FIGLA_HUMAN
ID FIGLA_HUMAN Reviewed; 219 AA.
AC Q6QHK4;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Factor in the germline alpha;
DE Short=FIGalpha;
DE AltName: Full=Class C basic helix-loop-helix protein 8;
DE Short=bHLHc8;
DE AltName: Full=Folliculogenesis-specific basic helix-loop-helix protein;
DE AltName: Full=Transcription factor FIGa;
GN Name=FIGLA; Synonyms=BHLHC8;
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], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH
RP TCF3/E12, AND VARIANT THR-141.
RX PubMed=15044608; DOI=10.1093/molehr/gah056;
RA Bayne R.A.L., Martins da Silva S.J., Anderson R.A.;
RT "Increased expression of the FIGLA transcription factor is associated with
RT primordial follicle formation in the human fetal ovary.";
RL Mol. Hum. Reprod. 10:373-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12468641; DOI=10.1093/molehr/8.12.1087;
RA Huntriss J., Gosden R., Hinkins M., Oliver B., Miller D., Rutherford A.J.,
RA Picton H.M.;
RT "Isolation, characterization and expression of the human Factor In the
RT Germline alpha (FIGLA) gene in ovarian follicles and oocytes.";
RL Mol. Hum. Reprod. 8:1087-1095(2002).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-219, AND VARIANT THR-141.
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 [5]
RP VARIANT POF6 ASN-140 DEL, AND VARIANT GLU-4.
RX PubMed=18499083; DOI=10.1016/j.ajhg.2008.04.018;
RA Zhao H., Chen Z.-J., Qin Y., Shi Y., Wang S., Choi Y., Simpson J.L.,
RA Rajkovic A.;
RT "Transcription factor FIGLA is mutated in patients with premature ovarian
RT failure.";
RL Am. J. Hum. Genet. 82:1342-1348(2008).
CC -!- FUNCTION: Germline specific transcription factor implicated in
CC postnatal oocyte-specific gene expression. Plays a key regulatory role
CC in the expression of multiple oocyte-specific genes, including those
CC that initiate folliculogenesis and those that encode the zona pellucida
CC (ZP1, ZP2 and ZP3) required for fertilization and early embryonic
CC survival. Essential for oocytes to survive and form primordial
CC follicles. The persistence of FIGLA in adult females suggests that it
CC may regulate additional pathways that are essential for normal ovarian
CC development. Binds to the E-box (5'-CANNTG-3') of the ZPs (ZP1, ZP2,
CC ZP3) promoters. {ECO:0000269|PubMed:15044608}.
CC -!- SUBUNIT: Heterodimer with TCF3/isoform E12.
CC -!- INTERACTION:
CC Q6QHK4; Q9UBR4-2: LHX3; NbExp=5; IntAct=EBI-11976617, EBI-12039345;
CC Q6QHK4; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-11976617, EBI-10258746;
CC Q6QHK4; Q68G74: LHX8; NbExp=8; IntAct=EBI-11976617, EBI-8474075;
CC Q6QHK4; P13349: MYF5; NbExp=3; IntAct=EBI-11976617, EBI-17491620;
CC Q6QHK4; P15172: MYOD1; NbExp=3; IntAct=EBI-11976617, EBI-488878;
CC Q6QHK4; P15173: MYOG; NbExp=5; IntAct=EBI-11976617, EBI-3906629;
CC Q6QHK4; Q99081-3: TCF12; NbExp=3; IntAct=EBI-11976617, EBI-11952764;
CC Q6QHK4; Q7RTU1: TCF23; NbExp=3; IntAct=EBI-11976617, EBI-12127592;
CC Q6QHK4; P15884-3: TCF4; NbExp=3; IntAct=EBI-11976617, EBI-13636688;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Germ cells. Expressed in the fetal ovary, but not
CC by a range of other tissues. Expression increases across mid-gestation,
CC rising some 40-fold by the time of primordial follicle formation.
CC {ECO:0000269|PubMed:12468641, ECO:0000269|PubMed:15044608}.
CC -!- DEVELOPMENTAL STAGE: Expressed in ovarian follicles (from the
CC primordial through to the secondary stage), in mature oocytes, and less
CC frequently in preimplantation embryos. {ECO:0000269|PubMed:12468641}.
CC -!- DISEASE: Premature ovarian failure 6 (POF6) [MIM:612310]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:18499083}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AY541030; AAS48452.1; -; mRNA.
DR EMBL; AC007395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039536; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS46320.1; -.
DR RefSeq; NP_001004311.2; NM_001004311.3.
DR AlphaFoldDB; Q6QHK4; -.
DR SMR; Q6QHK4; -.
DR BioGRID; 131285; 16.
DR IntAct; Q6QHK4; 9.
DR STRING; 9606.ENSP00000333097; -.
DR iPTMnet; Q6QHK4; -.
DR PhosphoSitePlus; Q6QHK4; -.
DR BioMuta; FIGLA; -.
DR DMDM; 296434505; -.
DR MassIVE; Q6QHK4; -.
DR PaxDb; Q6QHK4; -.
DR PRIDE; Q6QHK4; -.
DR Antibodypedia; 31154; 81 antibodies from 18 providers.
DR DNASU; 344018; -.
DR Ensembl; ENST00000332372.6; ENSP00000333097.6; ENSG00000183733.6.
DR GeneID; 344018; -.
DR KEGG; hsa:344018; -.
DR MANE-Select; ENST00000332372.6; ENSP00000333097.6; NM_001004311.3; NP_001004311.2.
DR UCSC; uc002she.1; human.
DR CTD; 344018; -.
DR DisGeNET; 344018; -.
DR GeneCards; FIGLA; -.
DR HGNC; HGNC:24669; FIGLA.
DR HPA; ENSG00000183733; Tissue enhanced (retina).
DR MalaCards; FIGLA; -.
DR MIM; 608697; gene.
DR MIM; 612310; phenotype.
DR neXtProt; NX_Q6QHK4; -.
DR OpenTargets; ENSG00000183733; -.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR PharmGKB; PA145008379; -.
DR VEuPathDB; HostDB:ENSG00000183733; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00440000033552; -.
DR HOGENOM; CLU_1380972_0_0_1; -.
DR InParanoid; Q6QHK4; -.
DR OMA; ELAHTCR; -.
DR OrthoDB; 1245774at2759; -.
DR PhylomeDB; Q6QHK4; -.
DR TreeFam; TF351992; -.
DR PathwayCommons; Q6QHK4; -.
DR SignaLink; Q6QHK4; -.
DR BioGRID-ORCS; 344018; 10 hits in 1089 CRISPR screens.
DR GeneWiki; FIGLA; -.
DR GenomeRNAi; 344018; -.
DR Pharos; Q6QHK4; Tbio.
DR PRO; PR:Q6QHK4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6QHK4; protein.
DR Bgee; ENSG00000183733; Expressed in oocyte and 58 other tissues.
DR Genevisible; Q6QHK4; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0048599; P:oocyte development; NAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Nucleus; Oogenesis;
KW Premature ovarian failure; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..219
FT /note="Factor in the germline alpha"
FT /id="PRO_0000127179"
FT DOMAIN 65..117
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 124..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 4
FT /note="A -> E (in dbSNP:rs71647803)"
FT /evidence="ECO:0000269|PubMed:18499083"
FT /id="VAR_046776"
FT VARIANT 140
FT /note="Missing (in POF6; one individual with premature
FT ovarian failure)"
FT /evidence="ECO:0000269|PubMed:18499083"
FT /id="VAR_046777"
FT VARIANT 141
FT /note="S -> T (in dbSNP:rs7566476)"
FT /evidence="ECO:0000269|PubMed:15044608,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_046778"
SQ SEQUENCE 219 AA; 24123 MW; 82FBD792C3AEB035 CRC64;
MDPAPGVLDP RAAPPALLGT PQAEVLEDVL REQFGPLPQL AAVCRLKRLP SGGYSSTENL
QLVLERRRVA NAKERERIKN LNRGFARLKA LVPFLPQSRK PSKVDILKGA TEYIQVLSDL
LEGAKDSKKQ DPDEQSYSNN SSESHTSSAR QLSRNITQHI SCAFGLKNEE EGPWADGGSG
EPAHACRHSV MSTTEIISPT RSLDRFPEVE LLSHRLPQV
