYQS LPYFESFGTN
STVLPFDLST CFPYVLKLYL MMLFIGMYFT YSHLYTERKD FLRVFSVKQK NV
