GLI3_HUMAN
ID GLI3_HUMAN Reviewed; 1580 AA.
AC P10071; A4D1W1; O75219; Q17RW4; Q75MT0; Q75MU9; Q9UDT5; Q9UJ39;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 6.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Transcriptional activator GLI3;
DE AltName: Full=GLI3 form of 190 kDa;
DE Short=GLI3-190;
DE AltName: Full=GLI3 full-length protein;
DE Short=GLI3FL;
DE Contains:
DE RecName: Full=Transcriptional repressor GLI3R;
DE AltName: Full=GLI3 C-terminally truncated form;
DE AltName: Full=GLI3 form of 83 kDa;
DE Short=GLI3-83;
GN Name=GLI3;
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], AND VARIANTS ALA-183 AND LEU-998.
RX PubMed=2118997; DOI=10.1128/mcb.10.10.5408-5415.1990;
RA Ruppert J.M., Vogelstein B., Arheden K., Kinzler K.W.;
RT "GLI3 encodes a 190-kilodalton protein with multiple regions of GLI
RT similarity.";
RL Mol. Cell. Biol. 10:5408-5415(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GCPS GLY-515 AND TYR-520, AND
RP VARIANTS ALA-183; GLU-440; MET-808; LEU-998 AND CYS-1537.
RX PubMed=10441342; DOI=10.1093/hmg/8.9.1769;
RA Kalff-Suske M., Wild A., Topp J., Wessling M., Jacobsen E.-M.,
RA Bornholdt D., Engel H., Heuer H., Aalfs C.M., Ausems M.G.E.M., Barone R.,
RA Herzog A., Heutink P., Homfray T., Gillessen-Kaesbach G., Koenig R.,
RA Kunze J., Meinecke P., Mueller D., Rizzo R., Strenge S., Superti-Furga A.,
RA Grzeschik K.-H.;
RT "Point mutations throughout the GLI3 gene cause Greig
RT cephalopolysyndactylysyndrome.";
RL Hum. Mol. Genet. 8:1769-1777(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-183 AND LEU-998.
RC TISSUE=Cerebellum;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-549.
RX PubMed=2850480; DOI=10.1128/mcb.8.8.3104-3113.1988;
RA Ruppert J.M., Kinzler K.W., Wong A.J., Bigner S.H., Kao F.T., Law M.L.,
RA Seuanez H.N., O'Brien S.J., Vogelstein B.;
RT "The GLI-Kruppel family of human genes.";
RL Mol. Cell. Biol. 8:3104-3113(1988).
RN [7]
RP FUNCTION, PROTEOLYTIC PROCESSING, PHOSPHORYLATION AT SER-849; SER-865;
RP SER-877; SER-907; SER-980 AND SER-1006, AND MUTAGENESIS OF SER-849;
RP SER-865; SER-877; SER-907; SER-980 AND SER-1006.
RX PubMed=10693759; DOI=10.1016/s0092-8674(00)80678-9;
RA Wang B., Fallon J.F., Beachy P.A.;
RT "Hedgehog-regulated processing of Gli3 produces an anterior/posterior
RT repressor gradient in the developing vertebrate limb.";
RL Cell 100:423-434(2000).
RN [8]
RP FUNCTION, INTERACTION WITH ZIC1, AND SUBCELLULAR LOCATION.
RX PubMed=11238441; DOI=10.1074/jbc.c000773200;
RA Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.;
RT "Physical and functional interactions between Zic and Gli proteins.";
RL J. Biol. Chem. 276:6889-6892(2001).
RN [9]
RP PROTEOLYTIC PROCESSING, PHOSPHORYLATION, INTERACTION WITH BTRC,
RP UBIQUITINATION AT LYS-773; LYS-779; LYS-784 AND LYS-800, AND MUTAGENESIS OF
RP LYS-773; LYS-779; LYS-784; LYS-800; SER-849; SER-855; SER-856; SER-861;
RP SER-864; SER-873; SER-877; SER-903 AND SER-907.
RX PubMed=16705181; DOI=10.1128/mcb.02183-05;
RA Tempe D., Casas M., Karaz S., Blanchet-Tournier M.F., Concordet J.P.;
RT "Multisite protein kinase A and glycogen synthase kinase 3beta
RT phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP.";
RL Mol. Cell. Biol. 26:4316-4326(2006).
RN [10]
RP PROTEOLYTIC PROCESSING, PHOSPHORYLATION, POLYUBIQUITINATION, AND
RP INTERACTION WITH BTRC.
RX PubMed=16371461; DOI=10.1073/pnas.0509927103;
RA Wang B., Li Y.;
RT "Evidence for the direct involvement of {beta}TrCP in Gli3 protein
RT processing.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:33-38(2006).
RN [11]
RP PHOSPHORYLATION.
RX PubMed=18455992; DOI=10.1016/j.cell.2008.02.047;
RA Varjosalo M., Bjorklund M., Cheng F., Syvanen H., Kivioja T., Kilpinen S.,
RA Sun Z., Kallioniemi O., Stunnenberg H.G., He W.W., Ojala P., Taipale J.;
RT "Application of active and kinase-deficient kinome collection for
RT identification of kinases regulating hedgehog signaling.";
RL Cell 133:537-548(2008).
RN [12]
RP FUNCTION, AND INTERACTION WITH ZIC3.
RX PubMed=17764085; DOI=10.1002/humu.20606;
RA Zhu L., Zhou G., Poole S., Belmont J.W.;
RT "Characterization of the interactions of human ZIC3 mutants with GLI3.";
RL Hum. Mutat. 29:99-105(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH KIF7.
RX PubMed=19592253; DOI=10.1016/j.cub.2009.06.046;
RA Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W.,
RA Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J.,
RA Peterson A.S.;
RT "The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh
RT signal transduction during development.";
RL Curr. Biol. 19:1320-1326(2009).
RN [15]
RP INTERACTION WITH TRPS1.
RX PubMed=19389374; DOI=10.1016/j.ydbio.2009.01.012;
RA Wuelling M., Kaiser F.J., Buelens L.A., Braunholz D., Shivdasani R.A.,
RA Depping R., Vortkamp A.;
RT "Trps1, a regulator of chondrocyte proliferation and differentiation,
RT interacts with the activator form of Gli3.";
RL Dev. Biol. 328:40-53(2009).
RN [16]
RP PHOSPHORYLATION.
RX PubMed=19878745; DOI=10.1016/j.yexcr.2009.10.018;
RA Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.;
RT "Identification of a novel serine/threonine kinase ULK3 as a positive
RT regulator of Hedgehog pathway.";
RL Exp. Cell Res. 316:627-637(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP INTERACTION WITH DZIP1.
RX PubMed=23955340; DOI=10.1074/jbc.m113.492066;
RA Wang C., Low W.C., Liu A., Wang B.;
RT "Centrosomal protein DZIP1 regulates Hedgehog signaling by promoting
RT cytoplasmic retention of transcription factor GLI3 and affecting
RT ciliogenesis.";
RL J. Biol. Chem. 288:29518-29529(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, AND IDENTIFICATION BY
RP 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 [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-438; LYS-462 AND LYS-779, AND
RP IDENTIFICATION BY MASS 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 [21]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 328-344 IN COMPLEX WITH SUFU, AND
RP INTERACTION WITH SUFU.
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 VARIANT GCPS SER-707.
RX PubMed=9302279; DOI=10.1093/hmg/6.11.1979;
RA Wild A., Kalff-Suske M., Vortkamp A., Bornholdt D., Koenig R.,
RA Grzeschik K.-H.;
RT "Point mutations in human GLI3 cause Greig syndrome.";
RL Hum. Mol. Genet. 6:1979-1984(1997).
RN [23]
RP VARIANT PAPA1 ARG-727, VARIANT PAPB ARG-727, INVOLVEMENT IN PAPA1,
RP INVOLVEMENT IN PAPB, INVOLVEMENT IN PHS, AND INVOLVEMENT IN PPD4.
RX PubMed=10441570; DOI=10.1086/302557;
RA Radhakrishna U., Bornholdt D., Scott H.S., Patel U.C., Rossier C.,
RA Engel H., Bottani A., Chandal D., Blouin J.-L., Solanki J.V.,
RA Grzeschik K.-H., Antonarakis S.E.;
RT "The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant
RT preaxial polydactyly type-IV and postaxial polydactyly type-A/B; no
RT phenotype prediction from the position of GLI3 mutations.";
RL Am. J. Hum. Genet. 65:645-655(1999).
RN [24]
RP VARIANT GCPS PRO-934.
RX PubMed=12414818; DOI=10.1136/jmg.39.11.804;
RA Elson E., Perveen R., Donnai D., Wall S., Black G.C.M.;
RT "De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic
RT spectrum of GLI3 defects and overlap with murine models.";
RL J. Med. Genet. 39:804-806(2002).
RN [25]
RP VARIANT GCPS TRP-625.
RX PubMed=12794692; DOI=10.1002/ajmg.a.20018;
RA Debeer P., Peeters H., Driess S., De Smet L., Freese K., Matthijs G.,
RA Bornholdt D., Devriendt K., Grzeschik K.-H., Fryns J.-P., Kalff-Suske M.;
RT "Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and
RT radiological findings in 4 independent families and 3 sporadic cases with
RT identified GLI3 mutations.";
RL Am. J. Med. Genet. A 120:49-58(2003).
RN [26]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-169 AND PRO-1304.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [27]
RP INTERACTION WITH SUFU.
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 [28]
RP INTERACTION WITH WDR11.
RX PubMed=29263200; DOI=10.15252/embr.201744632;
RA Kim Y.J., Osborn D.P., Lee J.Y., Araki M., Araki K., Mohun T.,
RA Kaensaekoski J., Brandstack N., Kim H.T., Miralles F., Kim C.H.,
RA Brown N.A., Kim H.G., Martinez-Barbera J.P., Ataliotis P., Raivio T.,
RA Layman L.C., Kim S.H.;
RT "WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy
RT related to Kallmann syndrome.";
RL EMBO Rep. 19:269-289(2018).
CC -!- FUNCTION: Has a dual function as a transcriptional activator and a
CC repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb
CC development. The full-length GLI3 form (GLI3FL) after phosphorylation
CC and nuclear translocation, acts as an activator (GLI3A) while GLI3R,
CC its C-terminally truncated form, acts as a repressor. A proper balance
CC between the GLI3 activator and the repressor GLI3R, rather than the
CC repressor gradient itself or the activator/repressor ratio gradient,
CC specifies limb digit number and identity. In concert with TRPS1, plays
CC a role in regulating the size of the zone of distal chondrocytes, in
CC restricting the zone of PTHLH expression in distal cells and in
CC activating chondrocyte proliferation. Binds to the minimal GLI-
CC consensus sequence 5'-GGGTGGTC-3'. {ECO:0000269|PubMed:10693759,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:17764085}.
CC -!- SUBUNIT: The full-length GLI3 form (GLI3FL) interacts with SUFU and
CC this interaction regulates the formation of either repressor or
CC activator forms of GLI3. Its association with SUFU is regulated by Hh
CC signaling and dissociation of the SUFU-GLI3 interaction requires the
CC presence of the ciliary motor KIF3A (By similarity). Interacts with
CC KIF7. The activator form of GLI3 (GLI3A) but not the repressor form
CC (GLI3R) can interact with TRPS1. The phosphorylated form interacts with
CC BTRC. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains
CC 3, 4 and 5); the interaction enhances its transcriptional activity.
CC Interacts with WRD11; the interaction associates EMX1 with GLI3
CC (PubMed:29263200). Interacts with DZIP1; retains GLI3 within the
CC cytoplasm (PubMed:23955340). {ECO:0000250|UniProtKB:Q61602,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:16371461,
CC ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:17764085,
CC ECO:0000269|PubMed:19389374, ECO:0000269|PubMed:19592253,
CC ECO:0000269|PubMed:23955340, ECO:0000269|PubMed:24311597,
CC ECO:0000269|PubMed:28965847, ECO:0000269|PubMed:29263200}.
CC -!- INTERACTION:
CC P10071; Q9UMX1: SUFU; NbExp=5; IntAct=EBI-308055, EBI-740595;
CC P10071; Q6ZWS8: Spop; Xeno; NbExp=2; IntAct=EBI-308055, EBI-7128920;
CC P10071; P46684: Zic1; Xeno; NbExp=2; IntAct=EBI-308055, EBI-308006;
CC P10071; Q62520: Zic2; Xeno; NbExp=2; IntAct=EBI-308055, EBI-308076;
CC PRO_0000406137; Q04741: EMX1; NbExp=3; IntAct=EBI-26568850, EBI-26568770;
CC PRO_0000406137; Q9BZH6: WDR11; NbExp=3; IntAct=EBI-26568850, EBI-2009923;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cell projection, cilium.
CC Note=GLI3FL is localized predominantly in the cytoplasm while GLI3R
CC resides mainly in the nucleus. Ciliary accumulation requires the
CC presence of KIF7 and SMO. Translocation to the nucleus is promoted by
CC interaction with ZIC1.
CC -!- TISSUE SPECIFICITY: Is expressed in a wide variety of normal adult
CC tissues, including lung, colon, spleen, placenta, testis, and
CC myometrium.
CC -!- PTM: Phosphorylated on multiple sites by protein kinase A (PKA) and
CC phosphorylation by PKA primes further phosphorylation by CK1 and GSK3.
CC Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for
CC its proteolytic processing.
CC -!- PTM: Transcriptional repressor GLI3R, a C-terminally truncated form, is
CC generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through
CC proteolytic processing. This process requires PKA-primed
CC phosphorylation of GLI3, ubiquitination of GLI3 and the presence of
CC BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained
CC in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is
CC recruited to cilia, leading to the efficient processing of GLI3FL into
CC GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it
CC to translocate into the nucleus, and repress Hh target genes. When Hh
CC signaling is initiated, SUFU dissociates from GLI3FL and this has two
CC consequences. First, GLI3R production is halted. Second, free GLI3FL
CC translocates to the nucleus, where it is phosphorylated, destabilized,
CC and converted to a transcriptional activator (GLI3A). Phosphorylated in
CC vitro by ULK3. {ECO:0000269|PubMed:16371461,
CC ECO:0000269|PubMed:16705181}.
CC -!- DISEASE: Greig cephalo-poly-syndactyly syndrome (GCPS) [MIM:175700]:
CC Autosomal dominant disorder affecting limb and craniofacial
CC development. It is characterized by pre- and postaxial polydactyly,
CC syndactyly of fingers and toes, macrocephaly and hypertelorism.
CC {ECO:0000269|PubMed:10441342, ECO:0000269|PubMed:12414818,
CC ECO:0000269|PubMed:12794692, ECO:0000269|PubMed:9302279}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pallister-Hall syndrome (PHS) [MIM:146510]: An autosomal
CC dominant disorder characterized by a wide range of clinical
CC manifestations. Clinical features include hypothalamic hamartoma,
CC pituitary dysfunction, central or postaxial polydactyly, and
CC syndactyly. Malformations are frequent in the viscera, e.g. anal
CC atresia, bifid uvula, congenital heart malformations, pulmonary or
CC renal dysplasia. {ECO:0000269|PubMed:10441570}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Polydactyly, postaxial A1 (PAPA1) [MIM:174200]: A condition
CC characterized by the occurrence of supernumerary digits in the upper
CC and/or lower extremities. In postaxial polydactyly type A, the extra
CC digit is well-formed and articulates with the fifth or a sixth
CC metacarpal/metatarsal. {ECO:0000269|PubMed:10441570}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Polydactyly, postaxial B (PAPB) [MIM:174200]: A condition
CC characterized by an extra digit in the occurrence of supernumerary
CC digits in the upper and/or lower extremities. In postaxial polydactyly
CC type B the extra digit is not well formed and is frequently in the form
CC of a skin. {ECO:0000269|PubMed:10441570}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Polydactyly, preaxial 4 (PPD4) [MIM:174700]: A form of
CC polydactyly, a condition defined by the occurrence of supernumerary
CC digits in the upper and/or lower extremities. Preaxial or radial
CC polydactyly refers to the presence of extra digits on the radial side
CC of the hand. PPD4 is an autosomal dominant form characterized by mild
CC duplication of the thumb, syndactyly of various degrees affects fingers
CC 3 and 4, duplication of part or all of the first or second toes and
CC variable toes syndactyly. Some patients have only foot involvement.
CC {ECO:0000269|PubMed:10441570}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52564.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M57609; AAA52564.1; ALT_FRAME; mRNA.
DR EMBL; AJ250408; CAB59315.1; -; Genomic_DNA.
DR EMBL; AC005026; AAP21869.1; -; Genomic_DNA.
DR EMBL; AC005028; AAS01998.1; -; Genomic_DNA.
DR EMBL; AC005158; AAS02015.1; -; Genomic_DNA.
DR EMBL; AC073852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236951; EAL24002.1; -; Genomic_DNA.
DR EMBL; M20674; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113616; AAI13617.1; -; mRNA.
DR EMBL; BC117168; AAI17169.1; -; mRNA.
DR CCDS; CCDS5465.1; -.
DR PIR; A35927; A35927.
DR RefSeq; NP_000159.3; NM_000168.5.
DR PDB; 4BLD; X-ray; 2.80 A; E/F/G/H=328-344.
DR PDBsum; 4BLD; -.
DR AlphaFoldDB; P10071; -.
DR SMR; P10071; -.
DR BioGRID; 108999; 70.
DR ComplexPortal; CPX-150; GLI3-SUFU complex.
DR CORUM; P10071; -.
DR DIP; DIP-32538N; -.
DR ELM; P10071; -.
DR IntAct; P10071; 46.
DR MINT; P10071; -.
DR STRING; 9606.ENSP00000379258; -.
DR GlyGen; P10071; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P10071; -.
DR PhosphoSitePlus; P10071; -.
DR BioMuta; GLI3; -.
DR DMDM; 269849770; -.
DR EPD; P10071; -.
DR jPOST; P10071; -.
DR MassIVE; P10071; -.
DR MaxQB; P10071; -.
DR PaxDb; P10071; -.
DR PeptideAtlas; P10071; -.
DR PRIDE; P10071; -.
DR ProteomicsDB; 52557; -.
DR ABCD; P10071; 1 sequenced antibody.
DR Antibodypedia; 647; 282 antibodies from 38 providers.
DR DNASU; 2737; -.
DR Ensembl; ENST00000395925.8; ENSP00000379258.3; ENSG00000106571.15.
DR Ensembl; ENST00000677605.1; ENSP00000503743.1; ENSG00000106571.15.
DR Ensembl; ENST00000678429.1; ENSP00000502957.1; ENSG00000106571.15.
DR GeneID; 2737; -.
DR KEGG; hsa:2737; -.
DR MANE-Select; ENST00000395925.8; ENSP00000379258.3; NM_000168.6; NP_000159.3.
DR UCSC; uc011kbh.3; human.
DR CTD; 2737; -.
DR DisGeNET; 2737; -.
DR GeneCards; GLI3; -.
DR GeneReviews; GLI3; -.
DR HGNC; HGNC:4319; GLI3.
DR HPA; ENSG00000106571; Low tissue specificity.
DR MalaCards; GLI3; -.
DR MIM; 146510; phenotype.
DR MIM; 165240; gene.
DR MIM; 174200; phenotype.
DR MIM; 174700; phenotype.
DR MIM; 175700; phenotype.
DR neXtProt; NX_P10071; -.
DR OpenTargets; ENSG00000106571; -.
DR Orphanet; 36; Acrocallosal syndrome.
DR Orphanet; 380; Greig cephalopolysyndactyly syndrome.
DR Orphanet; 672; Pallister-Hall syndrome.
DR Orphanet; 93338; Polysyndactyly.
DR Orphanet; 93334; Postaxial polydactyly type A.
DR Orphanet; 93335; Postaxial polydactyly type B.
DR Orphanet; 93322; Tibial hemimelia.
DR PharmGKB; PA28722; -.
DR VEuPathDB; HostDB:ENSG00000106571; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000155925; -.
DR HOGENOM; CLU_003666_3_0_1; -.
DR InParanoid; P10071; -.
DR OMA; CGQRSAV; -.
DR OrthoDB; 56870at2759; -.
DR PhylomeDB; P10071; -.
DR TreeFam; TF350216; -.
DR PathwayCommons; P10071; -.
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 Reactome; R-HSA-5635851; GLI proteins bind promoters of Hh responsive genes to promote transcription.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR SignaLink; P10071; -.
DR SIGNOR; P10071; -.
DR BioGRID-ORCS; 2737; 10 hits in 1091 CRISPR screens.
DR ChiTaRS; GLI3; human.
DR GeneWiki; GLI3; -.
DR GenomeRNAi; 2737; -.
DR Pharos; P10071; Tbio.
DR PRO; PR:P10071; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P10071; protein.
DR Bgee; ENSG00000106571; Expressed in ventricular zone and 197 other tissues.
DR ExpressionAtlas; P10071; baseline and differential.
DR Genevisible; P10071; HS.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0097546; C:ciliary base; TAS:Reactome.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1990788; C:GLI-SUFU complex; IPI:ComplexPortal.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0036033; F:mediator complex binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IEA:Ensembl.
DR GO; GO:0060873; P:anterior semicircular canal development; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0060840; P:artery development; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IEA:Ensembl.
DR GO; GO:0061005; P:cell differentiation involved in kidney development; IEA:Ensembl.
DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0048566; P:embryonic digestive tract development; TAS:BHF-UCL.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; TAS:BHF-UCL.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0021861; P:forebrain radial glial cell differentiation; IEA:Ensembl.
DR GO; GO:0060364; P:frontal suture morphogenesis; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007442; P:hindgut morphogenesis; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0060366; P:lambdoid suture morphogenesis; IEA:Ensembl.
DR GO; GO:0120223; P:larynx morphogenesis; IEA:Ensembl.
DR GO; GO:0022018; P:lateral ganglionic eminence cell proliferation; IEA:Ensembl.
DR GO; GO:0060875; P:lateral semicircular canal development; IEA:Ensembl.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IEA:Ensembl.
DR GO; GO:0035108; P:limb morphogenesis; IMP:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0060594; P:mammary gland specification; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0001656; P:metanephros development; IEA:Ensembl.
DR GO; GO:0046639; P:negative regulation of alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:1990787; P:negative regulation of hh target transcription factor activity; IDA:ComplexPortal.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:BHF-UCL.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045060; P:negative thymic T cell selection; ISS:BHF-UCL.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0043585; P:nose morphogenesis; TAS:BHF-UCL.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0021631; P:optic nerve morphogenesis; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:1903010; P:regulation of bone development; IEA:Ensembl.
DR GO; GO:1901620; P:regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl.
DR GO; GO:0060367; P:sagittal suture morphogenesis; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:FlyBase.
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:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:BHF-UCL.
DR GO; GO:0070242; P:thymocyte apoptotic process; ISS:BHF-UCL.
DR GO; GO:0043586; P:tongue development; IEA:Ensembl.
DR GO; GO:0071625; P:vocalization behavior; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR DisProt; DP01134; -.
DR InterPro; IPR043359; GLI-like.
DR InterPro; IPR032851; GLI3.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR45718; PTHR45718; 1.
DR PANTHER; PTHR45718:SF5; PTHR45718:SF5; 1.
DR Pfam; PF00096; zf-C2H2; 4.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Cell projection; Cilium; Cytoplasm;
KW Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..1580
FT /note="Transcriptional activator GLI3"
FT /id="PRO_0000047202"
FT CHAIN 1..?
FT /note="Transcriptional repressor GLI3R"
FT /id="PRO_0000406137"
FT ZN_FING 480..505
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 513..540
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 546..570
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 576..601
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 607..632
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..845
FT /note="Mediates interaction with DZIP1"
FT /evidence="ECO:0000250|UniProtKB:Q61602"
FT REGION 863..918
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 981..1042
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..652
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..688
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 983..1003
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1024..1042
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 175
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q61602"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 849
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT MOD_RES 865
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT MOD_RES 877
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT MOD_RES 907
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT MOD_RES 980
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT MOD_RES 1006
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:10693759"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 462
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 773
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16705181"
FT CROSSLNK 779
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 779
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:16705181"
FT CROSSLNK 784
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16705181"
FT CROSSLNK 800
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16705181"
FT VARIANT 169
FT /note="P -> L (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1419861206)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035560"
FT VARIANT 183
FT /note="T -> A (in dbSNP:rs846266)"
FT /evidence="ECO:0000269|PubMed:10441342,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2118997"
FT /id="VAR_028276"
FT VARIANT 440
FT /note="D -> E"
FT /evidence="ECO:0000269|PubMed:10441342"
FT /id="VAR_010052"
FT VARIANT 515
FT /note="C -> G (in GCPS)"
FT /evidence="ECO:0000269|PubMed:10441342"
FT /id="VAR_010053"
FT VARIANT 520
FT /note="C -> Y (in GCPS)"
FT /evidence="ECO:0000269|PubMed:10441342"
FT /id="VAR_010054"
FT VARIANT 625
FT /note="R -> W (in GCPS; dbSNP:rs121917712)"
FT /evidence="ECO:0000269|PubMed:12794692"
FT /id="VAR_021481"
FT VARIANT 707
FT /note="P -> S (in GCPS; dbSNP:rs121917716)"
FT /evidence="ECO:0000269|PubMed:9302279"
FT /id="VAR_010055"
FT VARIANT 727
FT /note="G -> R (in PAPA1 and PAPB; dbSNP:rs121917710)"
FT /evidence="ECO:0000269|PubMed:10441570"
FT /id="VAR_009876"
FT VARIANT 808
FT /note="I -> M (in dbSNP:rs62622373)"
FT /evidence="ECO:0000269|PubMed:10441342"
FT /id="VAR_010056"
FT VARIANT 934
FT /note="A -> P (in GCPS; the patient was originally
FT classifed as being affected by acrocallosal syndrome due to
FT the absence of corpus callosum; dbSNP:rs28933372)"
FT /evidence="ECO:0000269|PubMed:12414818"
FT /id="VAR_021482"
FT VARIANT 998
FT /note="P -> L (in dbSNP:rs929387)"
FT /evidence="ECO:0000269|PubMed:10441342,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2118997"
FT /id="VAR_028278"
FT VARIANT 1304
FT /note="S -> P (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1277170270)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035561"
FT VARIANT 1336
FT /note="G -> E (in dbSNP:rs35280470)"
FT /id="VAR_034865"
FT VARIANT 1537
FT /note="R -> C (in dbSNP:rs35364414)"
FT /evidence="ECO:0000269|PubMed:10441342"
FT /id="VAR_010057"
FT MUTAGEN 773
FT /note="K->R: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 779
FT /note="K->R: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 784
FT /note="K->R: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 800
FT /note="K->R: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 849
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759,
FT ECO:0000269|PubMed:16705181"
FT MUTAGEN 855
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 856
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 861
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 864
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 865
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759"
FT MUTAGEN 873
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 877
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759,
FT ECO:0000269|PubMed:16705181"
FT MUTAGEN 903
FT /note="S->A: Loss of proteolytic processing."
FT /evidence="ECO:0000269|PubMed:16705181"
FT MUTAGEN 907
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759,
FT ECO:0000269|PubMed:16705181"
FT MUTAGEN 980
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759"
FT MUTAGEN 1006
FT /note="S->A: Loss of phosphorylation and proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10693759"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:4BLD"
SQ SEQUENCE 1580 AA; 169863 MW; 423B7495FCE3C37C CRC64;
MEAQSHSSTT TEKKKVENSI VKCSTRTDVS EKAVASSTTS NEDESPGQTY HRERRNAITM
QPQNVQGLSK VSEEPSTSSD ERASLIKKEI HGSLPHVAEP SVPYRGTVFA MDPRNGYMEP
HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP SPIPPLHMTS ALSSSPTYPD LPFIRISPHR
NPTAASESPF SPPHPYINPY MDYIRSLHSS PSLSMISATR GLSPTDAPHA GVSPAEYYHQ
MALLTGQRSP YADIIPSAAT AGTGAIHMEY LHAMDSTRFS SPRLSARPSR KRTLSISPLS
DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY SSAPVSLHMH
QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL NPVQVSSGPS ESSQNKPTSE
SAVSSTGDPM HNKRSKIKPD EDLPSPGARG QQEQPEGTTL VKEEGDKDES KQEPEVIYET
NCHWEGCARE FDTQEQLVHH INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH
TGEKPHKCTF EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT
HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDIHPRP PPPRDSGSHS
QSRSPGRPTQ GALGEQQDLS NTTSKREECL QVKTVKAEKP MTSQPSPGGQ SSCSSQQSPI
SNYSNSGLEL PLTDGGSIGD LSAIDETPIM DSTISTATTA LALQARRNPA GTKWMEHVKL
ERLKQVNGMF PRLNPILPPK APAVSPLIGN GTQSNNTCSL GGPMTLLPGR SDLSGVDVTM
LNMLNRRDSS ASTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST
DASRRSSEAS QSDGLPSLLS LTPAQQYRLK AKYAAATGGP PPTPLPNMER MSLKTRLALL
GDALEPGVAL PPVHAPRRCS DGGAHGYGRR HLQPHDAPGH GVRRASDPVR TGSEGLALPR
VPRFSSLSSC NPPAMATSAE KRSLVLQNYT RPEGGQSRNF HSSPCPPSIT ENVTLESLTM
DADANLNDED FLPDDVVQYL NSQNQAGYEQ HFPSALPDDS KVPHGPGDFD APGLPDSHAG
QQFHALEQPC PEGSKTDLPI QWNEVSSGSA DLSSSKLKCG PRPAVPQTRA FGFCNGMVVH
PQNPLRSGPA GGYQTLGENS NPYGGPEHLM LHNSPGSGTS GNAFHEQPCK APQYGNCLNR
QPVAPGALDG ACGAGIQASK LKSTPMQGSG GQLNFGLPVA PNESAGSMVN GMQNQDPVGQ
GYLAHQLLGD SMQHPGAGRP GQQMLGQISA TSHINIYQGP ESCLPGAHGM GSQPSSLAVV
RGYQPCASFG GSRRQAMPRD SLALQSGQLS DTSQTCRVNG IKMEMKGQPH PLCSNLQNYS
GQFYDQTVGF SQQDTKAGSF SISDASCLLQ GTSAKNSELL SPGANQVTST VDSLDSHDLE
GVQIDFDAII DDGDHSSLMS GALSPSIIQN LSHSSSRLTT PRASLPFPAL SMSTTNMAIG
DMSSLLTSLA EESKFLAVMQ
