FEM1_CAEEL
ID FEM1_CAEEL Reviewed; 656 AA.
AC P17221; Q95ZU3;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Sex-determining protein fem-1;
DE AltName: Full=Feminization of XX and XO animals protein 1;
GN Name=fem-1; Synonyms=isx-1; ORFNames=F35D6.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=2317869; DOI=10.1016/0092-8674(90)90346-g;
RA Spence A.M., Coulson A., Hodgkin J.;
RT "The product of fem-1, a nematode sex-determining gene, contains a found in
RT cell cycle control proteins and receptors for cell-cell interactions.";
RL Cell 60:981-990(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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 [3]
RP INTERACTION WITH CED-4, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-320
RP AND ASP-344.
RX PubMed=10764728; DOI=10.1074/jbc.c000146200;
RA Chan S.L., Yee K.S., Tan K.M., Yu V.C.;
RT "The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3
RT substrate that associates with CED-4 and mediates apoptosis in mammalian
RT cells.";
RL J. Biol. Chem. 275:17925-17928(2000).
RN [4]
RP INTERACTION WITH SEL-10.
RX PubMed=15306688; DOI=10.1073/pnas.0405087101;
RA Jaeger S., Schwartz H.T., Horvitz H.R., Conradt B.;
RT "The Caenorhabditis elegans F-box protein SEL-10 promotes female
RT development and may target FEM-1 and FEM-3 for degradation by the
RT proteasome.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12549-12554(2004).
RN [5]
RP FUNCTION, IDENTIFICATION IN THE CBC(FEM-1) COMPLEX, INTERACTION WITH TRA-1;
RP CUL-2; ELC-1; FEM-2 AND FEM-3, AND MUTAGENESIS OF 541-LEU--ASP-548.
RX PubMed=17609115; DOI=10.1016/j.devcel.2007.05.008;
RA Starostina N.G., Lim J.M., Schvarzstein M., Wells L., Spence A.M.,
RA Kipreos E.T.;
RT "A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to
RT regulate C. elegans sex determination.";
RL Dev. Cell 13:127-139(2007).
RN [6]
RP IDENTIFICATION IN A COMPLEX WITH FEM-2 AND FEM-3, AND INTERACTION WITH
RP FEM-2.
RX PubMed=23760267; DOI=10.1074/jbc.m113.464339;
RA Zhang Y., Zhao H., Wang J., Ge J., Li Y., Gu J., Li P., Feng Y., Yang M.;
RT "Structural insight into Caenorhabditis elegans sex-determining protein
RT FEM-2.";
RL J. Biol. Chem. 288:22058-22066(2013).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=28118078; DOI=10.1080/15384101.2017.1284715;
RA Dankert J.F., Pagan J.K., Starostina N.G., Kipreos E.T., Pagano M.;
RT "FEM1 proteins are ancient regulators of SLBP degradation.";
RL Cell Cycle 16:556-564(2017).
CC -!- FUNCTION: Substrate-recognition component of the cullin-RING-based
CC CBC(fem-1) (Cul2-ElonginB-ElonginC) E3 ubiquitin-protein ligase complex
CC of the DesCEND (destruction via C-end degrons) pathway, which
CC recognizes a C-degron located at the extreme C terminus of target
CC proteins, leading to their ubiquitination and degradation (By
CC similarity). The C-degron recognized by the DesCEND pathway is usually
CC a motif of less than ten residues and can be present in full-length
CC proteins, truncated proteins or proteolytically cleaved forms (By
CC similarity). Sex-determining protein; essential for the adoption of the
CC male sexual fate in all tissues (PubMed:2317869). The CBC(fem-1)
CC complex mediates the ubiquitination and subsequent proteasomal
CC degradation of tra-1 (PubMed:17609115). Promotes ubiquitination and
CC degradation of cdl-1 (PubMed:28118078). {ECO:0000250|UniProtKB:Q9BSK4,
CC ECO:0000269|PubMed:17609115, ECO:0000269|PubMed:2317869,
CC ECO:0000269|PubMed:28118078}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:17609115, ECO:0000269|PubMed:28118078}.
CC -!- SUBUNIT: Component of a complex containing fem-1, fem-2 and fem-3
CC (PubMed:23760267). Interacts with fem-2 (via N-terminus) and fem-3
CC (PubMed:17609115, PubMed:23760267). Component of the CBC(fem-1) E3
CC ubiquitin-protein ligase complex, at least composed of cul-2, elc-1,
CC tra-1, fem-1, fem-2 and fem-3; mediates the ubiquitination and
CC subsequent proteasomal degradation of tra-1 (PubMed:17609115).
CC Interacts with cul-2 (PubMed:17609115). Interacts with tra-1
CC (PubMed:17609115). Interacts (via VHL-box motif) with elc-1
CC (PubMed:17609115). Interacts with sel-10 (PubMed:15306688). Interacts
CC with ced-4 (PubMed:10764728). {ECO:0000269|PubMed:10764728,
CC ECO:0000269|PubMed:15306688, ECO:0000269|PubMed:17609115,
CC ECO:0000269|PubMed:23760267}.
CC -!- INTERACTION:
CC P17221; Q9BKS1: elc-1; NbExp=3; IntAct=EBI-1998155, EBI-300574;
CC P17221; P49594: fem-2; NbExp=3; IntAct=EBI-1998155, EBI-1998402;
CC P17221; P34691: fem-3; NbExp=3; IntAct=EBI-1998155, EBI-445465;
CC P17221; Q93794: sel-10; NbExp=2; IntAct=EBI-1998155, EBI-323098;
CC P17221; P34708-1: tra-1; NbExp=2; IntAct=EBI-1998155, EBI-367214;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=P17221-1; Sequence=Displayed;
CC Name=b;
CC IsoId=P17221-2; Sequence=VSP_015676, VSP_015677;
CC -!- SIMILARITY: Belongs to the fem-1 family. {ECO:0000305}.
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DR EMBL; J03172; AAA28055.1; -; Genomic_DNA.
DR EMBL; FO080146; CCD61590.1; -; Genomic_DNA.
DR EMBL; FO080146; CCD61591.1; -; Genomic_DNA.
DR PIR; A34793; A34793.
DR RefSeq; NP_500824.1; NM_068423.5. [P17221-1]
DR RefSeq; NP_500825.1; NM_068424.3. [P17221-2]
DR AlphaFoldDB; P17221; -.
DR SMR; P17221; -.
DR BioGRID; 42457; 12.
DR ComplexPortal; CPX-3385; Fem-2 phosphatase complex.
DR IntAct; P17221; 7.
DR STRING; 6239.F35D6.1a; -.
DR EPD; P17221; -.
DR PaxDb; P17221; -.
DR PeptideAtlas; P17221; -.
DR EnsemblMetazoa; F35D6.1a.1; F35D6.1a.1; WBGene00001411. [P17221-1]
DR EnsemblMetazoa; F35D6.1b.1; F35D6.1b.1; WBGene00001411. [P17221-2]
DR GeneID; 177335; -.
DR KEGG; cel:CELE_F35D6.1; -.
DR UCSC; F35D6.1a; c. elegans. [P17221-1]
DR CTD; 37344; -.
DR WormBase; F35D6.1a; CE07175; WBGene00001411; fem-1. [P17221-1]
DR WormBase; F35D6.1b; CE28299; WBGene00001411; fem-1. [P17221-2]
DR eggNOG; KOG0508; Eukaryota.
DR GeneTree; ENSGT00940000161115; -.
DR HOGENOM; CLU_020042_1_0_1; -.
DR InParanoid; P17221; -.
DR OMA; DHCGARV; -.
DR OrthoDB; 252380at2759; -.
DR PhylomeDB; P17221; -.
DR Reactome; R-CEL-8951664; Neddylation.
DR SignaLink; P17221; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:P17221; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00001411; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IDA:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008287; C:protein serine/threonine phosphatase complex; IDA:ComplexPortal.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0019100; P:male germ-line sex determination; IMP:WormBase.
DR GO; GO:0030238; P:male sex determination; IMP:ComplexPortal.
DR GO; GO:0019102; P:male somatic sex determination; IMP:WormBase.
DR GO; GO:0042006; P:masculinization of hermaphroditic germ-line; IMP:WormBase.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0010468; P:regulation of gene expression; IGI:UniProtKB.
DR GO; GO:1905936; P:regulation of germ cell proliferation; IGI:UniProtKB.
DR GO; GO:0007530; P:sex determination; IMP:ComplexPortal.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0036369; P:transcription factor catabolic process; IDA:WormBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF13606; Ank_3; 1.
DR SMART; SM00248; ANK; 7.
DR SUPFAM; SSF48403; SSF48403; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 2.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; Developmental protein;
KW Differentiation; Phosphoprotein; Reference proteome; Repeat;
KW Sexual differentiation; TPR repeat; Ubl conjugation pathway.
FT CHAIN 1..656
FT /note="Sex-determining protein fem-1"
FT /id="PRO_0000067058"
FT REPEAT 47..76
FT /note="ANK 1"
FT REPEAT 88..118
FT /note="ANK 2"
FT REPEAT 122..151
FT /note="ANK 3"
FT REPEAT 155..184
FT /note="ANK 4"
FT REPEAT 188..217
FT /note="ANK 5"
FT REPEAT 220..250
FT /note="ANK 6"
FT REPEAT 346..379
FT /note="TPR"
FT REPEAT 557..588
FT /note="ANK 7"
FT MOTIF 541..548
FT /note="VHL-box"
FT /evidence="ECO:0000269|PubMed:17609115"
FT SITE 320..321
FT /note="Cleavage; by ced-3"
FT /evidence="ECO:0000269|PubMed:10764728"
FT VAR_SEQ 88..104
FT /note="QGTPPLWAASAAGHIEI -> LFRRNTSFVGCLRCWTH (in isoform
FT b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015676"
FT VAR_SEQ 105..656
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015677"
FT MUTAGEN 320
FT /note="D->A: No ced-3-mediated cleavage."
FT /evidence="ECO:0000269|PubMed:10764728"
FT MUTAGEN 344
FT /note="D->A: Does not affect ced-3-mediated cleavage."
FT /evidence="ECO:0000269|PubMed:10764728"
FT MUTAGEN 541..548
FT /note="LEQLLELD->SSSSSSSS: Loss of interaction with elc-1."
FT /evidence="ECO:0000269|PubMed:17609115"
SQ SEQUENCE 656 AA; 74286 MW; 4F5FC3FA3EA950D3 CRC64;
MTPNGHHFRT VIYNAAAVGN LQRIKVFTIN SRNDRQWIID CFNSDQDGRY PLVIAARNGH
ANVVEYLLEI GADPSVRGVV EFDNENIQGT PPLWAASAAG HIEIVKLLIE KANADVNQAT
NTRSTPLRGA CYDGHLDIVK YLLEKGADPH IPNRHGHTCL MIASYRNKVG IVEELLKTGI
DVNKKTERGN TALHDAAESG NVEVVKILLK HGSVLMKDIQ GVDPLMGAAL SGFLDVLNVL
ADQMPSGIHK RDALKLLGST LLDKKMDAMS AMNCWKQSME VPLHADDLRL VREMETFFEP
QEVYEYQREA QNIAQVELLD GNIEAQRMQA LVIRERILGG AHTDVHYYLR FRGAVYCDMG
QMNRCYDLWK HALELQQKHF APLYYGTITT LQSFHETFSM SLNDFVNNHH ANRNLRVRSS
WVKYVFNGVC LELERAAAWT GAPLLEDTEC CGKERCQHAT EESEYKKLVY VAVHLVNVLE
RLSLPSAHID DSDEEKEPKA DVRRLMIVCH ELHIPLLHHT LEERIPDSNS AELGLPKAAV
LEQLLELDLD VNATDKNNDT PMHILLRARE FRKSLVRALL VRGTWLFARN RHGDVVLNVM
KRMKALNHAN FDDLPLGRHI TLAGLVANAM RVKYPKKFVG VEEQMPLELR RFYLAH
