CDK16_MOUSE
ID CDK16_MOUSE Reviewed; 496 AA.
AC Q04735;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cyclin-dependent kinase 16;
DE EC=2.7.11.22;
DE AltName: Full=CRK5;
DE AltName: Full=Cell division protein kinase 16;
DE AltName: Full=PCTAIRE-motif protein kinase 1;
DE AltName: Full=Serine/threonine-protein kinase PCTAIRE-1;
GN Name=Cdk16; Synonyms=Crk5, Pctaire1, Pctk1;
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 LONG).
RC TISSUE=Fibroblast;
RX PubMed=1437147;
RA Okuda T., Cleveland J.L., Downing J.R.;
RT "PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein
RT kinase gene family.";
RL Oncogene 7:2249-2258(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 290-325.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [4]
RP INTERACTION WITH YWHAH; YWHAQ AND YWHAZ.
RX PubMed=9197417; DOI=10.1007/s004380050453;
RA Sladeczek F., Camonis J.H., Burnol A.-F., Le Bouffant F.;
RT "The Cdk-like protein PCTAIRE-1 from mouse brain associates with p11 and
RT 14-3-3 proteins.";
RL Mol. Gen. Genet. 254:571-577(1997).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH NSF.
RX PubMed=16461345; DOI=10.1074/jbc.m513496200;
RA Liu Y., Cheng K., Gong K., Fu A.K., Ip N.Y.;
RT "Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein:
RT implications in the regulation of its hexamerization and exocytosis.";
RL J. Biol. Chem. 281:9852-9858(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78; SER-95 AND SER-153, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
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).
RN [7]
RP FUNCTION, MUTAGENESIS OF SER-95, AND PHOSPHORYLATION AT SER-95.
RX PubMed=21335063; DOI=10.1016/j.neuroscience.2011.02.024;
RA Fu W.Y., Cheng K., Fu A.K., Ip N.Y.;
RT "Cyclin-dependent kinase 5-dependent phosphorylation of Pctaire1 regulates
RT dendrite development.";
RL Neuroscience 180:353-359(2011).
RN [8]
RP CATALYTIC ACTIVITY, INTERACTION WITH CCNY, AND TISSUE SPECIFICITY.
RX PubMed=22796189; DOI=10.1016/j.cellsig.2012.06.018;
RA Shehata S.N., Hunter R.W., Ohta E., Peggie M.W., Lou H.J., Sicheri F.,
RA Zeqiraj E., Turk B.E., Sakamoto K.;
RT "Analysis of substrate specificity and cyclin Y binding of PCTAIRE-1
RT kinase.";
RL Cell. Signal. 24:2085-2094(2012).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22798068; DOI=10.1074/jbc.m112.375618;
RA Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L.,
RA Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O.,
RA Yu L.;
RT "Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively
RT regulates glucose-stimulated insulin secretion in pancreatic beta-cells.";
RL J. Biol. Chem. 287:30368-30375(2012).
RN [10]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CCNY,
RP AND TISSUE SPECIFICITY.
RX PubMed=22184064; DOI=10.1128/mcb.06261-11;
RA Mikolcevic P., Sigl R., Rauch V., Hess M.W., Pfaller K., Barisic M.,
RA Pelliniemi L.J., Boesl M., Geley S.;
RT "Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and
RT is essential for spermatogenesis.";
RL Mol. Cell. Biol. 32:868-879(2012).
CC -!- FUNCTION: Protein kinase that plays a role in vesicle-mediated
CC transport processes and exocytosis. Can phosphorylate CCNY at 'Ser-336'
CC (in vitro) (By similarity). Plays a role in the regulation of insulin
CC secretion in response to changes in blood glucose levels. Regulates GH1
CC release by brain neurons. Phosphorylates NSF, and thereby regulates NSF
CC oligomerization. Required for normal spermatogenesis. Regulates neuron
CC differentiation and dendrite development. {ECO:0000250,
CC ECO:0000269|PubMed:16461345, ECO:0000269|PubMed:21335063,
CC ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22798068}.
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 Evidence={ECO:0000269|PubMed:16461345, ECO:0000269|PubMed:22184064,
CC ECO:0000269|PubMed:22796189};
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; Evidence={ECO:0000269|PubMed:16461345,
CC ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189};
CC -!- SUBUNIT: Found in a complex containing CABLES1, CDK17 and TDRD7.
CC Interacts with BRSK2. Identified in a complex with NSF, syntaxin-1,
CC synaptotagmin, SYN1, SYP and CDK5R1 (By similarity). Interacts with
CC YWHAH, YWHAQ and YWHAZ. Interacts with CCNY; this increases the CDK16
CC kinase activity. Interacts with NSF. {ECO:0000250,
CC ECO:0000269|PubMed:16461345, ECO:0000269|PubMed:22184064,
CC ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:9197417}.
CC -!- INTERACTION:
CC Q04735; Q8BGU5: Ccny; NbExp=3; IntAct=EBI-11615670, EBI-772904;
CC Q04735; D3YUJ3: Ccnyl1; NbExp=7; IntAct=EBI-11615670, EBI-11683033;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasmic vesicle,
CC secretory vesicle. Synapse, synaptosome. Note=Colocalizes with insulin
CC in pancreas islets. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q04735-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q04735-2; Sequence=VSP_004801, VSP_004802;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and brain, and detected
CC at lower levels in heart, skeletal muscle, adipose tissue, lung, spleen
CC and pancreas (at protein level). Ubiquitous with highest levels in
CC testis and brain, with longer form predominant in all tissues except
CC the testis. {ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189,
CC ECO:0000269|PubMed:22798068}.
CC -!- PTM: Phosphorylation at Ser-153 inhibits kinase activity.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in females; they are viable
CC and fertile. Male mice are infertile, due to a defect in late stages of
CC spermatogenesis. {ECO:0000269|PubMed:22184064}.
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; X69025; CAA48787.1; -; mRNA.
DR EMBL; BC011069; AAH11069.1; -; mRNA.
DR EMBL; X64606; CAA45890.1; -; mRNA.
DR CCDS; CCDS30045.1; -. [Q04735-1]
DR CCDS; CCDS81103.1; -. [Q04735-2]
DR PIR; S30435; S30435.
DR RefSeq; NP_001297385.1; NM_001310456.1. [Q04735-2]
DR RefSeq; NP_035179.1; NM_011049.5. [Q04735-1]
DR RefSeq; XP_006527633.1; XM_006527570.1. [Q04735-1]
DR AlphaFoldDB; Q04735; -.
DR SMR; Q04735; -.
DR CORUM; Q04735; -.
DR IntAct; Q04735; 3.
DR MINT; Q04735; -.
DR STRING; 10090.ENSMUSP00000033380; -.
DR iPTMnet; Q04735; -.
DR PhosphoSitePlus; Q04735; -.
DR jPOST; Q04735; -.
DR PaxDb; Q04735; -.
DR PeptideAtlas; Q04735; -.
DR PRIDE; Q04735; -.
DR ProteomicsDB; 281293; -. [Q04735-1]
DR ProteomicsDB; 281294; -. [Q04735-2]
DR Antibodypedia; 374; 235 antibodies from 31 providers.
DR DNASU; 18555; -.
DR Ensembl; ENSMUST00000033380; ENSMUSP00000033380; ENSMUSG00000031065. [Q04735-1]
DR Ensembl; ENSMUST00000115364; ENSMUSP00000111021; ENSMUSG00000031065. [Q04735-2]
DR GeneID; 18555; -.
DR KEGG; mmu:18555; -.
DR UCSC; uc009sto.1; mouse. [Q04735-1]
DR CTD; 5127; -.
DR MGI; MGI:97516; Cdk16.
DR VEuPathDB; HostDB:ENSMUSG00000031065; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000156963; -.
DR HOGENOM; CLU_000288_154_3_1; -.
DR InParanoid; Q04735; -.
DR OMA; CSHSEAA; -.
DR PhylomeDB; Q04735; -.
DR TreeFam; TF106508; -.
DR BRENDA; 2.7.11.22; 3474.
DR BioGRID-ORCS; 18555; 1 hit in 79 CRISPR screens.
DR ChiTaRS; Cdk16; mouse.
DR PRO; PR:Q04735; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q04735; protein.
DR Bgee; ENSMUSG00000031065; Expressed in bone fossa and 254 other tissues.
DR ExpressionAtlas; Q04735; baseline and differential.
DR Genevisible; Q04735; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IMP:UniProtKB.
DR GO; GO:0030252; P:growth hormone secretion; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
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; Cytoplasm; Cytoplasmic vesicle;
KW Differentiation; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Spermatogenesis;
KW Synapse; Synaptosome; Transferase.
FT CHAIN 1..496
FT /note="Cyclin-dependent kinase 16"
FT /id="PRO_0000086485"
FT DOMAIN 165..446
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 286
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 171..179
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 12
FT /note="Phosphoserine; by BRSK2"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 95
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:21335063,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63686"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00536"
FT VAR_SEQ 1..66
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_004801"
FT VAR_SEQ 67
FT /note="P -> MYTNGYDEEIYYIGGKRVFLTPKAWPFPLPTP (in isoform
FT Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_004802"
FT MUTAGEN 95
FT /note="S->A: Abolishes phosphorylation by CDK5. Impairs
FT normal denrite development."
FT /evidence="ECO:0000269|PubMed:21335063"
SQ SEQUENCE 496 AA; 55914 MW; 0746036524B1FB5F CRC64;
MDRMKKIKRQ LSMTLRGGRG IDKTNGVPEQ IGLDESGGGG GSDLGEAPTR IAPGELRSVR
GPLSSAPEIV HEDMKMGSDG ESDQASATSS DEVQSPVRVR MRNHPPRKIS TEDINKRLSL
PADIRLPEGY LEKLTLNSPI FDKPLSRRLR RVSLSEIGFG KLETYIKLDK LGEGTYATVY
KGKSKLTDNL VALKEIRLEH EEGAPCTAIR EVSLLKDLKH ANIVTLHDII HTEKSLTLVF
EYLDKDLKQY LDDCGNVINM HNVKLFLFQL LRGLAYCHRQ KVLHRDLKPQ NLLINERGEL
KLADFGLARA KSIPTKTYSN EVVTLWYRPP DILLGSTDYS TQIDMWGVGC IFYEMATGRP
LFPGSTVEEQ LHFIFRILGT PTEETWPGIL SNEEFRTYNY PKYRAEALLS HAPRLDSDGA
DLLTKLLQFE GRNRISAEDA RKHPFFLSLG ERIHKLPDTT SIFALKEVQL QKEANIRSTS
MPDSGRPAFR VVDTEF
