ZDH17_HUMAN
ID ZDH17_HUMAN Reviewed; 632 AA.
AC Q8IUH5; B4DR39; O75407; Q7Z2I0; Q86W89; Q86YK0; Q9P088; Q9UPZ8;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Palmitoyltransferase ZDHHC17 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000269|PubMed:15489887, ECO:0000269|PubMed:15603740, ECO:0000269|PubMed:24705354, ECO:0000269|PubMed:27911442, ECO:0000269|PubMed:28757145};
DE AltName: Full=Acyltransferase ZDHHC17 {ECO:0000250|UniProtKB:Q80TN5};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q80TN5};
DE AltName: Full=DHHC domain-containing cysteine-rich protein 17 {ECO:0000305|PubMed:28757145};
DE Short=DHHC17 {ECO:0000303|PubMed:28757145};
DE AltName: Full=Huntingtin yeast partner H {ECO:0000303|PubMed:9700202};
DE AltName: Full=Huntingtin-interacting protein 14 {ECO:0000303|PubMed:15489887};
DE Short=HIP-14 {ECO:0000303|PubMed:15489887};
DE AltName: Full=Huntingtin-interacting protein 3 {ECO:0000312|EMBL:BAC22089.1};
DE Short=HIP-3 {ECO:0000312|EMBL:BAC22089.1};
DE AltName: Full=Huntingtin-interacting protein H {ECO:0000303|PubMed:9700202};
DE AltName: Full=Putative MAPK-activating protein PM11 {ECO:0000305|PubMed:12761501};
DE AltName: Full=Putative NF-kappa-B-activating protein 205 {ECO:0000305|PubMed:12761501};
DE AltName: Full=Zinc finger DHHC domain-containing protein 17 {ECO:0000312|HGNC:HGNC:18412};
GN Name=ZDHHC17 {ECO:0000312|HGNC:HGNC:18412};
GN Synonyms=HIP14 {ECO:0000303|PubMed:12393793, ECO:0000303|PubMed:27911442},
GN HIP3 {ECO:0000312|EMBL:BAC22089.1}, HYPH {ECO:0000303|PubMed:9700202},
GN KIAA0946 {ECO:0000312|EMBL:BAA76790.1};
GN ORFNames=HSPC294 {ECO:0000312|EMBL:AAC26848.1};
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 1), INTERACTION WITH HTT, TISSUE
RP SPECIFICITY, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=12393793; DOI=10.1093/hmg/11.23.2815;
RA Singaraja R.R., Hadano S., Metzler M., Givan S., Wellington C.L., Warby S.,
RA Yanai A., Gutekunst C.-A., Leavitt B.R., Yi H., Fichter K., Gan L.,
RA McGutcheon K., Chopra V., Michel J., Hersch S.M., Ikeda J.E., Hayden M.R.;
RT "HIP14, a novel ankyrin domain-containing protein, links huntingtin to
RT intracellular trafficking and endocytosis.";
RL Hum. Mol. Genet. 11:2815-2828(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung fibroblast;
RX PubMed=12761501; DOI=10.1038/sj.onc.1206406;
RA Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y.,
RA Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.;
RT "Large-scale identification and characterization of human genes that
RT activate NF-kappaB and MAPK signaling pathways.";
RL Oncogene 22:3307-3318(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Bone marrow, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-182, AND INTERACTION WITH HTT.
RC TISSUE=Testis;
RX PubMed=9700202; DOI=10.1093/hmg/7.9.1463;
RA Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F.,
RA MacDonald M.E.;
RT "Huntingtin interacts with a family of WW domain proteins.";
RL Hum. Mol. Genet. 7:1463-1474(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-203 (ISOFORM 3).
RC TISSUE=Umbilical cord blood;
RA Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L.,
RA Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.;
RT "Human partial CDS from CD34+ stem cells.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, DHHC DOMAIN, SUBCELLULAR LOCATION, AND
RP AUTOPALMITOYLATION.
RX PubMed=15603740; DOI=10.1016/j.neuron.2004.11.027;
RA Huang K., Yanai A., Kang R., Arstikaitis P., Singaraja R.R., Metzler M.,
RA Mullard A., Haigh B., Gauthier-Campbell C., Gutekunst C.-A., Hayden M.R.,
RA El-Husseini A.;
RT "Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved
RT in palmitoylation and trafficking of multiple neuronal proteins.";
RL Neuron 44:977-986(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-467.
RX PubMed=15489887; DOI=10.1038/sj.onc.1208171;
RA Ducker C.E., Stettler E.M., French K.J., Upson J.J., Smith C.D.;
RT "Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl
RT acyltransferase.";
RL Oncogene 23:9230-9237(2004).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=18032660; DOI=10.1523/jneurosci.2464-07.2007;
RA Stowers R.S., Isacoff E.Y.;
RT "Drosophila huntingtin-interacting protein 14 is a presynaptic protein
RT required for photoreceptor synaptic transmission and expression of the
RT palmitoylated proteins synaptosome-associated protein 25 and cysteine
RT string protein.";
RL J. Neurosci. 27:12874-12883(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOPALMITOYLATION.
RX PubMed=18794299; DOI=10.1074/jbc.m801469200;
RA Goytain A., Hines R.M., Quamme G.A.;
RT "Huntingtin-interacting proteins, HIP14 and HIP14L, mediate dual functions,
RT palmitoyl acyltransferase and Mg2+ transport.";
RL J. Biol. Chem. 283:33365-33374(2008).
RN [12]
RP FUNCTION.
RX PubMed=19139280; DOI=10.1128/mcb.00754-08;
RA Ding J., Du K.;
RT "ClipR-59 interacts with Akt and regulates Akt cellular
RT compartmentalization.";
RL Mol. Cell. Biol. 29:1459-1471(2009).
RN [13]
RP RETRACTED PAPER.
RX PubMed=22496366; DOI=10.1074/jbc.m111.332981;
RA Lach A., Grzybek M., Heger E., Korycka J., Wolny M., Kubiak J.,
RA Kolondra A., Boguslawska D.M., Augoff K., Majkowski M., Podkalicka J.,
RA Kaczor J., Stefanko A., Kuliczkowski K., Sikorski A.F.;
RT "Palmitoylation of MPP1 (membrane-palmitoylated protein 1)/p55 is crucial
RT for lateral membrane organization in erythroid cells.";
RL J. Biol. Chem. 287:18974-18984(2012).
RN [14]
RP RETRACTION NOTICE OF PUBMED:22496366.
RX PubMed=29475958; DOI=10.1074/jbc.w118.002209;
RA Lach A., Grzybek M., Heger E., Korycka J., Wolny M., Kubiak J.,
RA Kolondra A., Boguslawska D.M., Augoff K., Majkowski M., Podkalicka J.,
RA Kaczor J., Stefanko A., Kuliczkowski K., Sikorski A.F.;
RT "Palmitoylation of MPP1 (membrane-palmitoylated protein 1)/p55 is crucial
RT for lateral membrane organization in erythroid cells.";
RL J. Biol. Chem. 293:2786-2786(2018).
RN [15]
RP ANKYRIN REPEATS.
RX PubMed=25547411; DOI=10.1186/s12859-014-0440-9;
RA Chakrabarty B., Parekh N.;
RT "Identifying tandem Ankyrin repeats in protein structures.";
RL BMC Bioinformatics 15:6599-6599(2014).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH SPRED1; SPRED3; GPM6A
RP AND OPTN.
RX PubMed=24705354; DOI=10.1093/hmg/ddu137;
RA Butland S.L., Sanders S.S., Schmidt M.E., Riechers S.P., Lin D.T.,
RA Martin D.D., Vaid K., Graham R.K., Singaraja R.R., Wanker E.E.,
RA Conibear E., Hayden M.R.;
RT "The palmitoyl acyltransferase HIP14 shares a high proportion of
RT interactors with huntingtin: implications for a role in the pathogenesis of
RT Huntington's disease.";
RL Hum. Mol. Genet. 23:4142-4160(2014).
RN [17]
RP INTERACTION WITH CLIP3; HTT AND MAP6.
RX PubMed=26198635; DOI=10.1074/jbc.m115.657668;
RA Lemonidis K., Sanchez-Perez M.C., Chamberlain L.H.;
RT "Identification of a novel sequence motif recognized by the ankyrin repeat
RT domain of zDHHC17/13 S-acyltransferases.";
RL J. Biol. Chem. 290:21939-21950(2015).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27911442; DOI=10.1038/cdd.2016.139;
RA Skotte N.H., Sanders S.S., Singaraja R.R., Ehrnhoefer D.E., Vaid K.,
RA Qiu X., Kannan S., Verma C., Hayden M.R.;
RT "Palmitoylation of caspase-6 by HIP14 regulates its activation.";
RL Cell Death Differ. 24:433-444(2017).
RN [19]
RP SUBUNIT, AND INTERACTION WITH SNAP23; SNAP25; HTT; CLIP3; DNAJC5 AND EVL.
RX PubMed=28882895; DOI=10.1074/jbc.m117.799650;
RA Lemonidis K., MacLeod R., Baillie G.S., Chamberlain L.H.;
RT "Peptide array based screening reveals a large number of proteins
RT interacting with the ankyrin repeat domain of the zDHHC17 S-
RT acyltransferase.";
RL J. Biol. Chem. 292:17190-17202(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 51-288, AND ANKYRIN REPEATS.
RX PubMed=19434754; DOI=10.1002/prot.22452;
RA Gao T., Collins R.E., Horton J.R., Zhang X., Zhang R., Dhayalan A.,
RA Tamas R., Jeltsch A., Cheng X.;
RT "The ankyrin repeat domain of Huntingtin interacting protein 14 contains a
RT surface aromatic cage, a potential site for methyl-lysine binding.";
RL Proteins 76:772-777(2009).
RN [21] {ECO:0007744|PDB:5W7I, ECO:0007744|PDB:5W7J}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 50-284 OF WILD-TYPE AND MUTANT
RP ALA-89 IN COMPLEX WITH SNAP25 PEPTIDE, CATALYTIC ACTIVITY, FUNCTION,
RP ANKYRIN REPEATS, INTERACTION WITH SNAP25 AND HTT, MUTAGENESIS OF TYR-67;
RP GLU-89; ASN-100; ASP-122; TRP-130 AND CYS-467, AND ACTIVE SITE.
RX PubMed=28757145; DOI=10.1016/j.str.2017.06.018;
RA Verardi R., Kim J.S., Ghirlando R., Banerjee A.;
RT "Structural basis for substrate recognition by the ankyrin repeat domain of
RT human DHHC17 palmitoyltransferase.";
RL Structure 0:0-0(2017).
CC -!- FUNCTION: Palmitoyltransferase that catalyzes the addition of palmitate
CC onto various protein substrates and is involved in a variety of
CC cellular processes (PubMed:15489887, PubMed:15603740, PubMed:24705354,
CC PubMed:27911442, PubMed:28757145). Has no stringent fatty acid
CC selectivity and in addition to palmitate can also transfer onto target
CC proteins myristate from tetradecanoyl-CoA and stearate from
CC octadecanoyl-CoA (By similarity). Palmitoyltransferase specific for a
CC subset of neuronal proteins, including SNAP25, DLG4/PSD95, GAD2, SYT1
CC and HTT (PubMed:15603740, PubMed:15489887, PubMed:19139280,
CC PubMed:28757145). Also palmitoylates neuronal protein GPM6A as well as
CC SPRED1 and SPRED3 (PubMed:24705354). Could also play a role in
CC axonogenesis through the regulation of NTRK1 and the downstream
CC ERK1/ERK2 signaling cascade (By similarity). May be involved in the
CC sorting or targeting of critical proteins involved in the initiating
CC events of endocytosis at the plasma membrane (PubMed:12393793). May
CC play a role in Mg(2+) transport (PubMed:18794299). Could also
CC palmitoylate DNAJC5 and regulate its localization to the Golgi membrane
CC (By similarity). Palmitoylates CASP6, thereby preventing its
CC dimerization and subsequent activation (PubMed:27911442).
CC {ECO:0000250|UniProtKB:Q80TN5, ECO:0000269|PubMed:12393793,
CC ECO:0000269|PubMed:15489887, ECO:0000269|PubMed:15603740,
CC ECO:0000269|PubMed:18794299, ECO:0000269|PubMed:19139280,
CC ECO:0000269|PubMed:24705354, ECO:0000269|PubMed:27911442,
CC ECO:0000269|PubMed:28757145}.
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:15489887,
CC ECO:0000269|PubMed:15603740, ECO:0000269|PubMed:24705354,
CC ECO:0000269|PubMed:27911442, ECO:0000269|PubMed:28757145};
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:Q80TN5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59737;
CC Evidence={ECO:0000250|UniProtKB:Q80TN5};
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:Q80TN5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59741;
CC Evidence={ECO:0000250|UniProtKB:Q80TN5};
CC -!- SUBUNIT: Interacts (via ANK repeats) with numerous proteins (via the
CC consensus sequence motif [VIAP]-[VIT]-x-x-Q-P) (PubMed:28882895).
CC Interacts (via ANK repeats) with CLIP3 (PubMed:26198635,
CC PubMed:28882895). Interacts (via ANK repeats) with HTT; this
CC interaction is inversely correlated to the length of the polyglutamine
CC tract added to the huntingtin protein in Huntington disease
CC (PubMed:12393793, PubMed:9700202, PubMed:26198635, PubMed:28882895,
CC PubMed:28757145). Interacts (via ANK repeats) with DNAJC5 (via C-
CC terminus) (PubMed:28882895). Interacts (via ANK repeats) with MAP6
CC (PubMed:26198635). Interacts (via ANK repeats) with SNAP23
CC (PubMed:28882895). Interacts (via ANK repeats) with SNAP25
CC (PubMed:28882895, PubMed:28757145). Interacts (via ANK repeats) with
CC EVL (PubMed:28882895). Interacts with SPRED1 and SPRED3
CC (PubMed:24705354). Interacts with GPM6A and OPTN (PubMed:24705354). May
CC interact (via ANK repeats) with SPRED2 (By similarity). May interact
CC with NTRK1; may regulate its localization and function (By similarity).
CC {ECO:0000250|UniProtKB:Q80TN5, ECO:0000269|PubMed:12393793,
CC ECO:0000269|PubMed:24705354, ECO:0000269|PubMed:26198635,
CC ECO:0000269|PubMed:28757145, ECO:0000269|PubMed:28882895,
CC ECO:0000269|PubMed:9700202}.
CC -!- INTERACTION:
CC Q8IUH5; Q7Z5R6: APBB1IP; NbExp=2; IntAct=EBI-524753, EBI-2818084;
CC Q8IUH5; Q9NP61: ARFGAP3; NbExp=2; IntAct=EBI-524753, EBI-2875816;
CC Q8IUH5; P15336: ATF2; NbExp=3; IntAct=EBI-524753, EBI-1170906;
CC Q8IUH5; Q9UQB8-3: BAIAP2; NbExp=3; IntAct=EBI-524753, EBI-9091996;
CC Q8IUH5; Q9UQB8-6: BAIAP2; NbExp=2; IntAct=EBI-524753, EBI-9092016;
CC Q8IUH5; P17655: CAPN2; NbExp=2; IntAct=EBI-524753, EBI-1028956;
CC Q8IUH5; Q96GN5-2: CDCA7L; NbExp=2; IntAct=EBI-524753, EBI-9091443;
CC Q8IUH5; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-524753, EBI-9087876;
CC Q8IUH5; Q9H3Z4: DNAJC5; NbExp=5; IntAct=EBI-524753, EBI-4324577;
CC Q8IUH5; P50570-2: DNM2; NbExp=3; IntAct=EBI-524753, EBI-10968534;
CC Q8IUH5; P68104: EEF1A1; NbExp=2; IntAct=EBI-524753, EBI-352162;
CC Q8IUH5; P60228: EIF3E; NbExp=2; IntAct=EBI-524753, EBI-347740;
CC Q8IUH5; Q9UI08-2: EVL; NbExp=2; IntAct=EBI-524753, EBI-6448852;
CC Q8IUH5; Q9UHY8: FEZ2; NbExp=4; IntAct=EBI-524753, EBI-396453;
CC Q8IUH5; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-524753, EBI-11110431;
CC Q8IUH5; Q08379: GOLGA2; NbExp=3; IntAct=EBI-524753, EBI-618309;
CC Q8IUH5; Q9H4A5: GOLPH3L; NbExp=2; IntAct=EBI-524753, EBI-4403434;
CC Q8IUH5; P51674: GPM6A; NbExp=5; IntAct=EBI-524753, EBI-7187133;
CC Q8IUH5; P49840: GSK3A; NbExp=3; IntAct=EBI-524753, EBI-1044067;
CC Q8IUH5; P42858: HTT; NbExp=30; IntAct=EBI-524753, EBI-466029;
CC Q8IUH5; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-524753, EBI-9091197;
CC Q8IUH5; Q9NWB7: IFT57; NbExp=2; IntAct=EBI-524753, EBI-725672;
CC Q8IUH5; O60259: KLK8; NbExp=3; IntAct=EBI-524753, EBI-3915857;
CC Q8IUH5; Q14847-2: LASP1; NbExp=3; IntAct=EBI-524753, EBI-9088686;
CC Q8IUH5; Q96CV9-2: OPTN; NbExp=2; IntAct=EBI-524753, EBI-9091423;
CC Q8IUH5; Q08499-8: PDE4D; NbExp=2; IntAct=EBI-524753, EBI-9090666;
CC Q8IUH5; O15530-4: PDPK1; NbExp=3; IntAct=EBI-524753, EBI-9087775;
CC Q8IUH5; P27986-2: PIK3R1; NbExp=2; IntAct=EBI-524753, EBI-9090282;
CC Q8IUH5; Q9UF11-4: PLEKHB1; NbExp=4; IntAct=EBI-524753, EBI-9089825;
CC Q8IUH5; Q16537: PPP2R5E; NbExp=2; IntAct=EBI-524753, EBI-968374;
CC Q8IUH5; Q96DA2: RAB39B; NbExp=3; IntAct=EBI-524753, EBI-9089467;
CC Q8IUH5; Q8WZ73-3: RFFL; NbExp=3; IntAct=EBI-524753, EBI-25839575;
CC Q8IUH5; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-524753, EBI-9090795;
CC Q8IUH5; Q8IVB4: SLC9A9; NbExp=2; IntAct=EBI-524753, EBI-9092184;
CC Q8IUH5; O00161: SNAP23; NbExp=4; IntAct=EBI-524753, EBI-745000;
CC Q8IUH5; P60880: SNAP25; NbExp=3; IntAct=EBI-524753, EBI-524785;
CC Q8IUH5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-524753, EBI-5235340;
CC Q8IUH5; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-524753, EBI-7082156;
CC Q8IUH5; O43597: SPRY2; NbExp=3; IntAct=EBI-524753, EBI-742487;
CC Q8IUH5; O43610: SPRY3; NbExp=3; IntAct=EBI-524753, EBI-12290641;
CC Q8IUH5; Q9C004: SPRY4; NbExp=2; IntAct=EBI-524753, EBI-354861;
CC Q8IUH5; Q8NFA0: USP32; NbExp=2; IntAct=EBI-524753, EBI-2511075;
CC Q8IUH5; Q9Y6W5: WASF2; NbExp=2; IntAct=EBI-524753, EBI-4290615;
CC Q8IUH5; O76024: WFS1; NbExp=3; IntAct=EBI-524753, EBI-720609;
CC Q8IUH5; Q8IUH5: ZDHHC17; NbExp=6; IntAct=EBI-524753, EBI-524753;
CC Q8IUH5; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-524753, EBI-25830993;
CC Q8IUH5; Q7Z783; NbExp=3; IntAct=EBI-524753, EBI-9088990;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:15603740, ECO:0000269|PubMed:18794299}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:18794299}; Multi-pass membrane protein
CC {ECO:0000255}. Presynaptic cell membrane {ECO:0000269|PubMed:18032660};
CC Multi-pass membrane protein {ECO:0000255}. Note=Low extracellular
CC Mg(2+) induces increase in Golgi and in post-Golgi membrane vesicles.
CC {ECO:0000269|PubMed:18794299}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IUH5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IUH5-2; Sequence=VSP_010021, VSP_010022, VSP_010024,
CC VSP_010025;
CC Name=3;
CC IsoId=Q8IUH5-3; Sequence=VSP_010023;
CC -!- TISSUE SPECIFICITY: Expressed in all brain regions. Expression is
CC highest in the cortex, cerebellum, occipital lobe and caudate and
CC lowest in the spinal cord. Expression is also seen in testis, pancreas,
CC heart and kidney. {ECO:0000269|PubMed:12393793}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000269|PubMed:15603740}.
CC -!- PTM: Autopalmitoylated (PubMed:15603740, PubMed:18794299).
CC Autopalmitoylation has a regulatory role in ZDHHC17-mediated Mg(2+)
CC transport (PubMed:18794299). {ECO:0000269|PubMed:15603740,
CC ECO:0000269|PubMed:18794299}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC AKR/ZDHHC17 subfamily. {ECO:0000305}.
CC -!- CAUTION: Thought to palmitoylate MPP1 (PubMed:22496366). This work was
CC later retracted due to image manipulation.
CC {ECO:0000269|PubMed:22496366, ECO:0000305|PubMed:29475958}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF28972.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH30990.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA76790.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC77366.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC77388.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB024494; BAC22089.1; -; mRNA.
DR EMBL; AB023163; BAA76790.1; ALT_INIT; mRNA.
DR EMBL; AB097013; BAC77366.1; ALT_INIT; mRNA.
DR EMBL; AB097035; BAC77388.1; ALT_INIT; mRNA.
DR EMBL; AK299089; BAG61151.1; -; mRNA.
DR EMBL; BC030990; AAH30990.1; ALT_INIT; mRNA.
DR EMBL; BC050324; AAH50324.1; -; mRNA.
DR EMBL; AF049612; AAC26848.1; -; mRNA.
DR EMBL; AF161412; AAF28972.1; ALT_FRAME; mRNA.
DR CCDS; CCDS44946.1; -. [Q8IUH5-1]
DR RefSeq; NP_056151.2; NM_015336.2. [Q8IUH5-1]
DR PDB; 3EU9; X-ray; 1.99 A; A/B/C=51-288.
DR PDB; 5W7I; X-ray; 2.10 A; A/C=50-284.
DR PDB; 5W7J; X-ray; 2.20 A; A/C=50-284.
DR PDBsum; 3EU9; -.
DR PDBsum; 5W7I; -.
DR PDBsum; 5W7J; -.
DR AlphaFoldDB; Q8IUH5; -.
DR SMR; Q8IUH5; -.
DR BioGRID; 116965; 294.
DR IntAct; Q8IUH5; 248.
DR MINT; Q8IUH5; -.
DR STRING; 9606.ENSP00000403397; -.
DR TCDB; 8.A.114.1.1; the huntington-interacting protein 14 (hip14) family.
DR iPTMnet; Q8IUH5; -.
DR PhosphoSitePlus; Q8IUH5; -.
DR SwissPalm; Q8IUH5; -.
DR BioMuta; ZDHHC17; -.
DR DMDM; 46395885; -.
DR EPD; Q8IUH5; -.
DR jPOST; Q8IUH5; -.
DR MassIVE; Q8IUH5; -.
DR MaxQB; Q8IUH5; -.
DR PaxDb; Q8IUH5; -.
DR PeptideAtlas; Q8IUH5; -.
DR PRIDE; Q8IUH5; -.
DR ProteomicsDB; 70572; -. [Q8IUH5-1]
DR ProteomicsDB; 70573; -. [Q8IUH5-2]
DR ProteomicsDB; 70574; -. [Q8IUH5-3]
DR Antibodypedia; 8807; 201 antibodies from 35 providers.
DR DNASU; 23390; -.
DR Ensembl; ENST00000426126.7; ENSP00000403397.2; ENSG00000186908.15. [Q8IUH5-1]
DR GeneID; 23390; -.
DR KEGG; hsa:23390; -.
DR MANE-Select; ENST00000426126.7; ENSP00000403397.2; NM_015336.4; NP_056151.2.
DR UCSC; uc001syk.2; human. [Q8IUH5-1]
DR CTD; 23390; -.
DR DisGeNET; 23390; -.
DR GeneCards; ZDHHC17; -.
DR HGNC; HGNC:18412; ZDHHC17.
DR HPA; ENSG00000186908; Low tissue specificity.
DR MIM; 607799; gene.
DR neXtProt; NX_Q8IUH5; -.
DR OpenTargets; ENSG00000186908; -.
DR PharmGKB; PA134991292; -.
DR VEuPathDB; HostDB:ENSG00000186908; -.
DR eggNOG; KOG0509; Eukaryota.
DR GeneTree; ENSGT00530000063074; -.
DR HOGENOM; CLU_012510_3_1_1; -.
DR InParanoid; Q8IUH5; -.
DR OMA; PWMAGIF; -.
DR OrthoDB; 445686at2759; -.
DR PhylomeDB; Q8IUH5; -.
DR TreeFam; TF317342; -.
DR BRENDA; 2.3.1.225; 2681.
DR PathwayCommons; Q8IUH5; -.
DR SignaLink; Q8IUH5; -.
DR BioGRID-ORCS; 23390; 68 hits in 1081 CRISPR screens.
DR ChiTaRS; ZDHHC17; human.
DR EvolutionaryTrace; Q8IUH5; -.
DR GeneWiki; ZDHHC17; -.
DR GenomeRNAi; 23390; -.
DR Pharos; Q8IUH5; Tbio.
DR PRO; PR:Q8IUH5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8IUH5; protein.
DR Bgee; ENSG00000186908; Expressed in corpus callosum and 216 other tissues.
DR ExpressionAtlas; Q8IUH5; baseline and differential.
DR Genevisible; Q8IUH5; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019705; F:protein-cysteine S-myristoyltransferase activity; IEA:RHEA.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0140439; F:protein-cysteine S-stearoyltransferase activity; IEA:RHEA.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0042953; P:lipoprotein transport; IDA:UniProtKB.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0051386; P:regulation of neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR InterPro; IPR030289; ZDHHC17.
DR PANTHER; PTHR24161:SF18; PTHR24161:SF18; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF01529; DHHC; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing; ANK repeat;
KW Cell membrane; Cell projection; Cytoplasmic vesicle; Golgi apparatus;
KW Lipoprotein; Membrane; Palmitate; Reference proteome; Repeat; Synapse;
KW Transferase; Transmembrane; Transmembrane helix; Tumor suppressor.
FT CHAIN 1..632
FT /note="Palmitoyltransferase ZDHHC17"
FT /id="PRO_0000212900"
FT TOPO_DOM 1..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..357
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 358..378
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 379..381
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..480
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..529
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 51..86
FT /note="ANK 1"
FT /evidence="ECO:0000305|PubMed:19434754,
FT ECO:0000305|PubMed:28757145"
FT REPEAT 89..118
FT /note="ANK 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT REPEAT 123..152
FT /note="ANK 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT REPEAT 156..185
FT /note="ANK 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT REPEAT 189..219
FT /note="ANK 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT REPEAT 224..253
FT /note="ANK 6"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT REPEAT 257..286
FT /note="ANK 7"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28757145"
FT DOMAIN 437..487
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT REGION 11..305
FT /note="Necessary and sufficient for interaction with DNAJC5
FT and SNAP25"
FT /evidence="ECO:0000250|UniProtKB:Q80TN5"
FT ACT_SITE 467
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000305|PubMed:15489887,
FT ECO:0000305|PubMed:28757145"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010021"
FT VAR_SEQ 51..66
FT /note="THIDDYSTWDIVKATQ -> MSTIPKRAVCPFSTQR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010022"
FT VAR_SEQ 204..632
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_010023"
FT VAR_SEQ 258..266
FT /note="GESALDLAK -> AILRCHMAL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010024"
FT VAR_SEQ 267..632
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010025"
FT VARIANT 383
FT /note="N -> S (in dbSNP:rs33996476)"
FT /id="VAR_052978"
FT MUTAGEN 67
FT /note="Y->A: Decreased binding affinity for SNAP25."
FT /evidence="ECO:0000269|PubMed:28757145"
FT MUTAGEN 89
FT /note="E->A: No effect on SNAP25 binding."
FT /evidence="ECO:0000269|PubMed:28757145"
FT MUTAGEN 100
FT /note="N->A: Abolishes SNAP25 binding."
FT /evidence="ECO:0000269|PubMed:28757145"
FT MUTAGEN 122
FT /note="D->A: Mildly decreased binding affinity for SNAP25."
FT /evidence="ECO:0000269|PubMed:28757145"
FT MUTAGEN 130
FT /note="W->A: Abolishes SNAP25 and HTT binding."
FT /evidence="ECO:0000269|PubMed:28757145"
FT MUTAGEN 467
FT /note="C->S: Abolishes palmitoyltransferase activity."
FT /evidence="ECO:0000269|PubMed:15489887,
FT ECO:0000269|PubMed:28757145"
FT CONFLICT 3
FT /note="R -> G (in Ref. 7; AAF28972)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="Y -> F (in Ref. 1; BAC22089)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="V -> VV (in Ref. 1; BAC22089)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="D -> E (in Ref. 7; AAF28972)"
FT /evidence="ECO:0000305"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 61..66
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 70..78
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 103..111
FT /evidence="ECO:0007829|PDB:3EU9"
FT TURN 121..124
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 127..134
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 137..145
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 160..166
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 170..178
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 193..200
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:3EU9"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:3EU9"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:3EU9"
SQ SEQUENCE 632 AA; 72640 MW; 3FD5FD592F2C617F CRC64;
MQREEGFNTK MADGPDEYDT EAGCVPLLHP EEIKPQSHYN HGYGEPLGRK THIDDYSTWD
IVKATQYGIY ERCRELVEAG YDVRQPDKEN VTLLHWAAIN NRIDLVKYYI SKGAIVDQLG
GDLNSTPLHW ATRQGHLSMV VQLMKYGADP SLIDGEGCSC IHLAAQFGHT SIVAYLIAKG
QDVDMMDQNG MTPLMWAAYR THSVDPTRLL LTFNVSVNLG DKYHKNTALH WAVLAGNTTV
ISLLLEAGAN VDAQNIKGES ALDLAKQRKN VWMINHLQEA RQAKGYDNPS FLRKLKADKE
FRQKVMLGTP FLVIWLVGFI ADLNIDSWLI KGLMYGGVWA TVQFLSKSFF DHSMHSALPL
GIYLATKFWM YVTWFFWFWN DLNFLFIHLP FLANSVALFY NFGKSWKSDP GIIKATEEQK
KKTIVELAET GSLDLSIFCS TCLIRKPVRS KHCGVCNRCI AKFDHHCPWV GNCVGAGNHR
YFMGYLFFLL FMICWMIYGC ISYWGLHCET TYTKDGFWTY ITQIATCSPW MFWMFLNSVF
HFMWVAVLLM CQMYQISCLG ITTNERMNAR RYKHFKVTTT SIESPFNHGC VRNIIDFFEF
RCCGLFRPVI VDWTRQYTIE YDQISGSGYQ LV
