ZDH15_MOUSE
ID ZDH15_MOUSE Reviewed; 337 AA.
AC Q8BGJ0; Q3TV63; Q8BMB7;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Palmitoyltransferase ZDHHC15 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000269|PubMed:15603741};
DE AltName: Full=Acyltransferase ZDHHC15 {ECO:0000305|PubMed:28167757};
DE EC=2.3.1.- {ECO:0000305|PubMed:28167757};
DE AltName: Full=Zinc finger DHHC domain-containing protein 15;
DE Short=DHHC-15;
GN Name=Zdhhc15 {ECO:0000312|MGI:MGI:1915336};
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].
RC STRAIN=C57BL/6J; TISSUE=Retina, Skin, Testis, and Wolffian duct;
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 FUNCTION, CATALYTIC ACTIVITY, PALMITOYLATION, TISSUE SPECIFICITY, ACTIVITY
RP REGULATION, MUTAGENESIS OF 156-ASP-HIS-157 AND CYS-159, ACTIVE SITE, AND
RP DOMAIN.
RX PubMed=15603741; DOI=10.1016/j.neuron.2004.12.005;
RA Fukata M., Fukata Y., Adesnik H., Nicoll R.A., Bredt D.S.;
RT "Identification of PSD-95 palmitoylating enzymes.";
RL Neuron 44:987-996(2004).
RN [3]
RP FUNCTION.
RX PubMed=17012030; DOI=10.1016/j.ymeth.2006.05.015;
RA Fukata Y., Iwanaga T., Fukata M.;
RT "Systematic screening for palmitoyl transferase activity of the DHHC
RT protein family in mammalian cells.";
RL Methods 40:177-182(2006).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18596047; DOI=10.1074/jbc.m802140200;
RA Greaves J., Salaun C., Fukata Y., Fukata M., Chamberlain L.H.;
RT "Palmitoylation and membrane interactions of the neuroprotective chaperone
RT cysteine-string protein.";
RL J. Biol. Chem. 283:25014-25026(2008).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=28167757; DOI=10.1073/pnas.1612254114;
RA Greaves J., Munro K.R., Davidson S.C., Riviere M., Wojno J., Smith T.K.,
RA Tomkinson N.C., Chamberlain L.H.;
RT "Molecular basis of fatty acid selectivity in the zDHHC family of S-
RT acyltransferases revealed by click chemistry.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E1365-E1374(2017).
CC -!- FUNCTION: Palmitoyltransferase that catalyzes the addition of palmitate
CC onto various protein substrates (PubMed:15603741, PubMed:17012030,
CC PubMed:28167757). Has no stringent fatty acid selectivity and in
CC addition to palmitate can also transfer onto target proteins myristate
CC from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable).
CC Palmitoylates IGF2R and SORT1, promoting their partitioning to an
CC endosomal membrane subdomain where they can interact with the retromer
CC cargo-selective complex (By similarity). Thereby, regulates retrograde
CC transport from endosomes to the Golgi apparatus of these lysosomal
CC sorting receptors and plays a role in trafficking of lysosomal proteins
CC (By similarity). In the nervous system, catalyzes the palmitoylation of
CC DLG4/PSD95 and regulates its synaptic clustering and function in
CC synaptogenesis (PubMed:15603741). Could be involved in the
CC differentiation of dopaminergic neurons and the development of the
CC diencephalon (By similarity). Could also catalyze the palmitoylation of
CC GAP43 (PubMed:15603741, PubMed:17012030). Could also palmitoylate
CC DNAJC5 and regulate its localization to the Golgi membrane
CC (PubMed:18596047). Could also palmitoylate FYN as shown in vitro (By
CC similarity). {ECO:0000250|UniProtKB:F1QXD3,
CC ECO:0000250|UniProtKB:Q96MV8, ECO:0000269|PubMed:15603741,
CC ECO:0000269|PubMed:17012030, ECO:0000269|PubMed:18596047,
CC ECO:0000269|PubMed:28167757, ECO:0000305|PubMed:28167757}.
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:15603741};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000269|PubMed:15603741};
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:0000305|PubMed:28167757};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59737;
CC Evidence={ECO:0000305|PubMed:28167757};
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:0000305|PubMed:28167757};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59741;
CC Evidence={ECO:0000305|PubMed:28167757};
CC -!- ACTIVITY REGULATION: Inhibited by 2-bromopalmitate.
CC {ECO:0000269|PubMed:15603741}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:18596047}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:F1QXD3}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q2TGJ4}.
CC -!- TISSUE SPECIFICITY: Expressed mainly in brain.
CC {ECO:0000269|PubMed:15603741}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000269|PubMed:15603741}.
CC -!- PTM: Autopalmitoylated (in vitro). {ECO:0000269|PubMed:15603741}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AK029137; BAC26317.1; -; mRNA.
DR EMBL; AK032922; BAC28087.1; -; mRNA.
DR EMBL; AK077949; BAC37081.1; -; mRNA.
DR EMBL; AK160360; BAE35757.1; -; mRNA.
DR CCDS; CCDS30332.1; -.
DR RefSeq; NP_780567.1; NM_175358.4.
DR AlphaFoldDB; Q8BGJ0; -.
DR SMR; Q8BGJ0; -.
DR BioGRID; 224365; 3.
DR IntAct; Q8BGJ0; 2.
DR STRING; 10090.ENSMUSP00000047615; -.
DR PhosphoSitePlus; Q8BGJ0; -.
DR SwissPalm; Q8BGJ0; -.
DR EPD; Q8BGJ0; -.
DR MaxQB; Q8BGJ0; -.
DR PaxDb; Q8BGJ0; -.
DR PeptideAtlas; Q8BGJ0; -.
DR PRIDE; Q8BGJ0; -.
DR ProteomicsDB; 275136; -.
DR Antibodypedia; 13846; 98 antibodies from 21 providers.
DR DNASU; 108672; -.
DR Ensembl; ENSMUST00000042070; ENSMUSP00000047615; ENSMUSG00000033906.
DR GeneID; 108672; -.
DR KEGG; mmu:108672; -.
DR UCSC; uc009uaj.2; mouse.
DR CTD; 158866; -.
DR MGI; MGI:1915336; Zdhhc15.
DR VEuPathDB; HostDB:ENSMUSG00000033906; -.
DR eggNOG; KOG1315; Eukaryota.
DR GeneTree; ENSGT00940000158214; -.
DR HOGENOM; CLU_027721_1_1_1; -.
DR InParanoid; Q8BGJ0; -.
DR OMA; AICVLKM; -.
DR OrthoDB; 1491968at2759; -.
DR PhylomeDB; Q8BGJ0; -.
DR TreeFam; TF316044; -.
DR BioGRID-ORCS; 108672; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q8BGJ0; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8BGJ0; protein.
DR Bgee; ENSMUSG00000033906; Expressed in lumbar dorsal root ganglion and 190 other tissues.
DR Genevisible; Q8BGJ0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; ISS:UniProtKB.
DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:MGI.
DR GO; GO:0019705; F:protein-cysteine S-myristoyltransferase activity; IC:UniProtKB.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0140439; F:protein-cysteine S-stearoyltransferase activity; IC:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0045184; P:establishment of protein localization; IDA:MGI.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IDA:UniProtKB.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISS:UniProtKB.
DR GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR GO; GO:0062237; P:protein localization to postsynapse; ISO:MGI.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0140450; P:protein targeting to Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0016188; P:synaptic vesicle maturation; IMP:MGI.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR Pfam; PF01529; DHHC; 1.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Golgi apparatus; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Reference proteome; Synapse; Transferase; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..337
FT /note="Palmitoyltransferase ZDHHC15"
FT /id="PRO_0000212894"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TOPO_DOM 42..56
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TOPO_DOM 78..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TOPO_DOM 194..210
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TRANSMEM 211..234
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT TOPO_DOM 235..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT DOMAIN 129..179
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT REGION 293..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 159
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067,
FT ECO:0000305|PubMed:15603741"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:F1QXD3"
FT MUTAGEN 156..157
FT /note="DH->AA: Fails to enhance DLG4 palmitoylation."
FT /evidence="ECO:0000269|PubMed:15603741"
FT MUTAGEN 159
FT /note="C->S: Fails to enhance DLG4 palmitoylation."
FT /evidence="ECO:0000269|PubMed:15603741"
SQ SEQUENCE 337 AA; 39269 MW; 93FFBDB720B09421 CRC64;
MRRGWKMALS GGLRCCRRVL SWVPVLVIVL VVLWSYYAYV FELCLVTVLS PAEKVIYLIL
YHAIFVFFAW TYWKSIFTLP QQPNQKFHLS YTDKERYKNE ERPEVQKQML VDMAKKLPVY
TRTGSGAVRF CDRCHLIKPD RCHHCSVCAM CVLKMDHHCP WVNNCIGFSN YKFFLQFLAY
SVLYCLYIAT TVFSYFIKYW RGELPSVRSK FHVLFLLFVA CMFFVSLVIL FGYHCWLVSR
NKTTLEAFCT PVFTSGPEKN GFNLGFIKNI QQVFGDNKKF WLIPIGSSPG DGHSFPMRSM
NESQNPLLAN EEPWEDNEDD SRDYPEGSSS LAVESET
