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UniProtKB - P49674 (KC1E_HUMAN)

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Protein

Casein kinase I isoform epsilon

Gene

CSNK1E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Phosphorylation leads to a decrease of the catalytic activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei38ATPPROSITE-ProRule annotation1
Active sitei128Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • RNA binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • ciliary basal body docking Source: Reactome
  • circadian regulation of gene expression Source: UniProtKB
  • DNA repair Source: ProtInc
  • endocytosis Source: GO_Central
  • G2/M transition of mitotic cell cycle Source: Reactome
  • negative regulation of protein binding Source: ParkinsonsUK-UCL
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of non-canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of Wnt-mediated midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • protein phosphorylation Source: UniProtKB
  • regulation of cell shape Source: GO_Central
  • regulation of cellular protein localization Source: ParkinsonsUK-UCL
  • regulation of circadian rhythm Source: UniProtKB
  • rRNA processing Source: Reactome
  • signal transduction Source: ProtInc
  • Wnt signaling pathway Source: GO_Central
Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-201688. WNT mediated activation of DVL.
R-HSA-2565942. Regulation of PLK1 Activity at G2/M Transition.
R-HSA-380259. Loss of Nlp from mitotic centrosomes.
R-HSA-380270. Recruitment of mitotic centrosome proteins and complexes.
R-HSA-380284. Loss of proteins required for interphase microtubule organization from the centrosome.
R-HSA-400253. Circadian Clock.
R-HSA-5620912. Anchoring of the basal body to the plasma membrane.
R-HSA-6791226. Major pathway of rRNA processing in the nucleolus and cytosol.
R-HSA-8854518. AURKA Activation by TPX2.
SABIO-RKiP49674.
SignaLinkiP49674.
SIGNORiP49674.

Names & Taxonomyi

Protein namesi
Recommended name:
Casein kinase I isoform epsilon (EC:2.7.11.1)
Short name:
CKI-epsilon
Short name:
CKIe
Gene namesi
Name:CSNK1E
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:2453. CSNK1E.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ParkinsonsUK-UCL
  • cytosol Source: Reactome
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1454.
OpenTargetsiENSG00000213923.
PharmGKBiPA26953.

Chemistry databases

ChEMBLiCHEMBL4937.
GuidetoPHARMACOLOGYi1998.

Polymorphism and mutation databases

BioMutaiCSNK1E.
DMDMi1346369.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001928371 – 416Casein kinase I isoform epsilonAdd BLAST416

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei343PhosphoserineCombined sources1
Modified residuei354PhosphoserineCombined sources1
Modified residuei362PhosphothreonineCombined sources1
Modified residuei363PhosphoserineCombined sources1
Modified residuei382Omega-N-methylarginineBy similarity1
Modified residuei389PhosphoserineCombined sources1
Modified residuei405PhosphoserineCombined sources1
Modified residuei408PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated. Partially dephosphorylated by PPP5C. May be dephosphorylated by PP1.

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP49674.
PaxDbiP49674.
PeptideAtlasiP49674.
PRIDEiP49674.

PTM databases

iPTMnetiP49674.
PhosphoSitePlusiP49674.

Expressioni

Tissue specificityi

Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.

Inductioni

Down-regulated during granulocytic differentiation.1 Publication

Gene expression databases

BgeeiENSG00000213923.
CleanExiHS_CSNK1E.
ExpressionAtlasiP49674. baseline and differential.
GenevisibleiP49674. HS.

Organism-specific databases

HPAiCAB009626.
HPA026288.

Interactioni

Subunit structurei

Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts with ANKRD6, DBNDD2, LRP5, LRP6 and SOCS3. Interacts with SNAI1 (via zinc fingers).6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi107838. 175 interactors.
DIPiDIP-38050N.
IntActiP49674. 111 interactors.
MINTiMINT-1444044.
STRINGi9606.ENSP00000352929.

Chemistry databases

BindingDBiP49674.

Structurei

Secondary structure

1416
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni6 – 8Combined sources3
Beta strandi14 – 16Combined sources3
Beta strandi22 – 28Combined sources7
Turni29 – 31Combined sources3
Beta strandi35 – 41Combined sources7
Helixi51 – 56Combined sources6
Turni57 – 61Combined sources5
Beta strandi68 – 74Combined sources7
Beta strandi77 – 83Combined sources7
Helixi89 – 95Combined sources7
Turni96 – 98Combined sources3
Helixi102 – 120Combined sources19
Turni121 – 123Combined sources3
Helixi131 – 133Combined sources3
Beta strandi134 – 136Combined sources3
Helixi139 – 141Combined sources3
Beta strandi145 – 147Combined sources3
Beta strandi154 – 157Combined sources4
Turni159 – 161Combined sources3
Helixi177 – 179Combined sources3
Helixi182 – 185Combined sources4
Helixi192 – 208Combined sources17
Turni212 – 215Combined sources4
Helixi221 – 234Combined sources14
Helixi237 – 240Combined sources4
Turni241 – 243Combined sources3
Helixi246 – 255Combined sources10
Helixi266 – 280Combined sources15
Helixi289 – 291Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HNIX-ray2.74A/B1-294[»]
4HOKX-ray2.77A/C/E/G/I/K/M/O/Q/S/U/W1-294[»]
ProteinModelPortaliP49674.
SMRiP49674.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 277Protein kinasePROSITE-ProRule annotationAdd BLAST269

Sequence similaritiesi

Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.Curated

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000182055.
HOVERGENiHBG000176.
InParanoidiP49674.
KOiK08960.
OrthoDBiEOG091G0AFG.
PhylomeDBiP49674.
TreeFamiTF300544.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
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.

Sequencei

Sequence statusi: Complete.

P49674-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELRVGNKYR LGRKIGSGSF GDIYLGANIA SGEEVAIKLE CVKTKHPQLH 
        60         70         80         90        100
IESKFYKMMQ GGVGIPSIKW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF 
       110        120        130        140        150
SLKTVLLLAD QMISRIEYIH SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF 
       160        170        180        190        200
GLAKKYRDAR THQHIPYREN KNLTGTARYA SINTHLGIEQ SRRDDLESLG 
       210        220        230        240        250
YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL CKGYPSEFST 
       260        270        280        290        300
YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGAARN 
       310        320        330        340        350
PEDVDRERRE HEREERMGQL RGSATRALPP GPPTGATANR LRSAAEPVAS 
       360        370        380        390        400
TPASRIQPAG NTSPRAISRV DRERKVSMRL HRGAPANVSS SDLTGRQEVS 
       410 
RIPASQTSVP FDHLGK
Length:416
Mass (Da):47,315
Last modified:February 1, 1996 - v1
Checksum:iEE1B1698AE914324
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042082256R → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042083413H → R1 PublicationCorresponds to variant dbSNP:rs35665927Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L37043 mRNA. Translation: AAC41761.1.
AB024597 mRNA. Translation: BAA92345.1.
AB091043 mRNA. Translation: BAC10902.1.
CR456429 mRNA. Translation: CAG30315.1.
AL020993 Genomic DNA. No translation available.
BC006490 mRNA. Translation: AAH06490.1.
CCDSiCCDS13970.1.
PIRiI61744.
RefSeqiNP_001276841.1. NM_001289912.1.
NP_001885.1. NM_001894.4.
NP_689407.1. NM_152221.2.
UniGeneiHs.474833.
Hs.720223.

Genome annotation databases

EnsembliENST00000359867; ENSP00000352929; ENSG00000213923.
ENST00000396832; ENSP00000380044; ENSG00000213923.
ENST00000403904; ENSP00000384074; ENSG00000213923.
GeneIDi102800317.
1454.
KEGGihsa:102800317.
hsa:1454.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiKC1E_HUMAN
AccessioniPrimary (citable) accession number: P49674
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 5, 2017
This is version 182 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families