ZDH21_HUMAN
ID ZDH21_HUMAN Reviewed; 265 AA.
AC Q8IVQ6; A8KA95; D3DRI7; Q5VWG1;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Palmitoyltransferase ZDHHC21 {ECO:0000305};
DE EC=2.3.1.225 {ECO:0000305|PubMed:22031296};
DE AltName: Full=DHHC domain-containing cysteine-rich protein 21 {ECO:0000303|PubMed:16647879};
DE Short=DHHC-21 {ECO:0000303|PubMed:16647879};
DE AltName: Full=Zinc finger DHHC domain-containing protein 21 {ECO:0000312|HGNC:HGNC:20750};
GN Name=ZDHHC21 {ECO:0000312|HGNC:HGNC:20750};
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=Trachea;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=22031296; DOI=10.1091/mbc.e11-07-0638;
RA Pedram A., Razandi M., Deschenes R.J., Levin E.R.;
RT "DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.";
RL Mol. Biol. Cell 23:188-199(2012).
CC -!- FUNCTION: Palmitoyltransferase that catalyzes the addition of palmitate
CC onto various protein substrates (PubMed:22031296). Palmitoylates sex
CC steroid hormone receptors, including ESR1, PGR and AR, thereby
CC regulating their targeting to the plasma membrane (PubMed:22031296).
CC This affects rapid intracellular signaling by sex hormones via ERK and
CC AKT kinases and the generation of cAMP, but does not affect that
CC mediated by their nuclear receptor (PubMed:22031296). Palmitoylates
CC FYN, regulates its localization in hair follicles and plays a key role
CC in epidermal homeostasis and hair follicle differentiation. Through the
CC palmitoylation of PLCB1 and the regulation of PLCB1 downstream
CC signaling may indirectly regulate the function of the endothelial
CC barrier and the adhesion of leukocytes to the endothelium. Has also a
CC palmitoyltransferase activity toward ADRA1D, positively regulating its
CC activity and expression and may thereby play a role in vascular
CC contraction. May also palmitoylate eNOS and LCK (By similarity).
CC {ECO:0000250|UniProtKB:Q9D270, ECO:0000269|PubMed:22031296}.
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:0000305|PubMed:22031296};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000305|PubMed:22031296};
CC -!- INTERACTION:
CC Q8IVQ6; Q13520: AQP6; NbExp=3; IntAct=EBI-2849773, EBI-13059134;
CC Q8IVQ6; Q9H9P2: CHODL; NbExp=3; IntAct=EBI-2849773, EBI-17447707;
CC Q8IVQ6; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-2849773, EBI-18535450;
CC Q8IVQ6; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-2849773, EBI-781551;
CC Q8IVQ6; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-2849773, EBI-18938272;
CC Q8IVQ6; Q96E29: MTERF3; NbExp=3; IntAct=EBI-2849773, EBI-7825321;
CC Q8IVQ6; P15941-11: MUC1; NbExp=3; IntAct=EBI-2849773, EBI-17263240;
CC Q8IVQ6; O15173: PGRMC2; NbExp=3; IntAct=EBI-2849773, EBI-1050125;
CC Q8IVQ6; Q6P5S7: RNASEK; NbExp=3; IntAct=EBI-2849773, EBI-18397230;
CC Q8IVQ6; Q9NRX6: TMEM167B; NbExp=3; IntAct=EBI-2849773, EBI-17684533;
CC Q8IVQ6; Q8IWR1: TRIM59; NbExp=3; IntAct=EBI-2849773, EBI-10262539;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000305|PubMed:22031296}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q9D270}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:16647879}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16647879}.
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; AK292960; BAF85649.1; -; mRNA.
DR EMBL; AL390732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58692.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58693.1; -; Genomic_DNA.
DR EMBL; BC042558; AAH42558.1; -; mRNA.
DR CCDS; CCDS6475.1; -.
DR RefSeq; NP_848661.1; NM_178566.4.
DR RefSeq; XP_016870171.1; XM_017014682.1.
DR RefSeq; XP_016870172.1; XM_017014683.1.
DR RefSeq; XP_016870173.1; XM_017014684.1.
DR RefSeq; XP_016870174.1; XM_017014685.1.
DR RefSeq; XP_016870175.1; XM_017014686.1.
DR RefSeq; XP_016870176.1; XM_017014687.1.
DR RefSeq; XP_016870177.1; XM_017014688.1.
DR RefSeq; XP_016870178.1; XM_017014689.1.
DR RefSeq; XP_016870179.1; XM_017014690.1.
DR AlphaFoldDB; Q8IVQ6; -.
DR SMR; Q8IVQ6; -.
DR BioGRID; 131055; 25.
DR IntAct; Q8IVQ6; 20.
DR MINT; Q8IVQ6; -.
DR STRING; 9606.ENSP00000370303; -.
DR iPTMnet; Q8IVQ6; -.
DR PhosphoSitePlus; Q8IVQ6; -.
DR SwissPalm; Q8IVQ6; -.
DR BioMuta; ZDHHC21; -.
DR DMDM; 37999848; -.
DR EPD; Q8IVQ6; -.
DR jPOST; Q8IVQ6; -.
DR MassIVE; Q8IVQ6; -.
DR MaxQB; Q8IVQ6; -.
DR PaxDb; Q8IVQ6; -.
DR PeptideAtlas; Q8IVQ6; -.
DR PRIDE; Q8IVQ6; -.
DR ProteomicsDB; 70753; -.
DR Antibodypedia; 42748; 113 antibodies from 18 providers.
DR DNASU; 340481; -.
DR Ensembl; ENST00000380916.9; ENSP00000370303.3; ENSG00000175893.12.
DR GeneID; 340481; -.
DR KEGG; hsa:340481; -.
DR MANE-Select; ENST00000380916.9; ENSP00000370303.3; NM_178566.6; NP_848661.1.
DR UCSC; uc003zlh.3; human.
DR CTD; 340481; -.
DR GeneCards; ZDHHC21; -.
DR HGNC; HGNC:20750; ZDHHC21.
DR HPA; ENSG00000175893; Low tissue specificity.
DR MIM; 614605; gene.
DR neXtProt; NX_Q8IVQ6; -.
DR OpenTargets; ENSG00000175893; -.
DR PharmGKB; PA134919189; -.
DR VEuPathDB; HostDB:ENSG00000175893; -.
DR eggNOG; KOG1311; Eukaryota.
DR GeneTree; ENSGT00940000158006; -.
DR HOGENOM; CLU_048061_3_0_1; -.
DR InParanoid; Q8IVQ6; -.
DR OMA; GTHWKIL; -.
DR OrthoDB; 1491968at2759; -.
DR PhylomeDB; Q8IVQ6; -.
DR TreeFam; TF319798; -.
DR PathwayCommons; Q8IVQ6; -.
DR Reactome; R-HSA-203615; eNOS activation.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR SignaLink; Q8IVQ6; -.
DR BioGRID-ORCS; 340481; 9 hits in 1041 CRISPR screens.
DR ChiTaRS; ZDHHC21; human.
DR GenomeRNAi; 340481; -.
DR Pharos; Q8IVQ6; Tbio.
DR PRO; PR:Q8IVQ6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8IVQ6; protein.
DR Bgee; ENSG00000175893; Expressed in epithelial cell of pancreas and 179 other tissues.
DR Genevisible; Q8IVQ6; HS.
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; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; ISS:UniProtKB.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IMP: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:1903140; P:regulation of establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:1904997; P:regulation of leukocyte adhesion to arterial endothelial cell; ISS:UniProtKB.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0048733; P:sebaceous gland development; IEA:Ensembl.
DR InterPro; IPR001594; Palmitoyltrfase_DHHC.
DR Pfam; PF01529; DHHC; 1.
DR PROSITE; PS50216; DHHC; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cell membrane; Golgi apparatus; Lipoprotein; Membrane;
KW Palmitate; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..265
FT /note="Palmitoyltransferase ZDHHC21"
FT /id="PRO_0000212908"
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..44
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 155..185
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 90..140
FT /note="DHHC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00067"
FT ACT_SITE 120
FT /note="S-palmitoyl cysteine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9D270"
SQ SEQUENCE 265 AA; 31385 MW; 3C0978532B088F97 CRC64;
MGLRIHFVVD PHGWCCMGLI VFVWLYNIVL IPKIVLFPHY EEGHIPGILI IIFYGISIFC
LVALVRASIT DPGRLPENPK IPHGEREFWE LCNKCNLMRP KRSHHCSRCG HCVRRMDHHC
PWINNCVGED NHWLFLQLCF YTELLTCYAL MFSFCHYYYF LPLKKRNLDL FVFRHELAIM
RLAAFMGITM LVGITGLFYT QLIGIITDTT SIEKMSNCCE DISRPRKPWQ QTFSEVFGTR
WKILWFIPFR QRQPLRVPYH FANHV
