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   24-JAN-2024, entry version 160.
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; 9606-ENSP00000319118; -.
DR   PeptideAtlas; Q9BZM3; -.
DR   ProteomicsDB; 79876; -.
DR   Antibodypedia; 12271; 133 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   AGR; HGNC:24959; -.
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   Orphanet; 319192; Diencephalic-mesencephalic junction dysplasia.
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; HGGCKCA; -.
DR   OrthoDB; 728401at2759; -.
DR   PhylomeDB; Q9BZM3; -.
DR   TreeFam; TF315938; -.
DR   PathwayCommons; Q9BZM3; -.
DR   SignaLink; Q9BZM3; -.
DR   BioGRID-ORCS; 170825; 11 hits in 1167 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 cell types or tissues.
DR   ExpressionAtlas; Q9BZM3; baseline and differential.
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   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR042191; GSH1/2.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   PANTHER; PTHR47421; GS HOMEOBOX 2; 1.
DR   PANTHER; PTHR47421:SF1; GS HOMEOBOX 2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; Q9BZM3; HS.
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
//