SUFU_HUMAN
ID SUFU_HUMAN Reviewed; 484 AA.
AC Q9UMX1; Q7LCP7; Q9NT90; Q9NZ07; Q9UHK2; Q9UHM8; Q9UMY0;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Suppressor of fused homolog {ECO:0000303|PubMed:10559945, ECO:0000303|PubMed:10564661};
DE Short=SUFUH {ECO:0000303|PubMed:10559945};
GN Name=SUFU {ECO:0000303|PubMed:12068298, ECO:0000312|HGNC:HGNC:16466};
GN ORFNames=UNQ650/PRO1280 {ECO:0000303|PubMed:12975309};
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 1; 2 AND 3), FUNCTION, INTERACTION
RP WITH GLI1; GLI2; GLI3 AND BTRC, HOMODIMERIZATION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Fetal kidney, Fetal lung, and Fetal testis;
RX PubMed=10564661; DOI=10.1242/jcs.112.23.4437;
RA Stone D.M., Murone M., Luoh S.-M., Ye W., Armanini M.P., Gurney A.,
RA Phillips H., Brush J., Goddard A., deSauvage F.J., Rosenthal A.;
RT "Characterization of the human suppressor of fused, a negative regulator of
RT the zinc-finger transcription factor Gli.";
RL J. Cell Sci. 112:4437-4448(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH GLI1,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10559945; DOI=10.1038/13031;
RA Kogerman P., Grimm T., Kogerman L., Krause D., Unden A.B., Sandstedt B.,
RA Toftgaard R., Zaphiropoulos P.G.;
RT "Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of
RT Gli-1.";
RL Nat. Cell Biol. 1:312-319(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, VARIANTS LEU-15 AND SER-340,
RP AND INVOLVEMENT IN MDB.
RX PubMed=12068298; DOI=10.1038/ng916;
RA Taylor M.D., Liu L., Raffel C., Hui C.-C., Mainprize T.G., Zhang X.,
RA Agatep R., Chiappa S., Gao L., Lowrance A., Hao A., Goldstein A.M.,
RA Stavrou T., Scherer S.W., Dura W.T., Wainwright B., Squire J.A.,
RA Rutka J.T., Hogg D.;
RT "Mutations in SUFU predispose to medulloblastoma.";
RL Nat. Genet. 31:306-310(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [MRNA] OF 3-484 (ISOFORM 1).
RC TISSUE=Neuron;
RX PubMed=11252182; DOI=10.1007/s004270050255;
RA Delattre M., Briand S., Paces-Fessy M., Blanchet-Tournier M.-F.;
RT "Suppressor of fused gene involved in hedgehog signal transduction in
RT Drosophila melanogaster is conserved in mammals.";
RL Dev. Genes Evol. 209:294-300(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 442-484 (ISOFORM 1).
RC TISSUE=Testis;
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 [9]
RP FUNCTION, AND INTERACTION WITH STK36.
RX PubMed=10806483; DOI=10.1038/35010610;
RA Murone M., Luoh S.-L., Stone D., Li W., Gurney A., Armanini M., Grey C.,
RA Rosenthal A., de Sauvage F.J.;
RT "Gli regulation by the opposing activities of fused and suppressor of
RT fused.";
RL Nat. Cell Biol. 2:310-312(2000).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP INVOLVEMENT IN BCNS.
RX PubMed=19533801; DOI=10.1002/ajmg.a.32944;
RA Pastorino L., Ghiorzo P., Nasti S., Battistuzzi L., Cusano R.,
RA Marzocchi C., Garre M.L., Clementi M., Scarra G.B.;
RT "Identification of a SUFU germline mutation in a family with Gorlin
RT syndrome.";
RL Am. J. Med. Genet. A 149A:1539-1543(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-303, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP INTERACTION WITH ULK3.
RX PubMed=20643644; DOI=10.1074/jbc.m110.133991;
RA Maloverjan A., Piirsoo M., Kasak L., Peil L., Osterlund T., Kogerman P.;
RT "Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog
RT signaling pathway.";
RL J. Biol. Chem. 285:30079-30090(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP INTERACTION WITH RAB23, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22365972; DOI=10.1016/j.cellsig.2012.02.004;
RA Chi S., Xie G., Liu H., Chen K., Zhang X., Li C., Xie J.;
RT "Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-
RT dependent manner.";
RL Cell. Signal. 24:1222-1228(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301; SER-342 AND SER-346, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, UBIQUITINATION AT LYS-257, PHOSPHORYLATION AT SER-342; SER-346;
RP SER-352 AND THR-353, AND MUTAGENESIS OF LYS-257 AND 342-SER--SER-346.
RX PubMed=27234298; DOI=10.15252/embj.201593374;
RA Raducu M., Fung E., Serres S., Infante P., Barberis A., Fischer R.,
RA Bristow C., Thezenas M.L., Finta C., Christianson J.C., Buffa F.M.,
RA Kessler B.M., Sibson N.R., Di Marcotullio L., Toftgaard R.,
RA D'Angiolella V.;
RT "SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and
RT medulloblastoma development.";
RL EMBO J. 35:1400-1416(2016).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GLI1 AND GLI3, INVOLVEMENT
RP IN JBTS32, VARIANTS JBTS32 ARG-176 AND THR-406, CHARACTERIZATION OF
RP VARIANTS JBTS32 ARG-176 AND THR-406, AND VARIANTS VAL-19; VAL-37; MET-77;
RP GLN-289; VAL-293; 299-ARG--HIS-484 DEL; LEU-382; ARG-442 AND ASN-481.
RX PubMed=28965847; DOI=10.1016/j.ajhg.2017.08.017;
RA De Mori R., Romani M., D'Arrigo S., Zaki M.S., Lorefice E., Tardivo S.,
RA Biagini T., Stanley V., Musaev D., Fluss J., Micalizzi A., Nuovo S.,
RA Illi B., Chiapparini L., Di Marcotullio L., Issa M.Y., Anello D.,
RA Casella A., Ginevrino M., Leggins A.S., Roosing S., Alfonsi R., Rosati J.,
RA Schot R., Mancini G.M.S., Bertini E., Dobyns W.B., Mazza T., Gleeson J.G.,
RA Valente E.M.;
RT "Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway
RT and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.";
RL Am. J. Hum. Genet. 101:552-563(2017).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-321, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 27-268, FUNCTION, INTERACTION
RP WITH GLI1, AND MUTAGENESIS OF GLU-106; ASP-111; THR-128; GLU-152; ASP-159;
RP GLU-181; GLU-221 AND ASP-262.
RX PubMed=15367681; DOI=10.1128/mcb.24.19.8627-8641.2004;
RA Merchant M., Vajdos F.F., Ultsch M., Maun H.R., Wendt U., Cannon J.,
RA Desmarais W., Lazarus R.A., de Vos A.M., de Sauvage F.J.;
RT "Suppressor of fused regulates Gli activity through a dual binding
RT mechanism.";
RL Mol. Cell. Biol. 24:8627-8641(2004).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 32-278 AND 361-483 IN COMPLEXES
RP WITH GLI1 AND GLI3, INTRINSICALLY DISORDERED REGION, FUNCTION, AND
RP INTERACTION WITH GLI1 AND GLI3.
RX PubMed=24311597; DOI=10.1107/s0907444913028473;
RA Cherry A.L., Finta C., Karlstrom M., Jin Q., Schwend T., Astorga-Wells J.,
RA Zubarev R.A., Del Campo M., Criswell A.R., de Sanctis D., Jovine L.,
RA Toftgard R.;
RT "Structural basis of SUFU-GLI interaction in human Hedgehog signalling
RT regulation.";
RL Acta Crystallogr. D 69:2563-2579(2013).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH GLI1, INTERACTION
RP WITH GLI1 AND GLI2, FUNCTION, AND MUTAGENESIS OF TYR-147; ASP-159 AND
RP LEU-380.
RX PubMed=24217340; DOI=10.1038/ncomms3608;
RA Zhang Y., Fu L., Qi X., Zhang Z., Xia Y., Jia J., Jiang J., Zhao Y., Wu G.;
RT "Structural insight into the mutual recognition and regulation between
RT Suppressor of Fused and Gli/Ci.";
RL Nat. Commun. 4:2608-2608(2013).
CC -!- FUNCTION: Negative regulator in the hedgehog/smoothened signaling
CC pathway (PubMed:10559945, PubMed:10564661, PubMed:10806483,
CC PubMed:12068298, PubMed:12975309, PubMed:27234298, PubMed:15367681,
CC PubMed:22365972, PubMed:24217340, PubMed:24311597, PubMed:28965847).
CC Down-regulates GLI1-mediated transactivation of target genes
CC (PubMed:15367681, PubMed:24217340, PubMed:24311597). Down-regulates
CC GLI2-mediated transactivation of target genes (PubMed:24311597,
CC PubMed:24217340). Part of a corepressor complex that acts on DNA-bound
CC GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1
CC to degradation by the proteasome (PubMed:10559945, PubMed:10564661,
CC PubMed:10806483, PubMed:24217340). Sequesters GLI1, GLI2 and GLI3 in
CC the cytoplasm, this effect is overcome by binding of STK36 to both SUFU
CC and a GLI protein (PubMed:10559945, PubMed:10564661, PubMed:10806483,
CC PubMed:24217340). Negative regulator of beta-catenin signaling (By
CC similarity). Regulates the formation of either the repressor form
CC (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3
CC (GLI3FL) (PubMed:24311597, PubMed:28965847). GLI3FL is complexed with
CC SUFU in the cytoplasm and is maintained in a neutral state
CC (PubMed:24311597, PubMed:28965847). Without the Hh signal, the SUFU-
CC GLI3 complex is recruited to cilia, leading to the efficient processing
CC of GLI3FL into GLI3R (PubMed:24311597, PubMed:28965847). When Hh
CC signaling is initiated, SUFU dissociates from GLI3FL and the latter
CC translocates to the nucleus, where it is phosphorylated, destabilized,
CC and converted to a transcriptional activator (GLI3A) (PubMed:24311597,
CC PubMed:28965847). Required for normal embryonic development (By
CC similarity). Required for the proper formation of hair follicles and
CC the control of epidermal differentiation (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z0P7, ECO:0000269|PubMed:10559945,
CC ECO:0000269|PubMed:10564661, ECO:0000269|PubMed:10806483,
CC ECO:0000269|PubMed:12068298, ECO:0000269|PubMed:12975309,
CC ECO:0000269|PubMed:15367681, ECO:0000269|PubMed:22365972,
CC ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597,
CC ECO:0000269|PubMed:27234298, ECO:0000269|PubMed:28965847}.
CC -!- SUBUNIT: May form homodimers (PubMed:10564661). Part of a DNA-bound
CC corepressor complex containing SAP18, GLI1 and SIN3 (By similarity).
CC Part of a complex containing CTNNB1 (By similarity). Binds BTRC, GLI2,
CC GLI3, SAP18 and STK36 (PubMed:10564661, PubMed:10806483). Binds both
CC free and DNA-bound GLI1 (PubMed:10559945, PubMed:15367681,
CC PubMed:24217340, PubMed:24311597, PubMed:28965847). Interacts with KIF7
CC (By similarity). Interacts with GLI3FL and this interaction regulates
CC the formation of either repressor or activator forms of GLI3
CC (PubMed:24311597, PubMed:28965847). Its association with GLI3FL is
CC regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction
CC requires the presence of the ciliary motor KIF3A (PubMed:24311597,
CC PubMed:28965847). Interacts with ULK3; inactivating the protein kinase
CC activity of ULK3 (PubMed:20643644). Interacts with RAB23
CC (PubMed:22365972). {ECO:0000250|UniProtKB:Q9Z0P7,
CC ECO:0000269|PubMed:10559945, ECO:0000269|PubMed:10564661,
CC ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:15367681,
CC ECO:0000269|PubMed:20643644, ECO:0000269|PubMed:22365972,
CC ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597,
CC ECO:0000269|PubMed:28965847}.
CC -!- INTERACTION:
CC Q9UMX1; Q9P2A4: ABI3; NbExp=3; IntAct=EBI-740595, EBI-742038;
CC Q9UMX1; Q86V38: ATN1; NbExp=3; IntAct=EBI-740595, EBI-11954292;
CC Q9UMX1; Q13515: BFSP2; NbExp=4; IntAct=EBI-740595, EBI-10229433;
CC Q9UMX1; Q53ET0: CRTC2; NbExp=5; IntAct=EBI-740595, EBI-1181987;
CC Q9UMX1; O43186: CRX; NbExp=3; IntAct=EBI-740595, EBI-748171;
CC Q9UMX1; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-740595, EBI-11988027;
CC Q9UMX1; P51114-2: FXR1; NbExp=3; IntAct=EBI-740595, EBI-11022345;
CC Q9UMX1; P08151: GLI1; NbExp=27; IntAct=EBI-740595, EBI-308084;
CC Q9UMX1; P10070: GLI2; NbExp=3; IntAct=EBI-740595, EBI-10821567;
CC Q9UMX1; P10071: GLI3; NbExp=5; IntAct=EBI-740595, EBI-308055;
CC Q9UMX1; Q8NEA6: GLIS3; NbExp=3; IntAct=EBI-740595, EBI-744456;
CC Q9UMX1; Q7Z353: HDX; NbExp=4; IntAct=EBI-740595, EBI-1052734;
CC Q9UMX1; Q92876: KLK6; NbExp=3; IntAct=EBI-740595, EBI-2432309;
CC Q9UMX1; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-740595, EBI-3044087;
CC Q9UMX1; O95678: KRT75; NbExp=3; IntAct=EBI-740595, EBI-2949715;
CC Q9UMX1; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-740595, EBI-11985629;
CC Q9UMX1; Q86VQ0: LCA5; NbExp=3; IntAct=EBI-740595, EBI-6658186;
CC Q9UMX1; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-740595, EBI-1216080;
CC Q9UMX1; Q9UJ55: MAGEL2; NbExp=3; IntAct=EBI-740595, EBI-5668174;
CC Q9UMX1; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-740595, EBI-16439278;
CC Q9UMX1; O00746: NME4; NbExp=3; IntAct=EBI-740595, EBI-744871;
CC Q9UMX1; Q7Z412: PEX26; NbExp=2; IntAct=EBI-740595, EBI-752057;
CC Q9UMX1; Q96D15: RCN3; NbExp=5; IntAct=EBI-740595, EBI-746283;
CC Q9UMX1; Q96GZ6: SLC41A3; NbExp=3; IntAct=EBI-740595, EBI-7225508;
CC Q9UMX1; Q9NRP7: STK36; NbExp=3; IntAct=EBI-740595, EBI-863797;
CC Q9UMX1; Q8N4C7: STX19; NbExp=3; IntAct=EBI-740595, EBI-8484990;
CC Q9UMX1; Q08117-2: TLE5; NbExp=3; IntAct=EBI-740595, EBI-11741437;
CC Q9UMX1; Q15915: ZIC1; NbExp=3; IntAct=EBI-740595, EBI-11963196;
CC Q9UMX1; Q8NC26: ZNF114; NbExp=3; IntAct=EBI-740595, EBI-10265237;
CC Q9UMX1; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-740595, EBI-373456;
CC Q9UMX1; Q9NWS9-2: ZNF446; NbExp=4; IntAct=EBI-740595, EBI-740232;
CC Q9UMX1; Q9BV97: ZNF747; NbExp=5; IntAct=EBI-740595, EBI-4395497;
CC Q9UMX1; Q0D2J5: ZNF763; NbExp=3; IntAct=EBI-740595, EBI-10226414;
CC Q9UMX1; Q96H86: ZNF764; NbExp=5; IntAct=EBI-740595, EBI-745775;
CC Q9UMX1; Q8TBC5: ZSCAN18; NbExp=3; IntAct=EBI-740595, EBI-3919096;
CC Q9UMX1; Q0VGT2: Gli2; Xeno; NbExp=3; IntAct=EBI-740595, EBI-9344284;
CC Q9UMX1-1; P08151: GLI1; NbExp=2; IntAct=EBI-740615, EBI-308084;
CC Q9UMX1-2; P08151: GLI1; NbExp=4; IntAct=EBI-740621, EBI-308084;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10559945,
CC ECO:0000269|PubMed:28965847}. Nucleus {ECO:0000269|PubMed:10559945,
CC ECO:0000269|PubMed:28965847}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Su(fu)484;
CC IsoId=Q9UMX1-1; Sequence=Displayed;
CC Name=2; Synonyms=Su(fu)433;
CC IsoId=Q9UMX1-2; Sequence=VSP_013278, VSP_013279;
CC Name=3;
CC IsoId=Q9UMX1-3; Sequence=VSP_013280;
CC -!- TISSUE SPECIFICITY: Ubiquitous in adult tissues. Detected in
CC osteoblasts of the perichondrium in the developing limb of 12-week old
CC embryos. Isoform 1 is detected in fetal brain, lung, kidney and testis.
CC Isoform 2 is detected in fetal testis, and at much lower levels in
CC fetal brain, lung and kidney. {ECO:0000269|PubMed:10559945,
CC ECO:0000269|PubMed:10564661}.
CC -!- PTM: Polyubiquitinated at Lys-257 by the SCF(FBXL17) complex, leading
CC to its subsequent degradation and allowing the release of GLI1 for
CC proper hedgehog/smoothened signal transduction (PubMed:27234298).
CC Ubiquitination is impaired by phosphorylation at Ser-342, Ser-346, Ser-
CC 352 and Thr-353 (PubMed:27234298). {ECO:0000269|PubMed:27234298}.
CC -!- PTM: Phosphorylation at Ser-342, Ser-346, Ser-352 and Thr-353 prevents
CC ubiquitination by the SCF(FBXL17) complex.
CC {ECO:0000269|PubMed:27234298}.
CC -!- DISEASE: Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive
CC embryonal tumor of the cerebellum with a preferential manifestation in
CC children. {ECO:0000269|PubMed:12068298}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Joubert syndrome 32 (JBTS32) [MIM:617757]: A form of Joubert
CC syndrome, a disorder presenting with cerebellar ataxia, oculomotor
CC apraxia, hypotonia, neonatal breathing abnormalities and psychomotor
CC delay. Neuroradiologically, it is characterized by cerebellar vermian
CC hypoplasia/aplasia, thickened and reoriented superior cerebellar
CC peduncles, and an abnormally large interpeduncular fossa, giving the
CC appearance of a molar tooth on transaxial slices (molar tooth sign).
CC Additional variable features include retinal dystrophy, renal disease,
CC liver fibrosis, and polydactyly. JBTS32 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:28965847}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Basal cell nevus syndrome (BCNS) [MIM:109400]: An autosomal
CC dominant disease characterized by nevoid basal cell carcinomas and
CC developmental abnormalities such as rib and craniofacial alterations,
CC polydactyly, syndactyly, and spina bifida. In addition, the patients
CC suffer from a multitude of tumors like basal cell carcinomas, fibromas
CC of the ovaries and heart, cysts of the skin, jaws and mesentery, as
CC well as medulloblastomas and meningiomas.
CC {ECO:0000269|PubMed:19533801}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC -!- SIMILARITY: Belongs to the SUFU family. {ECO:0000305}.
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DR EMBL; AF144231; AAF23890.1; -; mRNA.
DR EMBL; AF159447; AAF23893.1; -; mRNA.
DR EMBL; AF222345; AAF35866.1; -; mRNA.
DR EMBL; AF175770; AAD50501.1; -; mRNA.
DR EMBL; AY081829; AAM08947.1; -; Genomic_DNA.
DR EMBL; AY081818; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081819; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081820; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081822; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081824; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081825; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081821; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081823; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081826; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081828; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY081827; AAM08947.1; JOINED; Genomic_DNA.
DR EMBL; AY358550; AAQ88914.1; -; mRNA.
DR EMBL; AL121928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013291; AAH13291.1; -; mRNA.
DR EMBL; AF172319; AAD51655.1; -; mRNA.
DR EMBL; AL137465; CAB70752.1; -; mRNA.
DR CCDS; CCDS53571.1; -. [Q9UMX1-2]
DR CCDS; CCDS7537.1; -. [Q9UMX1-1]
DR PIR; T46409; T46409.
DR RefSeq; NP_001171604.1; NM_001178133.1. [Q9UMX1-2]
DR RefSeq; NP_057253.2; NM_016169.3. [Q9UMX1-1]
DR PDB; 1M1L; X-ray; 2.65 A; A/B/C/D=27-262.
DR PDB; 4BL8; X-ray; 3.04 A; A/B=32-483.
DR PDB; 4BL9; X-ray; 2.80 A; A/B/C/D=32-278, A/B/C/D=361-483.
DR PDB; 4BLA; X-ray; 3.50 A; A/B/C/D=32-278, A/B/C/D=361-483.
DR PDB; 4BLB; X-ray; 2.80 A; A/B/C/D=32-278, A/B/C/D=361-483.
DR PDB; 4BLD; X-ray; 2.80 A; A/B/C/D=32-278, A/B/C/D=361-483.
DR PDB; 4KM8; X-ray; 2.26 A; A=1-484.
DR PDB; 4KM9; X-ray; 3.19 A; A=1-484.
DR PDB; 4KMD; X-ray; 1.70 A; A=1-484.
DR PDB; 4KMH; X-ray; 3.04 A; A/B=1-484.
DR PDBsum; 1M1L; -.
DR PDBsum; 4BL8; -.
DR PDBsum; 4BL9; -.
DR PDBsum; 4BLA; -.
DR PDBsum; 4BLB; -.
DR PDBsum; 4BLD; -.
DR PDBsum; 4KM8; -.
DR PDBsum; 4KM9; -.
DR PDBsum; 4KMD; -.
DR PDBsum; 4KMH; -.
DR AlphaFoldDB; Q9UMX1; -.
DR SASBDB; Q9UMX1; -.
DR SMR; Q9UMX1; -.
DR BioGRID; 119676; 93.
DR ComplexPortal; CPX-148; GLI2-SUFU complex.
DR ComplexPortal; CPX-150; GLI3-SUFU complex.
DR ComplexPortal; CPX-56; GLI1-SUFU complex.
DR CORUM; Q9UMX1; -.
DR ELM; Q9UMX1; -.
DR IntAct; Q9UMX1; 100.
DR MINT; Q9UMX1; -.
DR STRING; 9606.ENSP00000358918; -.
DR ChEMBL; CHEMBL5390; -.
DR iPTMnet; Q9UMX1; -.
DR PhosphoSitePlus; Q9UMX1; -.
DR BioMuta; SUFU; -.
DR DMDM; 62511179; -.
DR CPTAC; CPTAC-1329; -.
DR EPD; Q9UMX1; -.
DR jPOST; Q9UMX1; -.
DR MassIVE; Q9UMX1; -.
DR MaxQB; Q9UMX1; -.
DR PaxDb; Q9UMX1; -.
DR PeptideAtlas; Q9UMX1; -.
DR PRIDE; Q9UMX1; -.
DR ProteomicsDB; 85217; -. [Q9UMX1-1]
DR ProteomicsDB; 85218; -. [Q9UMX1-2]
DR ProteomicsDB; 85219; -. [Q9UMX1-3]
DR Antibodypedia; 1768; 298 antibodies from 38 providers.
DR DNASU; 51684; -.
DR Ensembl; ENST00000369899.6; ENSP00000358915.2; ENSG00000107882.12. [Q9UMX1-2]
DR Ensembl; ENST00000369902.8; ENSP00000358918.4; ENSG00000107882.12. [Q9UMX1-1]
DR Ensembl; ENST00000423559.2; ENSP00000411597.2; ENSG00000107882.12. [Q9UMX1-3]
DR GeneID; 51684; -.
DR KEGG; hsa:51684; -.
DR MANE-Select; ENST00000369902.8; ENSP00000358918.4; NM_016169.4; NP_057253.2.
DR UCSC; uc001kvw.3; human. [Q9UMX1-1]
DR CTD; 51684; -.
DR DisGeNET; 51684; -.
DR GeneCards; SUFU; -.
DR GeneReviews; SUFU; -.
DR HGNC; HGNC:16466; SUFU.
DR HPA; ENSG00000107882; Low tissue specificity.
DR MalaCards; SUFU; -.
DR MIM; 109400; phenotype.
DR MIM; 155255; phenotype.
DR MIM; 607035; gene.
DR MIM; 617757; phenotype.
DR neXtProt; NX_Q9UMX1; -.
DR OpenTargets; ENSG00000107882; -.
DR Orphanet; 251863; Desmoplastic/nodular medulloblastoma.
DR Orphanet; 263662; Familial multiple meningioma.
DR Orphanet; 377; Gorlin syndrome.
DR Orphanet; 475; Joubert syndrome.
DR Orphanet; 251858; Medulloblastoma with extensive nodularity.
DR Orphanet; 2495; Meningioma.
DR Orphanet; 280200; Microform holoprosencephaly.
DR PharmGKB; PA38146; -.
DR VEuPathDB; HostDB:ENSG00000107882; -.
DR eggNOG; ENOG502QT57; Eukaryota.
DR GeneTree; ENSGT00390000009747; -.
DR HOGENOM; CLU_033906_0_0_1; -.
DR InParanoid; Q9UMX1; -.
DR OMA; LVPRMME; -.
DR OrthoDB; 1248959at2759; -.
DR PhylomeDB; Q9UMX1; -.
DR TreeFam; TF324548; -.
DR PathwayCommons; Q9UMX1; -.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome.
DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR SignaLink; Q9UMX1; -.
DR SIGNOR; Q9UMX1; -.
DR BioGRID-ORCS; 51684; 21 hits in 1100 CRISPR screens.
DR ChiTaRS; SUFU; human.
DR EvolutionaryTrace; Q9UMX1; -.
DR GeneWiki; SUFU; -.
DR GenomeRNAi; 51684; -.
DR Pharos; Q9UMX1; Tbio.
DR PRO; PR:Q9UMX1; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UMX1; protein.
DR Bgee; ENSG00000107882; Expressed in upper arm skin and 179 other tissues.
DR Genevisible; Q9UMX1; HS.
DR GO; GO:0097546; C:ciliary base; TAS:Reactome.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1990788; C:GLI-SUFU complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:UniProtKB.
DR GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR GO; GO:0060976; P:coronary vasculature development; IEA:Ensembl.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; TAS:BHF-UCL.
DR GO; GO:1990787; P:negative regulation of hh target transcription factor activity; IDA:ComplexPortal.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; TAS:BHF-UCL.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; TAS:BHF-UCL.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0060831; P:smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0021776; P:smoothened signaling pathway involved in spinal cord motor neuron cell fate specification; IEA:Ensembl.
DR GO; GO:0021775; P:smoothened signaling pathway involved in ventral spinal cord interneuron specification; IEA:Ensembl.
DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl.
DR DisProt; DP01312; -.
DR Gene3D; 3.30.1360.230; -; 1.
DR InterPro; IPR020941; SUFU-like_domain.
DR InterPro; IPR024314; SUFU_C.
DR InterPro; IPR038489; SUFU_C_sf.
DR InterPro; IPR037181; SUFU_N.
DR InterPro; IPR007768; Suppressor_of_fused.
DR InterPro; IPR016591; Suppressor_of_fused_euk.
DR PANTHER; PTHR10928; PTHR10928; 1.
DR Pfam; PF05076; SUFU; 1.
DR Pfam; PF12470; SUFU_C; 1.
DR PIRSF; PIRSF011844; Suppressor_of_fused_protein; 1.
DR SUPFAM; SSF103359; SSF103359; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Ciliopathy; Cytoplasm;
KW Developmental protein; Disease variant; Isopeptide bond; Joubert syndrome;
KW Nucleus; Phosphoprotein; Reference proteome; Tumor suppressor;
KW Ubl conjugation.
FT CHAIN 1..484
FT /note="Suppressor of fused homolog"
FT /id="PRO_0000072302"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 279..360
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:24311597"
FT COMPBIAS 9..24
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 303
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27234298,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27234298,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27234298"
FT MOD_RES 353
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27234298"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 257
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27234298"
FT CROSSLNK 321
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 433..484
FT /note="ILLTEEFVEKMLEDLEDLTSPEEFKLPKEYSWPEKKLKVSILPDVVFDSPLH
FT -> VRRPFFFSLLPFIDFLAHPSSSPLAALDGTPSWGAGHECLMDSGPGACV (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10564661"
FT /id="VSP_013280"
FT VAR_SEQ 433
FT /note="I -> L (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10564661,
FT ECO:0000303|PubMed:12975309"
FT /id="VSP_013278"
FT VAR_SEQ 434..484
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10564661,
FT ECO:0000303|PubMed:12975309"
FT /id="VSP_013279"
FT VARIANT 15
FT /note="P -> L (in dbSNP:rs28942088)"
FT /evidence="ECO:0000269|PubMed:12068298"
FT /id="VAR_021566"
FT VARIANT 19
FT /note="G -> V"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080418"
FT VARIANT 37
FT /note="I -> V (in dbSNP:rs745793517)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080419"
FT VARIANT 77
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080420"
FT VARIANT 176
FT /note="H -> R (in JBTS32; decreased stability; no effect on
FT nuclear and cytoplasmic localization; decreased interaction
FT with GLI3; no effect on interaction with GLI1; decreased
FT repression of the hedgehog/smoothened signaling pathway;
FT dbSNP:rs1554852272)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080421"
FT VARIANT 289
FT /note="R -> Q (in dbSNP:rs149016373)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080422"
FT VARIANT 293
FT /note="I -> V (in dbSNP:rs574002050)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080423"
FT VARIANT 299..484
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080424"
FT VARIANT 340
FT /note="A -> S (in dbSNP:rs34135067)"
FT /evidence="ECO:0000269|PubMed:12068298"
FT /id="VAR_021567"
FT VARIANT 382
FT /note="P -> L (in dbSNP:rs1401882800)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080425"
FT VARIANT 406
FT /note="I -> T (in JBTS32; decreased stability; forms
FT cytoplasmic aggregates; decreased interaction with GLI3; no
FT effect on interaction with GLI1; decreased repression of
FT the hedgehog/smoothened signaling pathway;
FT dbSNP:rs1554854758)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080426"
FT VARIANT 442
FT /note="K -> R (in dbSNP:rs772598739)"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080427"
FT VARIANT 481
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:28965847"
FT /id="VAR_080428"
FT MUTAGEN 106
FT /note="E->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 111
FT /note="D->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 128
FT /note="T->A,D: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 147
FT /note="Y->R: Impairs interaction with GLI1 and GLI2.
FT Abolishes interaction with GLI1 and GLI2; when associated
FT with R-159 and R-380."
FT /evidence="ECO:0000269|PubMed:24217340"
FT MUTAGEN 152
FT /note="E->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 159
FT /note="D->A: Abolishes down-regulation of GLI1 activity.
FT Has only slight effect on GLI1 binding."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 159
FT /note="D->R: Impairs interaction with GLI1 and GLI2.
FT Abolishes interaction with GLI1 and GLI2; when associated
FT with R-147 and R-380."
FT /evidence="ECO:0000269|PubMed:24217340"
FT MUTAGEN 181
FT /note="E->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 221
FT /note="E->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 257
FT /note="K->R: Abolishes ubiquitination by the SCF(FBXL17)
FT complex."
FT /evidence="ECO:0000269|PubMed:27234298"
FT MUTAGEN 262
FT /note="D->A: No effect on down-regulation of GLI1
FT activity."
FT /evidence="ECO:0000269|PubMed:15367681"
FT MUTAGEN 342..346
FT /note="SRKDS->ARKDA: Increased interaction with FBXL17 and
FT ubiquitination by the SCF(FBXL17) complex."
FT /evidence="ECO:0000269|PubMed:27234298"
FT MUTAGEN 342..346
FT /note="SRKDS->DRKDD: Phosphomimetic mutant; decreased
FT interaction with FBXL17 and ubiquitination by the
FT SCF(FBXL17) complex."
FT /evidence="ECO:0000269|PubMed:27234298"
FT MUTAGEN 380
FT /note="L->R: Impairs interaction with GLI1 and GLI2.
FT Abolishes interaction with GLI1 and GLI2; when associated
FT with R-147 and R-159."
FT /evidence="ECO:0000269|PubMed:24217340"
FT CONFLICT 336
FT /note="A -> P (in Ref. 2; AAD50501)"
FT /evidence="ECO:0000305"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:4KM8"
FT HELIX 32..44
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 87..96
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 110..125
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 136..151
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:4BLB"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 176..181
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 193..203
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 205..213
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 216..224
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:4KMD"
FT TURN 230..234
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 250..262
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 266..276
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 363..367
FT /evidence="ECO:0007829|PDB:4BL9"
FT STRAND 369..373
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 381..387
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 395..403
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 405..409
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 437..446
FT /evidence="ECO:0007829|PDB:4KMD"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 460..464
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 465..467
FT /evidence="ECO:0007829|PDB:4KMD"
FT STRAND 469..473
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 476..479
FT /evidence="ECO:0007829|PDB:4KMD"
SQ SEQUENCE 484 AA; 53947 MW; 4A9CD1CF75FC179A CRC64;
MAELRPSGAP GPTAPPAPGP TAPPAFASLF PPGLHAIYGE CRRLYPDQPN PLQVTAIVKY
WLGGPDPLDY VSMYRNVGSP SANIPEHWHY ISFGLSDLYG DNRVHEFTGT DGPSGFGFEL
TFRLKRETGE SAPPTWPAEL MQGLARYVFQ SENTFCSGDH VSWHSPLDNS ESRIQHMLLT
EDPQMQPVQT PFGVVTFLQI VGVCTEELHS AQQWNGQGIL ELLRTVPIAG GPWLITDMRR
GETIFEIDPH LQERVDKGIE TDGSNLSGVS AKCAWDDLSR PPEDDEDSRS ICIGTQPRRL
SGKDTEQIRE TLRRGLEINS KPVLPPINPQ RQNGLAHDRA PSRKDSLESD SSTAIIPHEL
IRTRQLESVH LKFNQESGAL IPLCLRGRLL HGRHFTYKSI TGDMAITFVS TGVEGAFATE
EHPYAAHGPW LQILLTEEFV EKMLEDLEDL TSPEEFKLPK EYSWPEKKLK VSILPDVVFD
SPLH
