ID ZDHC2_HUMAN Reviewed; 367 AA. AC Q9UIJ5; D3DSP5; DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 02-DEC-2020, entry version 144. DE RecName: Full=Palmitoyltransferase ZDHHC2 {ECO:0000305}; DE EC=2.3.1.225 {ECO:0000269|PubMed:23793055}; DE AltName: Full=Acyltransferase ZDHHC2 {ECO:0000250|UniProtKB:P59267}; DE EC=2.3.1.- {ECO:0000250|UniProtKB:P59267}; DE AltName: Full=Reduced expression associated with metastasis protein; DE Short=Ream; DE AltName: Full=Reduced expression in cancer protein; DE Short=Rec; DE AltName: Full=Zinc finger DHHC domain-containing protein 2 {ECO:0000312|HGNC:HGNC:18469}; DE Short=DHHC-2; DE AltName: Full=Zinc finger protein 372; GN Name=ZDHHC2 {ECO:0000312|HGNC:HGNC:18469}; Synonyms=REAM, REC, ZNF372; 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], TISSUE SPECIFICITY, AND VARIANTS PHE-306 AND RP ILE-356. RX PubMed=10918388; RX DOI=10.1002/1098-2264(2000)9999:9999<::aid-gcc1001>3.0.co;2-#; RA Oyama T., Miyoshi Y., Koyama K., Nakagawa H., Yamori T., Ito T., RA Matsuda H., Arakawa H., Nakamura Y.; RT "Isolation of a novel gene on 8p21.3-22 whose expression is reduced RT significantly in human colorectal cancers with liver metastasis."; RL Genes Chromosomes Cancer 29:9-15(2000). 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, and Duodenum; 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 FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION, AND MUTAGENESIS OF RP 154-ASP-HIS-155 AND CYS-157. RX PubMed=18508921; DOI=10.1091/mbc.e07-11-1164; RA Sharma C., Yang X.H., Hemler M.E.; RT "DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 RT and CD151."; RL Mol. Biol. Cell 19:3415-3425(2008). RN [5] RP FUNCTION. RX PubMed=18296695; DOI=10.1074/mcp.m800069-mcp200; RA Zhang J., Planey S.L., Ceballos C., Stevens S.M. Jr., Keay S.K., RA Zacharias D.A.; RT "Identification of CKAP4/p63 as a major substrate of the palmitoyl RT acyltransferase DHHC2, a putative tumor suppressor, using a novel RT proteomics method."; RL Mol. Cell. Proteomics 7:1378-1388(2008). RN [6] RP FUNCTION. RX PubMed=19144824; DOI=10.1091/mbc.e08-08-0849; RA Planey S.L., Keay S.K., Zhang C.O., Zacharias D.A.; RT "Palmitoylation of cytoskeleton associated protein 4 by DHHC2 regulates RT antiproliferative factor-mediated signaling."; RL Mol. Biol. Cell 20:1454-1463(2009). RN [7] RP FUNCTION. RX PubMed=21343290; DOI=10.1074/jbc.m110.193763; RA Jia L., Linder M.E., Blumer K.J.; RT "Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate RT cycling and shuttling of RGS7 family-binding protein."; RL J. Biol. Chem. 286:13695-13703(2011). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=21471008; DOI=10.1091/mbc.e10-11-0924; RA Greaves J., Carmichael J.A., Chamberlain L.H.; RT "The palmitoyl transferase DHHC2 targets a dynamic membrane cycling RT pathway: regulation by a C-terminal domain."; RL Mol. Biol. Cell 22:1887-1895(2011). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION, AND TISSUE SPECIFICITY. RX PubMed=22034844; DOI=10.3109/09687688.2011.630682; RA Zeidman R., Buckland G., Cebecauer M., Eissmann P., Davis D.M., Magee A.I.; RT "DHHC2 is a protein S-acyltransferase for Lck."; RL Mol. Membr. Biol. 28:473-486(2011). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF CYS-157, AND ACTIVE RP SITE. RX PubMed=23793055; DOI=10.1074/jbc.m113.458794; RA Lai J., Linder M.E.; RT "Oligomerization of DHHC protein S-acyltransferases."; RL J. Biol. Chem. 288:22862-22870(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=30404808; DOI=10.1128/jvi.01747-18; RA Zhang N., Zhao H., Zhang L.; RT "Fatty acid synthase promotes the palmitoylation of Chikungunya virus RT nsP1."; RL J. Virol. 0:0-0(2018). 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:18508921, PubMed:18296695, PubMed:19144824, CC PubMed:21343290, PubMed:22034844, PubMed:23793055). Has no stringent CC fatty acid selectivity and in addition to palmitate can also transfer CC onto target proteins myristate from tetradecanoyl-CoA and stearate from CC octadecanoyl-CoA (By similarity). In the nervous system, plays a role CC in long term synaptic potentiation by palmitoylating AKAP5 through CC which it regulates protein trafficking from the dendritic recycling CC endosomes to the plasma membrane and controls both structural and CC functional plasticity at excitatory synapses (By similarity). In CC dendrites, mediates the palmitoylation of DLG4 when synaptic activity CC decreases and induces synaptic clustering of DLG4 and associated AMPA- CC type glutamate receptors (By similarity). Also mediates the de novo and CC turnover palmitoylation of RGS7BP, a shuttle for Gi/o-specific GTPase- CC activating proteins/GAPs, promoting its localization to the plasma CC membrane in response to the activation of G protein-coupled receptors. CC Through the localization of these GTPase-activating proteins/GAPs, it CC also probably plays a role in G protein-coupled receptors signaling in CC neurons (By similarity). Also probably plays a role in cell adhesion by CC palmitoylating CD9 and CD151 to regulate their expression and function CC (PubMed:18508921). Palmitoylates the endoplasmic reticulum protein CC CKAP4 and regulates its localization to the plasma membrane CC (PubMed:18296695, PubMed:19144824). Could also palmitoylate LCK and CC regulate its localization to the plasma membrane (PubMed:22034844). CC {ECO:0000250|UniProtKB:P59267, ECO:0000250|UniProtKB:Q9JKR5, CC ECO:0000269|PubMed:18296695, ECO:0000269|PubMed:18508921, CC ECO:0000269|PubMed:19144824, ECO:0000269|PubMed:21343290, CC ECO:0000269|PubMed:22034844, ECO:0000269|PubMed:23793055}. CC -!- FUNCTION: (Microbial infection) Promotes Chikungunya virus (CHIKV) CC replication by mediating viral nsp1 palmitoylation. CC {ECO:0000269|PubMed:30404808}. 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:23793055}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684; CC Evidence={ECO:0000305|PubMed:23793055}; 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:P59267}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59737; CC Evidence={ECO:0000250|UniProtKB:P59267}; 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:P59267}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59741; CC Evidence={ECO:0000250|UniProtKB:P59267}; CC -!- SUBUNIT: Monomer (PubMed:23793055). Homodimer (PubMed:23793055). The CC monomeric form has a higher catalytic activity (PubMed:23793055). CC {ECO:0000269|PubMed:23793055}. CC -!- SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic density CC {ECO:0000250|UniProtKB:Q9JKR5}. Postsynaptic recycling endosome CC membrane {ECO:0000250|UniProtKB:P59267}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:21471008}; Multi-pass CC membrane protein {ECO:0000255}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:22034844}; Multi-pass membrane protein CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:18508921, CC ECO:0000269|PubMed:22034844}; Multi-pass membrane protein CC {ECO:0000255}. Note=Translocates to postsynaptic density when synaptic CC activity decreases. {ECO:0000250|UniProtKB:Q9JKR5}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:10918388, CC PubMed:22034844). Reduced expression in colorectal cancers with liver CC metastasis (PubMed:10918388). {ECO:0000269|PubMed:10918388, CC ECO:0000269|PubMed:22034844}. CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity. CC {ECO:0000250|UniProtKB:Q8IUH5}. CC -!- PTM: Autopalmitoylated. {ECO:0000269|PubMed:18508921, CC ECO:0000269|PubMed:22034844}. CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB023584; BAA88923.1; -; mRNA. DR EMBL; CH471080; EAW63824.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63825.1; -; Genomic_DNA. DR EMBL; BC039253; AAH39253.1; -; mRNA. DR EMBL; BC050272; AAH50272.1; -; mRNA. DR CCDS; CCDS47810.1; -. DR RefSeq; NP_057437.1; NM_016353.4. DR SMR; Q9UIJ5; -. DR BioGRID; 119374; 2. DR STRING; 9606.ENSP00000262096; -. DR SwissLipids; SLP:000001951; -. DR iPTMnet; Q9UIJ5; -. DR PhosphoSitePlus; Q9UIJ5; -. DR SwissPalm; Q9UIJ5; -. DR BioMuta; ZDHHC2; -. DR DMDM; 28202111; -. DR EPD; Q9UIJ5; -. DR jPOST; Q9UIJ5; -. DR MassIVE; Q9UIJ5; -. DR PaxDb; Q9UIJ5; -. DR PeptideAtlas; Q9UIJ5; -. DR PRIDE; Q9UIJ5; -. DR ProteomicsDB; 84534; -. DR Antibodypedia; 22244; 114 antibodies. DR DNASU; 51201; -. DR Ensembl; ENST00000262096; ENSP00000262096; ENSG00000104219. DR GeneID; 51201; -. DR KEGG; hsa:51201; -. DR UCSC; uc003wxe.4; human. DR CTD; 51201; -. DR DisGeNET; 51201; -. DR EuPathDB; HostDB:ENSG00000104219.12; -. DR GeneCards; ZDHHC2; -. DR HGNC; HGNC:18469; ZDHHC2. DR HPA; ENSG00000104219; Low tissue specificity. DR MIM; 618621; gene. DR neXtProt; NX_Q9UIJ5; -. DR OpenTargets; ENSG00000104219; -. DR PharmGKB; PA38336; -. DR eggNOG; KOG1315; Eukaryota. DR GeneTree; ENSGT00940000153716; -. DR HOGENOM; CLU_027721_1_3_1; -. DR InParanoid; Q9UIJ5; -. DR OMA; DFPTRSD; -. DR OrthoDB; 1491968at2759; -. DR PhylomeDB; Q9UIJ5; -. DR TreeFam; TF316044; -. DR BRENDA; 2.3.1.225; 2681. DR PathwayCommons; Q9UIJ5; -. DR Reactome; R-HSA-5683826; Surfactant metabolism. DR SIGNOR; Q9UIJ5; -. DR BioGRID-ORCS; 51201; 3 hits in 844 CRISPR screens. DR ChiTaRS; ZDHHC2; human. DR GeneWiki; ZDHHC2_(gene); -. DR GenomeRNAi; 51201; -. DR Pharos; Q9UIJ5; Tbio. DR PRO; PR:Q9UIJ5; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9UIJ5; protein. DR Bgee; ENSG00000104219; Expressed in epithelial cell of pancreas and 222 other tissues. DR ExpressionAtlas; Q9UIJ5; baseline and differential. DR Genevisible; Q9UIJ5; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0098837; C:postsynaptic recycling endosome; ISS:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; IEA:Ensembl. DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IDA:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IDA:UniProtKB. DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; ISS:UniProtKB. DR GO; GO:1905751; P:positive regulation of endosome to plasma membrane protein transport; ISS:UniProtKB. DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:1903539; P:protein localization to postsynaptic membrane; ISS: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:0022407; P:regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISS:UniProtKB. DR GO; GO:0042176; P:regulation of protein catabolic process; IMP:UniProtKB. DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:UniProtKB. DR GO; GO:0016188; P:synaptic vesicle maturation; IBA:GO_Central. DR InterPro; IPR001594; Palmitoyltrfase_DHHC. DR Pfam; PF01529; DHHC; 1. DR PROSITE; PS50216; DHHC; 1. PE 1: Evidence at protein level; KW Acyltransferase; Cell junction; Cell membrane; Endoplasmic reticulum; KW Endosome; Golgi apparatus; Lipoprotein; Membrane; Palmitate; KW Phosphoprotein; Polymorphism; Reference proteome; Synapse; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..367 FT /note="Palmitoyltransferase ZDHHC2" FT /id="PRO_0000212859" FT TOPO_DOM 1..16 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 17..37 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 38..54 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 55..75 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 76..170 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 171..191 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 192..208 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 209..229 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 230..367 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT DOMAIN 127..177 FT /note="DHHC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067" FT REGION 299..367 FT /note="Mediates localization to plasma membrane and FT recycling endosomes" FT /evidence="ECO:0000250|UniProtKB:P59267" FT MOTIF 335..336 FT /note="Non-canonical dileucine endocytic signal" FT /evidence="ECO:0000250|UniProtKB:P59267" FT MOTIF 358..361 FT /note="NPxY-like endocytic signal" FT /evidence="ECO:0000250|UniProtKB:P59267" FT ACT_SITE 157 FT /note="S-palmitoyl cysteine intermediate" FT /evidence="ECO:0000269|PubMed:23793055" FT MOD_RES 341 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT VARIANT 306 FT /note="S -> F (in a hepatocellular carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:10918388" FT /id="VAR_015229" FT VARIANT 356 FT /note="M -> I (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs568589179)" FT /evidence="ECO:0000269|PubMed:10918388" FT /id="VAR_015230" FT MUTAGEN 154..155 FT /note="DH->AA: Loss of protein-cysteine S- FT palmitoyltransferase activity." FT /evidence="ECO:0000269|PubMed:18508921" FT MUTAGEN 157 FT /note="C->S: Loss of protein-cysteine S- FT palmitoyltransferase activity." FT /evidence="ECO:0000269|PubMed:18508921, FT ECO:0000269|PubMed:23793055" SQ SEQUENCE 367 AA; 42022 MW; B7BFB82837B7EE98 CRC64; MAPSGPGSSA RRRCRRVLYW IPVVFITLLL GWSYYAYAIQ LCIVSMENTG EQVVCLMAYH LLFAMFVWSY WKTIFTLPMN PSKEFHLSYA EKDLLEREPR GEAHQEVLRR AAKDLPIYTR TMSGAIRYCD RCQLIKPDRC HHCSVCDKCI LKMDHHCPWV NNCVGFSNYK FFLLFLAYSL LYCLFIAATD LQYFIKFWTN GLPDTQAKFH IMFLFFAAAM FSVSLSSLFG YHCWLVSKNK STLEAFRSPV FRHGTDKNGF SLGFSKNMRQ VFGDEKKYWL LPIFSSLGDG CSFPTCLVNQ DPEQASTPAG LNSTAKNLEN HQFPAKPLRE SQSHLLTDSQ SWTESSINPG KCKAGMSNPA LTMENET //