Q8NEA6 (GLIS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein GLIS3

Alternative name(s):
GLI-similar 3
Zinc finger protein 515

Gene names

Name:	GLIS3
Synonyms:	ZNF515

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	775 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Acts as both a repressor and activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3' By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	In the adult, expressed at high levels in the kidney and at lower levels in the brain, skeletal muscle, pancreas, liver, lung, thymus and ovary. Ref.4
Involvement in disease	Diabetes mellitus, neonatal, with congenital hypothyroidism (NDH) [MIM:610199]: A syndrome of neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.5
Sequence similarities	Belongs to the GLI C2H2-type zinc-finger protein family. Contains 5 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital hypothyroidism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nuclear part Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8NEA6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8NEA6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MNGRSCSMSL...NNLVVTSSPM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 775	775	Zinc finger protein GLIS3		PRO_0000047211
Regions
	Zinc finger	345 – 370	26	C2H2-type 1
	Zinc finger	379 – 406	28	C2H2-type 2; atypical
	Zinc finger	412 – 436	25	C2H2-type 3
	Zinc finger	442 – 466	25	C2H2-type 4
	Zinc finger	472 – 496	25	C2H2-type 5
	Motif	491 – 507	17	Bipartite nuclear localization signal Potential
	Compositional bias	41 – 154	114	Ser-rich
	Compositional bias	289 – 306	18	Pro-rich
Natural variations
	Alternative sequence	1	1	M → MNGRSCSMSLHRTSGTPQGP RMVSGHHIPAIRAHSGTPGP SPCGSTSSPTMASLANNLHL KMPSGGGMAPQNNVAESRIH LPALSPRRQMLTNGKPRFQV TQAGGMSGSHTLKPKQQEFG SPFPPNPGKGALGFGPQCKS IGKGSCNNLVVTSSPM in isoform 2.		VSP_038299
	Natural variant	269	1	S → P. Ref.2 Corresponds to variant rs806052 [ dbSNP | Ensembl ].		VAR_047148
	Natural variant	301	1	P → Q. Ref.2 Corresponds to variant rs6415788 [ dbSNP | Ensembl ].		VAR_031062
	Natural variant	578	1	P → L. Corresponds to variant rs10973986 [ dbSNP | Ensembl ].		VAR_047149
Experimental info
	Sequence conflict	347	1	C → Y in AAH33899. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 8, 2011. Version 5. Checksum: 1C8519AFCDF6C813	FASTA	775	83,636
	10 20 30 40 50 60 MMVQRLGLIS PPASQVSTAC NQISPSLQRA MNAANLNIPP SDTRSLISRE SLASTTLSLT 70 80 90 100 110 120 ESQSASSMKQ EWSQGYRALP SLSNHGSQNG LDLGDLLSLP PGTSMSSNSV SNSLPSYLFG 130 140 150 160 170 180 TESSHSPYPS PRHSSTRSHS ARSKKRALSL SPLSDGIGID FNTIIRTSPT SLVAYINGSR 190 200 210 220 230 240 ASPANLSPQP EVYGHFLGVR GSCIPQPRPV PGSQKGVLVA PGGLALPAYG EDGALEHERM 250 260 270 280 290 300 QQLEHGGLQP GLVNHMVVQH GLPGPDSQSA GLFKTERLEE FPGSTVDLPP APPLPPLPPP 310 320 330 340 350 360 PGPPPPYHAH AHLHHPELGP HAQQLALPQA TLDDDGEMDG IGGKHCCRWI DCSALYDQQE 370 380 390 400 410 420 ELVRHIEKVH IDQRKGEDFT CFWAGCPRRY KPFNARYKLL IHMRVHSGEK PNKCTFEGCE 430 440 450 460 470 480 KAFSRLENLK IHLRSHTGEK PYLCQHPGCQ KAFSNSSDRA KHQRTHLDTK PYACQIPGCT 490 500 510 520 530 540 KRYTDPSSLR KHVKAHSSKE QQARKKLRSS TELHPDLLTD CLTVQSLQPA TSPRDAAAEG 550 560 570 580 590 600 TVGRSPGPGP DLYSAPIFSS NYSSRSGTAA GAVPPPHPVS HPSPGHNVQG SPHNPSSQLP 610 620 630 640 650 660 PLTAVDAGAE RFAPSAPSPH HISPRRVPAP SSILQRTQPP YTQQPSGSHL KSYQPETNSS 670 680 690 700 710 720 FQPNGIHVHG FYGQLQKFCP PHYPDSQRIV PPVSSCSVVP SFEDCLVPTS MGQASFDVFH 730 740 750 760 770 RAFSTHSGIT VYDLPSSSSS LFGESLRSGA EDATFLQIST VDRCPSQLSS VYTEG
	Isoform 2 [UniParc]. Checksum: B31E78045EB5C953	FASTA	930	99,605
	10 20 30 40 50 60 MNGRSCSMSL HRTSGTPQGP RMVSGHHIPA IRAHSGTPGP SPCGSTSSPT MASLANNLHL 70 80 90 100 110 120 KMPSGGGMAP QNNVAESRIH LPALSPRRQM LTNGKPRFQV TQAGGMSGSH TLKPKQQEFG 130 140 150 160 170 180 SPFPPNPGKG ALGFGPQCKS IGKGSCNNLV VTSSPMMVQR LGLISPPASQ VSTACNQISP 190 200 210 220 230 240 SLQRAMNAAN LNIPPSDTRS LISRESLAST TLSLTESQSA SSMKQEWSQG YRALPSLSNH 250 260 270 280 290 300 GSQNGLDLGD LLSLPPGTSM SSNSVSNSLP SYLFGTESSH SPYPSPRHSS TRSHSARSKK 310 320 330 340 350 360 RALSLSPLSD GIGIDFNTII RTSPTSLVAY INGSRASPAN LSPQPEVYGH FLGVRGSCIP 370 380 390 400 410 420 QPRPVPGSQK GVLVAPGGLA LPAYGEDGAL EHERMQQLEH GGLQPGLVNH MVVQHGLPGP 430 440 450 460 470 480 DSQSAGLFKT ERLEEFPGST VDLPPAPPLP PLPPPPGPPP PYHAHAHLHH PELGPHAQQL 490 500 510 520 530 540 ALPQATLDDD GEMDGIGGKH CCRWIDCSAL YDQQEELVRH IEKVHIDQRK GEDFTCFWAG 550 560 570 580 590 600 CPRRYKPFNA RYKLLIHMRV HSGEKPNKCT FEGCEKAFSR LENLKIHLRS HTGEKPYLCQ 610 620 630 640 650 660 HPGCQKAFSN SSDRAKHQRT HLDTKPYACQ IPGCTKRYTD PSSLRKHVKA HSSKEQQARK 670 680 690 700 710 720 KLRSSTELHP DLLTDCLTVQ SLQPATSPRD AAAEGTVGRS PGPGPDLYSA PIFSSNYSSR 730 740 750 760 770 780 SGTAAGAVPP PHPVSHPSPG HNVQGSPHNP SSQLPPLTAV DAGAERFAPS APSPHHISPR 790 800 810 820 830 840 RVPAPSSILQ RTQPPYTQQP SGSHLKSYQP ETNSSFQPNG IHVHGFYGQL QKFCPPHYPD 850 860 870 880 890 900 SQRIVPPVSS CSVVPSFEDC LVPTSMGQAS FDVFHRAFST HSGITVYDLP SSSSSLFGES 910 920 930 LRSGAEDATF LQISTVDRCP SQLSSVYTEG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS PRO-269 AND GLN-301. Tissue: Testis.
[3]	"Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism." Senee V., Chelala C., Duchatelet S., Feng D., Blanc H., Cossec J.-C., Charon C., Nicolino M., Boileau P., Cavener D.R., Bougneres P., Taha D., Julier C. Nat. Genet. 38:682-687(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INVOLVEMENT IN NDH.
[4]	"GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions." Kim Y.-S., Nakanishi G., Lewandoski M., Jetten A.M. Nucleic Acids Res. 31:5513-5525(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Novel GLIS3 mutations demonstrate an extended multisystem phenotype." Dimitri P., Warner J.T., Minton J.A., Patch A.M., Ellard S., Hattersley A.T., Barr S., Hawkes D., Wales J.K., Gregory J.W. Eur. J. Endocrinol. 164:437-443(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN NDH.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL158012, AL133283, AL137071 Genomic DNA. Translation: CAH70655.1. AL133283, AL137071, AL158012 Genomic DNA. Translation: CAH72449.1. AL137071, AL133283, AL158012 Genomic DNA. Translation: CAI39818.1. BC033899 mRNA. Translation: AAH33899.2. DQ438877 mRNA. Translation: ABE66434.1.
IPI	IPI00168641. IPI00761097.
RefSeq	NP_001035878.1. NM_001042413.1. NP_689842.3. NM_152629.3.
UniGene	Hs.162125.
3D structure databases
ProteinModelPortal	Q8NEA6.
SMR	Q8NEA6. Positions 347-530.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NEA6. 2 interactions.
STRING	9606.ENSP00000371398.
PTM databases
PhosphoSite	Q8NEA6.
Polymorphism databases
DMDM	212276519.
Proteomic databases
PaxDb	Q8NEA6.
PRIDE	Q8NEA6.
Protocols and materials databases
DNASU	169792.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324333; ENSP00000325494; ENSG00000107249. ENST00000381971; ENSP00000371398; ENSG00000107249.
GeneID	169792.
KEGG	hsa:169792.
UCSC	uc003zhw.1. human. uc003zhx.1. human.
Organism-specific databases
CTD	169792.
GeneCards	GC09M003816.
HGNC	HGNC:28510. GLIS3.
MIM	610192. gene. 610199. phenotype.
neXtProt	NX_Q8NEA6.
Orphanet	79118. Neonatal diabetes - congenital hypothyroidism - congenital glaucoma - hepatic fibrosis - polycystic kidneys.
PharmGKB	PA134878768.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOGENOM	HOG000231136.
HOVERGEN	HBG107950.
InParanoid	Q8NEA6.
KO	K09232.
OMA	GALEYER.
OrthoDB	EOG4Q84WV.
PhylomeDB	Q8NEA6.
Gene expression databases
ArrayExpress	Q8NEA6.
Bgee	Q8NEA6.
CleanEx	HS_GLIS3.
Genevestigator	Q8NEA6.
GermOnline	ENSG00000107249. Homo sapiens.
Family and domain databases
Gene3D	3.30.160.60. 5 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 5 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 4 hits. PS50157. ZINC_FINGER_C2H2_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	169792.
NextBio	88833.
SOURCE	Search...

Entry information

Entry name

GLIS3_HUMAN

Accession

Primary (citable) accession number: Q8NEA6
Secondary accession number(s): B1AL19, Q1PHK5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	February 8, 2011
Last modified:	May 1, 2013
This is version 91 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.