GLIS3_HUMAN
ID GLIS3_HUMAN Reviewed; 775 AA.
AC Q8NEA6; B1AL19; Q1PHK5;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 5.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Zinc finger protein GLIS3;
DE AltName: Full=GLI-similar 3;
DE AltName: Full=Zinc finger protein 515;
GN Name=GLIS3; Synonyms=ZNF515;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PRO-269
RP AND GLN-301.
RC TISSUE=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 [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INVOLVEMENT IN NDH.
RX PubMed=16715098; DOI=10.1038/ng1802;
RA Senee V., Chelala C., Duchatelet S., Feng D., Blanc H., Cossec J.-C.,
RA Charon C., Nicolino M., Boileau P., Cavener D.R., Bougneres P., Taha D.,
RA Julier C.;
RT "Mutations in GLIS3 are responsible for a rare syndrome with neonatal
RT diabetes mellitus and congenital hypothyroidism.";
RL Nat. Genet. 38:682-687(2006).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=14500813; DOI=10.1093/nar/gkg776;
RA Kim Y.-S., Nakanishi G., Lewandoski M., Jetten A.M.;
RT "GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger
RT proteins with repressor and activation functions.";
RL Nucleic Acids Res. 31:5513-5525(2003).
RN [5]
RP INVOLVEMENT IN NDH.
RX PubMed=21139041; DOI=10.1530/eje-10-0893;
RA Dimitri P., Warner J.T., Minton J.A., Patch A.M., Ellard S.,
RA Hattersley A.T., Barr S., Hawkes D., Wales J.K., Gregory J.W.;
RT "Novel GLIS3 mutations demonstrate an extended multisystem phenotype.";
RL Eur. J. Endocrinol. 164:437-443(2011).
CC -!- FUNCTION: Acts as both a repressor and activator of transcription.
CC Binds to the consensus sequence 5'-GACCACCCAC-3' (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q8NEA6; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-744456, EBI-740595;
CC Q8NEA6; P46937: YAP1; NbExp=2; IntAct=EBI-744456, EBI-1044059;
CC Q8NEA6-2; O95817: BAG3; NbExp=3; IntAct=EBI-12232117, EBI-747185;
CC Q8NEA6-2; Q99828: CIB1; NbExp=5; IntAct=EBI-12232117, EBI-372594;
CC Q8NEA6-2; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-12232117, EBI-12111050;
CC Q8NEA6-2; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-12232117, EBI-11750983;
CC Q8NEA6-2; Q13077: TRAF1; NbExp=3; IntAct=EBI-12232117, EBI-359224;
CC Q8NEA6-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-12232117, EBI-492476;
CC Q8NEA6-2; Q15654: TRIP6; NbExp=3; IntAct=EBI-12232117, EBI-742327;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NEA6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NEA6-2; Sequence=VSP_038299;
CC -!- TISSUE SPECIFICITY: In the adult, expressed at high levels in the
CC kidney and at lower levels in the brain, skeletal muscle, pancreas,
CC liver, lung, thymus and ovary. {ECO:0000269|PubMed:14500813}.
CC -!- DISEASE: Diabetes mellitus, neonatal, with congenital hypothyroidism
CC (NDH) [MIM:610199]: A syndrome of neonatal diabetes syndrome associated
CC with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis
CC and polycystic kidneys. {ECO:0000269|PubMed:16715098,
CC ECO:0000269|PubMed:21139041}. 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}.
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DR EMBL; AL158012; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033899; AAH33899.2; -; mRNA.
DR EMBL; DQ438877; ABE66434.1; -; mRNA.
DR CCDS; CCDS43784.1; -. [Q8NEA6-2]
DR CCDS; CCDS6451.1; -. [Q8NEA6-1]
DR RefSeq; NP_001035878.1; NM_001042413.1. [Q8NEA6-2]
DR RefSeq; NP_689842.3; NM_152629.3. [Q8NEA6-1]
DR RefSeq; XP_005251443.1; XM_005251386.4. [Q8NEA6-1]
DR RefSeq; XP_011516065.1; XM_011517763.2. [Q8NEA6-2]
DR RefSeq; XP_011516066.1; XM_011517764.2. [Q8NEA6-2]
DR RefSeq; XP_011516068.1; XM_011517766.2. [Q8NEA6-1]
DR RefSeq; XP_016869850.1; XM_017014361.1. [Q8NEA6-1]
DR AlphaFoldDB; Q8NEA6; -.
DR SMR; Q8NEA6; -.
DR BioGRID; 127988; 29.
DR CORUM; Q8NEA6; -.
DR IntAct; Q8NEA6; 13.
DR MINT; Q8NEA6; -.
DR STRING; 9606.ENSP00000371398; -.
DR iPTMnet; Q8NEA6; -.
DR PhosphoSitePlus; Q8NEA6; -.
DR BioMuta; GLIS3; -.
DR DMDM; 322510143; -.
DR jPOST; Q8NEA6; -.
DR MassIVE; Q8NEA6; -.
DR MaxQB; Q8NEA6; -.
DR PaxDb; Q8NEA6; -.
DR PeptideAtlas; Q8NEA6; -.
DR PRIDE; Q8NEA6; -.
DR ProteomicsDB; 73140; -. [Q8NEA6-1]
DR ProteomicsDB; 73141; -. [Q8NEA6-2]
DR Antibodypedia; 23977; 103 antibodies from 21 providers.
DR DNASU; 169792; -.
DR Ensembl; ENST00000324333.14; ENSP00000325494.10; ENSG00000107249.24. [Q8NEA6-1]
DR Ensembl; ENST00000381971.8; ENSP00000371398.3; ENSG00000107249.24. [Q8NEA6-2]
DR Ensembl; ENST00000682749.1; ENSP00000507306.1; ENSG00000107249.24. [Q8NEA6-1]
DR GeneID; 169792; -.
DR KEGG; hsa:169792; -.
DR MANE-Select; ENST00000381971.8; ENSP00000371398.3; NM_001042413.2; NP_001035878.1. [Q8NEA6-2]
DR UCSC; uc003zhw.2; human. [Q8NEA6-1]
DR CTD; 169792; -.
DR DisGeNET; 169792; -.
DR GeneCards; GLIS3; -.
DR HGNC; HGNC:28510; GLIS3.
DR HPA; ENSG00000107249; Tissue enhanced (brain).
DR MalaCards; GLIS3; -.
DR MIM; 610192; gene.
DR MIM; 610199; phenotype.
DR neXtProt; NX_Q8NEA6; -.
DR OpenTargets; ENSG00000107249; -.
DR Orphanet; 79118; Neonatal diabetes-congenital hypothyroidism-congenital glaucoma-hepatic fibrosis-polycystic kidneys syndrome.
DR PharmGKB; PA134878768; -.
DR VEuPathDB; HostDB:ENSG00000107249; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000156896; -.
DR HOGENOM; CLU_014147_1_0_1; -.
DR InParanoid; Q8NEA6; -.
DR OMA; GRHDWPY; -.
DR PhylomeDB; Q8NEA6; -.
DR TreeFam; TF350216; -.
DR PathwayCommons; Q8NEA6; -.
DR SignaLink; Q8NEA6; -.
DR SIGNOR; Q8NEA6; -.
DR BioGRID-ORCS; 169792; 15 hits in 1097 CRISPR screens.
DR ChiTaRS; GLIS3; human.
DR GenomeRNAi; 169792; -.
DR Pharos; Q8NEA6; Tbio.
DR PRO; PR:Q8NEA6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8NEA6; protein.
DR Bgee; ENSG00000107249; Expressed in buccal mucosa cell and 152 other tissues.
DR ExpressionAtlas; Q8NEA6; baseline and differential.
DR Genevisible; Q8NEA6; HS.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:BHF-UCL.
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; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR InterPro; IPR043359; GLI-like.
DR InterPro; IPR030405; GLIS3.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR45718; PTHR45718; 1.
DR PANTHER; PTHR45718:SF1; PTHR45718:SF1; 1.
DR Pfam; PF00096; zf-C2H2; 2.
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 Activator; Alternative splicing; Congenital hypothyroidism;
KW Diabetes mellitus; DNA-binding; Metal-binding; Nucleus; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..775
FT /note="Zinc finger protein GLIS3"
FT /id="PRO_0000047211"
FT ZN_FING 345..370
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 379..406
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 412..436
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 442..466
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 472..496
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 121..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 491..507
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 121..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..309
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..601
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 630..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1
FT /note="M -> MNGRSCSMSLHRTSGTPQGPRMVSGHHIPAIRAHSGTPGPSPCGSTS
FT SPTMASLANNLHLKMPSGGGMAPQNNVAESRIHLPALSPRRQMLTNGKPRFQVTQAGGM
FT SGSHTLKPKQQEFGSPFPPNPGKGALGFGPQCKSIGKGSCNNLVVTSSPM (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038299"
FT VARIANT 269
FT /note="S -> P (in dbSNP:rs806052)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047148"
FT VARIANT 301
FT /note="P -> Q (in dbSNP:rs6415788)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031062"
FT VARIANT 578
FT /note="P -> L (in dbSNP:rs10973986)"
FT /id="VAR_047149"
FT CONFLICT 347
FT /note="C -> Y (in Ref. 2; AAH33899)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 775 AA; 83636 MW; 1C8519AFCDF6C813 CRC64;
MMVQRLGLIS PPASQVSTAC NQISPSLQRA MNAANLNIPP SDTRSLISRE SLASTTLSLT
ESQSASSMKQ EWSQGYRALP SLSNHGSQNG LDLGDLLSLP PGTSMSSNSV SNSLPSYLFG
TESSHSPYPS PRHSSTRSHS ARSKKRALSL SPLSDGIGID FNTIIRTSPT SLVAYINGSR
ASPANLSPQP EVYGHFLGVR GSCIPQPRPV PGSQKGVLVA PGGLALPAYG EDGALEHERM
QQLEHGGLQP GLVNHMVVQH GLPGPDSQSA GLFKTERLEE FPGSTVDLPP APPLPPLPPP
PGPPPPYHAH AHLHHPELGP HAQQLALPQA TLDDDGEMDG IGGKHCCRWI DCSALYDQQE
ELVRHIEKVH IDQRKGEDFT CFWAGCPRRY KPFNARYKLL IHMRVHSGEK PNKCTFEGCE
KAFSRLENLK IHLRSHTGEK PYLCQHPGCQ KAFSNSSDRA KHQRTHLDTK PYACQIPGCT
KRYTDPSSLR KHVKAHSSKE QQARKKLRSS TELHPDLLTD CLTVQSLQPA TSPRDAAAEG
TVGRSPGPGP DLYSAPIFSS NYSSRSGTAA GAVPPPHPVS HPSPGHNVQG SPHNPSSQLP
PLTAVDAGAE RFAPSAPSPH HISPRRVPAP SSILQRTQPP YTQQPSGSHL KSYQPETNSS
FQPNGIHVHG FYGQLQKFCP PHYPDSQRIV PPVSSCSVVP SFEDCLVPTS MGQASFDVFH
RAFSTHSGIT VYDLPSSSSS LFGESLRSGA EDATFLQIST VDRCPSQLSS VYTEG
