GSX2_HUMAN
ID GSX2_HUMAN Reviewed; 304 AA.
AC Q9BZM3;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=GS homeobox 2;
DE AltName: Full=Genetic-screened homeobox 2;
DE AltName: Full=Homeobox protein GSH-2;
GN Name=GSX2; Synonyms=GSH2;
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 VARIANT SER-107.
RA Sakai T., Sakamoto S., Nakamura K., Muraki T.;
RT "Human homeobox protein GSH-2.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-107.
RA Cools J., Marynen P.;
RT "The sequence of the human GSH2 gene.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-107.
RA Dauwerse H.G., Peters D.J.M., Breuning M.H.;
RT "The genomic sequence of the human GSH-2 gene.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-107.
RC TISSUE=Brain;
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 INVOLVEMENT IN DMJDS2, VARIANTS DMJDS2 9-SER--LEU-304 DEL AND ARG-251,
RP CHARACTERIZATION OF VARIANTS DMJDS2 9-SER--LEU-304 DEL AND ARG-251,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31412107; DOI=10.1093/brain/awz247;
RA De Mori R., Severino M., Mancardi M.M., Anello D., Tardivo S., Biagini T.,
RA Capra V., Casella A., Cereda C., Copeland B.R., Gagliardi S., Gamucci A.,
RA Ginevrino M., Illi B., Lorefice E., Musaev D., Stanley V., Micalizzi A.,
RA Gleeson J.G., Mazza T., Rossi A., Valente E.M.;
RT "Agenesis of the putamen and globus pallidus caused by recessive mutations
RT in the homeobox gene GSX2.";
RL Brain 142:2965-2978(2019).
CC -!- FUNCTION: Transcription factor that binds 5'-CNAATTAG-3' DNA sequence
CC and regulates the expression of numerous genes including genes
CC important for brain development (PubMed:31412107). During telencephalic
CC development, causes ventralization of pallial progenitors and,
CC depending on the developmental stage, specifies different neuronal
CC fates. At early stages, necessary and sufficient to correctly specify
CC the ventral lateral ganglionic eminence (LGE) and its major
CC derivatives, the striatal projection neurons. At later stages, may
CC specify LGE progenitors toward dorsal LGE fates, including olfactory
CC bulb interneurons (By similarity). {ECO:0000250|UniProtKB:P31316,
CC ECO:0000269|PubMed:31412107}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:31412107}. Cytoplasm {ECO:0000269|PubMed:31412107}.
CC -!- DISEASE: Diencephalic-mesencephalic junction dysplasia syndrome 2
CC (DMJDS2) [MIM:618646]: An autosomal recessive neurodevelopmental
CC disorder with onset at birth, characterized by severe global
CC developmental delay, hypotonia, spastic tetraparesis, generalized
CC dystonia and severe intellectual impairment. Brain imaging shows a
CC unique brain malformation characterized by agenesis of putamina and
CC globi pallidi, dysgenesis of the caudate nuclei, olfactory bulbs
CC hypoplasia, and anomaly of the diencephalic-mesencephalic junction with
CC abnormal corticospinal tract course. {ECO:0000269|PubMed:31412107}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the Antp homeobox family. {ECO:0000305}.
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DR EMBL; AB028838; BAB84822.1; -; mRNA.
DR EMBL; AF306344; AAK00880.1; -; Genomic_DNA.
DR EMBL; AF306343; AAK00880.1; JOINED; Genomic_DNA.
DR EMBL; AF439445; AAM08285.1; -; Genomic_DNA.
DR EMBL; AC110298; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075089; AAH75089.1; -; mRNA.
DR EMBL; BC075090; AAH75090.1; -; mRNA.
DR CCDS; CCDS3494.1; -.
DR RefSeq; NP_573574.1; NM_133267.2.
DR AlphaFoldDB; Q9BZM3; -.
DR SMR; Q9BZM3; -.
DR BioGRID; 128089; 5.
DR IntAct; Q9BZM3; 1.
DR STRING; 9606.ENSP00000319118; -.
DR BioMuta; GSX2; -.
DR DMDM; 296434530; -.
DR MassIVE; Q9BZM3; -.
DR PaxDb; Q9BZM3; -.
DR PeptideAtlas; Q9BZM3; -.
DR PRIDE; Q9BZM3; -.
DR Antibodypedia; 12271; 117 antibodies from 23 providers.
DR DNASU; 170825; -.
DR Ensembl; ENST00000326902.7; ENSP00000319118.2; ENSG00000180613.11.
DR GeneID; 170825; -.
DR KEGG; hsa:170825; -.
DR MANE-Select; ENST00000326902.7; ENSP00000319118.2; NM_133267.3; NP_573574.2.
DR UCSC; uc010igp.2; human.
DR CTD; 170825; -.
DR DisGeNET; 170825; -.
DR GeneCards; GSX2; -.
DR HGNC; HGNC:24959; GSX2.
DR HPA; ENSG00000180613; Not detected.
DR MalaCards; GSX2; -.
DR MIM; 616253; gene.
DR MIM; 618646; phenotype.
DR neXtProt; NX_Q9BZM3; -.
DR OpenTargets; ENSG00000180613; -.
DR PharmGKB; PA162390374; -.
DR VEuPathDB; HostDB:ENSG00000180613; -.
DR eggNOG; KOG0489; Eukaryota.
DR GeneTree; ENSGT00940000156043; -.
DR HOGENOM; CLU_077153_0_0_1; -.
DR InParanoid; Q9BZM3; -.
DR OMA; HAPVCTP; -.
DR OrthoDB; 1341872at2759; -.
DR PhylomeDB; Q9BZM3; -.
DR TreeFam; TF315938; -.
DR PathwayCommons; Q9BZM3; -.
DR SignaLink; Q9BZM3; -.
DR BioGRID-ORCS; 170825; 11 hits in 1089 CRISPR screens.
DR ChiTaRS; GSX2; human.
DR GenomeRNAi; 170825; -.
DR Pharos; Q9BZM3; Tbio.
DR PRO; PR:Q9BZM3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9BZM3; protein.
DR Bgee; ENSG00000180613; Expressed in amygdala and 41 other tissues.
DR ExpressionAtlas; Q9BZM3; baseline and differential.
DR Genevisible; Q9BZM3; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0048853; P:forebrain morphogenesis; IEA:Ensembl.
DR GO; GO:0097154; P:GABAergic neuron differentiation; IEA:Ensembl.
DR GO; GO:0021575; P:hindbrain morphogenesis; IEA:Ensembl.
DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IEA:Ensembl.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; IEA:Ensembl.
DR GO; GO:0021527; P:spinal cord association neuron differentiation; IEA:Ensembl.
DR GO; GO:0060163; P:subpallium neuron fate commitment; IEA:Ensembl.
DR GO; GO:0021978; P:telencephalon regionalization; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR042191; GSH2.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR PANTHER; PTHR47421; PTHR47421; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; Disease variant; DNA-binding; Dystonia;
KW Homeobox; Intellectual disability; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..304
FT /note="GS homeobox 2"
FT /id="PRO_0000048896"
FT DNA_BIND 202..261
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 116..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..141
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 9..304
FT /note="Missing (in DMJDS2; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:31412107"
FT /id="VAR_083532"
FT VARIANT 107
FT /note="G -> S (in dbSNP:rs13144341)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.3"
FT /id="VAR_049580"
FT VARIANT 251
FT /note="Q -> R (in DMJDS2; decreased protein abundance;
FT decreased nuclear localization; increased localization to
FT the cytoplasm; changed regulation of gene expression;
FT dbSNP:rs1578005344)"
FT /evidence="ECO:0000269|PubMed:31412107"
FT /id="VAR_083533"
SQ SEQUENCE 304 AA; 32031 MW; 2C879AC635C07F0D CRC64;
MSRSFYVDSL IIKDTSRPAP SLPEPHPGPD FFIPLGMPPP LVMSVSGPGC PSRKSGAFCV
CPLCVTSHLH SSRGSVGAGS GGAGAGVTGA GGSGVAGAAG ALPLLKGQFS SAPGDAQFCP
RVNHAHHHHH PPQHHHHHHQ PQQPGSAAAA AAAAAAAAAA AALGHPQHHA PVCTATTYNV
ADPRRFHCLT MGGSDASQVP NGKRMRTAFT STQLLELERE FSSNMYLSRL RRIEIATYLN
LSEKQVKIWF QNRRVKHKKE GKGTQRNSHA GCKCVGSQVH YARSEDEDSL SPASANDDKE
ISPL
