P49594 (FEM2_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ca(2+)/calmodulin-dependent protein kinase phosphatase
Short name=CaM-kinase phosphatase
Short name=CaMKPase
EC=3.1.3.16

Alternative name(s):
Feminization of XX and XO animals protein 2
Sex-determining protein fem-2

Gene names

Name:	fem-2
ORF Names:	T19C3.8

Organism

Caenorhabditis elegans [Reference proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis

Protein attributes

Sequence length	449 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable phosphatase involved in the regulation of sex determination. Plays an important role in regulating a pathway transducing a non-cell-autonomous signal to a nuclear transcription factor. Promotes apoptosis. Together with fem-3 associates with the CBC(fem-1) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of tra-1. Ref.4
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity.
Subunit structure	Interacts with fem-1 and fem-3. Part of a E3 ubiquitin-protein ligase complex including fem-1, fem-2, fem-3, tra-1, cul-2 and elc-1. Ref.4
Sequence similarities	Belongs to the PP2C family.

Ontologies

Keywords
Biological process	Apoptosis Ubl conjugation pathway
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	male sex determination Inferred from mutant phenotype PubMed 8824590. Source: WormBase masculinization of hermaphroditic germ-line Inferred from mutant phenotype PubMed 8824590. Source: WormBase peptidyl-threonine dephosphorylation Inferred from direct assay Ref.3. Source: UniProtKB positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.3. Source: UniProtKB tail tip morphogenesis Inferred from mutant phenotype PubMed 8824590. Source: WormBase
Molecular_function	calmodulin-dependent protein phosphatase activity Inferred from direct assay Ref.3. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
fem-1	P17221	3	EBI-1998402,EBI-1998155
sel-10	Q93794	2	EBI-1998402,EBI-323098
tra-1	P34708-1	2	EBI-1998402,EBI-367214

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 449	449	Ca(2+)/calmodulin-dependent protein kinase phosphatase		PRO_0000057761
Sites
	Metal binding	202	1	Manganese 1 By similarity
	Metal binding	202	1	Manganese 2 By similarity
	Metal binding	203	1	Manganese 1; via carbonyl oxygen By similarity
	Metal binding	370	1	Manganese 2 By similarity
	Metal binding	415	1	Manganese 2 By similarity

Sequences

	Sequence		Length	Mass (Da)
	P49594 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: E51705B3DA0FF49D	FASTA	449	50,898
	10 20 30 40 50 60 MEKVNEERDA VFEDHIGDRR RSVRSLLEEA FADEMEKTSY DVEVADTPQP HIPIRFRHPP 70 80 90 100 110 120 IAGPVHDVFG DAIHDIFQKM MKRGQAVDFC HWVSHLIATE IDEKFSEVAF RDVQYNPDIY 130 140 150 160 170 180 VTDSTTEAKK LFNDKIWPAI DKILQQNAET CPILSEKWSG IHVSGDQLKG QRHKQEDRFL 190 200 210 220 230 240 AYPNGQYMDR GEDPISVLAV FDGHGGHECS QYAAGHLWET WLEVRKSRDP SDSLEDQLRK 250 260 270 280 290 300 SLELLDERMT VRSVKECWKG GSTAVCCAID MDQKLMALAW LGDSPGYVMS NIEFRQLTRG 310 320 330 340 350 360 HSPSDEREAR RVEEAGGQLF VIGGELRVNG VLNLTRALGD VPGRPMISNE PETCQVPIES 370 380 390 400 410 420 SDYLVLLACD GISDVFNERD LYQLVEAFAN DYPVEDYAEL SRFICTKAIE AGSADNVSVV 430 440 IGFLRPPQDV WKLMKHESDD EDSDVTDEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The C. elegans sex-determining gene fem-2 encodes a putative protein phosphatase." Pilgrim D.B., McGregor A., Jaeckle P., Johnson T., Hansen D. Mol. Biol. Cell 6:1159-1171(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Bristol N2.
[2]	"Genome sequence of the nematode C. elegans: a platform for investigating biology." The C. elegans sequencing consortium Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Bristol N2.
[3]	"The Caenorhabditis elegans sex-determining protein fem-2 and its human homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase phosphatases that promote apoptosis." Tan K.M.L., Chan S.-L., Tan K.O., Yu V.C. J. Biol. Chem. 276:44193-44202(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[4]	"A CUL-2 ubiquitin ligase containing three FEM proteins degrades TRA-1 to regulate C. elegans sex determination." Starostina N.G., Lim J.M., Schvarzstein M., Wells L., Spence A.M., Kipreos E.T. Dev. Cell 13:127-139(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FEM-1 AND FEM-3, IDENTIFICATION IN A COMPLEX WITH FEM-1; FEM-3; TRA-1; CUL-2 AND ELC-1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U29515 Genomic DNA. Translation: AAC06328.1. FO081735 Genomic DNA. Translation: CCD73740.1.
PIR	T16891.
RefSeq	NP_497224.1. NM_064823.6.
3D structure databases
ProteinModelPortal	P49594.
SMR	P49594. Positions 168-426.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49594. 13 interactions.
STRING	6239.T19C3.8.
Proteomic databases
PaxDb	P49594.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	T19C3.8; T19C3.8; T19C3.8.
GeneID	175217.
KEGG	cel:CELE_T19C3.8.
UCSC	T19C3.8. c. elegans.
Organism-specific databases
CTD	175217.
WormBase	T19C3.8; CE02878; WBGene00001412; fem-2.
Phylogenomic databases
eggNOG	COG0631.
GeneTree	ENSGT00690000101775.
HOGENOM	HOG000112566.
InParanoid	P49594.
KO	K01090.
OMA	CDGISDV.
Family and domain databases
Gene3D	3.60.40.10. 1 hit.
InterPro	IPR001932. PP2C-like. IPR000222. PP2C_Mn2_Asp60_BS. IPR015655. Protein_Pase_2C. [Graphical view]
PANTHER	PTHR13832. PTHR13832. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00331. PP2C_SIG. 1 hit. SM00332. PP2Cc. 1 hit. [Graphical view]
SUPFAM	SSF81606. PP2C-related. 1 hit.
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	887240.

Entry information

Entry name

FEM2_CAEEL

Accession

Primary (citable) accession number: P49594

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Caenorhabditis annotation project