ZDHC3_HUMAN
ID ZDHC3_HUMAN Reviewed; 299 AA.
AC Q9NYG2; Q53A17; Q96BL0;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Palmitoyltransferase ZDHHC3 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000269|PubMed:21926431, ECO:0000269|PubMed:23034182};
DE AltName: Full=Acyltransferase ZDHHC3 {ECO:0000250|UniProtKB:Q8R173};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q8R173};
DE AltName: Full=Protein DHHC1 {ECO:0000312|EMBL:AAF63570.1};
DE AltName: Full=Zinc finger DHHC domain-containing protein 3 {ECO:0000312|HGNC:HGNC:18470};
DE Short=DHHC-3 {ECO:0000312|EMBL:AAH15467.1};
GN Name=ZDHHC3 {ECO:0000312|HGNC:HGNC:18470};
GN ORFNames=HSD49 {ECO:0000312|EMBL:AAV83779.1};
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] (ISOFORM 2).
RA Hameed K.S., Greenberg A.H.;
RT "DHHC domain-containing protein from human T-cell.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
RA Hong G.S., Jung Y.K.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 103-284 (ISOFORM 2).
RC TISSUE=Testis;
RA Yuan L.G., Tian Y.Q., Qiao Y., Miao S.Y., Wang L.F.;
RT "A new spermatogenesis-related gene.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16647879; DOI=10.1016/j.bbalip.2006.03.010;
RA Ohno Y., Kihara A., Sano T., Igarashi Y.;
RT "Intracellular localization and tissue-specific distribution of human and
RT yeast DHHC cysteine-rich domain-containing proteins.";
RL Biochim. Biophys. Acta 1761:474-483(2006).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19001095; DOI=10.1128/mcb.01144-08;
RA Tsutsumi R., Fukata Y., Noritake J., Iwanaga T., Perez F., Fukata M.;
RT "Identification of G protein alpha subunit-palmitoylating enzyme.";
RL Mol. Cell. Biol. 29:435-447(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PALMITOYLATION, AND
RP MUTAGENESIS OF VAL-299.
RX PubMed=21926431; DOI=10.1074/jbc.m111.272369;
RA Gorleku O.A., Barns A.M., Prescott G.R., Greaves J., Chamberlain L.H.;
RT "Endoplasmic reticulum localization of DHHC palmitoyltransferases mediated
RT by lysine-based sorting signals.";
RL J. Biol. Chem. 286:39573-39584(2011).
RN [9]
RP FUNCTION, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF HIS-155 AND CYS-157.
RX PubMed=22240897; DOI=10.1038/cdd.2011.209;
RA Oh Y., Jeon Y.J., Hong G.S., Kim I., Woo H.N., Jung Y.K.;
RT "Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ
RT for TRAIL sensitivity in tumor cells.";
RL Cell Death Differ. 19:1196-1207(2012).
RN [10]
RP FUNCTION.
RX PubMed=22314500; DOI=10.1007/s00018-012-0924-6;
RA Sharma C., Rabinovitz I., Hemler M.E.;
RT "Palmitoylation by DHHC3 is critical for the function, expression, and
RT stability of integrin alpha6beta4.";
RL Cell. Mol. Life Sci. 69:2233-2244(2012).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23034182; DOI=10.1091/mbc.e12-05-0336;
RA Ohno Y., Kashio A., Ogata R., Ishitomi A., Yamazaki Y., Kihara A.;
RT "Analysis of substrate specificity of human DHHC protein acyltransferases
RT using a yeast expression system.";
RL Mol. Biol. Cell 23:4543-4551(2012).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26535572; DOI=10.1371/journal.pone.0140661;
RA Ebersole B., Petko J., Woll M., Murakami S., Sokolina K., Wong V.,
RA Stagljar I., Luescher B., Levenson R.;
RT "Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking
RT and Stability.";
RL PLoS ONE 10:e0140661-e0140661(2015).
CC -!- FUNCTION: Golgi-localized palmitoyltransferase that catalyzes the
CC addition of palmitate onto various protein substrates (PubMed:19001095,
CC PubMed:21926431, PubMed:22240897, PubMed:23034182, PubMed:22314500).
CC Has no stringent fatty acid selectivity and in addition to palmitate
CC can also transfer onto target proteins myristate from tetradecanoyl-CoA
CC and stearate from octadecanoyl-CoA (By similarity). Plays an important
CC role in G protein-coupled receptor signaling pathways involving GNAQ
CC and potentially other heterotrimeric G proteins by regulating their
CC dynamic association with the plasma membrane (PubMed:19001095).
CC Palmitoylates ITGA6 and ITGB4, thereby regulating the alpha-6/beta-4
CC integrin localization, expression and function in cell adhesion to
CC laminin (PubMed:22314500). Plays a role in the TRAIL-activated
CC apoptotic signaling pathway most probably through the palmitoylation
CC and localization to the plasma membrane of TNFRSF10A (PubMed:22240897).
CC In the brain, by palmitoylating the gamma subunit GABRG2 of GABA(A)
CC receptors and regulating their postsynaptic accumulation, plays a role
CC in synaptic GABAergic inhibitory function and GABAergic innervation.
CC Palmitoylates the neuronal protein GAP43 which is also involved in the
CC formation of GABAergic synapses. Palmitoylates NCDN thereby regulating
CC its association with endosome membranes. Probably palmitoylates PRCD
CC and is involved in its proper localization within the photoreceptor.
CC Could mediate the palmitoylation of NCAM1 and regulate neurite
CC outgrowth. Could palmitoylate DNAJC5 and regulate its localization to
CC Golgi membranes. Also constitutively palmitoylates DLG4. May also
CC palmitoylate SNAP25. Could palmitoylate the glutamate receptors GRIA1
CC and GRIA2 but this has not been confirmed in vivo (By similarity).
CC Could also palmitoylate the D(2) dopamine receptor DRD2
CC (PubMed:26535572). {ECO:0000250|UniProtKB:Q8R173,
CC ECO:0000269|PubMed:19001095, ECO:0000269|PubMed:21926431,
CC ECO:0000269|PubMed:22240897, ECO:0000269|PubMed:22314500,
CC ECO:0000269|PubMed:23034182, ECO:0000269|PubMed:26535572}.
CC -!- FUNCTION: May also function as a calcium transporter.
CC {ECO:0000250|UniProtKB:Q8R173}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-
CC hexadecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:36683, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:74151;
CC EC=2.3.1.225; Evidence={ECO:0000269|PubMed:21926431,
CC ECO:0000269|PubMed:23034182};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000305|PubMed:21926431};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteinyl-[protein] + tetradecanoyl-CoA = CoA + S-
CC tetradecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:59736, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:15433, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:143199;
CC Evidence={ECO:0000250|UniProtKB:Q8R173};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59737;
CC Evidence={ECO:0000250|UniProtKB:Q8R173};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteinyl-[protein] + octadecanoyl-CoA = CoA + S-
CC octadecanoyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:59740, Rhea:RHEA-
CC COMP:10131, Rhea:RHEA-COMP:15434, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57394, ChEBI:CHEBI:143200;
CC Evidence={ECO:0000250|UniProtKB:Q8R173};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59741;
CC Evidence={ECO:0000250|UniProtKB:Q8R173};
CC -!- SUBUNIT: Monomer. Homooligomers. The monomeric form has a higher
CC catalytic activity. Forms heterooligomers with ZDHHC7 (By similarity).
CC Interacts with TNFRSF10A (PubMed:22240897).
CC {ECO:0000250|UniProtKB:Q8R173, ECO:0000269|PubMed:22240897}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:16647879, ECO:0000269|PubMed:19001095,
CC ECO:0000269|PubMed:21926431, ECO:0000269|PubMed:26535572}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localizes to the Golgi cis
CC cisterna. {ECO:0000250|UniProtKB:Q8R173}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NYG2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NYG2-2; Sequence=VSP_006934;
CC -!- TISSUE SPECIFICITY: Widely expressed with significant expression in
CC heart, lung, liver, skeletal muscle, kidney, testis, thymus, small
CC intestine and leukocyte. {ECO:0000269|PubMed:16647879}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000250|UniProtKB:Q8IUH5}.
CC -!- PTM: Autopalmitoylated. {ECO:0000269|PubMed:21926431}.
CC -!- PTM: Phosphorylation by FGFR1 and SRC probably regulates the
CC palmitoyltransferase activity. {ECO:0000250|UniProtKB:Q8R173}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AF247703; AAF63570.1; -; mRNA.
DR EMBL; AF441791; AAL34547.1; -; mRNA.
DR EMBL; BC015467; AAH15467.1; -; mRNA.
DR EMBL; AY605661; AAV83779.1; -; mRNA.
DR CCDS; CCDS2724.1; -. [Q9NYG2-2]
DR CCDS; CCDS46811.1; -. [Q9NYG2-1]
DR RefSeq; NP_001128651.1; NM_001135179.1. [Q9NYG2-1]
DR RefSeq; NP_057682.1; NM_016598.2. [Q9NYG2-2]
DR RefSeq; XP_016862055.1; XM_017006566.1.
DR RefSeq; XP_016862056.1; XM_017006567.1.
DR AlphaFoldDB; Q9NYG2; -.
DR SMR; Q9NYG2; -.
DR BioGRID; 119455; 29.
DR IntAct; Q9NYG2; 7.
DR MINT; Q9NYG2; -.
DR STRING; 9606.ENSP00000296127; -.
DR iPTMnet; Q9NYG2; -.
DR PhosphoSitePlus; Q9NYG2; -.
DR SwissPalm; Q9NYG2; -.
DR BioMuta; ZDHHC3; -.
DR DMDM; 476007823; -.
DR EPD; Q9NYG2; -.
DR jPOST; Q9NYG2; -.
DR MassIVE; Q9NYG2; -.
DR MaxQB; Q9NYG2; -.
DR PeptideAtlas; Q9NYG2; -.
DR PRIDE; Q9NYG2; -.
DR ProteomicsDB; 83225; -. [Q9NYG2-1]
DR ProteomicsDB; 83226; -. [Q9NYG2-2]
DR Antibodypedia; 3251; 147 antibodies from 21 providers.
DR DNASU; 51304; -.
DR Ensembl; ENST00000296127.7; ENSP00000296127.3; ENSG00000163812.15. [Q9NYG2-2]
DR Ensembl; ENST00000424952.7; ENSP00000395502.2; ENSG00000163812.15. [Q9NYG2-1]
DR GeneID; 51304; -.
DR KEGG; hsa:51304; -.
DR MANE-Select; ENST00000424952.7; ENSP00000395502.2; NM_001135179.2; NP_001128651.1.
DR UCSC; uc003cod.4; human. [Q9NYG2-1]
DR CTD; 51304; -.
DR DisGeNET; 51304; -.
DR GeneCards; ZDHHC3; -.
DR HGNC; HGNC:18470; ZDHHC3.
DR HPA; ENSG00000163812; Low tissue specificity.
DR neXtProt; NX_Q9NYG2; -.
DR OpenTargets; ENSG00000163812; -.
DR PharmGKB; PA38544; -.
DR VEuPathDB; HostDB:ENSG00000163812; -.
DR eggNOG; KOG1311; Eukaryota.
DR GeneTree; ENSGT00940000155721; -.
DR HOGENOM; CLU_048061_1_1_1; -.
DR InParanoid; Q9NYG2; -.
DR OrthoDB; 1491968at2759; -.
DR TreeFam; TF319798; -.
DR BRENDA; 2.3.1.225; 2681.
DR PathwayCommons; Q9NYG2; -.
DR Reactome; R-HSA-9694548; Maturation of spike protein.
DR SignaLink; Q9NYG2; -.
DR BioGRID-ORCS; 51304; 10 hits in 1080 CRISPR screens.
DR ChiTaRS; ZDHHC3; human.
DR GeneWiki; ZDHHC3; -.
DR GenomeRNAi; 51304; -.
DR Pharos; Q9NYG2; Tbio.
DR PRO; PR:Q9NYG2; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NYG2; protein.
DR Bgee; ENSG00000163812; Expressed in left testis and 203 other tissues.
DR ExpressionAtlas; Q9NYG2; baseline and differential.
DR Genevisible; Q9NYG2; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019705; F:protein-cysteine S-myristoyltransferase activity; IEA:RHEA.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:UniProtKB.
DR GO; GO:0140439; F:protein-cysteine S-stearoyltransferase activity; IEA:RHEA.
DR GO; GO:0044873; P:lipoprotein localization to membrane; IMP:UniProtKB.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; ISS:UniProtKB.
DR GO; GO:1902685; P:positive regulation of receptor localization to synapse; ISS:UniProtKB.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISS:UniProtKB.
DR GO; GO:1903546; P:protein localization to photoreceptor outer segment; IDA:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0036462; P:TRAIL-activated apoptotic signaling pathway; IMP:UniProtKB.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR Pfam; PF01529; DHHC; 1.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Golgi apparatus; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..299
FT /note="Palmitoyltransferase ZDHHC3"
FT /id="PRO_0000422064"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..72
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 94..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 127..177
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT ACT_SITE 157
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067,
FT ECO:0000305|PubMed:22240897"
FT MOD_RES 18
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8R173"
FT LIPID 146
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q8R173"
FT VAR_SEQ 204
FT /note="K -> TYGLNREEMAETGISLHEKMQPLNFSSTE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1, ECO:0000303|Ref.4"
FT /id="VSP_006934"
FT MUTAGEN 155
FT /note="H->A: Probable loss of protein-cysteine S-
FT palmitoyltransferase activity. Loss of function in the
FT TRAIL-activated apoptotic signaling pathway."
FT /evidence="ECO:0000269|PubMed:22240897"
FT MUTAGEN 157
FT /note="C->S: Probable loss of protein-cysteine S-
FT palmitoyltransferase activity. Loss of function in the
FT TRAIL-activated apoptotic signaling pathway. No effect on
FT binding of the TNFRSF10A substrate."
FT /evidence="ECO:0000269|PubMed:22240897"
FT MUTAGEN 299
FT /note="V->VEKKNR,VKKKEK,VKGKRD: Impaired localization
FT leading to localization to the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:21926431"
SQ SEQUENCE 299 AA; 34170 MW; 345A960FCB46E0E1 CRC64;
MMLIPTHHFR NIERKPEYLQ PEKCVPPPYP GPVGTMWFIR DGCGIACAIV TWFLVLYAEF
VVLFVMLIPS RDYVYSIING IVFNLLAFLA LASHCRAMLT DPGAVPKGNA TKEFIESLQL
KPGQVVYKCP KCCSIKPDRA HHCSVCKRCI RKMDHHCPWV NNCVGENNQK YFVLFTMYIA
LISLHALIMV GFHFLHCFEE DWTKCSSFSP PTTVILLILL CFEGLLFLIF TSVMFGTQVH
SICTDETGIE QLKKEERRWA KKTKWMNMKA VFGHPFSLGW ASPFATPDQG KADPYQYVV
