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Protein

Cyclin-dependent kinase 14

Gene

CDK14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. May also play a role in meiosis, neuron differentiation and may indirectly act as a negative regulator of insulin-responsive glucose transport.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Serine/threonine-protein kinase activity is promoted by associated cyclins CCDN3 and CCNY and repressed by CDKN1A.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei164ATPCurated1
Active sitei256Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi141 – 149ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cyclin binding Source: UniProtKB
  • cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • regulation of canonical Wnt signaling pathway Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Wnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiO94921
SIGNORiO94921

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 14 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 14
Serine/threonine-protein kinase PFTAIRE-1
Short name:
hPFTAIRE1
Gene namesi
Name:CDK14
Synonyms:KIAA0834, PFTK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000058091.16
HGNCiHGNC:8883 CDK14
MIMi610679 gene
neXtProtiNX_O94921

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi164K → R: Abolishes protein kinase activity. 2 Publications1

Organism-specific databases

DisGeNETi5218
OpenTargetsiENSG00000058091
PharmGKBiPA33221

Chemistry databases

ChEMBLiCHEMBL6162
GuidetoPHARMACOLOGYi1967

Polymorphism and mutation databases

BioMutaiCDK14

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865061 – 469Cyclin-dependent kinase 14Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24PhosphoserineCombined sources1
Modified residuei78PhosphoserineCombined sources1
Modified residuei95PhosphoserineCombined sources1
Modified residuei134PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94921
MaxQBiO94921
PaxDbiO94921
PeptideAtlasiO94921
PRIDEiO94921
ProteomicsDBi50556
50557 [O94921-2]
50558 [O94921-3]

PTM databases

iPTMnetiO94921
PhosphoSitePlusiO94921

Expressioni

Tissue specificityi

Highly expressed in brain, pancreas, kidney, heart, testis and ovary. Also detected at lower levels in other tissues except in spleen and thymus where expression is barely detected.1 Publication

Gene expression databases

BgeeiENSG00000058091
CleanExiHS_PFTK1
ExpressionAtlasiO94921 baseline and differential
GenevisibleiO94921 HS

Organism-specific databases

HPAiHPA015267

Interactioni

Subunit structurei

Found in a complex with LRP6, CCNY and CAPRIN2 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus (PubMed:27821587). Interacts with CCNY; CCNY mediates its recruitment to the plasma membrane and promotes phosphorylation of LRP6 (PubMed:20059949, PubMed:19524571). Interacts with CCDN3 and CDKN1A (PubMed:17517622). Interacts with SEPT8 (PubMed:12098780). Interacts with 14-3-3 proteina YWHAB, YWHAE, YWHAH and YWHAQ (PubMed:16775625).6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cyclin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111239, 19 interactors
ComplexPortaliCPX-364 Cyclin Y-CDK14 complex
DIPiDIP-39618N
IntActiO94921, 13 interactors
MINTiO94921
STRINGi9606.ENSP00000265741

Chemistry databases

BindingDBiO94921

Structurei

3D structure databases

ProteinModelPortaliO94921
SMRiO94921
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini135 – 419Protein kinasePROSITE-ProRule annotationAdd BLAST285

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0594 Eukaryota
ENOG410XPP3 LUCA
GeneTreeiENSGT00900000140869
HOVERGENiHBG014652
InParanoidiO94921
KOiK08821
OMAiLQCFPKN
OrthoDBiEOG091G0CH0
PhylomeDBiO94921
TreeFamiTF106508

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94921-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MCDLIEPQPA EKIGKMKKLR RTLSESFSRI ALKKDDTTFD EICVTKMSTR
60 70 80 90 100
NCQGMDSVIK PLDTIPEDKK VRVQRTQSTF DPFEKPANQV KRVHSENNAC
110 120 130 140 150
INFKTSSTGK ESPKVRRHSS PSSPTSPKFG KADSYEKLEK LGEGSYATVY
160 170 180 190 200
KGKSKVNGKL VALKVIRLQE EEGTPFTAIR EASLLKGLKH ANIVLLHDII
210 220 230 240 250
HTKETLTLVF EYVHTDLCQY MDKHPGGLHP DNVKLFLFQL LRGLSYIHQR
260 270 280 290 300
YILHRDLKPQ NLLISDTGEL KLADFGLARA KSVPSHTYSN EVVTLWYRPP
310 320 330 340 350
DVLLGSTEYS TCLDMWGVGC IFVEMIQGVA AFPGMKDIQD QLERIFLVLG
360 370 380 390 400
TPNEDTWPGV HSLPHFKPER FTLYSSKNLR QAWNKLSYVN HAEDLASKLL
410 420 430 440 450
QCSPKNRLSA QAALSHEYFS DLPPRLWELT DMSSIFTVPN VRLQPEAGES
460
MRAFGKNNSY GKSLSNSKH
Length:469
Mass (Da):53,057
Last modified:April 18, 2006 - v3
Checksum:i32CF9B9B7BD9CE0E
GO
Isoform 2 (identifier: O94921-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MCDLIEPQPAEKIGKMKKLRRTLSESFSRIALKKDDTTFDE → MHGYFGCNAAAEPGYSAFVGTPQ

Show »
Length:451
Mass (Da):50,662
Checksum:i68210FCBC0D44031
GO
Isoform 3 (identifier: O94921-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: Missing.

Note: No experimental confirmation available.
Show »
Length:423
Mass (Da):47,760
Checksum:i5F5D5B2C611243FA
GO

Sequence cautioni

The sequence BAA74857 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8Q → R in BAG60284 (PubMed:14702039).Curated1
Sequence conflicti158G → W in AAG43234 (PubMed:11313143).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046765432M → I in an ovarian mucinous carcinoma; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs773301216Ensembl.1
Natural variantiVAR_046766463S → R1 PublicationCorresponds to variant dbSNP:rs35643773Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0387621 – 46Missing in isoform 3. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_0048031 – 41MCDLI…TTFDE → MHGYFGCNAAAEPGYSAFVG TPQ in isoform 2. 2 PublicationsAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF119833 mRNA Translation: AAG43234.1
AB020641 mRNA Translation: BAA74857.2 Different initiation.
AK289782 mRNA Translation: BAF82471.1
AK295086 mRNA Translation: BAG58127.1
AK297974 mRNA Translation: BAG60284.1
AK316026 mRNA Translation: BAH14397.1
AC000057 Genomic DNA Translation: AAS07411.1
AC000059 Genomic DNA No translation available.
AC002065 Genomic DNA Translation: AAM48566.1
AC002456 Genomic DNA No translation available.
AC002458 Genomic DNA Translation: AAS07412.1
AC006036 Genomic DNA Translation: AAF19245.1
CH236949 Genomic DNA Translation: EAL24162.1
CH471091 Genomic DNA Translation: EAW76873.1
CH471091 Genomic DNA Translation: EAW76874.1
BC136476 mRNA Translation: AAI36477.1
BC136477 mRNA Translation: AAI36478.1
BC152388 mRNA Translation: AAI52389.1
BC152436 mRNA Translation: AAI52437.1
BC167152 mRNA Translation: AAI67152.1
BC167156 mRNA Translation: AAI67156.1
CCDSiCCDS5619.1 [O94921-2]
CCDS75626.1 [O94921-1]
CCDS75627.1 [O94921-3]
RefSeqiNP_001274064.1, NM_001287135.1 [O94921-1]
NP_001274065.1, NM_001287136.1 [O94921-3]
NP_001274066.1, NM_001287137.1
NP_036527.1, NM_012395.3 [O94921-2]
XP_005250495.1, XM_005250438.3 [O94921-3]
XP_005250496.1, XM_005250439.2 [O94921-3]
XP_011514608.1, XM_011516306.2 [O94921-1]
XP_016867809.1, XM_017012320.1 [O94921-3]
XP_016867810.1, XM_017012321.1 [O94921-3]
XP_016867811.1, XM_017012322.1 [O94921-3]
UniGeneiHs.258576
Hs.430742
Hs.740065

Genome annotation databases

EnsembliENST00000265741; ENSP00000265741; ENSG00000058091 [O94921-2]
ENST00000380050; ENSP00000369390; ENSG00000058091 [O94921-1]
ENST00000406263; ENSP00000385034; ENSG00000058091 [O94921-3]
GeneIDi5218
KEGGihsa:5218
UCSCiuc003uky.4 human [O94921-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCDK14_HUMAN
AccessioniPrimary (citable) accession number: O94921
Secondary accession number(s): A4D1E6
, A6NK51, A8WFP6, B4DHG5, B4DNM2, Q75N06, Q75N22, Q8N764, Q9H3D7, Q9UDR0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2002
Last sequence update: April 18, 2006
Last modified: June 20, 2018
This is version 172 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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