HHAT_MOUSE
ID HHAT_MOUSE Reviewed; 499 AA.
AC Q8BMT9; B1ANS0; Q3TA33; Q922G3;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Protein-cysteine N-palmitoyltransferase HHAT;
DE EC=2.3.1.-;
DE AltName: Full=Hedgehog acyltransferase;
DE AltName: Full=Skinny hedgehog protein;
GN Name=Hhat; Synonyms=Skn;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, and Spleen;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND CATALYTIC ACTIVITY.
RX PubMed=15075292; DOI=10.1101/gad.1185804;
RA Chen M.-H., Li Y.-J., Kawakami T., Xu S.-M., Chuang P.-T.;
RT "Palmitoylation is required for the production of a soluble multimeric
RT Hedgehog protein complex and long-range signaling in vertebrates.";
RL Genes Dev. 18:641-659(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=18081866; DOI=10.1111/j.1742-4658.2007.06202.x;
RA Abe Y., Kita Y., Niikura T.;
RT "Mammalian Gup1, a homolog of Saccharomyces cerevisiae glycerol
RT uptake/transporter 1, acts as a negative regulator for N-terminal
RT palmitoylation of Sonic hedgehog.";
RL FEBS J. 275:318-331(2008).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24784881; DOI=10.1371/journal.pgen.1004340;
RA Callier P., Calvel P., Matevossian A., Makrythanasis P., Bernard P.,
RA Kurosaka H., Vannier A., Thauvin-Robinet C., Borel C., Mazaud-Guittot S.,
RA Rolland A., Desdoits-Lethimonier C., Guipponi M., Zimmermann C.,
RA Stevant I., Kuhne F., Conne B., Santoni F., Lambert S., Huet F.,
RA Mugneret F., Jaruzelska J., Faivre L., Wilhelm D., Jegou B., Trainor P.A.,
RA Resh M.D., Antonarakis S.E., Nef S.;
RT "Loss of function mutation in the palmitoyl-transferase HHAT leads to
RT syndromic 46,XY disorder of sex development by impeding Hedgehog protein
RT palmitoylation and signaling.";
RL PLoS Genet. 10:e1004340-e1004340(2014).
CC -!- FUNCTION: Palmitoyl acyltransferase that catalyzes N-terminal
CC palmitoylation of SHH; which is required for SHH signaling during limb
CC development (PubMed:15075292). It also catalyzes N-terminal
CC palmitoylation of DHH (By similarity). Promotes the transfer of
CC palmitoyl-CoA from the cytoplasmic to the luminal side of the
CC endoplasmic reticulum membrane, where SHH palmitoylation occurs (By
CC similarity). Plays a role in proper testis cord formation and the
CC differentiation of Leydig cells (PubMed:24784881).
CC {ECO:0000250|UniProtKB:Q5VTY9, ECO:0000269|PubMed:15075292,
CC ECO:0000269|PubMed:24784881}.
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:15075292};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59529;
CC Evidence={ECO:0000269|PubMed:15075292};
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:0000305|PubMed:15075292};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59581;
CC Evidence={ECO:0000305|PubMed:15075292};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15075292, ECO:0000269|PubMed:18081866}; Multi-pass
CC membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q5VTY9}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Co-localizes with SHH in the ER and Golgi membrane.
CC {ECO:0000250|UniProtKB:Q5VTY9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BMT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BMT9-2; Sequence=VSP_016690, VSP_016691;
CC -!- DEVELOPMENTAL STAGE: Broadly expressed from 7 dpc. At 10.5 dpc,
CC strongly expressed in anterior ectoderm, pharyngeal arches, and distal
CC part of the limb. {ECO:0000269|PubMed:15075292}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout embryos are characterized by
CC a smaller size and holoprosencephaly at 10.5 dpc, shortening of limbs
CC at 13.5 dpc, and severe short-limb dwarfism at birth. They die soon
CC after birth. Testicular development is significantly impaired in XY
CC embryos by 12.5 dpc. There is a massive reduction in testis size, a
CC reduction in the number of testis cords which are irregular in shape
CC and diameter, and an almost complete absence of Leydig cells
CC (PubMed:24784881). {ECO:0000269|PubMed:15075292,
CC ECO:0000269|PubMed:24784881}.
CC -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family. HHAT
CC subfamily. {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; AK028230; BAC25829.1; -; mRNA.
DR EMBL; AK172126; BAE42837.1; -; mRNA.
DR EMBL; AC105325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC115917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365317; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008159; AAH08159.1; -; mRNA.
DR CCDS; CCDS15628.1; -. [Q8BMT9-1]
DR RefSeq; NP_659130.2; NM_144881.4. [Q8BMT9-1]
DR AlphaFoldDB; Q8BMT9; -.
DR SMR; Q8BMT9; -.
DR STRING; 10090.ENSMUSP00000046686; -.
DR ChEMBL; CHEMBL1255153; -.
DR TCDB; 2.A.50.1.3; the glycerol uptake (gup) or membrane-bound acyl transferase (mboat) family.
DR PhosphoSitePlus; Q8BMT9; -.
DR PaxDb; Q8BMT9; -.
DR PRIDE; Q8BMT9; -.
DR ProteomicsDB; 269662; -. [Q8BMT9-1]
DR ProteomicsDB; 269663; -. [Q8BMT9-2]
DR Antibodypedia; 47111; 114 antibodies from 23 providers.
DR Ensembl; ENSMUST00000044190; ENSMUSP00000046686; ENSMUSG00000037375. [Q8BMT9-1]
DR Ensembl; ENSMUST00000128619; ENSMUSP00000120479; ENSMUSG00000037375. [Q8BMT9-2]
DR GeneID; 226861; -.
DR KEGG; mmu:226861; -.
DR UCSC; uc007edp.2; mouse. [Q8BMT9-1]
DR CTD; 55733; -.
DR MGI; MGI:2444681; Hhat.
DR VEuPathDB; HostDB:ENSMUSG00000037375; -.
DR eggNOG; KOG3860; Eukaryota.
DR GeneTree; ENSGT00530000063629; -.
DR HOGENOM; CLU_027533_3_1_1; -.
DR InParanoid; Q8BMT9; -.
DR OMA; IHYMSRD; -.
DR OrthoDB; 392243at2759; -.
DR PhylomeDB; Q8BMT9; -.
DR TreeFam; TF315826; -.
DR Reactome; R-MMU-5358346; Hedgehog ligand biogenesis.
DR BioGRID-ORCS; 226861; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Hhat; mouse.
DR PRO; PR:Q8BMT9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8BMT9; protein.
DR Bgee; ENSMUSG00000037375; Expressed in lumbar dorsal root ganglion and 126 other tissues.
DR ExpressionAtlas; Q8BMT9; baseline and differential.
DR Genevisible; Q8BMT9; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0016746; F:acyltransferase activity; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0016409; F:palmitoyltransferase activity; IMP:MGI.
DR GO; GO:0018009; P:N-terminal peptidyl-L-cysteine N-palmitoylation; IMP:UniProtKB.
DR GO; GO:0018345; P:protein palmitoylation; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR InterPro; IPR032981; HHAT.
DR InterPro; IPR004299; MBOAT_fam.
DR PANTHER; PTHR13285:SF20; PTHR13285:SF20; 1.
DR Pfam; PF03062; MBOAT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Developmental protein;
KW Endoplasmic reticulum; Golgi apparatus; GTP-binding; Lipoprotein; Membrane;
KW Nucleotide-binding; Palmitate; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..499
FT /note="Protein-cysteine N-palmitoyltransferase HHAT"
FT /id="PRO_0000213135"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 6..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 23..67
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 85..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 95..119
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..148
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 149..162
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 163..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 184..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 209..223
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 278..287
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..369
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 387..389
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 390..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..468
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..487
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 488..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 91..155
FT /note="Essential for palmitoylation of SHH"
FT /evidence="ECO:0000250|UniProtKB:Q5VTY9"
FT ACT_SITE 385
FT /evidence="ECO:0000255"
FT BINDING 454..461
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT LIPID 188
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT LIPID 248
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT LIPID 330
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT LIPID 416
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT VAR_SEQ 470..473
FT /note="GWPW -> AAFR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016690"
FT VAR_SEQ 474..499
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016691"
FT CONFLICT 489
FT /note="D -> G (in Ref. 1; BAE42837)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 57864 MW; 37A3B98D607CE06C CRC64;
MLPGWELTLC LLVSLGFHFR SFYEVYKVSR EHEEELDQEF ELEMDTLFGG LKKDPTDFEW
NFWMEWGKRR LVWLFIGHMA VSQLATLLTK KHRPWIVMVY GMWACWCVLG APGVVMVLLH
STIAFCVAQF RSVLLSWLCS LLLLSTLRLQ SVEEVKRRWY KTENEYYLLQ FTLTVRCLYY
TSFSLELCRQ PPSAQPTPSA QGASHSYPWL LTYVFYYPVF HNGPILNFPE FFRQMQQPEL
NSLQHSLCIV AKGLGRLLCW WWLAELMVHL MYMHALYSSA PLLESVSCWT LGGLALAQVL
FFYVKYLVLF GVPALLMRLD GLTPPPLPRC VSTMFSFTGM WRYFDVGLHN FLIRYVYIPL
GGSQHGLLGT LLSTATTFAF VSYWHGSYED LWCWAALNWL GVTVESGVRR LLETPCVRET
LARHLSPQAH HRLHALLAAC STSMLILFNL VFLGGIQVGK TYWNRIFLQG WPWVTLSVLG
FLYCYSHVDI AWAQTYTVL
