ID CC14A_HUMAN Reviewed; 594 AA.
AC Q9UNH5; B1AQ14; B1AQ15; O43171; O60727; O60728; Q52LH9; Q8IXX0;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 29-MAY-2013, entry version 107.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9367992; DOI=10.1074/jbc.272.47.29403;
RA Li L., Ernsting B.R., Wishart M.J., Lohse D.L., Dixon J.E.;
RT "A family of putative tumor suppressors is structurally and
RT functionally conserved in humans and yeast.";
RL J. Biol. Chem. 272:29403-29406(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10409437; DOI=10.1006/geno.1999.5863;
RA Wong A.K.C., Chen Y., Lian L., Ha P.C., Petersen K., Laity K.,
RA Carillo A., Emerson M., Heichman K., Gupte J., Tavtigian S.V.,
RA Teng D.H.-F.;
RT "Genomic structure, chromosomal location, and mutation analysis of the
RT human CDC14A gene.";
RL Genomics 59:248-251(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 2 AND 3).
RC TISSUE=Placenta;
RA Hao L., Baskerville C., Charbonneau H.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-345 AND PHE-589.
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP DEPHOSPHORYLATION OF FZR1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-278.
RX PubMed=11598127; DOI=10.1074/jbc.M108126200;
RA Bembenek J., Yu H.;
RT "Regulation of the anaphase-promoting complex by the dual specificity
RT phosphatase human Cdc14a.";
RL J. Biol. Chem. 276:48237-48242(2001).
RN [9]
RP SUBSTRATE SPECIFICITY, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF ASP-251; CYS-278 AND ARG-284.
RX PubMed=12134069; DOI=10.1091/mbc.01-11-0535;
RA Kaiser B.K., Zimmerman Z.A., Charbonneau H., Jackson P.K.;
RT "Disruption of centrosome structure, chromosome segregation, and
RT cytokinesis by misexpression of human Cdc14A phosphatase.";
RL Mol. Biol. Cell 13:2289-2300(2002).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF MET-362 AND
RP ILE-364.
RX PubMed=11901424; DOI=10.1038/ncb777;
RA Mailand N., Lukas C., Kaiser B.K., Jackson P.K., Bartek J., Lukas J.;
RT "Deregulated human Cdc14A phosphatase disrupts centrosome separation
RT and chromosome segregation.";
RL Nat. Cell Biol. 4:317-322(2002).
RN [11]
RP INTERACTION WITH KIF20A, AND SUBCELLULAR LOCATION.
RX PubMed=15263015; DOI=10.1083/jcb.200403084;
RA Gruneberg U., Neef R., Honda R., Nigg E.A., Barr F.A.;
RT "Relocation of Aurora B from centromeres to the central spindle at the
RT metaphase to anaphase transition requires MKlp2.";
RL J. Cell Biol. 166:167-172(2004).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-493.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Dual-specificity phosphatase. Required for centrosome
CC separation and productive cytokinesis during cell division. May
CC dephosphorylate the APC subunit FZR1/CDH1, thereby promoting APC-
CC FZR1 dependent degradation of mitotic cyclins and subsequent exit
CC from mitosis.
CC -!- CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein
CC tyrosine + phosphate.
CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- SUBUNIT: Interacts with KIF20A, which is required to localize
CC CDC14 to the midzone of the mitotic spindle.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton,
CC centrosome. Cytoplasm, cytoskeleton, spindle. Note=Centrosomal
CC during interphase, released into the cytoplasm at the onset of
CC mitosis. Subsequently localizes to the midzone of the mitotic
CC spindle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=CDC14A1;
CC IsoId=Q9UNH5-1; Sequence=Displayed;
CC Name=2; Synonyms=CDC14A2;
CC IsoId=Q9UNH5-2; Sequence=VSP_012037;
CC Name=3; Synonyms=CDC14A3;
CC IsoId=Q9UNH5-3; Sequence=VSP_012035, VSP_012036;
CC Name=4; Synonyms=CDC14A4;
CC IsoId=Q9UNH5-4; Sequence=VSP_012322, VSP_012323;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: Composed of two structurally equivalent A and B domains
CC that adopt a dual specificity protein phosphatase (DSP) fold (By
CC similarity).
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Non-receptor class CDC14 subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB88277.1; Type=Frameshift; Positions=6;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc14a/";
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DR EMBL; AF000367; AAB88277.1; ALT_FRAME; mRNA.
DR EMBL; AF122013; AAD49217.1; -; mRNA.
DR EMBL; AF064102; AAC16659.1; -; mRNA.
DR EMBL; AF064103; AAC16660.1; -; mRNA.
DR EMBL; AY623111; AAT38107.1; -; Genomic_DNA.
DR EMBL; AL589990; CAH70068.1; -; Genomic_DNA.
DR EMBL; AC104457; CAH70068.1; JOINED; Genomic_DNA.
DR EMBL; AL589990; CAH70069.1; -; Genomic_DNA.
DR EMBL; AC104457; CAH70069.1; JOINED; Genomic_DNA.
DR EMBL; AL589990; CAH70070.1; -; Genomic_DNA.
DR EMBL; AC104457; CAH70070.1; JOINED; Genomic_DNA.
DR EMBL; CH471097; EAW72956.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72958.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72959.1; -; Genomic_DNA.
DR EMBL; BC038979; AAH38979.1; -; mRNA.
DR EMBL; BC093916; AAH93916.1; -; mRNA.
DR EMBL; BC093918; AAH93918.1; -; mRNA.
DR IPI; IPI00021145; -.
DR IPI; IPI00031770; -.
DR IPI; IPI00217676; -.
DR IPI; IPI00219831; -.
DR RefSeq; NP_003663.2; NM_003672.3.
DR RefSeq; NP_201569.1; NM_033312.2.
DR RefSeq; NP_201570.1; NM_033313.2.
DR UniGene; Hs.127411; -.
DR ProteinModelPortal; Q9UNH5; -.
DR MINT; MINT-8330048; -.
DR STRING; 9606.ENSP00000354916; -.
DR PhosphoSite; Q9UNH5; -.
DR DMDM; 55976620; -.
DR PaxDb; Q9UNH5; -.
DR PRIDE; Q9UNH5; -.
DR Ensembl; ENST00000336454; ENSP00000336739; ENSG00000079335.
DR Ensembl; ENST00000361544; ENSP00000354916; ENSG00000079335.
DR Ensembl; ENST00000370124; ENSP00000359142; ENSG00000079335.
DR Ensembl; ENST00000370125; ENSP00000359143; ENSG00000079335.
DR GeneID; 8556; -.
DR KEGG; hsa:8556; -.
DR UCSC; uc001dte.4; human.
DR UCSC; uc001dtf.2; human.
DR UCSC; uc001dtg.4; human.
DR UCSC; uc009wec.1; human.
DR CTD; 8556; -.
DR GeneCards; GC01P100817; -.
DR HGNC; HGNC:1718; CDC14A.
DR HPA; HPA023783; -.
DR MIM; 603504; gene.
DR neXtProt; NX_Q9UNH5; -.
DR PharmGKB; PA26254; -.
DR eggNOG; COG2453; -.
DR HOVERGEN; HBG050818; -.
DR KO; K06639; -.
DR OMA; ACEFMKD; -.
DR Reactome; REACT_115566; Cell Cycle.
DR BindingDB; Q9UNH5; -.
DR ChEMBL; CHEMBL1772926; -.
DR GenomeRNAi; 8556; -.
DR NextBio; 32065; -.
DR ArrayExpress; Q9UNH5; -.
DR Bgee; Q9UNH5; -.
DR CleanEx; HS_CDC14A; -.
DR Genevestigator; Q9UNH5; -.
DR GermOnline; ENSG00000079335; Homo sapiens.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; TAS:ProtInc.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:EC.
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:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IEA:GOC.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR020422; Dual-sp_phosphatase_subgr_cat.
DR InterPro; IPR026068; Dual_Pase_CDC14.
DR InterPro; IPR000387; Tyr/Dual-sp_Pase.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR PANTHER; PTHR23339:SF27; PTHR23339:SF27; 1.
DR Pfam; PF00782; DSPc; 1.
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; Complete proteome;
KW Cytoplasm; Cytoskeleton; Hydrolase; Nucleus; Polymorphism;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1 594 Dual specificity protein phosphatase
FT CDC14A.
FT /FTId=PRO_0000094876.
FT REGION 7 162 A.
FT REGION 163 176 Linker.
FT REGION 177 343 B.
FT ACT_SITE 278 278 Phosphocysteine intermediate (By
FT similarity).
FT VAR_SEQ 174 191 RVENGDFNWIVPGKFLAF -> VILFTPLKPTFLISKSIM
FT (in isoform 4).
FT /FTId=VSP_012322.
FT VAR_SEQ 192 594 Missing (in isoform 4).
FT /FTId=VSP_012323.
FT VAR_SEQ 380 383 DNLE -> VSFP (in isoform 3).
FT /FTId=VSP_012035.
FT VAR_SEQ 384 594 Missing (in isoform 3).
FT /FTId=VSP_012036.
FT VAR_SEQ 586 594 SLQSEYVHY -> VSAQTPPPGPQNPECNFCALPSQPRLPP
FT KKFNSAKEAF (in isoform 2).
FT /FTId=VSP_012037.
FT VARIANT 345 345 R -> Q (in dbSNP:rs28364897).
FT /FTId=VAR_019957.
FT VARIANT 493 493 D -> Y (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035655.
FT VARIANT 589 589 S -> F (in dbSNP:rs28364923).
FT /FTId=VAR_019958.
FT MUTAGEN 251 251 D->A: Loss of phosphatase activity.
FT MUTAGEN 278 278 C->S: Loss of phosphatase activity.
FT MUTAGEN 284 284 R->A: Loss of phosphatase activity.
FT MUTAGEN 362 362 M->A: Inappropriate nucleolar
FT localization; when associated with A-364.
FT MUTAGEN 364 364 I->A: Inappropriate nucleolar
FT localization; when associated with A-362.
FT CONFLICT 164 164 F -> I (in Ref. 1; AAB88277).
FT CONFLICT 182 182 W -> C (in Ref. 1; AAB88277).
SQ SEQUENCE 594 AA; 66574 MW; D5552E2BAEEA84DF CRC64;
MAAESGELIG ACEFMKDRLY FATLRNRPKS TVNTHYFSID EELVYENFYA DFGPLNLAMV
YRYCCKLNKK LKSYSLSRKK IVHYTCFDQR KRANAAFLIG AYAVIYLKKT PEEAYRALLS
GSNPPYLPFR DASFGNCTYN LTILDCLQGI RKGLQHGFFD FETFDVDEYE HYERVENGDF
NWIVPGKFLA FSGPHPKSKI ENGYPLHAPE AYFPYFKKHN VTAVVRLNKK IYEAKRFTDA
GFEHYDLFFI DGSTPSDNIV RRFLNICENT EGAIAVHCKA GLGRTGTLIA CYVMKHYRFT
HAEIIAWIRI CRPGSIIGPQ QHFLEEKQAS LWVQGDIFRS KLKNRPSSEG SINKILSGLD
DMSIGGNLSK TQNMERFGED NLEDDDVEMK NGITQGDKLR ALKSQRQPRT SPSCAFRSDD
TKGHPRAVSQ PFRLSSSLQG SAVTLKTSKM ALSPSATAKR INRTSLSSGA TVRSFSINSR
LASSLGNLNA ATDDPENKKT SSSSKAGFTA SPFTNLLNGS SQPTTRNYPE LNNNQYNRSS
NSNGGNLNSP PGPHSAKTEE HTTILRPSYT GLSSSSARFL SRSIPSLQSE YVHY
//
