GCM2_HUMAN
ID GCM2_HUMAN Reviewed; 506 AA.
AC O75603; D3GDV6; Q5THN5;
DT 25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Chorion-specific transcription factor GCMb;
DE Short=hGCMb;
DE AltName: Full=GCM motif protein 2;
DE AltName: Full=Glial cells missing homolog 2 {ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9928992, ECO:0000303|Ref.3};
GN Name=GCM2 {ECO:0000312|HGNC:HGNC:4198};
GN Synonyms=GCMB {ECO:0000303|PubMed:10343099};
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].
RC TISSUE=Brain;
RX PubMed=9928992; DOI=10.1016/s0014-5793(98)01650-0;
RA Kanemura Y., Hiraga S., Arita N., Ohnishi T., Izumoto S., Mori K.,
RA Matsumura H., Yamasaki M., Fushiki S., Yoshimine T.;
RT "Isolation and expression analysis of a novel human homologue of the
RT Drosophila glial cells missing (gcm) gene.";
RL FEBS Lett. 442:151-156(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=10343099; DOI=10.1159/000015210;
RA Kammerer M., Pirola B., Giglio S., Giangrande A.;
RT "GCMB, a second human homolog of the fly glide/gcm gene.";
RL Cytogenet. Cell Genet. 84:43-47(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT FIH2 TRP-110.
RA Tomar N., Bora H., Gupta N., Sharma Y.D., Goswami R.;
RT "Presence of a functionally relevant novel R110W mutation in the DNA
RT binding domain of GCMB gene in patients with sporadic idiopathic
RT hypoparathyroidism: a genetic marker of the disease.";
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 VARIANT FIH2 SER-63.
RX PubMed=15728199; DOI=10.1210/jc.2004-2450;
RA Thomee C., Schubert S.W., Parma J., Le P.Q., Hashemolhosseini S.,
RA Wegner M., Abramowicz M.J.;
RT "GCMB mutation in familial isolated hypoparathyroidism with residual
RT secretion of parathyroid hormone.";
RL J. Clin. Endocrinol. Metab. 90:2487-2492(2005).
RN [8]
RP VARIANT FIH2 LEU-47, AND CHARACTERIZATION OF VARIANT FIH2 LEU-47.
RX PubMed=15863676; DOI=10.1136/jmg.2004.026898;
RA Baumber L., Tufarelli C., Patel S., King P., Johnson C.A., Maher E.R.,
RA Trembath R.C.;
RT "Identification of a novel mutation disrupting the DNA binding activity of
RT GCM2 in autosomal recessive familial isolated hypoparathyroidism.";
RL J. Med. Genet. 42:443-448(2005).
RN [9]
RP VARIANTS FIH2 LEU-47 AND TRP-110, VARIANT ASP-282, CHARACTERIZATION OF
RP VARIANTS FIH2 LEU-47 AND TRP-110, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20190276; DOI=10.1093/hmg/ddq084;
RA Bowl M.R., Mirczuk S.M., Grigorieva I.V., Piret S.E., Cranston T.,
RA Southam L., Allgrove J., Bahl S., Brain C., Loughlin J., Mughal Z.,
RA Ryan F., Shaw N., Thakker Y.V., Tiosano D., Nesbit M.A., Thakker R.V.;
RT "Identification and characterization of novel parathyroid-specific
RT transcription factor Glial Cells Missing Homolog B (GCMB) mutations in
RT eight families with autosomal recessive hypoparathyroidism.";
RL Hum. Mol. Genet. 19:2028-2038(2010).
RN [10]
RP VARIANT FIH2 HIS-502, AND CHARACTERIZATION OF VARIANT FIH2 HIS-502.
RX PubMed=20463099; DOI=10.1210/jc.2009-2532;
RA Mirczuk S.M., Bowl M.R., Nesbit M.A., Cranston T., Fratter C., Allgrove J.,
RA Brain C., Thakker R.V.;
RT "A missense glial cells missing homolog B (GCMB) mutation, Asn502His,
RT causes autosomal dominant hypoparathyroidism.";
RL J. Clin. Endocrinol. Metab. 95:3512-3516(2010).
RN [11]
RP VARIANTS ASP-282 AND MET-382, AND CHARACTERIZATION OF VARIANT MET-382.
RX PubMed=21642377; DOI=10.1530/joe-10-0247;
RA Mannstadt M., Holick E., Zhao W., Juppner H.;
RT "Mutational analysis of GCMB, a parathyroid-specific transcription factor,
RT in parathyroid adenoma of primary hyperparathyroidism.";
RL J. Endocrinol. 210:165-171(2011).
RN [12]
RP VARIANT FIH2 136-TYR--PHE-506 DEL, AND CHARACTERIZATION OF VARIANT FIH2
RP 136-TYR--PHE-506 DEL.
RX PubMed=23155703; DOI=10.1515/jpem-2012-0080;
RA Doyle D., Kirwin S.M., Sol-Church K., Levine M.A.;
RT "A novel mutation in the GCM2 gene causing severe congenital isolated
RT hypoparathyroidism.";
RL J. Pediatr. Endocrinol. Metab. 25:741-746(2012).
RN [13]
RP INVOLVEMENT IN HRPT4, VARIANTS HRPT4 GLU-251; GLN-379; MET-382 AND SER-394,
RP VARIANTS SER-203; VAL-227; ASP-282 AND ASP-315, CHARACTERIZATION OF
RP VARIANTS HRPT4 GLU-251; GLN-379; MET-382 AND SER-394, CHARACTERIZATION OF
RP VARIANTS SER-203; VAL-227; ASP-282 AND ASP-315, FUNCTION, AND REGION.
RX PubMed=27745835; DOI=10.1016/j.ajhg.2016.08.018;
RA Guan B., Welch J.M., Sapp J.C., Ling H., Li Y., Johnston J.J., Kebebew E.,
RA Biesecker L.G., Simonds W.F., Marx S.J., Agarwal S.K.;
RT "GCM2-activating mutations in familial isolated hyperparathyroidism.";
RL Am. J. Hum. Genet. 99:1034-1044(2016).
CC -!- FUNCTION: Transcription factor that binds specific sequences on gene
CC promoters and activate their transcription. Through the regulation of
CC gene transcription, may play a role in parathyroid gland development.
CC {ECO:0000269|PubMed:20190276, ECO:0000269|PubMed:27745835,
CC ECO:0000269|PubMed:9928992}.
CC -!- INTERACTION:
CC O75603; P40199: CEACAM6; NbExp=3; IntAct=EBI-10188645, EBI-4314501;
CC O75603; O43186: CRX; NbExp=11; IntAct=EBI-10188645, EBI-748171;
CC O75603; Q7L591-3: DOK3; NbExp=3; IntAct=EBI-10188645, EBI-10694655;
CC O75603; Q16610: ECM1; NbExp=3; IntAct=EBI-10188645, EBI-947964;
CC O75603; Q13643: FHL3; NbExp=11; IntAct=EBI-10188645, EBI-741101;
CC O75603; Q86YR5-3: GPSM1; NbExp=3; IntAct=EBI-10188645, EBI-10261098;
CC O75603; O15499: GSC2; NbExp=3; IntAct=EBI-10188645, EBI-19954058;
CC O75603; P49639: HOXA1; NbExp=3; IntAct=EBI-10188645, EBI-740785;
CC O75603; O75031: HSF2BP; NbExp=3; IntAct=EBI-10188645, EBI-7116203;
CC O75603; Q96LI6: HSFY2; NbExp=12; IntAct=EBI-10188645, EBI-3957665;
CC O75603; P0C870: JMJD7; NbExp=3; IntAct=EBI-10188645, EBI-9090173;
CC O75603; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-10188645, EBI-11962084;
CC O75603; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-10188645, EBI-18394498;
CC O75603; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-10188645, EBI-10261141;
CC O75603; Q14847-2: LASP1; NbExp=3; IntAct=EBI-10188645, EBI-9088686;
CC O75603; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-10188645, EBI-12039345;
CC O75603; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-10188645, EBI-16439278;
CC O75603; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-10188645, EBI-5662487;
CC O75603; P26367: PAX6; NbExp=3; IntAct=EBI-10188645, EBI-747278;
CC O75603; Q06710: PAX8; NbExp=3; IntAct=EBI-10188645, EBI-2683132;
CC O75603; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-10188645, EBI-949255;
CC O75603; P78424: POU6F2; NbExp=3; IntAct=EBI-10188645, EBI-12029004;
CC O75603; Q93062: RBPMS; NbExp=5; IntAct=EBI-10188645, EBI-740322;
CC O75603; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-10188645, EBI-740343;
CC O75603; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-10188645, EBI-6257312;
CC O75603; Q04837: SSBP1; NbExp=3; IntAct=EBI-10188645, EBI-353460;
CC O75603; O60806: TBX19; NbExp=3; IntAct=EBI-10188645, EBI-12096770;
CC O75603; Q13077: TRAF1; NbExp=3; IntAct=EBI-10188645, EBI-359224;
CC O75603; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-10188645, EBI-11975223;
CC O75603; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-10188645, EBI-12040603;
CC O75603; Q8NF64-3: ZMIZ2; NbExp=3; IntAct=EBI-10188645, EBI-12011330;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20190276}.
CC -!- DOMAIN: The C-terminal conserved inhibitory domain (CCID) negatively
CC regulates the transcriptional activity of the protein.
CC {ECO:0000269|PubMed:27745835}.
CC -!- DISEASE: Hypoparathyroidism, familial isolated, 2 (FIH2) [MIM:618883]:
CC An autosomal recessive form of hypoparathyroidism, a disorder
CC characterized by hypocalcemia and hyperphosphatemia due to a deficiency
CC of parathyroid hormone. Clinical features include seizures, tetany and
CC cramps. {ECO:0000269|PubMed:15728199, ECO:0000269|PubMed:15863676,
CC ECO:0000269|PubMed:20190276, ECO:0000269|PubMed:20463099,
CC ECO:0000269|PubMed:23155703, ECO:0000269|Ref.3}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Hyperparathyroidism 4 (HRPT4) [MIM:617343]: A form of familial
CC primary hyperparathyroidism, a hypercalcemic disorder caused by
CC inappropriate oversecretion of parathyroid hormone due to parathyroid
CC hyperplasia or neoplasms. Clinical features include hypercalcemia,
CC phosphaturia, and increased bone resorption. HRPT4 inheritance is
CC autosomal dominant. {ECO:0000269|PubMed:27745835}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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DR EMBL; AF079550; AAC33792.1; -; mRNA.
DR EMBL; AF091149; AAC98097.1; -; mRNA.
DR EMBL; FJ655849; ACV69998.1; -; Genomic_DNA.
DR EMBL; AL024498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55287.1; -; Genomic_DNA.
DR EMBL; BC069603; AAH69603.1; -; mRNA.
DR EMBL; BC117316; AAI17317.1; -; mRNA.
DR EMBL; BC117318; AAI17319.1; -; mRNA.
DR CCDS; CCDS4517.1; -.
DR RefSeq; NP_004743.1; NM_004752.3.
DR AlphaFoldDB; O75603; -.
DR SMR; O75603; -.
DR BioGRID; 114673; 46.
DR IntAct; O75603; 31.
DR STRING; 9606.ENSP00000368805; -.
DR iPTMnet; O75603; -.
DR PhosphoSitePlus; O75603; -.
DR BioMuta; GCM2; -.
DR PaxDb; O75603; -.
DR PRIDE; O75603; -.
DR Antibodypedia; 24867; 143 antibodies from 28 providers.
DR DNASU; 9247; -.
DR Ensembl; ENST00000379491.5; ENSP00000368805.4; ENSG00000124827.7.
DR GeneID; 9247; -.
DR KEGG; hsa:9247; -.
DR MANE-Select; ENST00000379491.5; ENSP00000368805.4; NM_004752.4; NP_004743.1.
DR UCSC; uc003mzn.5; human.
DR CTD; 9247; -.
DR DisGeNET; 9247; -.
DR GeneCards; GCM2; -.
DR HGNC; HGNC:4198; GCM2.
DR HPA; ENSG00000124827; Tissue enriched (parathyroid).
DR MalaCards; GCM2; -.
DR MIM; 603716; gene.
DR MIM; 617343; phenotype.
DR MIM; 618883; phenotype.
DR neXtProt; NX_O75603; -.
DR OpenTargets; ENSG00000124827; -.
DR Orphanet; 99879; Familial isolated hyperparathyroidism.
DR Orphanet; 2239; Familial isolated hypoparathyroidism due to agenesis of parathyroid gland.
DR PharmGKB; PA28615; -.
DR VEuPathDB; HostDB:ENSG00000124827; -.
DR eggNOG; ENOG502QU2X; Eukaryota.
DR GeneTree; ENSGT00390000006777; -.
DR HOGENOM; CLU_043105_0_0_1; -.
DR InParanoid; O75603; -.
DR OMA; FWRLDGK; -.
DR OrthoDB; 396012at2759; -.
DR PhylomeDB; O75603; -.
DR TreeFam; TF324146; -.
DR PathwayCommons; O75603; -.
DR SignaLink; O75603; -.
DR SIGNOR; O75603; -.
DR BioGRID-ORCS; 9247; 8 hits in 1086 CRISPR screens.
DR ChiTaRS; GCM2; human.
DR GeneWiki; GCM2; -.
DR GenomeRNAi; 9247; -.
DR Pharos; O75603; Tbio.
DR PRO; PR:O75603; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O75603; protein.
DR Bgee; ENSG00000124827; Expressed in embryo and 7 other tissues.
DR Genevisible; O75603; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP: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; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IMP:UniProtKB.
DR GO; GO:0042063; P:gliogenesis; IBA:GO_Central.
DR GO; GO:0060017; P:parathyroid gland development; IMP: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; IMP:UniProtKB.
DR Gene3D; 2.20.25.670; -; 1.
DR Gene3D; 3.30.70.3530; -; 1.
DR InterPro; IPR039791; GCM.
DR InterPro; IPR036115; GCM_dom_sf.
DR InterPro; IPR043020; GCM_large.
DR InterPro; IPR043021; GCM_small.
DR InterPro; IPR003902; Tscrpt_reg_GCM.
DR PANTHER; PTHR12414; PTHR12414; 1.
DR Pfam; PF03615; GCM; 1.
DR SUPFAM; SSF90073; SSF90073; 1.
DR PROSITE; PS50807; GCM; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disease variant; DNA-binding; Metal-binding;
KW Nucleus; Reference proteome; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..506
FT /note="Chorion-specific transcription factor GCMb"
FT /id="PRO_0000126650"
FT DNA_BIND 19..174
FT /note="GCM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT REGION 155..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 379..395
FT /note="C-terminal conserved inhibitory domain (CCID)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT COMPBIAS 156..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT VARIANT 47
FT /note="R -> L (in FIH2; abolishes normal DNA binding
FT ability of the protein; dbSNP:rs104893959)"
FT /evidence="ECO:0000269|PubMed:15863676,
FT ECO:0000269|PubMed:20190276"
FT /id="VAR_058044"
FT VARIANT 53
FT /note="D -> N (in dbSNP:rs11963186)"
FT /id="VAR_049130"
FT VARIANT 63
FT /note="G -> S (in FIH2; the mutation causes loss-of-
FT function; abolishes transactivation capacity despite normal
FT subcellular localization, protein stability and DNA-binding
FT specificity; dbSNP:rs104893960)"
FT /evidence="ECO:0000269|PubMed:15728199"
FT /id="VAR_058045"
FT VARIANT 110
FT /note="R -> W (in FIH2; abolishes DNA binding ability;
FT dbSNP:rs780594439)"
FT /evidence="ECO:0000269|PubMed:20190276, ECO:0000269|Ref.3"
FT /id="VAR_065495"
FT VARIANT 117
FT /note="A -> V (in dbSNP:rs35786951)"
FT /id="VAR_049131"
FT VARIANT 136..506
FT /note="Missing (in FIH2; transcription of mRNA, but loss of
FT protein expression)"
FT /evidence="ECO:0000269|PubMed:23155703"
FT /id="VAR_076838"
FT VARIANT 203
FT /note="G -> S (shows normal transcriptional activity;
FT dbSNP:rs7744163)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_049132"
FT VARIANT 227
FT /note="I -> V (shows normal transcriptional activity;
FT dbSNP:rs35395043)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_049133"
FT VARIANT 251
FT /note="Q -> E (in HRPT4; found on the same allele as Q-379;
FT gain-of-function mutation; increases transcriptional
FT activity; dbSNP:rs1057519581)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_078579"
FT VARIANT 282
FT /note="Y -> D (shows normal transcriptional activity;
FT dbSNP:rs61734277)"
FT /evidence="ECO:0000269|PubMed:20190276,
FT ECO:0000269|PubMed:21642377, ECO:0000269|PubMed:27745835"
FT /id="VAR_065496"
FT VARIANT 315
FT /note="N -> D (shows normal transcriptional activity;
FT dbSNP:rs114070356)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_078580"
FT VARIANT 379
FT /note="L -> Q (in HRPT4; found on the same allele as E-251;
FT gain-of-function mutation; increases transcriptional
FT activity; dbSNP:rs1057519582)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_078581"
FT VARIANT 382
FT /note="V -> M (in HRPT4; unknown pathological significance;
FT dbSNP:rs371918069)"
FT /evidence="ECO:0000269|PubMed:21642377,
FT ECO:0000269|PubMed:27745835"
FT /id="VAR_065497"
FT VARIANT 394
FT /note="Y -> S (in HRPT4; gain-of-function mutation;
FT increases transcriptional activity; dbSNP:rs142287570)"
FT /evidence="ECO:0000269|PubMed:27745835"
FT /id="VAR_078582"
FT VARIANT 502
FT /note="N -> H (in FIH2; exerts a dominant-negative effect
FT to abolish transactivation capacity; dbSNP:rs533942394)"
FT /evidence="ECO:0000269|PubMed:20463099"
FT /id="VAR_065498"
SQ SEQUENCE 506 AA; 56610 MW; 1B3864F65F54DA0F CRC64;
MPAAAVQEAV GVCSYGMQLS WDINDPQMPQ ELALFDQFRE WPDGYVRFIY SSDEKKAQRH
LSGWAMRNTN NHNGHILKKS CLGVVVCTQA CTLPDGSRLQ LRPAICDKAR LKQQKKACPN
CHSALELIPC RGHSGYPVTN FWRLDGNAIF FQAKGVHDHP RPESKSETEA RRSAIKRQMA
SFYQPQKKRI RESEAEENQD SSGHFSNIPP LENPEDFDIV TETSFPIPGQ PCPSFPKSDV
YKATCDLATF QGDKMPPFQK YSSPRIYLPR PPCSYELANP GYTNSSPYPT LYKDSTSIPN
DTDWVHLNTL QCNVNSYSSY ERSFDFTNKQ HGWKPALGKP SLVERTNHGQ FQAMATRPYY
NPELPCRYLT TPPPGAPALQ TVITTTTKVS YQAYQPPAMK YSDSVREVKS LSSCNYAPED
TGMSVYPEPW GPPVTVTRAA SPSGPPPMKI AGDCRAIRPT VAIPHEPVSS RTDEAETWDV
CLSGLGSAVS YSDRVGPFFT YNNEDF
