THC1_TETTS
ID THC1_TETTS Reviewed; 655 AA.
AC Q24FB1;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 2.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Squalene-tetrahymanol cyclase THC1 {ECO:0000303|PubMed:1892870};
DE Short=STC {ECO:0000303|PubMed:32561581};
DE EC=4.2.1.123 {ECO:0000269|PubMed:1892870, ECO:0000269|PubMed:32561581};
DE Flags: Precursor;
GN Name=THC1 {ECO:0000303|PubMed:32561581}; ORFNames=TTHERM_01008630;
OS Tetrahymena thermophila (strain SB210).
OC Eukaryota; Sar; Alveolata; Ciliophora; Intramacronucleata;
OC Oligohymenophorea; Hymenostomatida; Tetrahymenina; Tetrahymenidae;
OC Tetrahymena.
OX NCBI_TaxID=312017;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SB210;
RX PubMed=16933976; DOI=10.1371/journal.pbio.0040286;
RA Eisen J.A., Coyne R.S., Wu M., Wu D., Thiagarajan M., Wortman J.R.,
RA Badger J.H., Ren Q., Amedeo P., Jones K.M., Tallon L.J., Delcher A.L.,
RA Salzberg S.L., Silva J.C., Haas B.J., Majoros W.H., Farzad M.,
RA Carlton J.M., Smith R.K. Jr., Garg J., Pearlman R.E., Karrer K.M., Sun L.,
RA Manning G., Elde N.C., Turkewitz A.P., Asai D.J., Wilkes D.E., Wang Y.,
RA Cai H., Collins K., Stewart B.A., Lee S.R., Wilamowska K., Weinberg Z.,
RA Ruzzo W.L., Wloga D., Gaertig J., Frankel J., Tsao C.-C., Gorovsky M.A.,
RA Keeling P.J., Waller R.F., Patron N.J., Cherry J.M., Stover N.A.,
RA Krieger C.J., del Toro C., Ryder H.F., Williamson S.C., Barbeau R.A.,
RA Hamilton E.P., Orias E.;
RT "Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a
RT model eukaryote.";
RL PLoS Biol. 4:1620-1642(2006).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=1892870; DOI=10.1016/0304-4165(91)90080-z;
RA Saar J., Kader J.C., Poralla K., Ourisson G.;
RT "Purification and some properties of the squalene-tetrahymanol cyclase from
RT Tetrahymena thermophila.";
RL Biochim. Biophys. Acta 1075:93-101(1991).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOTECHNOLOGY.
RX PubMed=32561581; DOI=10.1128/aem.00672-20;
RA Wiersma S.J., Mooiman C., Giera M., Pronk J.T.;
RT "Squalene-tetrahymanol cyclase expression enables sterol-independent growth
RT of Saccharomyces cerevisiae.";
RL Appl. Environ. Microbiol. 86:0-0(2020).
RN [4]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=34303845; DOI=10.1016/j.ymben.2021.07.006;
RA Dekker W.J.C., Ortiz-Merino R.A., Kaljouw A., Battjes J., Wiering F.W.,
RA Mooiman C., Torre P., Pronk J.T.;
RT "Engineering the thermotolerant industrial yeast Kluyveromyces marxianus
RT for anaerobic growth.";
RL Metab. Eng. 67:347-364(2021).
CC -!- FUNCTION: Squalene cyclase that catalyzes the oxygen-independent
CC cyclization of squalene into tetrahymanol, a triterpenoid sterol with
CC five cyclohexyl rings that is involved in membrane integrity,
CC permeability and fluidity. {ECO:0000269|PubMed:1892870,
CC ECO:0000269|PubMed:32561581, ECO:0000269|PubMed:34303845}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetrahymanol = H2O + squalene; Xref=Rhea:RHEA:30675,
CC ChEBI:CHEBI:9493, ChEBI:CHEBI:15377, ChEBI:CHEBI:15440; EC=4.2.1.123;
CC Evidence={ECO:0000269|PubMed:1892870, ECO:0000269|PubMed:32561581};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30677;
CC Evidence={ECO:0000269|PubMed:1892870, ECO:0000269|PubMed:32561581};
CC -!- ACTIVITY REGULATION: 2,3-iminosqualene and N,N-dimethyldodecylamine~N-
CC oxlde are effective inhibitors with IC(50) values of 50 and 30 nM,
CC respectively. {ECO:0000269|PubMed:1892870}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 uM for sqna!ene {ECO:0000269|PubMed:1892870};
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:1892870};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius.
CC {ECO:0000269|PubMed:1892870};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:1892870}; Peripheral
CC membrane protein {ECO:0000269|PubMed:1892870}.
CC -!- BIOTECHNOLOGY: Expression of THC1 in Saccharomyces cerevisiae enables
CC to eliminate anaerobic sterol requirements and provides valuable
CC information for the design and construction of robust, sterol-
CC independent yeast strains for application in anaerobic industrial
CC processes. {ECO:0000269|PubMed:32561581, ECO:0000269|PubMed:34303845}.
CC -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; GG662290; EAS06451.2; -; Genomic_DNA.
DR RefSeq; XP_001026696.2; XM_001026696.2.
DR SMR; Q24FB1; -.
DR STRING; 5911.EAS06451; -.
DR EnsemblProtists; EAS06451; EAS06451; TTHERM_01008630.
DR GeneID; 7843402; -.
DR KEGG; tet:TTHERM_01008630; -.
DR eggNOG; KOG0497; Eukaryota.
DR HOGENOM; CLU_262960_0_0_1; -.
DR OrthoDB; 365003at2759; -.
DR BRENDA; 4.2.1.123; 6245.
DR Proteomes; UP000009168; Unassembled WGS sequence.
DR GO; GO:0005811; C:lipid droplet; IEA:InterPro.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016866; F:intramolecular transferase activity; IEA:InterPro.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR InterPro; IPR032696; SQ_cyclase_C.
DR InterPro; IPR032697; SQ_cyclase_N.
DR InterPro; IPR018333; Squalene_cyclase.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR InterPro; IPR026370; Tetrahymanol_synth.
DR PANTHER; PTHR11764; PTHR11764; 1.
DR Pfam; PF13243; SQHop_cyclase_C; 1.
DR Pfam; PF13249; SQHop_cyclase_N; 1.
DR SUPFAM; SSF48239; SSF48239; 2.
DR TIGRFAMs; TIGR04277; squa_tetra_cyc; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Lyase; Membrane;
KW Reference proteome; Repeat; Signal; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..655
FT /note="Squalene-tetrahymanol cyclase THC1"
FT /id="PRO_5004202317"
FT REPEAT 393..435
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 515..562
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT ACT_SITE 373
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT SITE 323
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT SITE 488
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 655 AA; 76021 MW; 638E124955C0C0B2 CRC64;
MKKILIGLII GLFLFSSVNA SVNLTEVQNA ISIQQGINWA EVHNNTWYYP PYLGEMFISE
YYFELLVLNW THKSAFNATY FTERLLQTQF EDGSWEQVRE QNLETGQLDA TVFNYWYLKS
INNNPKIEAA LQKARKWIVA QGGIEATQTM TKFKLAAFGQ YSWEDLWYVP LFIFKQNGIF
KYTYVKDIVA QWVYPHLTAL AYLRYQRTVF NVPVADLREL WINYPKNGIK ISPREYSTLN
PDSDLLILMD EIFKLKQPLG SFGAYTISTL LTLMSFKDFQ SKHPHLYQNE IQKAYEDGYY
FVEFNYFNFR EAYHGSLDDG RWWDTILISW AMLESGQDKE RIFPIVQNMV KEGLQPKKGI
GYGYDFEYAP DTDDTGLLLV VMSYYKEAFQ KQIPETIEWL FSMQNDDGGY PAFDKGKNED
NLLFKFAFNM AGIANSAEIF DPSCPDITGH IMEGLGEFGY QANHPQIQNM IKYQRKTQNK
WGSWQARWGV NYIMAVGAVV PGLARVNYDL NEQWVQNSIN YLLNKQNKDG GFGECVLSYN
DPEKWNGIGK STVTQTSWGL LALLEVYNQN EQIKHAADRA AQYLLDQFKR DDNTFYDHST
IGTGHRGLLY LQYPSYAQSF PLVALNRYQK ISQGQYHFSK NLYNGNGEPV QKQNI
