ZDH21_MOUSE
ID ZDH21_MOUSE Reviewed; 265 AA.
AC Q9D270; Q6EMK1; Q80XQ3;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Palmitoyltransferase ZDHHC21 {ECO:0000305|PubMed:19956733};
DE EC=2.3.1.225 {ECO:0000269|PubMed:19956733, ECO:0000269|PubMed:26715683, ECO:0000269|PubMed:27653213};
DE AltName: Full=DHHC domain-containing cysteine-rich protein 21 {ECO:0000303|PubMed:27653213};
DE Short=DHHC21 {ECO:0000303|PubMed:27653213};
DE AltName: Full=GABA-A receptor-associated membrane protein 3 {ECO:0000303|PubMed:15229235};
DE AltName: Full=Zinc finger DHHC domain-containing protein 21 {ECO:0000312|MGI:MGI:1915518};
GN Name=Zdhhc21 {ECO:0000312|MGI:MGI:1915518};
GN Synonyms=Gramp3 {ECO:0000303|PubMed:15229235};
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 [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum;
RX PubMed=15229235; DOI=10.1523/jneurosci.1037-04.2004;
RA Keller C.A., Yuan X., Panzanelli P., Martin M.L., Alldred M.,
RA Sassoe-Pognetto M., Luescher B.;
RT "The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation
RT by GODZ.";
RL J. Neurosci. 24:5881-5891(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, INVOLVEMENT IN DEP, MUTAGENESIS OF LEU-91; CYS-95;
RP CYS-106; CYS-120 AND PHE-233, AND ACTIVE SITE.
RX PubMed=19956733; DOI=10.1371/journal.pgen.1000748;
RA Mill P., Lee A.W., Fukata Y., Tsutsumi R., Fukata M., Keighren M.,
RA Porter R.M., McKie L., Smyth I., Jackson I.J.;
RT "Palmitoylation regulates epidermal homeostasis and hair follicle
RT differentiation.";
RL PLoS Genet. 5:e1000748-e1000748(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, DISEASE, TISSUE SPECIFICITY, MUTAGENESIS OF
RP CYS-120 AND PHE-233, AND ACTIVE SITE.
RX PubMed=26715683; DOI=10.1161/atvbaha.115.306942;
RA Marin E.P., Jozsef L., Di Lorenzo A., Held K.F., Luciano A.K., Melendez J.,
RA Milstone L.M., Velazquez H., Sessa W.C.;
RT "The Protein Acyl Transferase ZDHHC21 Modulates alpha1 Adrenergic Receptor
RT Function and Regulates Hemodynamics.";
RL Arterioscler. Thromb. Vasc. Biol. 36:370-379(2016).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISEASE.
RX PubMed=27653213; DOI=10.1038/ncomms12823;
RA Beard R.S. Jr., Yang X., Meegan J.E., Overstreet J.W., Yang C.G.,
RA Elliott J.A., Reynolds J.J., Cha B.J., Pivetti C.D., Mitchell D.A.,
RA Wu M.H., Deschenes R.J., Yuan S.Y.;
RT "Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in
RT systemic inflammatory response syndrome.";
RL Nat. Commun. 7:12823-12823(2016).
CC -!- FUNCTION: Palmitoyltransferase that catalyzes the addition of palmitate
CC onto various protein substrates (PubMed:19956733, PubMed:26715683,
CC PubMed:27653213). Palmitoylates sex steroid hormone receptors,
CC including ESR1, PGR and AR, thereby regulating their targeting to the
CC plasma membrane. This affects rapid intracellular signaling by sex
CC hormones via ERK and AKT kinases and the generation of cAMP, but does
CC not affect that mediated by their nuclear receptor (By similarity).
CC Palmitoylates FYN, regulates its localization in hair follicles and
CC plays a key role in epidermal homeostasis and hair follicle
CC differentiation (PubMed:19956733). Through the palmitoylation of PLCB1
CC and the regulation of PLCB1 downstream signaling may indirectly
CC regulate the function of the endothelial barrier and the adhesion of
CC leukocytes to the endothelium (PubMed:27653213). 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 (PubMed:26715683). May also palmitoylate eNOS and LCK
CC (PubMed:19956733). {ECO:0000250|UniProtKB:Q8IVQ6,
CC ECO:0000269|PubMed:19956733, ECO:0000269|PubMed:26715683,
CC ECO:0000269|PubMed:27653213}.
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:19956733,
CC ECO:0000269|PubMed:26715683, ECO:0000269|PubMed:27653213};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36684;
CC Evidence={ECO:0000269|PubMed:19956733};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q8IVQ6}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000269|PubMed:19956733}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q8IVQ6}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:26715683). Expressed in
CC Henle's layer within the hair bulb and the hair shaft cuticle (at
CC protein level) (PubMed:19956733). Expression is limited to the post-
CC mitotic lineages of inner root sheath (IRS) and cuticle
CC (PubMed:19956733). {ECO:0000269|PubMed:19956733,
CC ECO:0000269|PubMed:26715683}.
CC -!- DEVELOPMENTAL STAGE: In the developing skin, expression is not be
CC detected prior to hair follicle induction (13 dpc). Expression is
CC initially detected in the inner root sheath (IRS) of developing
CC vibrissae follicles at 16 dpc and later in the developing IRS of 18.5
CC dpc pelage follicles. {ECO:0000269|PubMed:19956733}.
CC -!- DOMAIN: The DHHC domain is required for palmitoyltransferase activity.
CC {ECO:0000250|UniProtKB:Q8IUH5}.
CC -!- DISEASE: Note=Defects in zdhhc21 are the cause of the depilated (dep)
CC phenotype. It is a recessive phenotype characterized by variable hair
CC loss, with thinner and shorter hairs remaining in a greasy coat which
CC is due to a defect in the epidermis, rather than the dermis
CC (PubMed:19956733). Depilated (dep) mutant mice are protected against
CC endothelial dysfunction in systemic inflammatory response syndrome
CC (PubMed:27653213). They are also tachycardic and hypotensive
CC (PubMed:26715683). {ECO:0000269|PubMed:19956733,
CC ECO:0000269|PubMed:26715683, ECO:0000269|PubMed:27653213}.
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; AY166674; AAO27361.1; -; mRNA.
DR EMBL; AK020293; BAB32059.1; -; mRNA.
DR EMBL; AL671005; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043110; AAH43110.1; -; mRNA.
DR CCDS; CCDS18294.1; -.
DR RefSeq; NP_080923.2; NM_026647.3.
DR RefSeq; XP_006538279.1; XM_006538216.3.
DR RefSeq; XP_011248395.1; XM_011250093.2.
DR RefSeq; XP_011248396.1; XM_011250094.2.
DR RefSeq; XP_017175861.1; XM_017320372.1.
DR RefSeq; XP_017175862.1; XM_017320373.1.
DR AlphaFoldDB; Q9D270; -.
DR SMR; Q9D270; -.
DR BioGRID; 212771; 2.
DR STRING; 10090.ENSMUSP00000030110; -.
DR PhosphoSitePlus; Q9D270; -.
DR SwissPalm; Q9D270; -.
DR EPD; Q9D270; -.
DR MaxQB; Q9D270; -.
DR PaxDb; Q9D270; -.
DR PeptideAtlas; Q9D270; -.
DR PRIDE; Q9D270; -.
DR ProteomicsDB; 274973; -.
DR Antibodypedia; 42748; 113 antibodies from 18 providers.
DR DNASU; 68268; -.
DR Ensembl; ENSMUST00000030110; ENSMUSP00000030110; ENSMUSG00000028403.
DR Ensembl; ENSMUST00000107239; ENSMUSP00000102859; ENSMUSG00000028403.
DR GeneID; 68268; -.
DR KEGG; mmu:68268; -.
DR UCSC; uc008tkj.2; mouse.
DR CTD; 340481; -.
DR MGI; MGI:1915518; Zdhhc21.
DR VEuPathDB; HostDB:ENSMUSG00000028403; -.
DR eggNOG; KOG1311; Eukaryota.
DR GeneTree; ENSGT00940000158006; -.
DR HOGENOM; CLU_048061_3_0_1; -.
DR InParanoid; Q9D270; -.
DR OMA; GTHWKIL; -.
DR OrthoDB; 1491968at2759; -.
DR PhylomeDB; Q9D270; -.
DR TreeFam; TF319798; -.
DR Reactome; R-MMU-203615; eNOS activation.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 68268; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Zdhhc21; mouse.
DR PRO; PR:Q9D270; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9D270; protein.
DR Bgee; ENSMUSG00000028403; Expressed in otolith organ and 222 other tissues.
DR ExpressionAtlas; Q9D270; baseline and differential.
DR Genevisible; Q9D270; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:MGI.
DR GO; GO:0019706; F:protein-cysteine S-palmitoyltransferase activity; IMP:UniProtKB.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0018230; P:peptidyl-L-cysteine S-palmitoylation; IMP:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IMP:MGI.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:1904997; P:regulation of leukocyte adhesion to arterial endothelial cell; IMP:UniProtKB.
DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; IMP:UniProtKB.
DR GO; GO:0048733; P:sebaceous gland development; 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; 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_0000212909"
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:0000269|PubMed:19956733,
FT ECO:0000269|PubMed:26715683"
FT MUTAGEN 91
FT /note="L->F: No effect on protein-cysteine S-
FT palmitoyltransferase activity. No effect on localization to
FT the cis-Golgi network."
FT /evidence="ECO:0000269|PubMed:19956733"
FT MUTAGEN 95
FT /note="C->S: Loss of protein-cysteine S-
FT palmitoyltransferase activity. Decreased localization to
FT the cis-Golgi network. Relocalized to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:19956733"
FT MUTAGEN 106
FT /note="C->S: Loss of protein-cysteine S-
FT palmitoyltransferase activity. Decreased localization to
FT the cis-Golgi network. Relocalized to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:19956733"
FT MUTAGEN 120
FT /note="C->S: Loss of protein-cysteine S-
FT palmitoyltransferase activity. Decreased localization to
FT the cis-Golgi network. Relocalized to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:19956733,
FT ECO:0000269|PubMed:26715683"
FT MUTAGEN 233
FT /note="Missing: In depilated (dep) mutant mice. Loss of
FT protein-cysteine S-palmitoyltransferase activity.
FT Relocalized to the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:19956733,
FT ECO:0000269|PubMed:26715683"
FT CONFLICT 67
FT /note="A -> T (in Ref. 1; AAO27361 and 2; BAB32059)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 265 AA; 31331 MW; BA3F428AAE4637DB CRC64;
MGLRIHFVVD PHGWCCMGLI VFVWLYNIVI IPKIVLFPHY EEGHIPGILI IIFYGISIFC
LVALVRASLT DPGRLPENPK IPHAERELWE LCNKCNLMRP KRSHHCSRCG HCVRRMDHHC
PWINNCVGED NHWLFLQLCF YTELLTCYAL MFSFCHYYYF LPLKKRNLDL FVVRHELAIM
RLAAFMGITM LVGITGLFYT QLIGIITDTT SIEKMSNCCE EISRPRKPWQ QTFSEVFGTR
WKILWFIPFR QRQPLRVPYH FANHV
