GCM1_HUMAN
ID GCM1_HUMAN Reviewed; 436 AA.
AC Q9NP62; Q4VAQ7; Q5T0X0; Q99468; Q9P1X3;
DT 25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Chorion-specific transcription factor GCMa;
DE Short=hGCMa;
DE AltName: Full=GCM motif protein 1;
DE AltName: Full=Glial cells missing homolog 1;
GN Name=GCM1; Synonyms=GCMA;
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=Placenta;
RX PubMed=8962155; DOI=10.1073/pnas.93.25.14912;
RA Akiyama Y., Hosoya T., Poole A.M., Hotta Y.;
RT "The gcm-motif: a novel DNA binding motif conserved in Drosophila and
RT mammals.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14912-14916(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Liver, and Placenta;
RA Nishizawa M., Ito S.;
RT "Structure of human GCMa cDNA and gene.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=10542267; DOI=10.1074/jbc.274.45.32279;
RA Yamada K., Ogawa H., Honda S., Harada N., Okazaki T.;
RT "A GCM motif protein is involved in placenta-specific expression of human
RT aromatase gene.";
RL J. Biol. Chem. 274:32279-32286(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11071865; DOI=10.1006/bbrc.2000.3775;
RA Yamada K., Ogawa H., Tamiya G., Ikeno M., Morita M., Asakawa S.,
RA Shimizu N., Okazaki T.;
RT "Genomic organization, chromosomal localization, and the complete 22 kb DNA
RT sequence of the human GCMa/GCM1, a placenta-specific transcription factor
RT gene.";
RL Biochem. Biophys. Res. Commun. 278:134-139(2000).
RN [5]
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 [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 FUNCTION.
RX PubMed=18160678; DOI=10.1095/biolreprod.107.065599;
RA Chang M., Mukherjea D., Gobble R.M., Groesch K.A., Torry R.J., Torry D.S.;
RT "Glial cell missing 1 regulates placental growth factor (PGF) gene
RT transcription in human trophoblast.";
RL Biol. Reprod. 78:841-851(2008).
RN [8]
RP POLYUBIQUITINATION.
RX PubMed=18703417; DOI=10.1095/biolreprod.108.071407;
RA Chiang M.H., Chen L.F., Chen H.;
RT "Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD
RT repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog
RT 1) ubiquitination and degradation.";
RL Biol. Reprod. 79:914-920(2008).
RN [9]
RP FUNCTION.
RX PubMed=19219068; DOI=10.1038/cdd.2009.1;
RA Baczyk D., Drewlo S., Proctor L., Dunk C., Lye S., Kingdom J.;
RT "Glial cell missing-1 transcription factor is required for the
RT differentiation of the human trophoblast.";
RL Cell Death Differ. 16:719-727(2009).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27917469; DOI=10.1002/path.4835;
RA Lo H.F., Tsai C.Y., Chen C.P., Wang L.J., Lee Y.S., Chen C.Y., Liang C.T.,
RA Cheong M.L., Chen H.;
RT "Association of dysfunctional synapse defective 1 (SYDE1) with restricted
RT fetal growth - SYDE1 regulates placental cell migration and invasion.";
RL J. Pathol. 241:324-336(2017).
CC -!- FUNCTION: Transcription factor involved in the control of expression of
CC placental growth factor (PGF) and other placenta-specific genes
CC (PubMed:10542267, PubMed:18160678). Binds to the trophoblast-specific
CC element 2 (TSE2) of the aromatase gene enhancer (PubMed:10542267).
CC Binds to the SYDE1 promoter (PubMed:27917469). Has a central role in
CC mediating the differentiation of trophoblast cells along both the
CC villous and extravillous pathways in placental development
CC (PubMed:19219068). {ECO:0000269|PubMed:10542267,
CC ECO:0000269|PubMed:18160678, ECO:0000269|PubMed:19219068,
CC ECO:0000269|PubMed:27917469}.
CC -!- INTERACTION:
CC Q9NP62; O60479: DLX3; NbExp=2; IntAct=EBI-21194843, EBI-3908248;
CC Q9NP62; Q9UKT8: FBXW2; NbExp=4; IntAct=EBI-21194843, EBI-914727;
CC Q9NP62; P23771: GATA3; NbExp=9; IntAct=EBI-21194843, EBI-6664760;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00245}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the placenta (PubMed:10542267).
CC Expressed in trophoblast cells of the villi (PubMed:27917469).
CC {ECO:0000269|PubMed:10542267, ECO:0000269|PubMed:27917469}.
CC -!- PTM: Polyubiquitinated in the presence of UBE2D2 and FBXW2 (in vitro).
CC {ECO:0000269|PubMed:18703417}.
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DR EMBL; D88613; BAA13651.1; -; mRNA.
DR EMBL; AB041714; BAA94757.1; -; mRNA.
DR EMBL; AB041716; BAA94758.1; -; Genomic_DNA.
DR EMBL; AB026493; BAA77250.2; -; mRNA.
DR EMBL; AB047819; BAB18039.1; -; Genomic_DNA.
DR EMBL; AL512347; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096288; AAH96288.1; -; mRNA.
DR CCDS; CCDS4950.1; -.
DR RefSeq; NP_003634.2; NM_003643.3.
DR AlphaFoldDB; Q9NP62; -.
DR SMR; Q9NP62; -.
DR BioGRID; 114093; 67.
DR IntAct; Q9NP62; 59.
DR STRING; 9606.ENSP00000259803; -.
DR iPTMnet; Q9NP62; -.
DR PhosphoSitePlus; Q9NP62; -.
DR BioMuta; GCM1; -.
DR DMDM; 33516903; -.
DR MassIVE; Q9NP62; -.
DR PaxDb; Q9NP62; -.
DR PeptideAtlas; Q9NP62; -.
DR PRIDE; Q9NP62; -.
DR ProteomicsDB; 81893; -.
DR Antibodypedia; 17251; 318 antibodies from 31 providers.
DR DNASU; 8521; -.
DR Ensembl; ENST00000259803.8; ENSP00000259803.7; ENSG00000137270.11.
DR GeneID; 8521; -.
DR KEGG; hsa:8521; -.
DR MANE-Select; ENST00000259803.8; ENSP00000259803.7; NM_003643.4; NP_003634.2.
DR UCSC; uc003pbp.4; human.
DR CTD; 8521; -.
DR DisGeNET; 8521; -.
DR GeneCards; GCM1; -.
DR HGNC; HGNC:4197; GCM1.
DR HPA; ENSG00000137270; Tissue enriched (placenta).
DR MIM; 603715; gene.
DR neXtProt; NX_Q9NP62; -.
DR OpenTargets; ENSG00000137270; -.
DR PharmGKB; PA28614; -.
DR VEuPathDB; HostDB:ENSG00000137270; -.
DR eggNOG; ENOG502QWH2; Eukaryota.
DR GeneTree; ENSGT00390000006777; -.
DR HOGENOM; CLU_043105_0_0_1; -.
DR InParanoid; Q9NP62; -.
DR OMA; FPLTNWP; -.
DR OrthoDB; 396012at2759; -.
DR PhylomeDB; Q9NP62; -.
DR TreeFam; TF324146; -.
DR PathwayCommons; Q9NP62; -.
DR SignaLink; Q9NP62; -.
DR SIGNOR; Q9NP62; -.
DR BioGRID-ORCS; 8521; 9 hits in 1091 CRISPR screens.
DR ChiTaRS; GCM1; human.
DR GeneWiki; GCM1; -.
DR GenomeRNAi; 8521; -.
DR Pharos; Q9NP62; Tbio.
DR PRO; PR:Q9NP62; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NP62; protein.
DR Bgee; ENSG00000137270; Expressed in placenta and 48 other tissues.
DR Genevisible; Q9NP62; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0060018; P:astrocyte fate commitment; IEA:Ensembl.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0060706; P:cell differentiation involved in embryonic placenta development; IBA:GO_Central.
DR GO; GO:0042063; P:gliogenesis; IBA:GO_Central.
DR GO; GO:0060143; P:positive regulation of syncytium formation by plasma membrane fusion; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0060800; P:regulation of cell differentiation involved in embryonic placenta development; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0000768; P:syncytium formation by plasma membrane fusion; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA: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; DNA-binding; Metal-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc.
FT CHAIN 1..436
FT /note="Chorion-specific transcription factor GCMa"
FT /id="PRO_0000126647"
FT DNA_BIND 14..169
FT /note="GCM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT REGION 171..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 173..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00245"
FT CONFLICT 6
FT /note="F -> S (in Ref. 1; BAA13651)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="E -> G (in Ref. 1; BAA13651)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 436 AA; 49268 MW; E16CDD2DDEB25678 CRC64;
MEPDDFDSED KEILSWDIND VKLPQNVKKT DWFQEWPDSY AKHIYSSEDK NAQRHLSSWA
MRNTNNHNSR ILKKSCLGVV VCGRDCLAEE GRKIYLRPAI CDKARQKQQR KRCPNCDGPL
KLIPCRGHGG FPVTNFWRHD GRFIFFQSKG EHDHPKPETK LEAEARRAMK KVNTAPSSVS
LSLKGSTETR SLPGETQSQG SLPLTWSFQE GVQLPGSYSG HLIANTPQQN SLNDCFSFSK
SYGLGGITDL TDQTSTVDPM KLYEKRKLSS SRTYSSGDLL PPSASGVYSD HGDLQAWSKN
AALGRNHLAD NCYSNYPFPL TSWPCSFSPS QNSSEPFYQQ LPLEPPAAKT GCPPLWPNPA
GNLYEEKVHV DFNSYVQSPA YHSPQEDPFL FTYASHPHQQ YSLPSKSSKW DFEEEMTYLG
LDHCNNDMLL NLCPLR
