Q04735 (CDK16_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 16
EC=2.7.11.22

Alternative name(s):
CRK5
Cell division protein kinase 16
PCTAIRE-motif protein kinase 1
Serine/threonine-protein kinase PCTAIRE-1

Gene names

Name:	Cdk16
Synonyms:	Crk5, Pctaire1, Pctk1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	496 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Can phosphorylate CCNY at 'Ser-336' (in vitro) By similarity. Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development. Ref.5 Ref.7 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.5 Ref.8 Ref.10
Subunit structure	Found in a complex containing CABLES1, CDK17 and TDRD7. Interacts with BRSK2. Identified in a complex with NSF, syntaxin-1, synaptotagmin, SYN1, SYP and CDK5R1 By similarity. Interacts with YWHAH, YWHAQ and YWHAZ. Interacts with CCNY; this increases the CDK16 kinase activity. Interacts with NSF. Ref.4 Ref.5 Ref.8 Ref.10
Subcellular location	Cytoplasm By similarity. Cytoplasmic vesicle › secretory vesicle. Cell junction › synapse › synaptosome. Note: Colocalizes with insulin in pancreas islets By similarity.
Tissue specificity	Highly expressed in testis and brain, and detected at lower levels in heart, skeletal muscle, adipose tissue, lung, spleen and pancreas (at protein level). Ubiquitous with highest levels in testis and brain, with longer form predominant in all tissues except the testis. Ref.8 Ref.9 Ref.10
Post-translational modification	Phosphorylation at Ser-153 inhibits kinase activity By similarity.
Disruption phenotype	No visible phenotype in females; they are viable and fertile. Male mice are infertile, due to a defect in late stages of spermatogenesis. Ref.10
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Cell junction Cytoplasm Cytoplasmic vesicle Synapse Synaptosome
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: GOC exocytosis Inferred from mutant phenotype Ref.5. Source: UniProtKB growth hormone secretion Inferred from mutant phenotype Ref.5. Source: UniProtKB neuron projection development Inferred from mutant phenotype Ref.7. Source: UniProtKB regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from mutant phenotype Ref.9. Source: UniProtKB spermatogenesis Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB neuron projection Inferred from electronic annotation. Source: UniProtKB-SubCell synapse Inferred from electronic annotation. Source: UniProtKB-KW transport vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent protein serine/threonine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from mutant phenotype Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q04735-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: Q04735-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.
     67-67: P → MYTNGYDEEIYYIGGKRVFLTPKAWPFPLPTP

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 496	496	Cyclin-dependent kinase 16		PRO_0000086485
Regions
	Domain	165 – 446	282	Protein kinase
	Nucleotide binding	171 – 179	9	ATP By similarity
Sites
	Active site	286	1	Proton acceptor By similarity
	Binding site	194	1	ATP By similarity
Amino acid modifications
	Modified residue	12	1	Phosphoserine; by BRSK2 By similarity
	Modified residue	42	1	Phosphoserine By similarity
	Modified residue	78	1	Phosphoserine By similarity
	Modified residue	82	1	Phosphoserine By similarity
	Modified residue	95	1	Phosphoserine; by CDK5 Ref.7
	Modified residue	110	1	Phosphoserine Ref.6
	Modified residue	119	1	Phosphoserine By similarity
	Modified residue	138	1	Phosphoserine By similarity
	Modified residue	153	1	Phosphoserine Ref.6
	Modified residue	155	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 66	66	Missing in isoform Short.		VSP_004801
	Alternative sequence	67	1	P → MYTNGYDEEIYYIGGKRVFL TPKAWPFPLPTP in isoform Short.		VSP_004802
Experimental info
	Mutagenesis	95	1	S → A: Abolishes phosphorylation by CDK5. Impairs normal denrite development. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified October 1, 1993. Version 1. Checksum: 0746036524B1FB5F	FASTA	496	55,914
	10 20 30 40 50 60 MDRMKKIKRQ LSMTLRGGRG IDKTNGVPEQ IGLDESGGGG GSDLGEAPTR IAPGELRSVR 70 80 90 100 110 120 GPLSSAPEIV HEDMKMGSDG ESDQASATSS DEVQSPVRVR MRNHPPRKIS TEDINKRLSL 130 140 150 160 170 180 PADIRLPEGY LEKLTLNSPI FDKPLSRRLR RVSLSEIGFG KLETYIKLDK LGEGTYATVY 190 200 210 220 230 240 KGKSKLTDNL VALKEIRLEH EEGAPCTAIR EVSLLKDLKH ANIVTLHDII HTEKSLTLVF 250 260 270 280 290 300 EYLDKDLKQY LDDCGNVINM HNVKLFLFQL LRGLAYCHRQ KVLHRDLKPQ NLLINERGEL 310 320 330 340 350 360 KLADFGLARA KSIPTKTYSN EVVTLWYRPP DILLGSTDYS TQIDMWGVGC IFYEMATGRP 370 380 390 400 410 420 LFPGSTVEEQ LHFIFRILGT PTEETWPGIL SNEEFRTYNY PKYRAEALLS HAPRLDSDGA 430 440 450 460 470 480 DLLTKLLQFE GRNRISAEDA RKHPFFLSLG ERIHKLPDTT SIFALKEVQL QKEANIRSTS 490 MPDSGRPAFR VVDTEF
	Isoform Short [UniParc]. Checksum: 51AA256DB758DA34	FASTA	461	52,718
	10 20 30 40 50 60 MYTNGYDEEI YYIGGKRVFL TPKAWPFPLP TPEIVHEDMK MGSDGESDQA SATSSDEVQS 70 80 90 100 110 120 PVRVRMRNHP PRKISTEDIN KRLSLPADIR LPEGYLEKLT LNSPIFDKPL SRRLRRVSLS 130 140 150 160 170 180 EIGFGKLETY IKLDKLGEGT YATVYKGKSK LTDNLVALKE IRLEHEEGAP CTAIREVSLL 190 200 210 220 230 240 KDLKHANIVT LHDIIHTEKS LTLVFEYLDK DLKQYLDDCG NVINMHNVKL FLFQLLRGLA 250 260 270 280 290 300 YCHRQKVLHR DLKPQNLLIN ERGELKLADF GLARAKSIPT KTYSNEVVTL WYRPPDILLG 310 320 330 340 350 360 STDYSTQIDM WGVGCIFYEM ATGRPLFPGS TVEEQLHFIF RILGTPTEET WPGILSNEEF 370 380 390 400 410 420 RTYNYPKYRA EALLSHAPRL DSDGADLLTK LLQFEGRNRI SAEDARKHPF FLSLGERIHK 430 440 450 460 LPDTTSIFAL KEVQLQKEAN IRSTSMPDSG RPAFRVVDTE F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family." Okuda T., Cleveland J.L., Downing J.R. Oncogene 7:2249-2258(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Fibroblast.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[3]	"Novel CDC2-related protein kinases produced in murine hematopoietic stem cells." Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V. Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 290-325. Strain: CBA. Tissue: Bone marrow.
[4]	"The Cdk-like protein PCTAIRE-1 from mouse brain associates with p11 and 14-3-3 proteins." Sladeczek F., Camonis J.H., Burnol A.-F., Le Bouffant F. Mol. Gen. Genet. 254:571-577(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH YWHAH; YWHAQ AND YWHAZ.
[5]	"Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications in the regulation of its hexamerization and exocytosis." Liu Y., Cheng K., Gong K., Fu A.K., Ip N.Y. J. Biol. Chem. 281:9852-9858(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH NSF.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110 AND SER-153, MASS SPECTROMETRY. Tissue: Melanoma.
[7]	"Cyclin-dependent kinase 5-dependent phosphorylation of Pctaire1 regulates dendrite development." Fu W.Y., Cheng K., Fu A.K., Ip N.Y. Neuroscience 180:353-359(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-95, PHOSPHORYLATION AT SER-95.
[8]	"Analysis of substrate specificity and cyclin Y binding of PCTAIRE-1 kinase." Shehata S.N., Hunter R.W., Ohta E., Peggie M.W., Lou H.J., Sicheri F., Zeqiraj E., Turk B.E., Sakamoto K. Cell. Signal. 24:2085-2094(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, INTERACTION WITH CCNY, TISSUE SPECIFICITY.
[9]	"Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic beta-cells." Chen X.Y., Gu X.T., Saiyin H., Wan B., Zhang Y.J., Li J., Wang Y.L., Gao R., Wang Y.F., Dong W.P., Najjar S.M., Zhang C.Y., Ding H.F., Liu J.O., Yu L. J. Biol. Chem. 287:30368-30375(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]	"Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis." Mikolcevic P., Sigl R., Rauch V., Hess M.W., Pfaller K., Barisic M., Pelliniemi L.J., Boesl M., Geley S. Mol. Cell. Biol. 32:868-879(2012) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CCNY, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X69025 mRNA. Translation: CAA48787.1. BC011069 mRNA. Translation: AAH11069.1. X64606 mRNA. Translation: CAA45890.1.
IPI	IPI00109670. IPI00228556.
PIR	S30435.
RefSeq	NP_035179.1. NM_011049.4.
UniGene	Mm.102574.
3D structure databases
ProteinModelPortal	Q04735.
SMR	Q04735. Positions 71-472.
ModBase	Search...
PTM databases
PhosphoSite	Q04735.
Proteomic databases
PaxDb	Q04735.
PRIDE	Q04735.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033380; ENSMUSP00000033380; ENSMUSG00000031065. ENSMUST00000115364; ENSMUSP00000111021; ENSMUSG00000031065.
GeneID	18555.
KEGG	mmu:18555.
Organism-specific databases
CTD	5127.
MGI	MGI:97516. Cdk16.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
InParanoid	Q04735.
KO	K08820.
OrthoDB	EOG44BB24.
Enzyme and pathway databases
BRENDA	2.7.11.22. 3474.
Gene expression databases
ArrayExpress	Q04735.
Bgee	Q04735.
CleanEx	MM_PCTK1.
Genevestigator	Q04735.
GermOnline	ENSMUSG00000031065. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CDK16. mouse.
NextBio	294376.
SOURCE	Search...

Entry information

Entry name

CDK16_MOUSE

Accession

Primary (citable) accession number: Q04735

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program