GSC_HUMAN
ID GSC_HUMAN Reviewed; 257 AA.
AC P56915; Q86YR1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Homeobox protein goosecoid;
GN Name=GSC;
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=Leukocyte;
RX PubMed=7916327; DOI=10.1006/geno.1994.1281;
RA Blum M., De Robertis E.M., Kojis T., Heinzmann C., Klisak I., Geissert D.,
RA Sparkes R.S.;
RT "Molecular cloning of the human homeobox gene goosecoid (GSC) and mapping
RT of the gene to human chromosome 14q32.1.";
RL Genomics 21:388-393(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RA Guo J.H., Chen S., Chen L., Yu L.;
RT "Cloning and expression pattern, DNA binding study of two novel human Hox
RT genes.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone;
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 [4]
RP FUNCTION, AND INVOLVEMENT IN SAMS.
RX PubMed=24290375; DOI=10.1016/j.ajhg.2013.10.027;
RA Parry D.A., Logan C.V., Stegmann A.P., Abdelhamed Z.A., Calder A., Khan S.,
RA Bonthron D.T., Clowes V., Sheridan E., Ghali N., Chudley A.E., Dobbie A.,
RA Stumpel C.T., Johnson C.A.;
RT "SAMS, a syndrome of short stature, auditory-canal atresia, mandibular
RT hypoplasia, and skeletal abnormalities is a unique neurocristopathy caused
RT by mutations in Goosecoid.";
RL Am. J. Hum. Genet. 93:1135-1142(2013).
RN [5]
RP STRUCTURE BY NMR OF 161-217.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the homeobox domain of homeobox protein goosecoid.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Regulates chordin (CHRD). May play a role in spatial
CC programing within discrete embryonic fields or lineage compartments
CC during organogenesis. In concert with NKX3-2, plays a role in defining
CC the structural components of the middle ear; required for the
CC development of the entire tympanic ring (By similarity). Probably
CC involved in the regulatory networks that define neural crest cell fate
CC specification and determine mesoderm cell lineages in mammals.
CC {ECO:0000250, ECO:0000269|PubMed:24290375}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DISEASE: Short stature, auditory canal atresia, mandibular hypoplasia,
CC skeletal abnormalities (SAMS) [MIM:602471]: An autosomal recessive
CC developmental disorder with features of a first and second branchial
CC arch syndrome, and with unique rhizomelic skeletal anomalies.
CC Craniofacial abnormalities can lead to conductive hearing loss,
CC respiratory insufficiency, and feeding difficulties. Skeletal features
CC include bilateral humeral hypoplasia, humeroscapular synostosis, pelvic
CC abnormalities, and proximal defects of the femora. Affected individuals
CC may also have some features of a neurocristopathy or abnormal mesoderm
CC development, such as urogenital anomalies, that are distinct from other
CC branchial arch syndromes. {ECO:0000269|PubMed:24290375}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AY177407; AAO18645.1; -; mRNA.
DR EMBL; BC063580; AAH63580.1; -; mRNA.
DR CCDS; CCDS9930.1; -.
DR PIR; A54677; A54677.
DR RefSeq; NP_776248.1; NM_173849.2.
DR PDB; 2DMU; NMR; -; A=161-217.
DR PDBsum; 2DMU; -.
DR AlphaFoldDB; P56915; -.
DR SMR; P56915; -.
DR BioGRID; 126899; 7.
DR ELM; P56915; -.
DR IntAct; P56915; 2.
DR STRING; 9606.ENSP00000238558; -.
DR iPTMnet; P56915; -.
DR PhosphoSitePlus; P56915; -.
DR BioMuta; GSC; -.
DR DMDM; 61252078; -.
DR MassIVE; P56915; -.
DR PaxDb; P56915; -.
DR PeptideAtlas; P56915; -.
DR PRIDE; P56915; -.
DR ProteomicsDB; 56956; -.
DR Antibodypedia; 27137; 503 antibodies from 32 providers.
DR CPTC; P56915; 4 antibodies.
DR DNASU; 145258; -.
DR Ensembl; ENST00000238558.5; ENSP00000238558.3; ENSG00000133937.5.
DR GeneID; 145258; -.
DR KEGG; hsa:145258; -.
DR MANE-Select; ENST00000238558.5; ENSP00000238558.3; NM_173849.3; NP_776248.1.
DR UCSC; uc001ydu.4; human.
DR CTD; 145258; -.
DR DisGeNET; 145258; -.
DR GeneCards; GSC; -.
DR HGNC; HGNC:4612; GSC.
DR HPA; ENSG00000133937; Tissue enhanced (adipose tissue, breast).
DR MalaCards; GSC; -.
DR MIM; 138890; gene.
DR MIM; 602471; phenotype.
DR neXtProt; NX_P56915; -.
DR OpenTargets; ENSG00000133937; -.
DR Orphanet; 397623; Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome.
DR PharmGKB; PA29004; -.
DR VEuPathDB; HostDB:ENSG00000133937; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000160635; -.
DR HOGENOM; CLU_096519_0_0_1; -.
DR InParanoid; P56915; -.
DR OMA; AGPPCCG; -.
DR OrthoDB; 1270742at2759; -.
DR PhylomeDB; P56915; -.
DR TreeFam; TF351613; -.
DR PathwayCommons; P56915; -.
DR SignaLink; P56915; -.
DR SIGNOR; P56915; -.
DR BioGRID-ORCS; 145258; 7 hits in 1094 CRISPR screens.
DR EvolutionaryTrace; P56915; -.
DR GeneWiki; GSC_(gene); -.
DR GenomeRNAi; 145258; -.
DR Pharos; P56915; Tbio.
DR PRO; PR:P56915; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P56915; protein.
DR Bgee; ENSG00000133937; Expressed in calcaneal tendon and 61 other tissues.
DR Genevisible; P56915; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; NAS:UniProtKB.
DR GO; GO:0042474; P:middle ear morphogenesis; ISS:UniProtKB.
DR GO; GO:0048644; P:muscle organ morphogenesis; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0014036; P:neural crest cell fate specification; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR IDEAL; IID00202; -.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR Pfam; PF00046; Homeodomain; 1.
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 3D-structure; Developmental protein; DNA-binding; Dwarfism; Homeobox;
KW Nucleus; Reference proteome.
FT CHAIN 1..257
FT /note="Homeobox protein goosecoid"
FT /id="PRO_0000048885"
FT DNA_BIND 160..219
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 213..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..257
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 26..28
FT /note="AHS -> RT (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 45..47
FT /note="Missing (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="Missing (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="S -> T (in Ref. 1)"
FT /evidence="ECO:0000305"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:2DMU"
FT HELIX 187..196
FT /evidence="ECO:0007829|PDB:2DMU"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:2DMU"
SQ SEQUENCE 257 AA; 28150 MW; BA2A56144F921407 CRC64;
MPASMFSIDN ILAARPRCKD SVLPVAHSAA APVVFPALHG DSLYGASGGA SSDYGAFYPR
PVAPGGAGLP AAVSGSRLGY NNYFYGQLHV QAAPVGPACC GAVPPLGAQQ CSCVPTPPGY
EGPGSVLVSP VPHQMLPYMN VGTLSRTELQ LLNQLHCRRK RRHRTIFTDE QLEALENLFQ
ETKYPDVGTR EQLARKVHLR EEKVEVWFKN RRAKWRRQKR SSSEESENAE KWNKTSSSKA
SPEKREEEGK SDLDSDS
