HHAT_HUMAN
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 03-AUG-2022, entry version 154.
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}.
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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; 114 antibodies from 23 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