CDK14_MOUSE
ID CDK14_MOUSE Reviewed; 469 AA.
AC O35495; O35848; Q3TNN9; Q3V319; Q6ZQ37;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Cyclin-dependent kinase 14;
DE EC=2.7.11.22;
DE AltName: Full=Cell division protein kinase 14;
DE AltName: Full=Serine/threonine-protein kinase PFTAIRE-1;
GN Name=Cdk14; Synonyms=Kiaa0834, Pftk1;
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 [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Testis;
RX PubMed=9547506;
RX DOI=10.1002/(sici)1098-2795(199805)50:1<18::aid-mrd3>3.0.co;2-#;
RA Besset V., Rhee K., Wolgemuth D.J.;
RT "The identification and characterization of expression of Pftaire-1, a
RT novel Cdk family member, suggest its function in the mouse testis and
RT nervous system.";
RL Mol. Reprod. Dev. 50:18-29(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=NIH Swiss; TISSUE=Brain;
RX PubMed=9202329; DOI=10.1046/j.1471-4159.1997.69010348.x;
RA Lazzaro M.A., Albert P.R., Julien J.-P.;
RT "A novel cdc2-related protein kinase expressed in the nervous system.";
RL J. Neurochem. 69:348-364(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-469 (ISOFORM 1).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in the control of
CC the eukaryotic cell cycle, whose activity is controlled by an
CC associated cyclin. Acts as a cell-cycle regulator of Wnt signaling
CC pathway during G2/M phase by mediating the phosphorylation of LRP6 at
CC 'Ser-1490', leading to the activation of the Wnt signaling pathway.
CC Acts as a regulator of cell cycle progression and cell proliferation
CC via its interaction with CCDN3. Phosphorylates RB1 in vitro, however
CC the relevance of such result remains to be confirmed in vivo. May also
CC play a role in meiosis, neuron differentiation and may indirectly act
CC as a negative regulator of insulin-responsive glucose transport (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:9547506}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22;
CC -!- ACTIVITY REGULATION: Serine/threonine-protein kinase activity is
CC promoted by associated cyclins CCDN3 and CCNY and repressed by CDKN1A.
CC {ECO:0000250}.
CC -!- SUBUNIT: Found in a complex with LRP6, CCNY and CAPRIN2 during G2/M
CC stage; CAPRIN2 functions as a scaffold for the complex by binding to
CC CCNY via its N terminus and to CDK14 via its C terminus. Interacts with
CC CCNY; CCNY mediates its recruitment to the plasma membrane and promotes
CC phosphorylation of LRP6. Interacts with CCDN3 and CDKN1A. Interacts
CC with SEPT8. Interacts with 14-3-3 proteina YWHAB, YWHAE, YWHAH and
CC YWHAQ. {ECO:0000250|UniProtKB:O94921}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cytoplasm. Nucleus. Note=Recruited to the cell
CC membrane by CCNY. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O35495-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O35495-2; Sequence=VSP_038763;
CC Name=3;
CC IsoId=O35495-3; Sequence=VSP_038764;
CC -!- TISSUE SPECIFICITY: In the adult, widely expressed at low levels except
CC in brain, kidney and testis where expression is high. In the brain,
CC detected in cortex, hippocampus, dentate gyrus, amygdala cortex,
CC parasubiculum and cerebellum. In the embryo, expressed predominantly in
CC the nervous system. {ECO:0000269|PubMed:9547506}.
CC -!- DEVELOPMENTAL STAGE: In the testis, expressed at low levels in Sertoli
CC cells of 7-day-old mice, barely detected at day 17, and detected at
CC much higher levels in late pachytene/diplotene spermatocytes in the
CC adult. In the nervous system, expressed at highest levels in the adult.
CC {ECO:0000269|PubMed:9202329, ECO:0000269|PubMed:9547506}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; AF033655; AAB87504.1; -; mRNA.
DR EMBL; U62391; AAB70455.1; -; mRNA.
DR EMBL; AK165149; BAE38049.1; -; mRNA.
DR EMBL; AK051283; BAE43346.1; -; mRNA.
DR EMBL; AK129226; BAC98036.1; -; mRNA.
DR CCDS; CCDS19073.1; -. [O35495-1]
DR CCDS; CCDS80203.1; -. [O35495-2]
DR RefSeq; NP_035204.2; NM_011074.3. [O35495-1]
DR AlphaFoldDB; O35495; -.
DR SMR; O35495; -.
DR BioGRID; 202129; 8.
DR ComplexPortal; CPX-367; Cyclin Y-Cdk14 complex.
DR IntAct; O35495; 1.
DR MINT; O35495; -.
DR STRING; 10090.ENSMUSP00000030763; -.
DR iPTMnet; O35495; -.
DR PhosphoSitePlus; O35495; -.
DR jPOST; O35495; -.
DR MaxQB; O35495; -.
DR PaxDb; O35495; -.
DR PeptideAtlas; O35495; -.
DR PRIDE; O35495; -.
DR ProteomicsDB; 281287; -. [O35495-1]
DR ProteomicsDB; 281288; -. [O35495-2]
DR ProteomicsDB; 281289; -. [O35495-3]
DR Antibodypedia; 15462; 238 antibodies from 28 providers.
DR DNASU; 18647; -.
DR Ensembl; ENSMUST00000030763; ENSMUSP00000030763; ENSMUSG00000028926. [O35495-1]
DR Ensembl; ENSMUST00000115450; ENSMUSP00000111110; ENSMUSG00000028926. [O35495-2]
DR Ensembl; ENSMUST00000115451; ENSMUSP00000111111; ENSMUSG00000028926. [O35495-2]
DR GeneID; 18647; -.
DR KEGG; mmu:18647; -.
DR UCSC; uc008wih.2; mouse. [O35495-1]
DR UCSC; uc008wik.2; mouse. [O35495-3]
DR CTD; 5218; -.
DR MGI; MGI:894318; Cdk14.
DR VEuPathDB; HostDB:ENSMUSG00000028926; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000157640; -.
DR HOGENOM; CLU_000288_181_6_1; -.
DR InParanoid; O35495; -.
DR OMA; NSRHGCA; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; O35495; -.
DR TreeFam; TF106508; -.
DR BioGRID-ORCS; 18647; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Cdk14; mouse.
DR PRO; PR:O35495; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O35495; protein.
DR Bgee; ENSMUSG00000028926; Expressed in cingulate cortex and 267 other tissues.
DR ExpressionAtlas; O35495; baseline and differential.
DR Genevisible; O35495; MM.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0000308; C:cytoplasmic cyclin-dependent protein kinase holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cell membrane; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..469
FT /note="Cyclin-dependent kinase 14"
FT /id="PRO_0000086507"
FT DOMAIN 135..419
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 103..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 256
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 141..149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94921"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94921"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94921"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:9202329"
FT /id="VSP_038763"
FT VAR_SEQ 349..469
FT /note="LGTPNEDTWPGVHSLPHFKPERFTVYSSKSLRQAWNKLSYVNHAEDLASKLL
FT QCSPKNRLSAQAALSHEYFSDLPPRLWELTDMSSIFTVPNVRLQPEAGESMRAFGKNNS
FT YGKSLSNSKH -> SSAQSASQKNLFLISYLVT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038764"
FT CONFLICT 219
FT /note="Q -> R (in Ref. 3; BAE38049)"
FT /evidence="ECO:0000305"
FT CONFLICT 222..223
FT /note="DK -> EQ (in Ref. 1; AAB87504)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="S -> N (in Ref. 2; AAB70455)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 469 AA; 52996 MW; 2042D0A66655A8B0 CRC64;
MCDLIEPQPA EKIGKMKKLR RTLSESFSRI ALKKEDTTFD EICVTKMSTR NCQGTDSVIK
HLDTIPEDKK VRVQRTQSTF DPFEKPANQV KRVHSENNAC INFKSSSAGK ESPKVRRHSS
PSSPTSPKFG KADSYEKLEK LGEGSYATVY KGKSKVNGKL VALKVIRLQE EEGTPFTAIR
EASLLKGLKH ANIVLLHDII HTKETLTLVF EYVHTDLCQY MDKHPGGLHP DNVKLFLFQL
LRGLSYIHQR YILHRDLKPQ NLLISDTGEL KLADFGLARA KSVPSHTYSN EVVTLWYRPP
DVLLGSTEYS TCLDMWGVGC IFVEMIQGVA AFPGMKDIQD QLERIFLVLG TPNEDTWPGV
HSLPHFKPER FTVYSSKSLR QAWNKLSYVN HAEDLASKLL QCSPKNRLSA QAALSHEYFS
DLPPRLWELT DMSSIFTVPN VRLQPEAGES MRAFGKNNSY GKSLSNSKH
