ID CDC14_CAEEL Reviewed; 709 AA. AC P81299; A0A0K3AQY3; A0A0K3ATW0; P81300; Q09955; Q09976; Q6DLY2; Q6DLY3; AC Q6DLY4; Q6DLY5; Q6DLY6; Q8MQD6; DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 12-SEP-2018, sequence version 3. DT 27-MAR-2024, entry version 174. DE RecName: Full=Tyrosine-protein phosphatase cdc-14; DE EC=3.1.3.48 {ECO:0000255|PROSITE-ProRule:PRU10044, ECO:0000269|PubMed:12213836}; DE AltName: Full=Cell division cycle-related protein 14; GN Name=cdc-14 {ECO:0000303|PubMed:12213836, ECO:0000303|PubMed:15247923, GN ECO:0000312|WormBase:C17G10.4h}; GN ORFNames=C17G10.4 {ECO:0000312|WormBase:C17G10.4h}; 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 [MRNA] (ISOFORMS A; C; D AND E), FUNCTION, SUBCELLULAR RP LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 446-GLN--SER-709. RX PubMed=15247923; DOI=10.1038/ncb1154; RA Saito R.M., Perreault A., Peach B., Satterlee J.S., van den Heuvel S.; RT "The CDC-14 phosphatase controls developmental cell-cycle arrest in C. RT elegans."; RL Nat. Cell Biol. 6:777-783(2004). RN [2] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C). RA Ernsting B.R., Li L., Wishart M.J., Dixon J.E.; RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases. RN [3] 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 [4] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-295. RX PubMed=12213836; DOI=10.1083/jcb.200202054; RA Gruneberg U., Glotzer M., Gartner A., Nigg E.A.; RT "The CeCDC-14 phosphatase is required for cytokinesis in the Caenorhabditis RT elegans embryo."; RL J. Cell Biol. 158:901-914(2002). RN [5] RP FUNCTION, SUBCELLULAR LOCATION (ISOFORM C), DEVELOPMENTAL STAGE, DISRUPTION RP PHENOTYPE, NUCLEAR EXPORT SIGNAL, NUCLEAR LOCALIZATION SIGNAL, AND RP MUTAGENESIS OF 366-LYS--ARG-371 AND 372-LEU--LEU-381. RX PubMed=21723944; DOI=10.1016/j.mod.2011.06.001; RA Roy S.H., Clayton J.E., Holmen J., Beltz E., Saito R.M.; RT "Control of Cdc14 activity coordinates cell cycle and development in RT Caenorhabditis elegans."; RL Mech. Dev. 128:317-326(2011). CC -!- FUNCTION: Protein phosphatase that negatively regulates the G1-to-S CC phase transition to inhibit the cell cycle and establish quiescence in CC cells of multiple lineages including vulval, hypodermal and intestinal CC (PubMed:15247923, PubMed:21723944). Promotes nuclear accumulation and CC activity of the cyclin-dependent kinase inhibitor cki-1 which leads to CC inhibition of G1 progression during vulval tissue development CC (PubMed:15247923). Has been shown to not be required for cytokinesis CC (PubMed:15247923). However, in the embryo, in a contrasting study, has CC been shown to act as a regulator of central spindle formation and CC cytokinesis, and may be required for localization of the spindle CC component zen-4, and its interacting partner air-2 at the spindle CC during late cell divisions (PubMed:12213836). CC {ECO:0000269|PubMed:12213836, ECO:0000269|PubMed:15247923, CC ECO:0000269|PubMed:21723944}. CC -!- FUNCTION: [Isoform c]: Main regulator of cell cycle arrest in vulval CC precursor cells. {ECO:0000269|PubMed:21723944}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10044, ECO:0000269|PubMed:12213836}; CC -!- ACTIVITY REGULATION: Inhibited by sodium orthovanadate. Weakly CC inhibited by sodium fluoride and okadaic acid. CC {ECO:0000269|PubMed:12213836}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12213836, CC ECO:0000269|PubMed:15247923}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:15247923}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:12213836, CC ECO:0000269|PubMed:15247923}. Midbody {ECO:0000269|PubMed:12213836}. CC Nucleus {ECO:0000269|PubMed:15247923}. Note=Localizes to the cytoplasm CC throughout interphase (PubMed:15247923). As cells enter prophase, CC accumulates at the centrosomes (PubMed:15247923). During metaphase and CC anaphase, localizes to the spindle, in particular spindle asters and CC the spindle mid zone (PubMed:15247923, PubMed:12213836). During late CC telophase, localizes to cytoplasmic aggregates (PubMed:15247923). In CC some studies, localizes to the midbody during late telophase CC (PubMed:12213836). Localizes to the cytoplasm in G1-arrested cells CC (PubMed:15247923). Localizes to the nucleus or nucleolus in postmitotic CC cells (PubMed:15247923). Some studies report no localization to CC centrosomes or nuclei (PubMed:12213836). Co-localizes with zen-4 at the CC spindle, and localization may be dependent on each other CC (PubMed:12213836). {ECO:0000269|PubMed:12213836, CC ECO:0000269|PubMed:15247923}. CC -!- SUBCELLULAR LOCATION: [Isoform c]: Cytoplasm CC {ECO:0000269|PubMed:21723944}. Nucleus {ECO:0000269|PubMed:21723944}. CC Note=Localizes to the cytoplasm during interphase, but localizes to the CC nucleus during cell cycle arrest. {ECO:0000269|PubMed:21723944}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=h {ECO:0000312|WormBase:C17G10.4h}; CC IsoId=P81299-1; Sequence=Displayed; CC Name=a {ECO:0000312|WormBase:C17G10.4a}; CC IsoId=P81299-2; Sequence=VSP_059807, VSP_059811; CC Name=c {ECO:0000312|WormBase:C17G10.4c}; CC IsoId=P81299-3; Sequence=VSP_059807, VSP_059808; CC Name=d {ECO:0000312|WormBase:C17G10.4d}; CC IsoId=P81299-4; Sequence=VSP_059807; CC Name=e {ECO:0000312|WormBase:C17G10.4e}; CC IsoId=P81299-5; Sequence=VSP_059811; CC Name=g {ECO:0000312|WormBase:C17G10.4g}; CC IsoId=P81299-7; Sequence=VSP_059809, VSP_059810; CC -!- DEVELOPMENTAL STAGE: Expressed in the soma during early embryogenesis, CC and widely expressed after hatching. Isoform C: Expressed in the soma CC during early embryogenesis, but after hatching, expression in larvae is CC restricted to V and P lineages, the postembryonic lineages that CC contribute to the seam cells and vulval precursor cells, respectively. CC {ECO:0000269|PubMed:21723944}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in extra cell CC divisions in the vulval lineage, but does not result in defects in CC cytokinesis (PubMed:15247923, PubMed:21723944). RNAi-mediated knockdown CC decreases cki-1 expression in the nucleus of vulval precursor cells CC (PubMed:15247923). In contrasting studies RNAi-mediated knockdown CC results in embryonic lethality with the production of multinucleated CC embryos that exhibit cytokinesis failure during telophase, no central CC spindle formation, and failed localization of the spindle component CC zen-4 and its interacting partner air-2 at the spindle in either CC anaphase or telophase (PubMed:12213836). {ECO:0000269|PubMed:12213836, CC ECO:0000269|PubMed:15247923, ECO:0000269|PubMed:21723944}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class CDC14 subfamily. {ECO:0000305}. CC -!- CAUTION: Has been shown in one report to not be localized to CC centrosomes or nuclei, and based on RNAi-mediated knockdown studies, CC has been shown to play a role in cytokinesis (PubMed:12213836). CC However, has also been reported to localize to centrosomes and nuclei CC and to have no role in cytokinesis, based on results obtained using the CC cdc-14 he118 mutant and RNAi-mediated knockdown (PubMed:15247923). CC {ECO:0000269|PubMed:12213836, ECO:0000269|PubMed:15247923}. CC -!- SEQUENCE CAUTION: CC Sequence=AAT74543.1; Type=Miscellaneous discrepancy; Evidence={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; AY661743; AAT74542.1; -; mRNA. DR EMBL; AY661744; AAT74543.1; ALT_SEQ; mRNA. DR EMBL; AY661745; AAT74544.1; -; mRNA. DR EMBL; AY661746; AAT74545.1; -; mRNA. DR EMBL; AY661747; AAT74546.1; -; mRNA. DR EMBL; AF000363; AAB94407.1; -; mRNA. DR EMBL; BX284602; CCD64951.1; -; Genomic_DNA. DR EMBL; BX284602; CCD64953.1; -; Genomic_DNA. DR EMBL; BX284602; CCD64954.1; -; Genomic_DNA. DR EMBL; BX284602; CCD64955.1; -; Genomic_DNA. DR EMBL; BX284602; CTQ86448.1; -; Genomic_DNA. DR EMBL; BX284602; CTQ86449.1; -; Genomic_DNA. DR PIR; E88158; E88158. DR PIR; T34097; T34097. DR RefSeq; NP_001021969.1; NM_001026798.5. [P81299-5] DR RefSeq; NP_001300509.1; NM_001313580.1. DR RefSeq; NP_001300510.1; NM_001313581.1. [P81299-1] DR RefSeq; NP_495085.2; NM_062684.5. DR RefSeq; NP_495086.1; NM_062685.3. DR RefSeq; NP_740991.1; NM_170993.4. DR AlphaFoldDB; P81299; -. DR SMR; P81299; -. DR BioGRID; 39287; 7. DR DIP; DIP-25903N; -. DR STRING; 6239.C17G10.4h.1; -. DR iPTMnet; P81299; -. DR EPD; P81299; -. DR PaxDb; 6239-C17G10-4b-2; -. DR PeptideAtlas; P81299; -. DR EnsemblMetazoa; C17G10.4a.1; C17G10.4a.1; WBGene00000383. [P81299-2] DR EnsemblMetazoa; C17G10.4c.1; C17G10.4c.1; WBGene00000383. [P81299-3] DR EnsemblMetazoa; C17G10.4d.1; C17G10.4d.1; WBGene00000383. [P81299-4] DR EnsemblMetazoa; C17G10.4e.1; C17G10.4e.1; WBGene00000383. [P81299-5] DR EnsemblMetazoa; C17G10.4g.1; C17G10.4g.1; WBGene00000383. [P81299-7] DR EnsemblMetazoa; C17G10.4h.1; C17G10.4h.1; WBGene00000383. [P81299-1] DR GeneID; 173945; -. DR UCSC; C17G10.4b; c. elegans. [P81299-1] DR AGR; WB:WBGene00000383; -. DR WormBase; C17G10.4a; CE30868; WBGene00000383; cdc-14. [P81299-2] DR WormBase; C17G10.4c; CE08288; WBGene00000383; cdc-14. [P81299-3] DR WormBase; C17G10.4d; CE06845; WBGene00000383; cdc-14. [P81299-4] DR WormBase; C17G10.4e; CE36916; WBGene00000383; cdc-14. [P81299-5] DR WormBase; C17G10.4g; CE50122; WBGene00000383; cdc-14. [P81299-7] DR WormBase; C17G10.4h; CE01789; WBGene00000383; cdc-14. [P81299-1] DR eggNOG; KOG1720; Eukaryota. DR GeneTree; ENSGT00940000170847; -. DR HOGENOM; CLU_288890_0_0_1; -. DR InParanoid; P81299; -. DR OMA; MQKFCWS; -. DR OrthoDB; 9871at2759; -. DR PRO; PR:P81299; -. DR Proteomes; UP000001940; Chromosome II. DR Bgee; WBGene00000383; Expressed in embryo and 4 other cell types or tissues. DR GO; GO:0000235; C:astral microtubule; IDA:WormBase. DR GO; GO:0005813; C:centrosome; IDA:WormBase. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:1902636; C:kinociliary basal body; IBA:GO_Central. DR GO; GO:0030496; C:midbody; IDA:WormBase. DR GO; GO:0072686; C:mitotic spindle; IBA:GO_Central. DR GO; GO:1990023; C:mitotic spindle midzone; IDA:WormBase. DR GO; GO:0005730; C:nucleolus; IDA:WormBase. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IDA:UniProtKB. DR GO; GO:0051233; C:spindle midzone; IDA:WormBase. DR GO; GO:0000922; C:spindle pole; IBA:GO_Central. DR GO; GO:0016791; F:phosphatase activity; IDA:WormBase. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:WormBase. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central. DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro. DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central. DR GO; GO:0016311; P:dephosphorylation; IDA:WormBase. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:WormBase. DR GO; GO:0051256; P:mitotic spindle midzone assembly; IMP:WormBase. DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB. DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IMP:UniProtKB. DR GO; GO:0040038; P:polar body extrusion after meiotic divisions; IMP:WormBase. DR GO; GO:0032467; P:positive regulation of cytokinesis; IBA:GO_Central. DR GO; GO:1903452; P:positive regulation of G1 to G0 transition; IMP:WormBase. DR GO; GO:0060284; P:regulation of cell development; IMP:UniProtKB. DR GO; GO:0007096; P:regulation of exit from mitosis; IBA:GO_Central. DR GO; GO:0040028; P:regulation of vulval development; IMP:UniProtKB. DR CDD; cd14499; CDC14_C; 1. DR CDD; cd17657; CDC14_N; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 2. DR InterPro; IPR044506; CDC14_C. DR InterPro; IPR029260; DSPn. DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR000387; Tyr_Pase_dom. DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom. DR PANTHER; PTHR23339:SF27; PROTEIN-TYROSINE-PHOSPHATASE; 1. DR PANTHER; PTHR23339; TYROSINE SPECIFIC PROTEIN PHOSPHATASE AND DUAL SPECIFICITY PROTEIN PHOSPHATASE; 1. DR Pfam; PF00782; DSPc; 1. DR Pfam; PF14671; DSPn; 1. DR SMART; SM00195; DSPc; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 2. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell cycle; Cell division; Cytoplasm; Cytoskeleton; KW Hydrolase; Microtubule; Nucleus; Protein phosphatase; Reference proteome. FT CHAIN 1..709 FT /note="Tyrosine-protein phosphatase cdc-14" FT /id="PRO_0000094880" FT DOMAIN 196..354 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 403..541 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 573..594 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 628..661 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 366..371 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:21723944" FT MOTIF 372..381 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:21723944" FT COMPBIAS 403..427 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 428..443 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..490 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 497..541 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 573..592 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 638..652 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 295 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT VAR_SEQ 542..555 FT /note="Missing (in isoform a, isoform c and isoform d)" FT /evidence="ECO:0000305" FT /id="VSP_059807" FT VAR_SEQ 620..709 FT /note="ITKCSLTAESKPPKRILSMPGTSKSTSSLKKIQVSRPRPYPSTGVRVELCAN FT GKSYDIRPRKEAHVIPGAGLAANTEALLGVCKLVNTLS -> FGLVRVPPDSPHSIMAH FT RPPPTTSSRAPLSPHNYSTTQGYSTSSRGLYGDKKPLARGSVSTSTLPSMYMTRSCERK FT (in isoform c)" FT /evidence="ECO:0000305" FT /id="VSP_059808" FT VAR_SEQ 620..695 FT /note="ITKCSLTAESKPPKRILSMPGTSKSTSSLKKIQVSRPRPYPSTGVRVELCAN FT GKSYDIRPRKEAHVIPGAGLAANT -> FGLVRVPPDSPHSIMAHRPPPTTSSRAPLSP FT HNYSTTQGYSTSSRGLYGDKKPLARGSVSTSTLPSMYMTRSCERK (in isoform FT g)" FT /evidence="ECO:0000305" FT /id="VSP_059809" FT VAR_SEQ 696..709 FT /note="Missing (in isoform g)" FT /evidence="ECO:0000305" FT /id="VSP_059810" FT VAR_SEQ 701..708 FT /note="VCKLVNTL -> KRRKTA (in isoform a and isoform e)" FT /evidence="ECO:0000305" FT /id="VSP_059811" FT MUTAGEN 295 FT /note="C->S: Abolishes phosphatase activity." FT /evidence="ECO:0000269|PubMed:12213836" FT MUTAGEN 366..371 FT /note="KRNVRR->AANVAA: Disrupts nuclear localization. FT Localizes to the cytoplasm; when associated with FT 372-A--A-381." FT /evidence="ECO:0000269|PubMed:21723944" FT MUTAGEN 372..381 FT /note="LVNQVDDINL->AVNQVDDANA: Impairs nuclear export FT signal. Disrupts cytoplasmic localization, conferring FT nuclear localization during interphase. Localizes to the FT cytoplasm; when associated with 366-A--A-371." FT /evidence="ECO:0000269|PubMed:21723944" FT MUTAGEN 446..709 FT /note="Missing: In he118; no effect on viability, FT embryogenesis or fertility. Disrupts cell cycle arrest of FT vulval precursor, intestinal, and hypodermal cells, and of FT precursor cells that give rise to male specific structures FT during postembryonic development. Vulval precursor cells FT undergo an extra round of cell division during the L2 FT larval stage of development, but the additional precursor FT cells do not disrupt formation of the vulval structure and FT animals undergo normal vulval morphogenesis during the L4 FT larval stage. Does not result in defects in cytokinesis. FT Overexpression of the cyclin dependent kinase inhibitor FT cki-1, or knockout with the G1/S-specific cyclin-E cye-1 FT (eh10), rescues the cell division phenotype." FT /evidence="ECO:0000269|PubMed:15247923" SQ SEQUENCE 709 AA; 79740 MW; AB5873D8C7FEDB0C CRC64; MREDHSPRRN NTIENTLTEL LPNRLYFGCF PNPDAIDKSD KSVKKTCFIN INNKFHYEPF YEDFGPWNLS VLYRLCVQVG KLLEVEEKRS RRVVLFCQDD GTGQYDKIRV NTAYVLGAYL IIYQGFSADD AYLKVSSGET VKFVGFRDAS MGSPQYLLHL HDVLRGIEKA LKFGWLDFSD FDYEEYEFYE RVENGDFNWI IPGKILSFCG PHNESREENG YPYHAPDVYF DYFRENKVST IVRLNAKNYD ASKFTKAGFD HVDLFFIDGS TPSDEIMLKF IKVVDNTKGG VAVHCKAGLG RTGTLIACWM MKEYGLTAGE CMGWLRVCRP GSVIGPQQPY LIEKQKFCWS LSQSNGVHLT QNKEEKRNVR RLVNQVDDIN LGEERISPKS RENTRPNILR RRVQVQNGRS TAPVTIAPAG TSESRRSTKP SRVVDETALD DQGRSQGDRL LQLKAKHQHE SETTSPNSSS SRRFVKSSTP QMTVPSQAYL NRNREPIIVT PSKNGTSSGT SSRQLKTTPN GNVAYRTRNS SGNTTSTLTR TGNESYRFHN SLFYEPASAV FPSMASRRSE TTRYLSPTTP IKPMSPSYTD GTSPRYKARL RSENPIGSTT STPFSLQPQI TKCSLTAESK PPKRILSMPG TSKSTSSLKK IQVSRPRPYP STGVRVELCA NGKSYDIRPR KEAHVIPGAG LAANTEALLG VCKLVNTLS //