SEH1_DROME
ID SEH1_DROME Reviewed; 354 AA.
AC Q7K2X8;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Nucleoporin seh1 {ECO:0000303|PubMed:21521741};
DE AltName: Full=GATOR complex protein seh1 {ECO:0000303|PubMed:27166823};
DE AltName: Full=Nucleoporin complex protein 44A {ECO:0000312|FlyBase:FBgn0033247};
GN Name=Nup44A {ECO:0000312|FlyBase:FBgn0033247};
GN Synonyms=seh1 {ECO:0000303|PubMed:21521741};
GN ORFNames=CG8722 {ECO:0000312|FlyBase:FBgn0033247};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAL25519.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RC TISSUE=Embryo {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MIO, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=21521741; DOI=10.1242/dev.057372;
RA Senger S., Csokmay J., Akbar T., Tanveer A., Jones T.I., Sengupta P.,
RA Lilly M.A.;
RT "The nucleoporin Seh1 forms a complex with Mio and serves an essential
RT tissue-specific function in Drosophila oogenesis.";
RL Development 138:2133-2142(2011).
RN [5]
RP ERRATUM OF PUBMED:21521741.
RA Senger S., Csokmay J., Akbar T., Tanveer A., Jones T.I., Sengupta P.,
RA Lilly M.A.;
RL Development 138:2631-2631(2011).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=23723238; DOI=10.1126/science.1232044;
RA Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A.,
RA Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M.;
RT "A Tumor suppressor complex with GAP activity for the Rag GTPases that
RT signal amino acid sufficiency to mTORC1.";
RL Science 340:1100-1106(2013).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25512509; DOI=10.1073/pnas.1419156112;
RA Wei Y., Reveal B., Reich J., Laursen W.J., Senger S., Akbar T.,
RA Iida-Jones T., Cai W., Jarnik M., Lilly M.A.;
RT "TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte
RT development in Drosophila.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5670-E5677(2014).
RN [8] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN THE GATOR COMPLEX, INTERACTION WITH WDR24, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=27166823; DOI=10.1371/journal.pgen.1006036;
RA Cai W., Wei Y., Jarnik M., Reich J., Lilly M.A.;
RT "The GATOR2 component Wdr24 regulates TORC1 activity and lysosome
RT function.";
RL PLoS Genet. 12:E1006036-E1006036(2016).
CC -!- FUNCTION: Probable component of the nuclear pore complex (NPC) (By
CC similarity). Involved in maintaining the localization of another
CC nucleoporin Mtor to the nuclear envelope of early meiotic female
CC germline cells (PubMed:21521741). It is not involved in recruiting the
CC nucleoporins Mtor, Nup107, Nup153 and FG-containing nucleoporins to the
CC NPC (PubMed:21521741). {ECO:0000250|UniProtKB:Q96EE3,
CC ECO:0000269|PubMed:21521741}.
CC -!- FUNCTION: An essential component of the GATOR subcomplex GATOR2 which
CC functions as an activator of the amino acid-sensing branch of the TORC1
CC signaling pathway (PubMed:27166823, PubMed:23723238). The two GATOR
CC subcomplexes, GATOR1 and GATOR2, regulate the TORC1 pathway in order to
CC mediate metabolic homeostasis, female gametogenesis and the response to
CC amino acid limitation and complete starvation (PubMed:27166823,
CC PubMed:23723238, PubMed:25512509). GATOR2 activates the TORC1 signaling
CC pathway through the inhibition of the GATOR1 subcomplex, controlling
CC the switch to cell proliferation growth under nutrient replete
CC conditions and growth during female oocyte development
CC (PubMed:21521741, PubMed:25512509, PubMed:23723238, PubMed:27166823).
CC This component is required for activating TORC1 specifically in
CC germline cells to promote cell growth and maintain the oocyte fate,
CC probably influences the organization and/or function of microtubules
CC within ovarian cysts, and promotes accumulation of another GATOR2
CC complex member mio in germline and somatic tissues (PubMed:27166823,
CC PubMed:23723238, PubMed:25512509, PubMed:21521741). GATOR1 and GATOR2
CC act at different stages of oogenesis to regulate TORC1 in order to
CC control meiotic entry and promote oocyte growth and development
CC (PubMed:25512509). After exactly four mitotic cyst divisions, the
CC GATOR1 complex members (Iml1, Nprl2 and Nprl3) down-regulate TORC1 to
CC slow cellular metabolism and promote the mitotic/meiotic transition
CC (PubMed:25512509). At later stages of oogenesis, the mio and Nup44A
CC components of the GATOR2 complex inhibit GATOR1 and thus activate TORC1
CC to promote meiotic progression, and drive oocyte growth and development
CC (PubMed:21521741, PubMed:25512509). In addition to its role in the
CC regulation of the TORC1 complex, functions independently of TORC1 to
CC prevent the inappropriate accumulation of autolysosomes in germline
CC tissues (PubMed:27166823). {ECO:0000269|PubMed:21521741,
CC ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25512509,
CC ECO:0000269|PubMed:27166823}.
CC -!- SUBUNIT: Probable component of the nuclear pore complex (NPC) (By
CC similarity). Component of the GATOR complex consisting of mio,
CC Nup44A/Seh1, Im11, Nplr3, Nplr2, Wdr24, Wdr59 and Sec13
CC (PubMed:27166823). Within the GATOR complex, probable component of the
CC GATOR2 subcomplex which is likely composed of mio, Nup44A/Seh1, Wdr24,
CC Wdr59 and Sec13 (PubMed:27166823). Interacts with mio
CC (PubMed:21521741). Interacts with Wdr24 (PubMed:27166823).
CC {ECO:0000250|UniProtKB:Q96EE3, ECO:0000269|PubMed:21521741,
CC ECO:0000269|PubMed:27166823}.
CC -!- SUBCELLULAR LOCATION: Nucleus envelope {ECO:0000269|PubMed:21521741}.
CC Lysosome {ECO:0000269|PubMed:25512509}. Note=Enriched on the nuclear
CC envelope of nurse cells, oocytes and syncytial embryos
CC (PubMed:21521741). In egg chambers detected in lysosomes and
CC autolysosomes of both fed and starved females (PubMed:25512509).
CC {ECO:0000269|PubMed:21521741, ECO:0000269|PubMed:25512509}.
CC -!- TISSUE SPECIFICITY: Expressed in ovarian cysts.
CC {ECO:0000269|PubMed:21521741}.
CC -!- DISRUPTION PHENOTYPE: Adults develop normally, however females display
CC ovarian defects and reduced fertility likely due to the significant
CC decrease in TORC1 activity within the germline cells (PubMed:21521741,
CC PubMed:25512509). Ovarian defects include adherent cyst divisions due
CC to mitotic delay, accumulation of autolysosomes resulting in reduced
CC number of egg chambers and reduced number of eggs laid per female per
CC day (PubMed:21521741, PubMed:25512509). Spindle defects and mitotic
CC delay results in egg chambers often containing 16 polyploid nurse cells
CC and no oocyte because the oocyte enters the endocycle and develops as a
CC polyploid nurse cell (PubMed:21521741). In early meiotic germline
CC cells, the nucleoporin Mtor is displaced from the nuclear envelope to
CC the nucleoplasm, most notably as cysts enter the meiotic cycle
CC beginning in R2a of the germarium (PubMed:21521741). However, there is
CC no effect on the recruitment of Mtor or other nucleoporins (Nup107,
CC Nup153, Mtor and FG-containing nucleoporins) to the nuclear pore
CC complex (PubMed:21521741). In contrast, somatic tissues do not display
CC any obvious developmental defects; there is no decrease in TORC1
CC activity and no accumulation of autolysosomes in the larval fat body
CC (PubMed:25512509, PubMed:21521741, PubMed:27166823). Increasing TORC1
CC activity in the mutant female germline via RNAi-mediated knockdown of
CC the GATOR1 subcomplex members Nprl2, Nprl3, Iml1 or knockdown of Tsc1
CC rescues the ovarian defects (PubMed:25512509). However, knockdown of
CC Nprl2 or Nprl3 does not rescue the accumulation of autolysosomes
CC (PubMed:27166823). {ECO:0000269|PubMed:21521741,
CC ECO:0000269|PubMed:25512509, ECO:0000269|PubMed:27166823}.
CC -!- SIMILARITY: Belongs to the WD repeat SEC13 family. {ECO:0000305}.
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DR EMBL; AE013599; AAF59154.1; -; Genomic_DNA.
DR EMBL; AY060480; AAL25519.1; -; mRNA.
DR EMBL; AE013599; AAM68880.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68881.1; -; Genomic_DNA.
DR RefSeq; NP_610343.1; NM_136499.3.
DR RefSeq; NP_724637.1; NM_165582.2.
DR RefSeq; NP_724638.1; NM_165583.2.
DR AlphaFoldDB; Q7K2X8; -.
DR SMR; Q7K2X8; -.
DR IntAct; Q7K2X8; 1.
DR STRING; 7227.FBpp0087936; -.
DR PaxDb; Q7K2X8; -.
DR PRIDE; Q7K2X8; -.
DR DNASU; 35762; -.
DR EnsemblMetazoa; FBtr0088860; FBpp0087936; FBgn0033247.
DR EnsemblMetazoa; FBtr0088861; FBpp0087937; FBgn0033247.
DR EnsemblMetazoa; FBtr0088862; FBpp0087938; FBgn0033247.
DR GeneID; 35762; -.
DR KEGG; dme:Dmel_CG8722; -.
DR UCSC; CG8722-RA; d. melanogaster.
DR CTD; 35762; -.
DR FlyBase; FBgn0033247; Nup44A.
DR VEuPathDB; VectorBase:FBgn0033247; -.
DR eggNOG; KOG2445; Eukaryota.
DR GeneTree; ENSGT00940000153393; -.
DR HOGENOM; CLU_032441_1_1_1; -.
DR InParanoid; Q7K2X8; -.
DR OMA; NAPTRRW; -.
DR OrthoDB; 944756at2759; -.
DR PhylomeDB; Q7K2X8; -.
DR Reactome; R-DME-159227; Transport of the SLBP independent Mature mRNA.
DR Reactome; R-DME-159230; Transport of the SLBP Dependant Mature mRNA.
DR Reactome; R-DME-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR Reactome; R-DME-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-DME-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-DME-3301854; Nuclear Pore Complex (NPC) Disassembly.
DR Reactome; R-DME-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-DME-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-DME-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-DME-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-DME-5578749; Transcriptional regulation by small RNAs.
DR Reactome; R-DME-9615933; Postmitotic nuclear pore complex (NPC) reformation.
DR BioGRID-ORCS; 35762; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 35762; -.
DR PRO; PR:Q7K2X8; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033247; Expressed in eye disc (Drosophila) and 24 other tissues.
DR GO; GO:0044754; C:autolysosome; IDA:FlyBase.
DR GO; GO:0061700; C:GATOR2 complex; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:FlyBase.
DR GO; GO:0005635; C:nuclear envelope; IDA:FlyBase.
DR GO; GO:0031080; C:nuclear pore outer ring; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IPI:FlyBase.
DR GO; GO:0035859; C:Seh1-associated complex; IDA:FlyBase.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0007293; P:germarium-derived egg chamber formation; IMP:FlyBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:FlyBase.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0051445; P:regulation of meiotic cell cycle; IMP:FlyBase.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:FlyBase.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR037597; Nucleoporin_Seh1.
DR InterPro; IPR037363; Sec13/Seh1_fam.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR11024; PTHR11024; 1.
DR PANTHER; PTHR11024:SF3; PTHR11024:SF3; 1.
DR Pfam; PF00400; WD40; 2.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Differentiation; Lysosome; Meiosis; Mitosis;
KW Nucleus; Oogenesis; Protein transport; Reference proteome; Repeat;
KW Transport; WD repeat.
FT CHAIN 1..354
FT /note="Nucleoporin seh1"
FT /id="PRO_0000447023"
FT REPEAT 10..49
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 55..96
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 112..153
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 161..209
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 216..259
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 270..309
FT /note="WD 6"
FT /evidence="ECO:0000255"
SQ SEQUENCE 354 AA; 39515 MW; 235785A7B9246C81 CRC64;
MFDVEPIIAD HKDVIHDVVF DYYGRRMATC SSDQTVKIWD EDGQGKWNVT SSWKAHSGSI
WRVSWAHPEF GQVVATCSFD RTASVWEEVI GEKVSSTNTP TRRWVRRTTL VDSRTSVTDV
EFAPKYLGLL LATASADGII RIYEAPDIMN LSQWPVQHEI SNKLPLSCLS WNTSTYMVTQ
LLAAGSDEAA TPTGKVFLFA YSENSRKCVK IDTVNDITDP VTDVAFAPNA GRTFHMLAVA
SKDLYIVNLR GVTDATDISK LDIQTIKFSE HNCPVWRVCW NMLATMLIST GDDGCVRLWR
MNYNRQWRCA AVLKAEGSGP TYEPAPPTPT LATTASATAK FYKKGTIGNQ VPWH
