STRA8_MOUSE
ID STRA8_MOUSE Reviewed; 393 AA.
AC P70278; Q496Q5;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Stimulated by retinoic acid gene 8 protein {ECO:0000303|PubMed:8896602};
GN Name=Stra8 {ECO:0000303|PubMed:8896602, ECO:0000312|MGI:MGI:107917};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA99711.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION, AND PHOSPHORYLATION.
RC TISSUE=Embryonic carcinoma {ECO:0000312|EMBL:CAA99711.1};
RX PubMed=8896602; DOI=10.1083/jcb.135.2.469;
RA Oulad-Abdelghani M., Bouillet P., Decimo D., Gansmuller A., Heyberger S.,
RA Dolle P., Bronner S., Lutz Y., Chambon P.;
RT "Characterization of a premeiotic germ cell-specific cytoplasmic protein
RT encoded by Stra8, a novel retinoic acid-responsive gene.";
RL J. Cell Biol. 135:469-477(1996).
RN [2] {ECO:0000312|EMBL:AAI03591.1}
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 [3] {ECO:0000305}
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=14550793; DOI=10.1016/s0012-1606(03)00391-9;
RA Menke D.B., Koubova J., Page D.C.;
RT "Sexual differentiation of germ cells in XX mouse gonads occurs in an
RT anterior-to-posterior wave.";
RL Dev. Biol. 262:303-312(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17115059; DOI=10.1038/ng1919;
RA Baltus A.E., Menke D.B., Hu Y.-C., Goodheart M.L., Carpenter A.E.,
RA de Rooij D.G., Page D.C.;
RT "In germ cells of mouse embryonic ovaries, the decision to enter meiosis
RT precedes premeiotic DNA replication.";
RL Nat. Genet. 38:1430-1434(2006).
RN [5] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16461896; DOI=10.1073/pnas.0510813103;
RA Koubova J., Menke D.B., Zhou Q., Capel B., Griswold M.D., Page D.C.;
RT "Retinoic acid regulates sex-specific timing of meiotic initiation in
RT mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:2474-2479(2006).
RN [6]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18322276; DOI=10.1095/biolreprod.107.066795;
RA Zhou Q., Nie R., Li Y., Friel P., Mitchell D., Hess R.A., Small C.,
RA Griswold M.D.;
RT "Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic
RT cells induced by retinoic acid: an in vivo study in vitamin A-sufficient
RT postnatal murine testes.";
RL Biol. Reprod. 79:35-42(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18799751; DOI=10.1073/pnas.0807297105;
RA Anderson E.L., Baltus A.E., Roepers-Gajadien H.L., Hassold T.J.,
RA de Rooij D.G., van Pelt A.M., Page D.C.;
RT "Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both
RT spermatogenesis and oogenesis in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:14976-14980(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18799790; DOI=10.1242/jcs.035071;
RA Mark M., Jacobs H., Oulad-Abdelghani M., Dennefeld C., Feret B., Vernet N.,
RA Codreanu C.A., Chambon P., Ghyselinck N.B.;
RT "STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and
RT undergo premature chromosome condensation.";
RL J. Cell Sci. 121:3233-3242(2008).
RN [9]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH XPO1.
RX PubMed=19805549; DOI=10.1074/jbc.m109.056481;
RA Tedesco M., La Sala G., Barbagallo F., De Felici M., Farini D.;
RT "STRA8 shuttles between nucleus and cytoplasm and displays transcriptional
RT activity.";
RL J. Biol. Chem. 284:35781-35793(2009).
RN [10]
RP INDUCTION.
RX PubMed=20951351; DOI=10.1016/j.devcel.2010.09.010;
RA Matson C.K., Murphy M.W., Griswold M.D., Yoshida S., Bardwell V.J.,
RA Zarkower D.;
RT "The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that
RT controls the mitosis versus meiosis decision in male germ cells.";
RL Dev. Cell 19:612-624(2010).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25902548; DOI=10.1073/pnas.1505683112;
RA Endo T., Romer K.A., Anderson E.L., Baltus A.E., de Rooij D.G., Page D.C.;
RT "Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell
RT competencies to regulate spermatogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E2347-E2356(2015).
RN [12]
RP FUNCTION, INTERACTION WITH MEIOSIN, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=32032549; DOI=10.1016/j.devcel.2020.01.010;
RA Ishiguro K.I., Matsuura K., Tani N., Takeda N., Usuki S., Yamane M.,
RA Sugimoto M., Fujimura S., Hosokawa M., Chuma S., Ko M.S.H., Araki K.,
RA Niwa H.;
RT "MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ
RT Cells.";
RL Dev. Cell 52:429-445.e10(2020).
RN [13]
RP FUNCTION.
RX PubMed=32054698; DOI=10.1126/science.aaw4115;
RA Nagaoka S.I., Nakaki F., Miyauchi H., Nosaka Y., Ohta H., Yabuta Y.,
RA Kurimoto K., Hayashi K., Nakamura T., Yamamoto T., Saitou M.;
RT "ZGLP1 is a determinant for the oogenic fate in mice.";
RL Science 0:0-0(2020).
CC -!- FUNCTION: Meiosis-inducer required for the transition into meiosis for
CC both female and male germ cells (PubMed:16461896, PubMed:17115059,
CC PubMed:18799751, PubMed:18799790, PubMed:19805549, PubMed:32054698,
CC PubMed:32032549). In female germ cells, acts downstream of ZGLP1 as a
CC key effector of the meiotic program: required for premeiotic DNA
CC replication and subsequent events in meiotic prophase (PubMed:16461896,
CC PubMed:17115059, PubMed:18799751, PubMed:18799790, PubMed:32054698).
CC During spermatogenesis, next to its role in meiotic initiation,
CC promotes (but is not required for) spermatogonial differentiation
CC (PubMed:25902548). In complex with MEIOSIN, directly activates the
CC transcription of a subset of critical meiotic genes playing a central
CC role in cell-cycle switching from mitosis to meiosis (PubMed:19805549,
CC PubMed:32032549). {ECO:0000269|PubMed:16461896,
CC ECO:0000269|PubMed:17115059, ECO:0000269|PubMed:18799751,
CC ECO:0000269|PubMed:18799790, ECO:0000269|PubMed:19805549,
CC ECO:0000269|PubMed:25902548, ECO:0000269|PubMed:32032549,
CC ECO:0000269|PubMed:32054698}.
CC -!- SUBUNIT: Interacts with XPO1. Interacts with MEIOSIN (PubMed:32032549).
CC {ECO:0000269|PubMed:19805549, ECO:0000269|PubMed:32032549}.
CC -!- INTERACTION:
CC P70278; A2CG63: Arid4b; NbExp=4; IntAct=EBI-6394115, EBI-6394082;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19805549,
CC ECO:0000269|PubMed:32032549, ECO:0000269|PubMed:8896602}. Nucleus
CC {ECO:0000269|PubMed:19805549, ECO:0000269|PubMed:32032549}.
CC Note=Shuttles between nucleus and cytoplasm (PubMed:19805549). Nuclear
CC export is XPO1-dependent (PubMed:19805549).
CC {ECO:0000269|PubMed:19805549}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in premeiotic germ cells in
CC both sexes. In females, is expressed in the embryonic ovary. In males,
CC is expressed in pubertal and adult testes, in premeiotic spermatogenic
CC cells. Expressed by some type A and B spermatogonia, preleptotene
CC spermatocytes, and early leptotene spermatocytes (at protein level).
CC Expression begins in late undifferentiated spermatogonia and persists
CC during differentiating spermatogonia (at protein level).
CC {ECO:0000269|PubMed:16461896, ECO:0000269|PubMed:18799790,
CC ECO:0000269|PubMed:25902548, ECO:0000269|PubMed:32032549,
CC ECO:0000269|PubMed:8896602}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated in embryonic germ cells of the female
CC gonads in an anterior-to-posterior wave from 12.5 dpc to 16.5 dpc. In
CC male gonads, expression is first detected after birth.
CC {ECO:0000269|PubMed:14550793, ECO:0000269|PubMed:16461896,
CC ECO:0000269|PubMed:32032549}.
CC -!- INDUCTION: Up-regulated by retinoic acid in embryonic ovaries and adult
CC testes, and by all-trans and 9-cis retinoic acid in P19 embryonic
CC carcinoma (EC) cells. Transcription is repressed by DMRT1 in
CC undifferentiated spermatogonia. {ECO:0000269|PubMed:16461896,
CC ECO:0000269|PubMed:18322276, ECO:0000269|PubMed:20951351,
CC ECO:0000269|PubMed:8896602}.
CC -!- PTM: Phosphorylated in P19 EC cells. {ECO:0000269|PubMed:8896602}.
CC -!- DISRUPTION PHENOTYPE: Female and male mice are infertile due to severe
CC gametogenesis impairment. In female mutant embryos, the initial mitotic
CC development of germ cells is normal, but they fail to undergo
CC promeiotic DNA replication and meiotic chromosome condensation. In male
CC mutants, the premeiotic DNA replication is conserved and germ cells are
CC able to partly condense chromosomes and initiate meiotic recombination.
CC However, they fail to regularily continue over the leptotene stage of
CC prophase I. {ECO:0000269|PubMed:17115059, ECO:0000269|PubMed:18799751,
CC ECO:0000269|PubMed:18799790}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Z75287; CAA99711.1; -; mRNA.
DR EMBL; BC100746; AAI00747.1; -; mRNA.
DR EMBL; BC103590; AAI03591.1; -; mRNA.
DR EMBL; BC103591; AAI03592.1; -; mRNA.
DR CCDS; CCDS39458.1; -.
DR RefSeq; NP_033318.1; NM_009292.1.
DR RefSeq; XP_011239572.1; XM_011241270.1.
DR AlphaFoldDB; P70278; -.
DR SMR; P70278; -.
DR BioGRID; 203556; 2.
DR IntAct; P70278; 6.
DR STRING; 10090.ENSMUSP00000031876; -.
DR iPTMnet; P70278; -.
DR PhosphoSitePlus; P70278; -.
DR jPOST; P70278; -.
DR PaxDb; P70278; -.
DR PRIDE; P70278; -.
DR ProteomicsDB; 258665; -.
DR Antibodypedia; 53744; 198 antibodies from 25 providers.
DR DNASU; 20899; -.
DR Ensembl; ENSMUST00000031876; ENSMUSP00000031876; ENSMUSG00000029848.
DR Ensembl; ENSMUST00000114999; ENSMUSP00000110651; ENSMUSG00000029848.
DR GeneID; 20899; -.
DR KEGG; mmu:20899; -.
DR UCSC; uc009bia.1; mouse.
DR CTD; 346673; -.
DR MGI; MGI:107917; Stra8.
DR VEuPathDB; HostDB:ENSMUSG00000029848; -.
DR eggNOG; ENOG502RT8C; Eukaryota.
DR GeneTree; ENSGT00390000017181; -.
DR HOGENOM; CLU_049039_0_0_1; -.
DR InParanoid; P70278; -.
DR OMA; LQLIMAT; -.
DR OrthoDB; 879443at2759; -.
DR PhylomeDB; P70278; -.
DR TreeFam; TF335594; -.
DR BioGRID-ORCS; 20899; 1 hit in 72 CRISPR screens.
DR PRO; PR:P70278; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P70278; protein.
DR Bgee; ENSMUSG00000029848; Expressed in spermatogonium and 31 other tissues.
DR ExpressionAtlas; P70278; baseline and differential.
DR Genevisible; P70278; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090427; P:activation of meiosis; IMP:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0048133; P:male germ-line stem cell asymmetric division; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IMP:UniProtKB.
DR GO; GO:0048477; P:oogenesis; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR InterPro; IPR033537; Stra8.
DR PANTHER; PTHR35254; PTHR35254; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Differentiation; DNA replication; Meiosis; Nucleus;
KW Oogenesis; Phosphoprotein; Reference proteome; Spermatogenesis;
KW Transcription; Transcription regulation.
FT CHAIN 1..393
FT /note="Stimulated by retinoic acid gene 8 protein"
FT /id="PRO_0000318115"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 66..95
FT /evidence="ECO:0000255"
FT MOTIF 28..33
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000269|PubMed:19805549"
FT MOTIF 209..218
FT /note="Nuclear export signal (NES)"
FT /evidence="ECO:0000269|PubMed:19805549"
FT COMPBIAS 138..193
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 52..63
FT /note="KAVYSQSDITAS -> SVEGAWFTVVAL (in Ref. 2; AAI00747)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 393 AA; 44555 MW; B81DBF3D28082E9F CRC64;
MATPGEGNQP SDDGAPQPLA QLQKLEPRVV RRRLSQARHR ATLVGLFNNL RKAVYSQSDI
TASKWQVLNR TKIHIQEQEE SLDKLLKLKA SFNLQDGNPN SLEEVKEEYA RMYSENDSVF
LNSFLQDSPP EWFPSEAVGP DAEEEGEEEG EEEGEEGEEE EEGDEEGEEE EENGEEREVE
EYQEEEEEEE EEEKKVDLSH SSSTLLPDLM EFERYLNFYK QTMDLLTMNS IISAHEVTLP
IVSAAISHLW QTLSEEKKAR LLQVWEQQHS AFADLTEACL ELAGVEGSMK DSGVDSQGAS
CSLESTPEEI LFEDAFDVAS FLDKSEAQHM SNISAMFATC NSENPEEKFQ LYIQIIEFFK
SLGCVNTPLN QEPEPPDDDD AMLLKCLETF DDL
