ID HHAT_HUMAN Reviewed; 493 AA. AC Q5VTY9; B7Z4D5; B7Z5I1; B7Z868; B7ZA75; D3DT91; F5H444; Q17RZ7; Q4G0K3; AC Q5CZ95; Q5TGI2; Q9NVH9; Q9Y3N8; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 1. DT 12-OCT-2022, entry version 155. DE RecName: Full=Protein-cysteine N-palmitoyltransferase HHAT; DE EC=2.3.1.-; DE AltName: Full=Hedgehog acyltransferase; DE AltName: Full=Melanoma antigen recognized by T-cells 2; DE Short=MART-2; DE AltName: Full=Skinny hedgehog protein 1; GN Name=HHAT; Synonyms=MART2, SKI1; 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 [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, RP GTP-BINDING, CHARACTERIZATION OF VARIANT GLU-448, AND VARIANT SER-450. RC TISSUE=Melanoma; RX PubMed=11160356; DOI=10.4049/jimmunol.166.4.2871; RA Kawakami Y., Wang X., Shofuda T., Sumimoto H., Tupesis J., Fitzgerald E., RA Rosenberg S.; RT "Isolation of a new melanoma antigen, MART-2, containing a mutated epitope RT recognized by autologous tumor-infiltrating T lymphocytes."; RL J. Immunol. 166:2871-2877(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5; 6 AND 7), AND RP VARIANT ARG-188. RC TISSUE=Brain, Lung, Teratocarcinoma, Testis, and 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain cortex; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-182. RC TISSUE=Brain, and 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 32-335 (ISOFORM 2). RA Rhodes S.; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 328-390 (ISOFORM 1). 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 [9] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY RP REGULATION, REGION, MUTAGENESIS OF HIS-379, AND SUBCELLULAR LOCATION. RX PubMed=18534984; DOI=10.1074/jbc.m803901200; RA Buglino J.A., Resh M.D.; RT "Hhat is a palmitoylacyltransferase with specificity for N-palmitoylation RT of Sonic Hedgehog."; RL J. Biol. Chem. 283:22076-22088(2008). RN [10] RP SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=25488661; DOI=10.1074/jbc.m114.625764; RA Matevossian A., Resh M.D.; RT "Membrane topology of hedgehog acyltransferase."; RL J. Biol. Chem. 290:2235-2243(2015). RN [11] RP SUBCELLULAR LOCATION, TOPOLOGY, AND PALMITOYLATION AT CYS-188; CYS-242; RP CYS-324 AND CYS-410. RX PubMed=25505265; DOI=10.1074/jbc.m114.614578; RA Konitsiotis A.D., Jovanovic B., Ciepla P., Spitaler M., Lanyon-Hogg T., RA Tate E.W., Magee A.I.; RT "Topological analysis of Hedgehog acyltransferase, a multipalmitoylated RT transmembrane protein."; RL J. Biol. Chem. 290:3293-3307(2015). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-351 AND HIS-379. RX PubMed=31875564; DOI=10.1016/j.celrep.2019.11.110; RA Asciolla J.J., Resh M.D.; RT "Hedgehog Acyltransferase Promotes Uptake of Palmitoyl-CoA across the RT Endoplasmic Reticulum Membrane."; RL Cell Rep. 29:4608-4619(2019). RN [13] RP VARIANT NNMS VAL-287, INVOLVEMENT IN NNMS, CHARACTERIZATION OF VARIANT NNMS RP VAL-287, FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY. 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). RN [14] RP VARIANT NNMS PRO-257, AND INVOLVEMENT IN NNMS. RX PubMed=30912300; DOI=10.1002/ajmg.a.61133; RA Abdel-Salam G.M.H., Mazen I., Eid M., Ewida N., Shaheen R., Alkuraya F.S.; RT "Biallelic novel missense HHAT variant causes syndromic microcephaly and RT cerebellar-vermis hypoplasia."; RL Am. J. Med. Genet. A 179:1053-1057(2019). CC -!- FUNCTION: Palmitoyl acyltransferase that catalyzes N-terminal CC palmitoylation of SHH; which is required for SHH signaling CC (PubMed:18534984, PubMed:31875564, PubMed:24784881). It also catalyzes CC N-terminal palmitoylation of DHH (PubMed:24784881). Promotes the CC transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of CC the endoplasmic reticulum membrane, where SHH palmitoylation occurs CC (PubMed:31875564). It is an essential factor for proper embryonic CC development and testicular organogenesis (PubMed:24784881). CC {ECO:0000269|PubMed:11486055, ECO:0000269|PubMed:18534984, CC ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:31875564}. 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:18534984, ECO:0000269|PubMed:24784881, CC ECO:0000269|PubMed:31875564}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59529; CC Evidence={ECO:0000305|PubMed:18534984}; 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:18534984}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59581; CC Evidence={ECO:0000305|PubMed:18534984}; CC -!- ACTIVITY REGULATION: Inhibited by NaCl concentrations above 150 mM. CC {ECO:0000269|PubMed:18534984}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.25 uM for SHH {ECO:0000269|PubMed:18534984}; CC KM=3.0 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:18534984}; CC Vmax=0.25 pmol/min/mg enzyme for SHH {ECO:0000269|PubMed:18534984}; CC Vmax=0.21 pmol/min/mg enzyme for hexadecanoyl-CoA CC {ECO:0000269|PubMed:18534984}; CC pH dependence: CC Optimum pH is 6.5. {ECO:0000269|PubMed:18534984}; CC -!- INTERACTION: CC Q5VTY9; O00560: SDCBP; NbExp=3; IntAct=EBI-12951255, EBI-727004; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:25488661, ECO:0000269|PubMed:25505265, CC ECO:0000305|PubMed:18534984}; Multi-pass membrane protein CC {ECO:0000269|PubMed:25488661, ECO:0000269|PubMed:25505265}. Golgi CC apparatus membrane {ECO:0000305|PubMed:18534984}; Multi-pass membrane CC protein {ECO:0000255}. Note=Co-localizes with SHH in the ER and Golgi CC membrane. {ECO:0000305|PubMed:18534984}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=Q5VTY9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5VTY9-2; Sequence=VSP_016686, VSP_016689; CC Name=3; CC IsoId=Q5VTY9-3; Sequence=VSP_016689; CC Name=4; CC IsoId=Q5VTY9-4; Sequence=VSP_016685, VSP_016687, VSP_016688; CC Name=5; CC IsoId=Q5VTY9-5; Sequence=VSP_016686; CC Name=6; CC IsoId=Q5VTY9-6; Sequence=VSP_043481; CC Name=7; CC IsoId=Q5VTY9-7; Sequence=VSP_044968; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in fetal ovary and CC testis, with high levels of expression observed in Sertoli cells CC (PubMed:24784881). {ECO:0000269|PubMed:11160356, CC ECO:0000269|PubMed:24784881}. CC -!- DISEASE: Nivelon-Nivelon-Mabille syndrome (NNMS) [MIM:600092]: An CC autosomal recessive syndrome characterized by progressive microcephaly, CC cerebellar vermis hypoplasia, and skeletal dysplasia. Additional CC variable features include early infantile-onset seizures, intrauterine CC and postnatal growth retardation, generalized chondrodysplasia, and CC micromelia. 46,XY gonadal dysgenesis may be present. CC {ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:30912300}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; AK001586; BAA91772.1; -; mRNA. DR EMBL; AK297193; BAH12521.1; -; mRNA. DR EMBL; AK298991; BAH12917.1; -; mRNA. DR EMBL; AK302955; BAH13854.1; -; mRNA. DR EMBL; AK316190; BAH14561.1; -; mRNA. DR EMBL; AK316524; BAH14895.1; -; mRNA. DR EMBL; CR936628; CAI56771.1; -; mRNA. DR EMBL; AC096636; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL034351; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL035414; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL691441; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX255872; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471100; EAW93427.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93428.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93430.1; -; Genomic_DNA. DR EMBL; BC117130; AAI17131.1; -; mRNA. DR EMBL; AL049848; CAB42852.1; -; mRNA. DR CCDS; CCDS1495.1; -. [Q5VTY9-1] DR CCDS; CCDS53471.1; -. [Q5VTY9-7] DR CCDS; CCDS53472.1; -. [Q5VTY9-5] DR CCDS; CCDS53473.1; -. [Q5VTY9-6] DR RefSeq; NP_001116306.1; NM_001122834.3. [Q5VTY9-1] DR RefSeq; NP_001164035.1; NM_001170564.2. [Q5VTY9-6] DR RefSeq; NP_001164051.1; NM_001170580.2. [Q5VTY9-1] DR RefSeq; NP_001164058.1; NM_001170587.2. [Q5VTY9-7] DR RefSeq; NP_001164059.1; NM_001170588.2. [Q5VTY9-5] DR RefSeq; NP_060664.2; NM_018194.5. [Q5VTY9-1] DR RefSeq; XP_011508041.1; XM_011509739.2. [Q5VTY9-3] DR RefSeq; XP_011508042.1; XM_011509740.2. [Q5VTY9-3] DR RefSeq; XP_011508043.1; XM_011509741.2. [Q5VTY9-3] DR RefSeq; XP_011508048.1; XM_011509746.2. [Q5VTY9-2] DR RefSeq; XP_016857218.1; XM_017001729.1. [Q5VTY9-3] DR RefSeq; XP_016857221.1; XM_017001732.1. [Q5VTY9-5] DR RefSeq; XP_016857224.1; XM_017001735.1. [Q5VTY9-5] DR RefSeq; XP_016857226.1; XM_017001737.1. [Q5VTY9-6] DR PDB; 6P64; X-ray; 3.05 A; C/H=68-76. DR PDB; 6UJO; X-ray; 2.25 A; C=68-76. DR PDB; 6UJQ; X-ray; 2.55 A; C=68-76. DR PDB; 6UK2; X-ray; 3.14 A; C=68-76. DR PDB; 6UK4; X-ray; 2.70 A; C=68-76. DR PDB; 7MHY; EM; 2.70 A; A=1-493. DR PDB; 7MHZ; EM; 3.20 A; A=1-493. DR PDB; 7Q6Z; EM; 3.59 A; A=1-493. DR PDBsum; 6P64; -. DR PDBsum; 6UJO; -. DR PDBsum; 6UJQ; -. DR PDBsum; 6UK2; -. DR PDBsum; 6UK4; -. DR PDBsum; 7MHY; -. DR PDBsum; 7MHZ; -. DR PDBsum; 7Q6Z; -. DR AlphaFoldDB; Q5VTY9; -. DR SMR; Q5VTY9; -. DR BioGRID; 120852; 1. DR IntAct; Q5VTY9; 1. DR STRING; 9606.ENSP00000438468; -. DR BindingDB; Q5VTY9; -. DR ChEMBL; CHEMBL4296243; -. DR SwissLipids; SLP:000001949; -. DR TCDB; 2.A.50.1.4; the glycerol uptake (gup) or membrane-bound acyl transferase (mboat) family. DR iPTMnet; Q5VTY9; -. DR PhosphoSitePlus; Q5VTY9; -. DR SwissPalm; Q5VTY9; -. DR BioMuta; HHAT; -. DR DMDM; 74747010; -. DR jPOST; Q5VTY9; -. DR MassIVE; Q5VTY9; -. DR PaxDb; Q5VTY9; -. DR PeptideAtlas; Q5VTY9; -. DR PRIDE; Q5VTY9; -. DR ProteomicsDB; 26462; -. DR ProteomicsDB; 65361; -. [Q5VTY9-1] DR ProteomicsDB; 65362; -. [Q5VTY9-2] DR ProteomicsDB; 65363; -. [Q5VTY9-3] DR ProteomicsDB; 65365; -. [Q5VTY9-5] DR ProteomicsDB; 65366; -. [Q5VTY9-6] DR Antibodypedia; 47111; 113 antibodies from 22 providers. DR DNASU; 55733; -. DR Ensembl; ENST00000261458.8; ENSP00000261458.3; ENSG00000054392.13. [Q5VTY9-1] DR Ensembl; ENST00000367010.5; ENSP00000355977.1; ENSG00000054392.13. [Q5VTY9-1] DR Ensembl; ENST00000413764.6; ENSP00000416845.2; ENSG00000054392.13. [Q5VTY9-1] DR Ensembl; ENST00000537898.5; ENSP00000442625.1; ENSG00000054392.13. [Q5VTY9-5] DR Ensembl; ENST00000541565.5; ENSP00000444995.1; ENSG00000054392.13. [Q5VTY9-6] DR Ensembl; ENST00000545154.5; ENSP00000438468.1; ENSG00000054392.13. [Q5VTY9-7] DR Ensembl; ENST00000625523.2; ENSP00000486634.1; ENSG00000280680.3. [Q5VTY9-6] DR Ensembl; ENST00000625820.2; ENSP00000486054.1; ENSG00000280680.3. [Q5VTY9-1] DR Ensembl; ENST00000626327.2; ENSP00000487414.1; ENSG00000280680.3. [Q5VTY9-5] DR Ensembl; ENST00000627903.2; ENSP00000487400.1; ENSG00000280680.3. [Q5VTY9-1] DR Ensembl; ENST00000628693.2; ENSP00000486611.1; ENSG00000280680.3. [Q5VTY9-7] DR Ensembl; ENST00000629360.3; ENSP00000486128.1; ENSG00000280680.3. [Q5VTY9-1] DR GeneID; 55733; -. DR KEGG; hsa:55733; -. DR MANE-Select; ENST00000261458.8; ENSP00000261458.3; NM_018194.6; NP_060664.2. DR UCSC; uc001hhz.5; human. [Q5VTY9-1] DR CTD; 55733; -. DR DisGeNET; 55733; -. DR GeneCards; HHAT; -. DR HGNC; HGNC:18270; HHAT. DR HPA; ENSG00000054392; Low tissue specificity. DR MalaCards; HHAT; -. DR MIM; 600092; phenotype. DR MIM; 605743; gene. DR neXtProt; NX_Q5VTY9; -. DR OpenTargets; ENSG00000054392; -. DR Orphanet; 1422; Chondrodysplasia-disorder of sex development syndrome. DR PharmGKB; PA134926499; -. DR VEuPathDB; HostDB:ENSG00000054392; -. DR eggNOG; KOG3860; Eukaryota. DR GeneTree; ENSGT00530000063629; -. DR HOGENOM; CLU_027533_3_1_1; -. DR InParanoid; Q5VTY9; -. DR OMA; IHYMSRD; -. DR OrthoDB; 392243at2759; -. DR PhylomeDB; Q5VTY9; -. DR TreeFam; TF315826; -. DR PathwayCommons; Q5VTY9; -. DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis. DR Reactome; R-HSA-5658034; HHAT G278V doesn't palmitoylate Hh-Np. DR SignaLink; Q5VTY9; -. DR SIGNOR; Q5VTY9; -. DR BioGRID-ORCS; 55733; 10 hits in 1065 CRISPR screens. DR ChiTaRS; HHAT; human. DR GenomeRNAi; 55733; -. DR Pharos; Q5VTY9; Tchem. DR PRO; PR:Q5VTY9; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5VTY9; protein. DR Bgee; ENSG00000054392; Expressed in olfactory segment of nasal mucosa and 103 other tissues. DR ExpressionAtlas; Q5VTY9; baseline and differential. DR Genevisible; Q5VTY9; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA: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:0008374; F:O-acyltransferase activity; TAS:Reactome. DR GO; GO:0016409; F:palmitoyltransferase activity; IBA:GO_Central. DR GO; GO:0018009; P:N-terminal peptidyl-L-cysteine N-palmitoylation; IMP:UniProtKB. DR GO; GO:0018345; P:protein palmitoylation; IBA:GO_Central. DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl. 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 3D-structure; Acyltransferase; Alternative splicing; Developmental protein; KW Disease variant; Dwarfism; Endoplasmic reticulum; Golgi apparatus; KW GTP-binding; Lipoprotein; Membrane; Nucleotide-binding; Palmitate; KW Reference proteome; Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..493 FT /note="Protein-cysteine N-palmitoyltransferase HHAT" FT /id="PRO_0000213134" 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..202 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT INTRAMEM 203..217 FT /evidence="ECO:0000255" FT TOPO_DOM 218..243 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 244..271 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 272..281 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 282..310 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 311..363 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 364..380 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 381..383 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 384..399 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 400..427 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 428..448 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 449..462 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 463..481 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 482..493 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 91..155 FT /note="Essential for palmitoylation of SHH" FT /evidence="ECO:0000269|PubMed:18534984" FT ACT_SITE 379 FT /evidence="ECO:0000255" FT BINDING 448..455 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000305|PubMed:11160356" FT LIPID 188 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:25505265" FT LIPID 242 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:25505265" FT LIPID 324 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:25505265" FT LIPID 410 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000305|PubMed:25505265" FT VAR_SEQ 1..369 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_016685" FT VAR_SEQ 1..30 FT /note="MLPRWELALYLLASLGFHFYSFYEVYKVSR -> MSLGLGSAERGVLGTRGA FT RERCRRRRPGQPG (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044968" FT VAR_SEQ 91..155 FT /note="Missing (in isoform 2 and isoform 5)" FT /evidence="ECO:0000303|PubMed:11160356, FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7" FT /id="VSP_016686" FT VAR_SEQ 92..228 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043481" FT VAR_SEQ 416..451 FT /note="ARYFSPQARRRFHAALASCSTSMLILSNLVFLGGNE -> VSRILAPVLGDS FT GTRQIRFIRDGAIRFPAPTMGPFY (in isoform 4)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_016687" FT VAR_SEQ 452..493 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_016688" FT VAR_SEQ 465..493 FT /note="WPWVTLSVLGFLYCYSHVGIAWAQTYATD -> GLFLFFLLNPCWETAFQGF FT PVFLHFLQTEVLATFVPNYFSWNICIENTSELSSY (in isoform 2 and FT isoform 3)" FT /evidence="ECO:0000303|PubMed:11160356, ECO:0000303|Ref.7" FT /id="VSP_016689" FT VARIANT 165 FT /note="E -> G (in dbSNP:rs2228898)" FT /id="VAR_050024" FT VARIANT 182 FT /note="S -> N (in dbSNP:rs2294851)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_024743" FT VARIANT 188 FT /note="C -> R (in dbSNP:rs34228541)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_061336" FT VARIANT 257 FT /note="L -> P (in NNMS; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:30912300" FT /id="VAR_085239" FT VARIANT 287 FT /note="G -> V (in NNMS; loss of palmitoyltransferase FT activity; unable to carry out SHH and DHH palmitoylation; FT does not affect HHAT protein levels)" FT /evidence="ECO:0000269|PubMed:24784881" FT /id="VAR_085240" FT VARIANT 448 FT /note="G -> E (in a melanoma cell line; abolishes GTP- FT binding; dbSNP:rs757163023)" FT /evidence="ECO:0000269|PubMed:11160356" FT /id="VAR_024744" FT VARIANT 450 FT /note="N -> S (in a lung cancer cell line; FT dbSNP:rs147954610)" FT /evidence="ECO:0000269|PubMed:11160356" FT /id="VAR_024745" FT MUTAGEN 351 FT /note="Y->A: No significant effect on catalytic activity. FT Defective HHAT-mediated palmitoyl-CoA uptake into FT microsomal membranes." FT /evidence="ECO:0000269|PubMed:31875564" FT MUTAGEN 379 FT /note="H->A: Reduced catalytic activity. Defective HHAT- FT mediated palmitoyl-CoA uptake into microsomal membranes." FT /evidence="ECO:0000269|PubMed:18534984, FT ECO:0000269|PubMed:31875564" FT CONFLICT 2 FT /note="L -> P (in Ref. 2; BAA91772)" FT /evidence="ECO:0000305" FT CONFLICT 204 FT /note="M -> V (in Ref. 2; BAH14561)" FT /evidence="ECO:0000305" FT CONFLICT 450 FT /note="N -> D (in Ref. 2; BAA91772)" FT /evidence="ECO:0000305" FT HELIX 4..27 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 33..37 FT /evidence="ECO:0007829|PDB:7MHY" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7MHY" FT TURN 46..50 FT /evidence="ECO:0007829|PDB:7MHZ" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 59..69 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 71..88 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 93..128 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 133..147 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 150..157 FT /evidence="ECO:0007829|PDB:7MHY" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 164..189 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:7MHZ" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 201..208 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 211..213 FT /evidence="ECO:0007829|PDB:7MHY" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 222..229 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 237..264 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 267..271 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 274..277 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 282..314 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 331..337 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 340..349 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 351..354 FT /evidence="ECO:0007829|PDB:7MHY" FT TURN 355..358 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 361..378 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 383..406 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 409..418 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 421..448 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 450..460 FT /evidence="ECO:0007829|PDB:7MHY" FT TURN 465..467 FT /evidence="ECO:0007829|PDB:7MHY" FT HELIX 468..487 FT /evidence="ECO:0007829|PDB:7MHY" FT TURN 488..490 FT /evidence="ECO:0007829|PDB:7MHY" SQ SEQUENCE 493 AA; 57313 MW; 5E962E2A61F2DE15 CRC64; MLPRWELALY LLASLGFHFY SFYEVYKVSR EHEEELDQEF ELETDTLFGG LKKDATDFEW SFWMEWGKQW LVWLLLGHMV VSQMATLLAR KHRPWILMLY GMWACWCVLG TPGVAMVLLH TTISFCVAQF RSQLLTWLCS LLLLSTLRLQ GVEEVKRRWY KTENEYYLLQ FTLTVRCLYY TSFSLELCWQ QLPAASTSYS FPWMLAYVFY YPVLHNGPIL SFSEFIKQMQ QQEHDSLKAS LCVLALGLGR LLCWWWLAEL MAHLMYMHAI YSSIPLLETV SCWTLGGLAL AQVLFFYVKY LVLFGVPALL MRLDGLTPPA LPRCVSTMFS FTGMWRYFDV GLHNFLIRYV YIPVGGSQHG LLGTLFSTAM TFAFVSYWHG GYDYLWCWAA LNWLGVTVEN GVRRLVETPC IQDSLARYFS PQARRRFHAA LASCSTSMLI LSNLVFLGGN EVGKTYWNRI FIQGWPWVTL SVLGFLYCYS HVGIAWAQTY ATD //