ZDHC6_MOUSE
ID ZDHC6_MOUSE Reviewed; 413 AA.
AC Q9CPV7; Q3U3I8; Q3UT70; Q544H1;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Palmitoyltransferase ZDHHC6 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000250|UniProtKB:Q9H6R6};
DE AltName: Full=Stearoyltransferase ZDHHC6 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q9H6R6};
DE AltName: Full=Zinc finger DHHC domain-containing protein 6 {ECO:0000250|UniProtKB:Q9H6R6};
DE Short=DHHC-6 {ECO:0000250|UniProtKB:Q9H6R6};
GN Name=Zdhhc6 {ECO:0000312|MGI:MGI:1914230};
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; 2; 3 AND 4).
RC STRAIN=C57BL/6J;
RC TISSUE=Egg, Embryo, Embryonic stem cell, Limb, Liver, Spleen, and Thymus;
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 MRNA] (ISOFORM 1).
RC STRAIN=FVB/N;
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 [3]
RP FUNCTION, AND INTERACTION WITH SELENOK.
RX PubMed=25368151; DOI=10.1073/pnas.1417176111;
RA Fredericks G.J., Hoffmann F.W., Rose A.H., Osterheld H.J., Hess F.M.,
RA Mercier F., Hoffmann P.R.;
RT "Stable expression and function of the inositol 1,4,5-triphosphate receptor
RT requires palmitoylation by a DHHC6/selenoprotein K complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:16478-16483(2014).
RN [4]
RP PALMITOYLATION.
RX PubMed=28826475; DOI=10.7554/elife.27826;
RA Abrami L., Dallavilla T., Sandoz P.A., Demir M., Kunz B., Savoglidis G.,
RA Hatzimanikatis V., van der Goot F.G.;
RT "Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation
RT cascade.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Endoplasmic reticulum palmitoyl acyltransferase that mediates
CC palmitoylation of proteins such as AMFR, CALX, ITPR1 and TFRC
CC (PubMed:25368151). Palmitoylates calnexin (CALX), which is required for
CC its association with the ribosome-translocon complex and efficient
CC folding of glycosylated proteins (By similarity). Mediates
CC palmitoylation of AMFR, promoting AMFR distribution to the peripheral
CC endoplasmic reticulum (By similarity). Together with SELENOK,
CC palmitoylates ITPR1 in immune cells, leading to regulate ITPR1
CC stability and function (PubMed:25368151). Stearoyltransferase that
CC mediates stearoylation of TFRC to inhibit TFRC-mediated activation of
CC the JNK pathway and mitochondrial fragmentation (By similarity).
CC {ECO:0000250|UniProtKB:Q9H6R6, ECO:0000269|PubMed:25368151}.
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:0000250|UniProtKB:Q9H6R6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000250|UniProtKB:Q9H6R6};
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:Q9H6R6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59741;
CC Evidence={ECO:0000250|UniProtKB:Q9H6R6};
CC -!- SUBUNIT: Homooligomerizes (By similarity). Interacts with SELENOK
CC (PubMed:25368151). {ECO:0000250|UniProtKB:Q9H6R6,
CC ECO:0000269|PubMed:25368151}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9H6R6}; Multi-pass membrane protein
CC {ECO:0000255}. Note=When not palmitoylated, accumulates to dot-like
CC structures in the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q9H6R6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9CPV7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CPV7-2; Sequence=VSP_006939, VSP_006940;
CC Name=3;
CC IsoId=Q9CPV7-3; Sequence=VSP_006941;
CC Name=4;
CC IsoId=Q9CPV7-4; Sequence=VSP_016270;
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000250|UniProtKB:Q8IUH5}.
CC -!- DOMAIN: The C-terminal di-lysine motif confers endoplasmic reticulum
CC localization. {ECO:0000250|UniProtKB:Q9H6R6}.
CC -!- PTM: Palmitoylated at 3 different sites by ZDHHC16. The combination of
CC the different palmitoylation events strongly affects the quaternary
CC assembly of ZDHHC6, its localization, stability and function.
CC Palmitoylation at Cys-328 accelerates the turnover of ZDHHC6.
CC Depalmitoylated by LYPLA2. {ECO:0000250|UniProtKB:Q9H6R6,
CC ECO:0000269|PubMed:28826475}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AK011373; BAB27576.1; -; mRNA.
DR EMBL; AK010296; BAB26831.1; -; mRNA.
DR EMBL; AK077693; BAC36960.1; -; mRNA.
DR EMBL; AK050388; BAC34229.1; -; mRNA.
DR EMBL; AK035172; BAC28968.1; -; mRNA.
DR EMBL; AK038177; BAC29944.1; -; mRNA.
DR EMBL; AK077838; BAC37027.1; -; mRNA.
DR EMBL; AK139707; BAE24110.1; -; mRNA.
DR EMBL; AK144128; BAE25717.1; -; mRNA.
DR EMBL; AK154741; BAE32798.1; -; mRNA.
DR EMBL; AK157494; BAE34103.1; -; mRNA.
DR EMBL; AK159304; BAE34974.1; -; mRNA.
DR EMBL; BC033317; AAH33317.1; -; mRNA.
DR CCDS; CCDS29909.1; -. [Q9CPV7-1]
DR RefSeq; NP_001028745.1; NM_001033573.1. [Q9CPV7-1]
DR RefSeq; NP_080159.3; NM_025883.3. [Q9CPV7-1]
DR RefSeq; XP_006527331.1; XM_006527268.2. [Q9CPV7-1]
DR RefSeq; XP_011245618.1; XM_011247316.1. [Q9CPV7-1]
DR AlphaFoldDB; Q9CPV7; -.
DR SMR; Q9CPV7; -.
DR BioGRID; 211853; 8.
DR IntAct; Q9CPV7; 8.
DR STRING; 10090.ENSMUSP00000076157; -.
DR iPTMnet; Q9CPV7; -.
DR PhosphoSitePlus; Q9CPV7; -.
DR SwissPalm; Q9CPV7; -.
DR EPD; Q9CPV7; -.
DR MaxQB; Q9CPV7; -.
DR PaxDb; Q9CPV7; -.
DR PeptideAtlas; Q9CPV7; -.
DR PRIDE; Q9CPV7; -.
DR ProteomicsDB; 275343; -. [Q9CPV7-1]
DR ProteomicsDB; 275344; -. [Q9CPV7-2]
DR ProteomicsDB; 275345; -. [Q9CPV7-3]
DR ProteomicsDB; 275346; -. [Q9CPV7-4]
DR Antibodypedia; 18429; 98 antibodies from 17 providers.
DR DNASU; 66980; -.
DR Ensembl; ENSMUST00000076891; ENSMUSP00000076157; ENSMUSG00000024982. [Q9CPV7-1]
DR Ensembl; ENSMUST00000224291; ENSMUSP00000153221; ENSMUSG00000024982. [Q9CPV7-4]
DR Ensembl; ENSMUST00000224897; ENSMUSP00000153014; ENSMUSG00000024982. [Q9CPV7-1]
DR Ensembl; ENSMUST00000225495; ENSMUSP00000152962; ENSMUSG00000024982. [Q9CPV7-2]
DR Ensembl; ENSMUST00000225963; ENSMUSP00000153159; ENSMUSG00000024982. [Q9CPV7-3]
DR Ensembl; ENSMUST00000226103; ENSMUSP00000153404; ENSMUSG00000024982. [Q9CPV7-1]
DR GeneID; 66980; -.
DR KEGG; mmu:66980; -.
DR UCSC; uc008hxs.2; mouse. [Q9CPV7-1]
DR CTD; 64429; -.
DR MGI; MGI:1914230; Zdhhc6.
DR VEuPathDB; HostDB:ENSMUSG00000024982; -.
DR eggNOG; KOG1314; Eukaryota.
DR GeneTree; ENSGT00940000155642; -.
DR HOGENOM; CLU_044394_1_0_1; -.
DR InParanoid; Q9CPV7; -.
DR OMA; FIYPYDL; -.
DR OrthoDB; 1491968at2759; -.
DR PhylomeDB; Q9CPV7; -.
DR TreeFam; TF320809; -.
DR BioGRID-ORCS; 66980; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Zdhhc6; mouse.
DR PRO; PR:Q9CPV7; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9CPV7; protein.
DR Bgee; ENSMUSG00000024982; Expressed in right kidney and 247 other tissues.
DR ExpressionAtlas; Q9CPV7; baseline and differential.
DR Genevisible; Q9CPV7; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016409; F:palmitoyltransferase activity; ISS:UniProtKB.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IBA:GO_Central.
DR GO; GO:0140439; F:protein-cysteine S-stearoyltransferase activity; ISS:UniProtKB.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IBA:GO_Central.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0140438; P:protein stearoylation; ISS:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF01529; DHHC; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50216; DHHC; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Endoplasmic reticulum; Lipoprotein;
KW Membrane; Palmitate; Reference proteome; SH3 domain; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..413
FT /note="Palmitoyltransferase ZDHHC6"
FT /id="PRO_0000212872"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..57
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..194
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 99..149
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT DOMAIN 313..398
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT MOTIF 410..413
FT /note="Di-lysine motif"
FT /evidence="ECO:0000250|UniProtKB:Q9H6R6"
FT ACT_SITE 129
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q8IUH5"
FT LIPID 328
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9H6R6"
FT LIPID 329
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9H6R6"
FT LIPID 343
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9H6R6"
FT VAR_SEQ 380..413
FT /note="GTSRVRGWFPRNCVEKCPCDGDSDPAPEGEKKNR -> DQDVELSAPSPAPC
FT LPRCCHVSHHDDNGLNL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006941"
FT VAR_SEQ 381..413
FT /note="TSRVRGWFPRNCVEKCPCDGDSDPAPEGEKKNR -> VSVEKKKSTIAWNLI
FT AESLALQKKKVSKPKIVFDMEHRGVV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016270"
FT VAR_SEQ 381..399
FT /note="TSRVRGWFPRNCVEKCPCD -> SHCVTQPQTCSALALAS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006939"
FT VAR_SEQ 400..413
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_006940"
FT CONFLICT 269
FT /note="W -> R (in Ref. 1; BAC28968)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 413 AA; 47527 MW; F1A491B4F9DDDB4C CRC64;
MGIFCSVIKF ENLQDLRRLC HWGPIIALGV IAICSTMAMI DSVLWYWPLH TTGGSVNFIM
LINWTVMILY NYFNAMFAGP GFVPRGWKPE KSQDSMYLQY CKVCQAYKAP RSHHCRKCNR
CVMKMDHHCP WINNCCGHQN HASFTLFLLL APLGCTHAAF IFVMTMYTQL YNRLSFGWNT
VKIDMSAARR DPPPIVPFGL AAFAATLFAL GLALGTTIAV GMLFFIQIKI ILRNKTSIES
WIEEKAKDRI QYYQLDEVFI FPYDMGSKWK NFKQVFTWSG VPEGDGLEWP IREGCDQYSL
TIEQLKQKAD KRVRSVRYKV IEDYNGACCP LNRGVRTFFT SPCTEEPRIR LQKGEFILAT
RGLRYWLYGD KILDDSFIEG TSRVRGWFPR NCVEKCPCDG DSDPAPEGEK KNR
