FEM2_CAEEL
ID FEM2_CAEEL Reviewed; 449 AA.
AC P49594;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Protein phosphatase fem-2 {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000269|PubMed:11559703, ECO:0000269|PubMed:23760267, ECO:0000269|PubMed:8824590};
DE AltName: Full=Ca(2+)/calmodulin-dependent protein kinase phosphatase {ECO:0000303|PubMed:11559703};
DE Short=CaM-kinase phosphatase {ECO:0000303|PubMed:11559703};
DE Short=CaMKPase {ECO:0000303|PubMed:11559703};
DE AltName: Full=Feminization of XX and XO animals protein 2 {ECO:0000312|WormBase:T19C3.8};
DE AltName: Full=Sex-determining protein fem-2 {ECO:0000303|PubMed:8534913};
GN Name=fem-2 {ECO:0000312|WormBase:T19C3.8};
GN ORFNames=T19C3.8 {ECO:0000312|WormBase:T19C3.8};
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].
RC STRAIN=Bristol N2;
RX PubMed=8534913; DOI=10.1091/mbc.6.9.1159;
RA Pilgrim D.B., McGregor A., Jaeckle P., Johnson T., Hansen D.;
RT "The C. elegans sex-determining gene fem-2 encodes a putative protein
RT phosphatase.";
RL Mol. Biol. Cell 6:1159-1171(1995).
RN [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH FEM-3, AND
RP MUTAGENESIS OF ARG-336.
RX PubMed=8824590; DOI=10.1101/gad.10.18.2314;
RA Chin-Sang I.D., Spence A.M.;
RT "Caenorhabditis elegans sex-determining protein FEM-2 is a protein
RT phosphatase that promotes male development and interacts directly with FEM-
RT 3.";
RL Genes Dev. 10:2314-2325(1996).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=11559703; DOI=10.1074/jbc.m105880200;
RA Tan K.M.L., Chan S.-L., Tan K.O., Yu V.C.;
RT "The Caenorhabditis elegans sex-determining protein fem-2 and its human
RT homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase
RT phosphatases that promote apoptosis.";
RL J. Biol. Chem. 276:44193-44202(2001).
RN [5]
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 [6]
RP FUNCTION, IDENTIFICATION IN THE CBC(FEM-1) COMPLEX, AND INTERACTION WITH
RP TRA-1; FEM-1 AND FEM-3.
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH MAGNESIUM,
RP IDENTIFICATION IN A COMPLEX WITH FEM-1 AND FEM-3, INTERACTION WITH FEM-1
RP AND FEM-3, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 2-GLU--ASP-41;
RP 28-GLU--GLU-34; 54-ILE--PHE-56; 71-ASP--ASP-75; ASP-202; ASP-370 AND
RP ASP-415.
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).
CC -!- FUNCTION: Dephosphorylates auto-phosphorylated Ca(2+)/calmodulin-
CC dependent protein kinase unc-43/CAMKII in vitro (PubMed:11559703,
CC PubMed:23760267). Involved in the regulation of sex determination
CC (PubMed:8824590). Together with fem-3, required for male sexual
CC development by promoting the proteasomal-mediated degradation of tra-1,
CC a transcription repressor of male-specific genes (PubMed:17609115).
CC Promotes apoptosis (PubMed:11559703). {ECO:0000269|PubMed:11559703,
CC ECO:0000269|PubMed:17609115, ECO:0000269|PubMed:23760267,
CC ECO:0000269|PubMed:8824590}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:11559703, ECO:0000269|PubMed:23760267,
CC ECO:0000269|PubMed:8824590};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000269|PubMed:11559703, ECO:0000269|PubMed:23760267,
CC ECO:0000269|PubMed:8824590};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11559703, ECO:0000269|PubMed:23760267,
CC ECO:0000269|PubMed:8824590};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11559703};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000269|PubMed:23760267};
CC -!- SUBUNIT: Component of a complex containing fem-1, fem-2 and fem-3
CC (PubMed:23760267). Interacts (via N-terminus) with fem-1 and fem-3
CC (PubMed:17609115, PubMed:23760267, PubMed:8824590). Component of the
CC CBC(fem-1) E3 ubiquitin-protein ligase complex, at least composed of
CC cul-2, elc-1, tra-1, fem-1, fem-2 and fem-3; mediates the
CC ubiquitination and subsequent proteasomal degradation of tra-1
CC (PubMed:17609115). Interacts with tra-1 (PubMed:17609115). Interacts
CC with sel-10 (PubMed:15306688). {ECO:0000269|PubMed:15306688,
CC ECO:0000269|PubMed:17609115, ECO:0000269|PubMed:23760267,
CC ECO:0000269|PubMed:8824590}.
CC -!- INTERACTION:
CC P49594; P17221: fem-1; NbExp=3; IntAct=EBI-1998402, EBI-1998155;
CC P49594; Q93794: sel-10; NbExp=2; IntAct=EBI-1998402, EBI-323098;
CC P49594; P34708-1: tra-1; NbExp=2; IntAct=EBI-1998402, EBI-367214;
CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}.
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DR EMBL; U29515; AAC06328.1; -; Genomic_DNA.
DR EMBL; FO081735; CCD73740.1; -; Genomic_DNA.
DR PIR; T16891; T16891.
DR RefSeq; NP_497224.1; NM_064823.6.
DR PDB; 4JND; X-ray; 1.65 A; A=1-449.
DR PDBsum; 4JND; -.
DR AlphaFoldDB; P49594; -.
DR SMR; P49594; -.
DR BioGRID; 40488; 17.
DR ComplexPortal; CPX-3385; Fem-2 phosphatase complex.
DR IntAct; P49594; 14.
DR MINT; P49594; -.
DR STRING; 6239.T19C3.8; -.
DR EPD; P49594; -.
DR PaxDb; P49594; -.
DR PeptideAtlas; P49594; -.
DR EnsemblMetazoa; T19C3.8.1; T19C3.8.1; WBGene00001412.
DR GeneID; 175217; -.
DR KEGG; cel:CELE_T19C3.8; -.
DR UCSC; T19C3.8; c. elegans.
DR CTD; 175217; -.
DR WormBase; T19C3.8; CE02878; WBGene00001412; fem-2.
DR eggNOG; KOG0698; Eukaryota.
DR GeneTree; ENSGT00940000156633; -.
DR HOGENOM; CLU_610072_0_0_1; -.
DR InParanoid; P49594; -.
DR OMA; GGHECSQ; -.
DR OrthoDB; 1044139at2759; -.
DR PhylomeDB; P49594; -.
DR SignaLink; P49594; -.
DR PRO; PR:P49594; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00001412; 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:0008287; C:protein serine/threonine phosphatase complex; IDA:ComplexPortal.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0033192; F:calmodulin-dependent protein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:WormBase.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030238; P:male sex determination; IMP:WormBase.
DR GO; GO:0042006; P:masculinization of hermaphroditic germ-line; IMP:WormBase.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; IDA:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:WormBase.
DR GO; GO:0007530; P:sex determination; IMP:ComplexPortal.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR InterPro; IPR015655; PP2C.
DR InterPro; IPR000222; PP2C_BS.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR PANTHER; PTHR13832; PTHR13832; 1.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00331; PP2C_SIG; 1.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS01032; PPM_1; 1.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Developmental protein; Differentiation; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Protein phosphatase;
KW Reference proteome; Sexual differentiation; Ubl conjugation pathway.
FT CHAIN 1..449
FT /note="Protein phosphatase fem-2"
FT /id="PRO_0000057761"
FT DOMAIN 160..424
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 28..34
FT /note="Interaction with fem-1 and fem-3"
FT /evidence="ECO:0000269|PubMed:23760267"
FT REGION 54..56
FT /note="Interaction with fem-3"
FT /evidence="ECO:0000269|PubMed:23760267"
FT BINDING 202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23760267,
FT ECO:0007744|PDB:4JND"
FT BINDING 202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23760267,
FT ECO:0007744|PDB:4JND"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23760267,
FT ECO:0007744|PDB:4JND"
FT BINDING 370
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23760267,
FT ECO:0007744|PDB:4JND"
FT BINDING 415
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23760267,
FT ECO:0007744|PDB:4JND"
FT MUTAGEN 2..41
FT /note="Missing: Severe reduction in the interaction with
FT fem-1 and fem-3."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 28..34
FT /note="EEAFADE->AAAFAAA: Severe reduction in the
FT interaction with fem-1 and fem-3."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 54..56
FT /note="IRF->AAA: Abolishes the interaction with fem-3 but
FT not with fem-1."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 71..75
FT /note="DAIHD->AAIAA: No effect on the interaction with fem-
FT 3 and fem-1."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 202
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 336
FT /note="R->K,A: Loss of catalytic activity. Prevents male
FT development. No effect on the interaction with fem-3."
FT /evidence="ECO:0000269|PubMed:8824590"
FT MUTAGEN 370
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23760267"
FT MUTAGEN 415
FT /note="D->A: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:23760267"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 68..82
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 87..105
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 136..144
FT /evidence="ECO:0007829|PDB:4JND"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:4JND"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 196..207
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 208..227
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 234..256
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:4JND"
FT TURN 271..274
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 286..292
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 306..314
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:4JND"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:4JND"
FT TURN 344..346
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 352..357
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 362..368
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 370..373
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 378..391
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 394..399
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 400..410
FT /evidence="ECO:0007829|PDB:4JND"
FT STRAND 417..425
FT /evidence="ECO:0007829|PDB:4JND"
FT HELIX 427..434
FT /evidence="ECO:0007829|PDB:4JND"
SQ SEQUENCE 449 AA; 50898 MW; E51705B3DA0FF49D CRC64;
MEKVNEERDA VFEDHIGDRR RSVRSLLEEA FADEMEKTSY DVEVADTPQP HIPIRFRHPP
IAGPVHDVFG DAIHDIFQKM MKRGQAVDFC HWVSHLIATE IDEKFSEVAF RDVQYNPDIY
VTDSTTEAKK LFNDKIWPAI DKILQQNAET CPILSEKWSG IHVSGDQLKG QRHKQEDRFL
AYPNGQYMDR GEDPISVLAV FDGHGGHECS QYAAGHLWET WLEVRKSRDP SDSLEDQLRK
SLELLDERMT VRSVKECWKG GSTAVCCAID MDQKLMALAW LGDSPGYVMS NIEFRQLTRG
HSPSDEREAR RVEEAGGQLF VIGGELRVNG VLNLTRALGD VPGRPMISNE PETCQVPIES
SDYLVLLACD GISDVFNERD LYQLVEAFAN DYPVEDYAEL SRFICTKAIE AGSADNVSVV
IGFLRPPQDV WKLMKHESDD EDSDVTDEE
