HHAT_DROME
ID HHAT_DROME Reviewed; 500 AA.
AC Q9VZU2; Q95VY0;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Protein-cysteine N-palmitoyltransferase Rasp;
DE EC=2.3.1.-;
DE AltName: Full=Protein central missing;
DE AltName: Full=Protein sightless;
DE AltName: Full=Protein skinny hedgehog;
GN Name=rasp; Synonyms=cmn, sit, ski; ORFNames=CG11495;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|EMBL:AAK73748.1};
RN [1] {ECO:0000312|EMBL:AAK73748.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Embryo {ECO:0000269|PubMed:11509241};
RX PubMed=11509241; DOI=10.1016/s0960-9822(01)00323-2;
RA Lee J.D., Treisman J.E.;
RT "Sightless has homology to transmembrane acyltransferases and is required
RT to generate active Hedgehog protein.";
RL Curr. Biol. 11:1147-1152(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=11748147; DOI=10.1242/dev.128.24.5119;
RA Amanai K., Jiang J.;
RT "Distinct roles of Central missing and Dispatched in sending the Hedgehog
RT signal.";
RL Development 128:5119-5127(2001).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND CATALYTIC
RP ACTIVITY.
RX PubMed=11486055; DOI=10.1126/science.1064437;
RA Chamoun Z., Mann R.K., Nellen D., von Kessler D.P., Bellotto M.,
RA Beachy P.A., Basler K.;
RT "Skinny hedgehog, an acyltransferase required for palmitoylation and
RT activity of the hedgehog signal.";
RL Science 293:2080-2084(2001).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP FUNCTION.
RX PubMed=11861468; DOI=10.1242/dev.129.4.843;
RA Micchelli C.A., The I., Selva E., Mogila V., Perrimon N.;
RT "Rasp, a putative transmembrane acyltransferase, is required for Hedgehog
RT signaling.";
RL Development 129:843-851(2002).
CC -!- FUNCTION: Required in hedgehog (hh) expressing cells for production of
CC appropriate signaling activity in embryos and in the imaginal
CC precursors of adult tissues. Acts within the secretory pathway to
CC catalyze N-terminal palmitoylation of Hh; this lipid modification is
CC required for the embryonic and larval patterning activities of the Hh
CC signal. Not required for Wg signaling. {ECO:0000269|PubMed:11486055,
CC ECO:0000269|PubMed:11509241, ECO:0000269|PubMed:11748147,
CC ECO:0000269|PubMed:11861468}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + N-terminal L-cysteinyl-[protein] = CoA +
CC H(+) + N-terminal N-hexadecanoyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:59528, Rhea:RHEA-COMP:12707, Rhea:RHEA-COMP:15376,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:65250, ChEBI:CHEBI:143147;
CC Evidence={ECO:0000269|PubMed:11486055};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59529;
CC Evidence={ECO:0000269|PubMed:11486055};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-CoA + N-terminal L-cysteinyl-[protein]-C-terminal
CC glycyl cholesterol ester = CoA + H(+) + N-terminal N-hexadecanoyl-L-
CC cysteinyl-[protein]-C-terminal glycyl cholesterol ester;
CC Xref=Rhea:RHEA:59580, Rhea:RHEA-COMP:15388, Rhea:RHEA-COMP:15389,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:65250, ChEBI:CHEBI:143135, ChEBI:CHEBI:143147;
CC Evidence={ECO:0000250|UniProtKB:Q5VTY9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59581;
CC Evidence={ECO:0000250|UniProtKB:Q5VTY9};
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:11486055}.
CC -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family. HHAT
CC subfamily. {ECO:0000305}.
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DR EMBL; AF393157; AAK73748.1; -; mRNA.
DR EMBL; AF398410; AAK97480.1; -; mRNA.
DR EMBL; AE014296; AAF47725.1; -; Genomic_DNA.
DR EMBL; AY119202; AAM51062.1; -; mRNA.
DR RefSeq; NP_523898.1; NM_079174.2.
DR AlphaFoldDB; Q9VZU2; -.
DR SMR; Q9VZU2; -.
DR BioGRID; 68830; 6.
DR IntAct; Q9VZU2; 1.
DR STRING; 7227.FBpp0072893; -.
DR TCDB; 2.A.50.1.5; the glycerol uptake (gup) or membrane-bound acyl transferase (mboat) family.
DR PaxDb; Q9VZU2; -.
DR EnsemblMetazoa; FBtr0073029; FBpp0072893; FBgn0024194.
DR GeneID; 44098; -.
DR KEGG; dme:Dmel_CG11495; -.
DR CTD; 44098; -.
DR FlyBase; FBgn0024194; rasp.
DR VEuPathDB; VectorBase:FBgn0024194; -.
DR eggNOG; KOG3860; Eukaryota.
DR GeneTree; ENSGT00530000063629; -.
DR HOGENOM; CLU_027533_3_0_1; -.
DR InParanoid; Q9VZU2; -.
DR OMA; IHYMSRD; -.
DR OrthoDB; 392243at2759; -.
DR PhylomeDB; Q9VZU2; -.
DR Reactome; R-DME-209471; Formation and transport of the N-HH ligand.
DR Reactome; R-DME-5358346; Hedgehog ligand biogenesis.
DR SignaLink; Q9VZU2; -.
DR BioGRID-ORCS; 44098; 0 hits in 3 CRISPR screens.
DR ChiTaRS; rin; fly.
DR GenomeRNAi; 44098; -.
DR PRO; PR:Q9VZU2; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0024194; Expressed in eye disc (Drosophila) and 23 other tissues.
DR ExpressionAtlas; Q9VZU2; baseline and differential.
DR Genevisible; Q9VZU2; DM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0016746; F:acyltransferase activity; IMP:UniProtKB.
DR GO; GO:0016409; F:palmitoyltransferase activity; IDA:FlyBase.
DR GO; GO:0046843; P:dorsal appendage formation; IMP:FlyBase.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; IMP:FlyBase.
DR GO; GO:0018009; P:N-terminal peptidyl-L-cysteine N-palmitoylation; IDA:UniProtKB.
DR GO; GO:0007225; P:patched ligand maturation; IMP:FlyBase.
DR GO; GO:0018345; P:protein palmitoylation; IDA:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IMP:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; TAS:Reactome.
DR GO; GO:0048100; P:wing disc anterior/posterior pattern formation; IMP:FlyBase.
DR InterPro; IPR004299; MBOAT_fam.
DR Pfam; PF03062; MBOAT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Developmental protein; Membrane; Reference proteome;
KW Segmentation polarity protein; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..500
FT /note="Protein-cysteine N-palmitoyltransferase Rasp"
FT /id="PRO_0000213136"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 73..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 372..392
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 381
FT /evidence="ECO:0000255"
FT CONFLICT 91
FT /note="G -> V (in Ref. 1 and 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 58106 MW; 4498DC306976F2A2 CRC64;
MSRLPDRSLL TRCEIFVYFG VYIAYIVVGL YKIYGLRDHI VKEAKFQFPE GWSLYPFSQR
RRDDSNDELE NFGDFIVSFW PFYLLHVAVQ GFIRWKRPRL QCLGFIGVCA LALSVNLDWS
SMVLLVTLIA SYYIVSLLSL KFLVWLLSAG WILCINVMQK NVWWTDRVGY TEYVLVIVTM
SWSVLRGCSY SLSKIGAKQE DLTRYSLVQY LGYAMYFPCL TYGPIISYQR FAARREDEVQ
NWLGFVGGVL RSAIWWLVMQ CALHYFYIHY MSRDVRMVEM MDSVFWQHSA GYFMGQFFFL
YYVVTYGLGI AFAVQDGIPA PNRPRCIGRI HFYSDMWKYF DEGLYEFLFQ NIYAELCGKR
SSAAAKFGAT ALTFAFVFVW HGCYTYVLIW SILNFLCLAA EKVFKTFTAM PEYQRWTQRH
LGAVGAQRLY AMLATQLFIP AAFSNVYFIG GQEIGDFLMR GAYLSGVGNY VALCFCSYCF
FQCSELLLTK SDGRSKTKTF
