HACD4_HUMAN
ID HACD4_HUMAN Reviewed; 232 AA.
AC Q5VWC8; Q7Z385;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4 {ECO:0000305};
DE EC=4.2.1.134 {ECO:0000269|PubMed:18554506};
DE AltName: Full=3-hydroxyacyl-CoA dehydratase 4 {ECO:0000303|PubMed:18554506};
DE Short=HACD4 {ECO:0000303|PubMed:18554506};
DE AltName: Full=Protein-tyrosine phosphatase-like A domain-containing protein 2 {ECO:0000312|HGNC:HGNC:20920};
GN Name=HACD4 {ECO:0000303|PubMed:18554506, ECO:0000312|HGNC:HGNC:20920};
GN Synonyms=PTPLAD2;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 40-232.
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND INTERACTION WITH
RP ELOVL FAMILY.
RX PubMed=18554506; DOI=10.1016/j.febslet.2008.06.007;
RA Ikeda M., Kanao Y., Yamanaka M., Sakuraba H., Mizutani Y., Igarashi Y.,
RA Kihara A.;
RT "Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved
RT in very long-chain fatty acid synthesis.";
RL FEBS Lett. 582:2435-2440(2008).
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:0000269|PubMed:18554506}.
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:0000269|PubMed:18554506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45813;
CC Evidence={ECO:0000305|PubMed:18554506};
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:0000269|PubMed:18554506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39160;
CC Evidence={ECO:0000305|PubMed:18554506};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.8 uM for 3-hydroxypalmitoyl-CoA (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:18554506};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:18554506}.
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:0000269|PubMed:18554506}.
CC -!- INTERACTION:
CC Q5VWC8; P11912: CD79A; NbExp=3; IntAct=EBI-18076069, EBI-7797864;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18554506}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:18554506}.
CC -!- TISSUE SPECIFICITY: Highly expressed in leukocytes, and low expression
CC in heart, spleen, kidney, and placenta. {ECO:0000269|PubMed:18554506}.
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. {ECO:0000250|UniProtKB:Q6Y1H2,
CC ECO:0000305|PubMed:18554506}.
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DR EMBL; AL390882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58626.1; -; Genomic_DNA.
DR EMBL; BC114215; AAI14216.1; -; mRNA.
DR EMBL; BX538052; CAD97990.1; -; mRNA.
DR CCDS; CCDS43791.1; -.
DR RefSeq; NP_001010915.2; NM_001010915.4.
DR RefSeq; NP_001308812.1; NM_001321883.1.
DR AlphaFoldDB; Q5VWC8; -.
DR BioGRID; 135110; 1.
DR IntAct; Q5VWC8; 1.
DR STRING; 9606.ENSP00000419503; -.
DR SwissLipids; SLP:000000440; -.
DR PhosphoSitePlus; Q5VWC8; -.
DR BioMuta; HACD4; -.
DR DMDM; 74747375; -.
DR jPOST; Q5VWC8; -.
DR MassIVE; Q5VWC8; -.
DR PaxDb; Q5VWC8; -.
DR PeptideAtlas; Q5VWC8; -.
DR PRIDE; Q5VWC8; -.
DR ProteomicsDB; 65525; -.
DR TopDownProteomics; Q5VWC8; -.
DR Antibodypedia; 24843; 31 antibodies from 14 providers.
DR DNASU; 401494; -.
DR Ensembl; ENST00000495827.3; ENSP00000419503.1; ENSG00000188921.14.
DR GeneID; 401494; -.
DR KEGG; hsa:401494; -.
DR MANE-Select; ENST00000495827.3; ENSP00000419503.1; NM_001010915.5; NP_001010915.2.
DR UCSC; uc010miq.3; human.
DR CTD; 401494; -.
DR DisGeNET; 401494; -.
DR GeneCards; HACD4; -.
DR HGNC; HGNC:20920; HACD4.
DR HPA; ENSG00000188921; Tissue enhanced (bone).
DR MIM; 615941; gene.
DR neXtProt; NX_Q5VWC8; -.
DR OpenTargets; ENSG00000188921; -.
DR PharmGKB; PA142671114; -.
DR VEuPathDB; HostDB:ENSG00000188921; -.
DR eggNOG; KOG3187; Eukaryota.
DR GeneTree; ENSGT00530000062962; -.
DR HOGENOM; CLU_034302_3_0_1; -.
DR InParanoid; Q5VWC8; -.
DR OMA; IGMYYTY; -.
DR OrthoDB; 1458293at2759; -.
DR PhylomeDB; Q5VWC8; -.
DR TreeFam; TF313326; -.
DR PathwayCommons; Q5VWC8; -.
DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR SABIO-RK; Q5VWC8; -.
DR SignaLink; Q5VWC8; -.
DR SIGNOR; Q5VWC8; -.
DR UniPathway; UPA00094; -.
DR BioGRID-ORCS; 401494; 16 hits in 1042 CRISPR screens.
DR ChiTaRS; HACD4; human.
DR GenomeRNAi; 401494; -.
DR Pharos; Q5VWC8; Tbio.
DR PRO; PR:Q5VWC8; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5VWC8; protein.
DR Bgee; ENSG00000188921; Expressed in bronchial epithelial cell and 145 other tissues.
DR Genevisible; Q5VWC8; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA: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; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; IDA: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 Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Lyase; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..232
FT /note="Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
FT 4"
FT /id="PRO_0000313730"
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 VARIANT 36
FT /note="T -> A (in dbSNP:rs2298260)"
FT /id="VAR_037714"
FT CONFLICT 133
FT /note="M -> V (in Ref. 4; CAD97990)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 232 AA; 27520 MW; 696D578BA5239DDD CRC64;
MGPLALPAWL QPRYRKNAYL FIYYLIQFCG HSWIFTNMTV RFFSFGKDSM VDTFYAIGLV
MRLCQSVSLL ELLHIYVGIE SNHLLPRFLQ LTERIIILFV VITSQEEVQE KYVVCVLFVF
WNLLDMVRYT YSMLSVIGIS YAVLTWLSQT LWMPIYPLCV LAEAFAIYQS LPYFESFGTY
STKLPFDLSI YFPYVLKIYL MMLFIGMYFT YSHLYSERRD ILGIFPIKKK KM
