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 27-MAR-2024, entry version 165. 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}. 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; 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; 18. DR ComplexPortal; CPX-3385; Fem-2 phosphatase complex. DR IntAct; P49594; 14. DR MINT; P49594; -. DR STRING; 6239.T19C3.8.2; -. DR EPD; P49594; -. DR PaxDb; 6239-T19C3-8; -. 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 AGR; WB:WBGene00001412; -. 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; GQLLYIQ; -. DR OrthoDB; 202023at2759; -. 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 cell types or 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:0007530; P:sex determination; IMP:ComplexPortal. DR CDD; cd00143; PP2Cc; 1. DR Gene3D; 1.10.1740.220; -; 1. DR Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1. DR InterPro; IPR015655; PP2C. DR InterPro; IPR000222; PP2C_BS. DR InterPro; IPR036457; PPM-type-like_dom_sf. DR InterPro; IPR001932; PPM-type_phosphatase-like_dom. DR PANTHER; PTHR47992:SF267; ALPHABET, ISOFORM E; 1. DR PANTHER; PTHR47992; PROTEIN PHOSPHATASE; 1. DR Pfam; PF00481; PP2C; 1. DR SMART; SM00331; PP2C_SIG; 1. DR SMART; SM00332; PP2Cc; 1. DR SUPFAM; SSF81606; PP2C-like; 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 FT fem-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 //