ZDHC1_HUMAN
ID ZDHC1_HUMAN Reviewed; 485 AA.
AC Q8WTX9; O15461;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Palmitoyltransferase ZDHHC1 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000250|UniProtKB:Q8R0N9};
DE AltName: Full=DHHC domain-containing cysteine-rich protein 1 {ECO:0000303|PubMed:16647879};
DE AltName: Full=Zinc finger DHHC domain-containing protein 1 {ECO:0000312|HGNC:HGNC:17916};
DE Short=DHHC-1 {ECO:0000303|PubMed:16647879};
DE AltName: Full=Zinc finger protein 377;
GN Name=ZDHHC1 {ECO:0000312|HGNC:HGNC:17916};
GN Synonyms=C16orf1 {ECO:0000312|HGNC:HGNC:17916}, ZNF377;
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 [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-293, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Pancreas;
RX PubMed=10395086; DOI=10.1023/a:1006932522197;
RA Putilina T., Wong P., Gentleman S.;
RT "The DHHC domain: a new highly conserved cysteine-rich motif.";
RL Mol. Cell. Biochem. 195:219-226(1999).
RN [3]
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 [4]
RP FUNCTION, INTERACTION WITH STING1, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=25299331; DOI=10.1016/j.chom.2014.09.006;
RA Zhou Q., Lin H., Wang S., Wang S., Ran Y., Liu Y., Ye W., Xiong X.,
RA Zhong B., Shu H.B., Wang Y.Y.;
RT "The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-
RT triggered, MITA/STING-dependent innate immune signaling.";
RL Cell Host Microbe 16:450-461(2014).
CC -!- FUNCTION: Palmitoyltransferase that could catalyze the addition of
CC palmitate onto various protein substrates (By similarity). Has a
CC palmitoyltransferase activity toward NCDN and regulates NCDN
CC association with endosome membranes through this palmitoylation.
CC {ECO:0000250|UniProtKB:Q8R0N9}.
CC -!- FUNCTION: Has also a palmitoyltransferase activity-independent function
CC in DNA virus-triggered and CGAS-mediated innate immune response
CC (PubMed:25299331). Functions as an activator of STING1 by promoting its
CC cGAMP-induced oligomerization and the recruitment of downstream
CC signaling components (PubMed:25299331). {ECO:0000269|PubMed:25299331}.
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:Q8R0N9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000250|UniProtKB:Q8R0N9};
CC -!- SUBUNIT: Interacts with STING1; ZDHHC1 constitutively interacts with
CC STING1 and in presence of DNA viruses activates it by promoting its
CC cGAMP-induced oligomerization and the recruitment of downstream
CC signaling components. {ECO:0000269|PubMed:25299331}.
CC -!- INTERACTION:
CC Q8WTX9; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2818796, EBI-3867333;
CC Q8WTX9; Q9HD26-2: GOPC; NbExp=3; IntAct=EBI-2818796, EBI-11102276;
CC Q8WTX9; Q15323: KRT31; NbExp=3; IntAct=EBI-2818796, EBI-948001;
CC Q8WTX9; O76011: KRT34; NbExp=3; IntAct=EBI-2818796, EBI-1047093;
CC Q8WTX9; P78385: KRT83; NbExp=3; IntAct=EBI-2818796, EBI-10221390;
CC Q8WTX9; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-2818796, EBI-11959885;
CC Q8WTX9; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-2818796, EBI-11749135;
CC Q8WTX9; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2818796, EBI-10171774;
CC Q8WTX9; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-2818796, EBI-10176379;
CC Q8WTX9; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-2818796, EBI-11953334;
CC Q8WTX9; Q9BYP8: KRTAP17-1; NbExp=3; IntAct=EBI-2818796, EBI-11988175;
CC Q8WTX9; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-2818796, EBI-14065470;
CC Q8WTX9; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-2818796, EBI-1044640;
CC Q8WTX9; Q99750: MDFI; NbExp=3; IntAct=EBI-2818796, EBI-724076;
CC Q8WTX9; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-2818796, EBI-22310682;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q8R0N9};
CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:16647879, ECO:0000269|PubMed:25299331};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus
CC {ECO:0000269|PubMed:25299331}.
CC -!- TISSUE SPECIFICITY: Widely expressed with significant expression in
CC heart, brain, placenta, lung, liver, kidney, testis, thymus and small
CC intestine (PubMed:16647879). Expressed at lower levels in adult
CC pancreas and lung (PubMed:10395086). {ECO:0000269|PubMed:10395086,
CC ECO:0000269|PubMed:16647879}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in fetal lung, kidney and
CC heart. {ECO:0000269|PubMed:10395086}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000250|UniProtKB:Q8IUH5}.
CC -!- SIMILARITY: Belongs to the DHHC palmitoyltransferase family.
CC {ECO:0000305}.
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DR EMBL; BC021908; AAH21908.1; -; mRNA.
DR EMBL; U90653; AAB86591.2; -; mRNA.
DR CCDS; CCDS10836.1; -.
DR RefSeq; NP_001310556.1; NM_001323627.1.
DR RefSeq; NP_037436.1; NM_013304.2.
DR AlphaFoldDB; Q8WTX9; -.
DR BioGRID; 118924; 33.
DR IntAct; Q8WTX9; 22.
DR STRING; 9606.ENSP00000340299; -.
DR iPTMnet; Q8WTX9; -.
DR PhosphoSitePlus; Q8WTX9; -.
DR BioMuta; ZDHHC1; -.
DR DMDM; 28202100; -.
DR jPOST; Q8WTX9; -.
DR MassIVE; Q8WTX9; -.
DR PaxDb; Q8WTX9; -.
DR PeptideAtlas; Q8WTX9; -.
DR PRIDE; Q8WTX9; -.
DR ProteomicsDB; 74613; -.
DR Antibodypedia; 56070; 149 antibodies from 22 providers.
DR DNASU; 29800; -.
DR Ensembl; ENST00000348579.6; ENSP00000340299.2; ENSG00000159714.12.
DR GeneID; 29800; -.
DR KEGG; hsa:29800; -.
DR UCSC; uc010vjm.3; human.
DR CTD; 29800; -.
DR DisGeNET; 29800; -.
DR GeneCards; ZDHHC1; -.
DR HGNC; HGNC:17916; ZDHHC1.
DR HPA; ENSG00000159714; Low tissue specificity.
DR neXtProt; NX_Q8WTX9; -.
DR OpenTargets; ENSG00000159714; -.
DR PharmGKB; PA38261; -.
DR VEuPathDB; HostDB:ENSG00000159714; -.
DR eggNOG; KOG1311; Eukaryota.
DR GeneTree; ENSGT00940000159191; -.
DR HOGENOM; CLU_020283_0_0_1; -.
DR InParanoid; Q8WTX9; -.
DR OrthoDB; 1216670at2759; -.
DR PhylomeDB; Q8WTX9; -.
DR TreeFam; TF317498; -.
DR PathwayCommons; Q8WTX9; -.
DR SignaLink; Q8WTX9; -.
DR BioGRID-ORCS; 29800; 8 hits in 1072 CRISPR screens.
DR ChiTaRS; ZDHHC1; human.
DR GenomeRNAi; 29800; -.
DR Pharos; Q8WTX9; Tdark.
DR PRO; PR:Q8WTX9; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8WTX9; protein.
DR Bgee; ENSG00000159714; Expressed in right uterine tube and 92 other tissues.
DR ExpressionAtlas; Q8WTX9; baseline and differential.
DR Genevisible; Q8WTX9; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IBA:GO_Central.
DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IBA:GO_Central.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; 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; Endoplasmic reticulum; Endosome; Golgi apparatus;
KW Lipoprotein; Membrane; Palmitate; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..485
FT /note="Palmitoyltransferase ZDHHC1"
FT /id="PRO_0000212857"
FT TOPO_DOM 1..52
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..77
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 78..98
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..241
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 263..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 134..184
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT REGION 1..271
FT /note="Mediates interaction with STING1"
FT /evidence="ECO:0000269|PubMed:25299331"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 462..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..41
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 164
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT VARIANT 124
FT /note="R -> Q (in dbSNP:rs34229857)"
FT /id="VAR_052972"
SQ SEQUENCE 485 AA; 54818 MW; 6B75B077D782F358 CRC64;
MYKMNICNKP SNKTAPEKSV WTAPAQPSGP SPELQGQRSR RNGWSWPPHP LQIVAWLLYL
FFAVIGFGIL VPLLPHHWVP AGYACMGAIF AGHLVVHLTA VSIDPADANV RDKSYAGPLP
IFNRSQHAHV IEDLHCNLCN VDVSARSKHC SACNKCVCGF DHHCKWLNNC VGERNYRLFL
HSVASALLGV LLLVLVATYV FVEFFVNPMR LRTNRHFEVL KNHTDVWFVF LPAAPVETQA
PAILALAALL ILLGLLSTAL LGHLLCFHIY LMWHKLTTYE YIVQHRPPQE AKGVHRELES
CPPKMRPIQE MEFYMRTFRH MRPEPPGQAG PAAVNAKHSR PASPDPTPGR RDCAGPPVQV
EWDRKKPLPW RSPLLLLAMW GPQAPPCLCR KRGRGACIKC ERLRPRIRRR GLGPPAAAPA
RRRIPRTPAL CTPLALPAPT TRRRQSPWTR FQWRRRAWAA PLWPPRGAGA DSPRWRGRRV
RPPFS
