CC14A_MOUSE
ID CC14A_MOUSE Reviewed; 603 AA.
AC Q6GQT0; Q8BZ66;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Dual specificity protein phosphatase CDC14A;
DE EC=3.1.3.16;
DE EC=3.1.3.48;
DE AltName: Full=CDC14 cell division cycle 14 homolog A;
GN Name=Cdc14a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 72-603 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=27259055; DOI=10.1016/j.ajhg.2016.04.015;
RA Delmaghani S., Aghaie A., Bouyacoub Y., El Hachmi H., Bonnet C., Riahi Z.,
RA Chardenoux S., Perfettini I., Hardelin J.P., Houmeida A., Herbomel P.,
RA Petit C.;
RT "Mutations in CDC14A, encoding a protein phosphatase involved in hair cell
RT ciliogenesis, cause autosomal-recessive severe to profound deafness.";
RL Am. J. Hum. Genet. 98:1266-1270(2016).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-278.
RX PubMed=29293958; DOI=10.1093/hmg/ddx440;
RA Imtiaz A., Belyantseva I.A., Beirl A.J., Fenollar-Ferrer C., Bashir R.,
RA Bukhari I., Bouzid A., Shaukat U., Azaiez H., Booth K.T., Kahrizi K.,
RA Najmabadi H., Maqsood A., Wilson E.A., Fitzgerald T.S., Tlili A.,
RA Olszewski R., Lund M., Chaudhry T., Rehman A.U., Starost M.F., Waryah A.M.,
RA Hoa M., Dong L., Morell R.J., Smith R.J.H., Riazuddin S., Masmoudi S.,
RA Kindt K.S., Naz S., Friedman T.B.;
RT "CDC14A phosphatase is essential for hearing and male fertility in mouse
RT and human.";
RL Hum. Mol. Genet. 27:780-798(2018).
CC -!- FUNCTION: Dual-specificity phosphatase. Required for centrosome
CC separation and productive cytokinesis during cell division.
CC Dephosphorylates SIRT2 around early anaphase. May dephosphorylate the
CC APC subunit FZR1/CDH1, thereby promoting APC-FZR1 dependent degradation
CC of mitotic cyclins and subsequent exit from mitosis (By similarity).
CC Required for normal hearing (PubMed:29293958).
CC {ECO:0000250|UniProtKB:Q9UNH5, ECO:0000269|PubMed:29293958}.
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};
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 -!- 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 -!- SUBUNIT: Interacts with KIF20A. Interaction is required to localize
CC CDC14 to the midzone of the mitotic spindle (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UNH5}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q9UNH5}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q9UNH5}. Cell projection, kinocilium
CC {ECO:0000269|PubMed:27259055, ECO:0000269|PubMed:29293958}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q9UNH5}. Cell
CC projection, stereocilium {ECO:0000269|PubMed:29293958}.
CC Note=Centrosomal during interphase, released into the cytoplasm at the
CC onset of mitosis. Subsequently localizes to the mitotic spindle pole
CC and at the central spindle (By similarity). Present along both the
CC transient kinocilia of developing cochlear hair cells and the
CC persistent kinocilia of vestibular hair cells (PubMed:27259055).
CC {ECO:0000250|UniProtKB:Q9UNH5, ECO:0000269|PubMed:27259055}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6GQT0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6GQT0-2; Sequence=VSP_012324;
CC -!- TISSUE SPECIFICITY: Expressed in the inner ear.
CC {ECO:0000269|PubMed:29293958}.
CC -!- DOMAIN: Composed of two structurally equivalent A and B domains that
CC adopt a dual specificity protein phosphatase (DSP) fold. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class CDC14 subfamily. {ECO:0000305}.
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DR EMBL; BC072644; AAH72644.1; -; mRNA.
DR EMBL; AK036556; BAC29476.1; -; mRNA.
DR CCDS; CCDS38611.1; -. [Q6GQT0-1]
DR CCDS; CCDS51058.1; -. [Q6GQT0-2]
DR RefSeq; NP_001074287.1; NM_001080818.2. [Q6GQT0-1]
DR RefSeq; NP_001167024.1; NM_001173553.1. [Q6GQT0-2]
DR AlphaFoldDB; Q6GQT0; -.
DR SMR; Q6GQT0; -.
DR STRING; 10090.ENSMUSP00000087950; -.
DR iPTMnet; Q6GQT0; -.
DR PhosphoSitePlus; Q6GQT0; -.
DR jPOST; Q6GQT0; -.
DR MaxQB; Q6GQT0; -.
DR PaxDb; Q6GQT0; -.
DR PRIDE; Q6GQT0; -.
DR ProteomicsDB; 265578; -. [Q6GQT0-1]
DR ProteomicsDB; 265579; -. [Q6GQT0-2]
DR Antibodypedia; 19991; 322 antibodies from 32 providers.
DR DNASU; 229776; -.
DR Ensembl; ENSMUST00000090464; ENSMUSP00000087950; ENSMUSG00000033502. [Q6GQT0-1]
DR Ensembl; ENSMUST00000106491; ENSMUSP00000102100; ENSMUSG00000033502. [Q6GQT0-2]
DR GeneID; 229776; -.
DR KEGG; mmu:229776; -.
DR UCSC; uc008rca.1; mouse. [Q6GQT0-1]
DR UCSC; uc012cwq.1; mouse. [Q6GQT0-2]
DR CTD; 8556; -.
DR MGI; MGI:2442676; Cdc14a.
DR VEuPathDB; HostDB:ENSMUSG00000033502; -.
DR eggNOG; KOG1720; Eukaryota.
DR GeneTree; ENSGT00940000155899; -.
DR HOGENOM; CLU_017787_2_2_1; -.
DR InParanoid; Q6GQT0; -.
DR OMA; QPTARNY; -.
DR OrthoDB; 1357618at2759; -.
DR PhylomeDB; Q6GQT0; -.
DR TreeFam; TF101053; -.
DR Reactome; R-MMU-176407; Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR BioGRID-ORCS; 229776; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cdc14a; mouse.
DR PRO; PR:Q6GQT0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q6GQT0; protein.
DR Bgee; ENSMUSG00000033502; Expressed in ciliary body and 202 other tissues.
DR ExpressionAtlas; Q6GQT0; baseline and differential.
DR Genevisible; Q6GQT0; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:1902636; C:kinociliary basal body; IDA:UniProtKB.
DR GO; GO:0060091; C:kinocilium; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000922; C:spindle pole; IBA:GO_Central.
DR GO; GO:0032426; C:stereocilium tip; IDA:UniProtKB.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0007096; P:regulation of exit from mitosis; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR CDD; cd14499; CDC14_C; 1.
DR CDD; cd17657; CDC14_N; 1.
DR Gene3D; 3.90.190.10; -; 2.
DR InterPro; IPR044506; CDC14_C.
DR InterPro; IPR029260; DSPn.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR026068; Dual_Pase_CDC14A.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR PANTHER; PTHR23339:SF77; PTHR23339:SF77; 1.
DR Pfam; PF00782; DSPc; 1.
DR Pfam; PF14671; DSPn; 1.
DR SMART; SM00195; DSPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 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; Cell projection;
KW Cytoplasm; Cytoskeleton; Hearing; Hydrolase; Nucleus; Phosphoprotein;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..603
FT /note="Dual specificity protein phosphatase CDC14A"
FT /id="PRO_0000094877"
FT DOMAIN 179..336
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 7..162
FT /note="A"
FT REGION 163..176
FT /note="Linker"
FT REGION 177..343
FT /note="B"
FT REGION 518..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..565
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 278
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH5"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH5"
FT VAR_SEQ 104..152
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012324"
FT MUTAGEN 278
FT /note="C->S: Mutant mice are deaf, show fusion of
FT stereocilia and degeneration of hair cells, and have low
FT sperm counts."
FT /evidence="ECO:0000269|PubMed:29293958"
SQ SEQUENCE 603 AA; 67634 MW; 496676322A54C078 CRC64;
MAAESGELIG ACEFMKDRLY FATLRNRPKS TINIHYFSID EELVYENFYA DFGPLNLAMV
YRYCCKLNKK LKSYSLSRKK IVHYTSFDQR KRANAAFLIG AYAVIYLKKT PEEAYRALLS
GSNPPYLPFR DASFGNCTYN LTVLDCLQGI RKGLQHGFFD FETFDAEEYE HYERVENGDF
NWIVPGKFLA FSGPHPKSKI ENGYPLHAPE AYFPYFKKNN VTTIVRLNKK IYEAKRFTDA
GFEHYDLFFI DGSTPSDNIV RRFLNICENT EGAIAVHCKA GLGRTGTLIA CYVMKHYRFT
HAEIIAWIRI CRPGSIIGPQ QHFLKEKQAS LWVQGDIFRS KLKNRPSSEG SITKIISTLD
DMSIGANLSK LQSTERIGEN NFEDEDMEIK NNVTQGDKLR ALKSQRHPRS SPSCAFRSDD
MKGHQRAMAQ TFRLSSSPQP TMSTMKTSKV CLSPSVTAKK ISRGSLSSGA NIRSFSINSR
LASSLGNLNA GTEEPETKKT TSLTKAAFIA SPFTSFLNGS TQTPGRNYPE LNNNQYTRSS
NSNSSSSSSG LGGNLNSSPV PQSAKPEEHT TILRPSFPGS LSSSSVRFLS RSIPSLQSEY
VHY
