LET99_CAEEL
ID LET99_CAEEL Reviewed; 698 AA.
AC Q21341;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Protein let-99;
DE AltName: Full=Lethal protein 99;
GN Name=let-99; ORFNames=K08E7.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:CAB01225.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=9477332; DOI=10.1242/dev.125.7.1337;
RA Rose L.S., Kemphues K.;
RT "The let-99 gene is required for proper spindle orientation during cleavage
RT of the C. elegans embryo.";
RL Development 125:1337-1346(1998).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11003841; DOI=10.1242/dev.127.20.4419;
RA Berkowitz L.A., Strome S.;
RT "MES-1, a protein required for unequal divisions of the germline in early
RT C. elegans embryos, resembles receptor tyrosine kinases and is localized to
RT the boundary between the germline and gut cells.";
RL Development 127:4419-4431(2000).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12223405; DOI=10.1242/dev.129.19.4469;
RA Tsou M.-F.B., Hayashi A., DeBella L.R., McGrath G., Rose L.S.;
RT "LET-99 determines spindle position and is asymmetrically enriched in
RT response to PAR polarity cues in C. elegans embryos.";
RL Development 129:4469-4481(2002).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-409 AND ARG-515.
RX PubMed=14534135; DOI=10.1242/dev.00790;
RA Tsou M.-F.B., Hayashi A., Rose L.S.;
RT "LET-99 opposes Galpha/GPR signaling to generate asymmetry for spindle
RT positioning in response to PAR and MES-1/SRC-1 signaling.";
RL Development 130:5717-5730(2003).
CC -!- FUNCTION: Required for the proper orientation of spindles after the
CC establishment of polarity (PubMed:9477332, PubMed:14534135). May play a
CC role in interactions between the astral microtubules and the cortical
CC cytoskeleton (PubMed:9477332). Required for asymmetric forces on nuclei
CC and spindles (PubMed:9477332). Acts downstream of the PAR signaling as
CC an intermediate that transduces polarity information to the machinery
CC that positions the mitotic spindle, possibly by regulating force
CC generation (PubMed:12223405). Regulates gpr-1/2 asymmetric cortical
CC localization during the first embryonic cell divisions
CC (PubMed:14534135). Acts antagonistically to the gpr-1/2 signaling
CC pathway (PubMed:14534135). Regulates mes-1 expression and/or
CC localization pattern during early embryogenesis (PubMed:11003841).
CC {ECO:0000269|PubMed:11003841, ECO:0000269|PubMed:12223405,
CC ECO:0000269|PubMed:14534135, ECO:0000269|PubMed:9477332}.
CC -!- INTERACTION:
CC Q21341; Q9TW45: par-1; NbExp=2; IntAct=EBI-1811800, EBI-1811687;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12223405}.
CC Cytoplasm, cell cortex {ECO:0000269|PubMed:11003841,
CC ECO:0000269|PubMed:12223405}. Note=Enriched at the cell cortex during
CC both meiosis and mitosis (PubMed:12223405). Enriched asymmetrically at
CC the cell cortex in 1-cell embryos (PubMed:14534135). Localizes at the
CC contact site between EMS and P2 in interphase and is excluded from the
CC contact site during prophase (PubMed:14534135).
CC {ECO:0000269|PubMed:12223405, ECO:0000269|PubMed:14534135}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:9477332}.
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DR EMBL; Z77666; CAB01225.1; -; Genomic_DNA.
DR PIR; T23469; T23469.
DR RefSeq; NP_502407.1; NM_070006.3.
DR AlphaFoldDB; Q21341; -.
DR BioGRID; 43302; 6.
DR IntAct; Q21341; 3.
DR STRING; 6239.K08E7.3; -.
DR iPTMnet; Q21341; -.
DR EPD; Q21341; -.
DR PaxDb; Q21341; -.
DR PeptideAtlas; Q21341; -.
DR PRIDE; Q21341; -.
DR EnsemblMetazoa; K08E7.3.1; K08E7.3.1; WBGene00002368.
DR GeneID; 178210; -.
DR KEGG; cel:CELE_K08E7.3; -.
DR UCSC; K08E7.3; c. elegans.
DR CTD; 178210; -.
DR WormBase; K08E7.3; CE06147; WBGene00002368; let-99.
DR eggNOG; ENOG502RT6V; Eukaryota.
DR GeneTree; ENSGT00950000182976; -.
DR HOGENOM; CLU_393910_0_0_1; -.
DR InParanoid; Q21341; -.
DR OMA; GRMYESI; -.
DR OrthoDB; 571547at2759; -.
DR Reactome; R-CEL-8980692; RHOA GTPase cycle.
DR Reactome; R-CEL-9013026; RHOB GTPase cycle.
DR Reactome; R-CEL-9013106; RHOC GTPase cycle.
DR Reactome; R-CEL-9013148; CDC42 GTPase cycle.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9013405; RHOD GTPase cycle.
DR Reactome; R-CEL-9013420; RHOU GTPase cycle.
DR Reactome; R-CEL-9013424; RHOV GTPase cycle.
DR Reactome; R-CEL-9035034; RHOF GTPase cycle.
DR SignaLink; Q21341; -.
DR PRO; PR:Q21341; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00002368; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:WormBase.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000591; DEP_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00610; DEP; 1.
DR SMART; SM00049; DEP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS50186; DEP; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Developmental protein; Mitosis;
KW Reference proteome.
FT CHAIN 1..698
FT /note="Protein let-99"
FT /id="PRO_0000084408"
FT DOMAIN 23..107
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066,
FT ECO:0000305"
FT REGION 115..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 409
FT /note="L->H: In or204ts; temperature sensitive mutant.
FT During EMS blastomere cell division, loss of nuclear
FT rotation resulting in the transversal localization of the
FT mitotic spindle; when associated with H-515."
FT /evidence="ECO:0000269|PubMed:14534135"
FT MUTAGEN 515
FT /note="R->H: In or204ts; temperature sensitive mutant.
FT During EMS blastomere cell division, loss of nuclear
FT rotation resulting in the transversal localization of the
FT mitotic spindle; when associated with H-409."
FT /evidence="ECO:0000269|PubMed:14534135"
SQ SEQUENCE 698 AA; 80085 MW; 7C33AB90F8F1AB49 CRC64;
MSADYSSEKF KATHLFDEIL WHFRSNLSLK TNRRGLATAE NSFSGKEAVD FLMIEMPRII
PNNVPERDKM QKFLEFMMDM NVISEAFPKK VKQRRPFSES RIYLFMKTLD ELKHPKPRSR
RSASFSGARK SAKVAQPASP AATMHRPPKA RLPRRLSRSN GNIDKAGIDN SSGGVENHGF
DDHKDDEIPK KQRTPKILNR SLESICTEEY TEKREVSEMK EKVYDWLPFF KSRRNHTKVN
QPTRRSASLD RNHCVLEQEK AEAALRSQKV TTPPIREAPK DVVFMHPQGP LPAVPSRYQN
HRTSIAGSNP ALLSRGRMYE SIMRRSSVVP VADSVQANNE CSFWKTELLG RLEQIYDRTL
PCEWASKVDG YDIQWNMIEI DHADGIVKSR CQGLQPDYPQ TVIQFMDYLV RYPFVTHKKM
DTGLEYNVNR IFITLVNRLE DLNAPLQFDE CSLIVNLLCK IDSFAAMLDN GPARRWSKVM
ISSSASSIEE AGLMVDGFSR DLPACGIRAS KYRRRALSPF DNRVNLEIQD EKSYEIREQW
LIEAIQLVLL SLPTSRRRKL HKFVTFIQSI ETNAVFDLAD PSNGSSNNRE AAIIGLWTGV
CSKCRKQQGM LITAVLLANF QSLFAVPVEF IEQVKRLECE EKDRYSGPRY AKITRSRNDW
QPPVPDKPQA SPAVFKKPLR EVACEKTKKG LFTRLLRK
