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Protein

Casein kinase I isoform alpha

Gene

CSNK1A1

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

Functioni

Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46ATPPROSITE-ProRule annotation1
Active sitei136Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi23 – 31ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • beta-catenin destruction complex assembly Source: Reactome
  • beta-catenin destruction complex disassembly Source: Reactome
  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cell morphogenesis Source: Ensembl
  • cell surface receptor signaling pathway Source: ProtInc
  • Golgi organization Source: ParkinsonsUK-UCL
  • intermediate filament cytoskeleton organization Source: UniProtKB
  • negative regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • phagocytosis Source: GO_Central
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: Reactome
  • protein phosphorylation Source: UniProtKB
  • regulation of cell shape Source: GO_Central
  • regulation of GTP binding Source: ParkinsonsUK-UCL
  • signal transduction Source: ProtInc
  • Wnt signaling pathway Source: GO_Central

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5635838 Activation of SMO
SignaLinkiP48729
SIGNORiP48729

Names & Taxonomyi

Protein namesi
Recommended name:
Casein kinase I isoform alpha (EC:2.7.11.1)
Short name:
CKI-alpha
Alternative name(s):
CK1
Gene namesi
Name:CSNK1A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113712.16
HGNCiHGNC:2451 CSNK1A1
MIMi600505 gene
neXtProtiNX_P48729

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 projection, Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1452
OpenTargetsiENSG00000113712
PharmGKBiPA26951

Chemistry databases

ChEMBLiCHEMBL2793
GuidetoPHARMACOLOGYi1995

Polymorphism and mutation databases

BioMutaiCSNK1A1
DMDMi31077177

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001928222 – 337Casein kinase I isoform alphaAdd BLAST336

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei4PhosphoserineCombined sources1
Modified residuei8N6-acetyllysineCombined sources1
Isoform 2 (identifier: P48729-2)
Modified residuei156PhosphoserineCombined sources1
Isoform 3 (identifier: P48729-3)
Modified residuei321PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP48729
MaxQBiP48729
PeptideAtlasiP48729
PRIDEiP48729
TopDownProteomicsiP48729-1 [P48729-1]

PTM databases

iPTMnetiP48729
PhosphoSitePlusiP48729
SwissPalmiP48729

Expressioni

Gene expression databases

BgeeiENSG00000113712
CleanExiHS_CSNK1A1
ExpressionAtlasiP48729 baseline and differential
GenevisibleiP48729 HS

Organism-specific databases

HPAiCAB016680
HPA051334

Interactioni

Subunit structurei

Monomer. Interacts with the Axin complex. Interacts with TUT1, leading to TUT1 phosphorylation. Interacts with FAM83H; recruits CSNK1A1 to keratin filaments (PubMed:23902688).2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi107836, 127 interactors
DIPiDIP-40367N
IntActiP48729, 86 interactors
MINTiP48729

Chemistry databases

BindingDBiP48729

Structurei

Secondary structure

1337
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni14 – 16Combined sources3
Beta strandi17 – 24Combined sources8
Beta strandi27 – 36Combined sources10
Turni37 – 39Combined sources3
Beta strandi42 – 49Combined sources8
Helixi57 – 67Combined sources11
Beta strandi76 – 82Combined sources7
Beta strandi85 – 91Combined sources7
Helixi97 – 103Combined sources7
Helixi110 – 129Combined sources20
Helixi139 – 141Combined sources3
Beta strandi142 – 144Combined sources3
Helixi147 – 149Combined sources3
Beta strandi153 – 155Combined sources3
Turni167 – 169Combined sources3
Turni185 – 187Combined sources3
Helixi190 – 193Combined sources4
Helixi200 – 215Combined sources16
Beta strandi216 – 218Combined sources3
Turni220 – 223Combined sources4
Helixi229 – 242Combined sources14
Helixi245 – 248Combined sources4
Turni249 – 251Combined sources3
Helixi254 – 264Combined sources11
Helixi274 – 287Combined sources14
Helixi297 – 301Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FQDX-ray2.45C/F1-337[»]
ProteinModelPortaliP48729
SMRiP48729
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 285Protein kinasePROSITE-ProRule annotationAdd BLAST269

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00760000119040
HOGENOMiHOG000182055
HOVERGENiHBG000176
InParanoidiP48729
KOiK08957
OMAiGPDYMYL
OrthoDBiEOG091G0AFG
PhylomeDBiP48729
TreeFamiTF354246

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.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P48729-1) [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
MASSSGSKAE FIVGGKYKLV RKIGSGSFGD IYLAINITNG EEVAVKLESQ
60 70 80 90 100
KARHPQLLYE SKLYKILQGG VGIPHIRWYG QEKDYNVLVM DLLGPSLEDL
110 120 130 140 150
FNFCSRRFTM KTVLMLADQM ISRIEYVHTK NFIHRDIKPD NFLMGIGRHC
160 170 180 190 200
NKLFLIDFGL AKKYRDNRTR QHIPYREDKN LTGTARYASI NAHLGIEQSR
210 220 230 240 250
RDDMESLGYV LMYFNRTSLP WQGLKAATKK QKYEKISEKK MSTPVEVLCK
260 270 280 290 300
GFPAEFAMYL NYCRGLRFEE APDYMYLRQL FRILFRTLNH QYDYTFDWTM
310 320 330
LKQKAAQQAA SSSGQGQQAQ TPTGKQTDKT KSNMKGF
Length:337
Mass (Da):38,915
Last modified:May 23, 2003 - v2
Checksum:i1B2085AE33CAFAC2
GO
Isoform 2 (identifier: P48729-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     152-152: K → KCLESPVGKRKRSMTVSTSQDPSFSGLNQ

Show »
Length:365
Mass (Da):41,937
Checksum:i11756FB15947D9F5
GO
Isoform 3 (identifier: P48729-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     324-335: Missing.

Show »
Length:325
Mass (Da):37,567
Checksum:iB84DC84BDDC17854
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45V → L in CAA56710 (PubMed:8050587).Curated1
Sequence conflicti74P → T in AAV38633 (Ref. 6) Curated1
Sequence conflicti122S → A AA sequence (PubMed:1409656).Curated1
Sequence conflicti129T → TK AA sequence (PubMed:1409656).Curated1
Sequence conflicti231Q → K in AAH08717 (PubMed:15489334).Curated1
Sequence conflicti250K → E in AAY84562 (Ref. 7) Curated1
Sequence conflicti330T → S in CAA56710 (PubMed:8050587).Curated1
Sequence conflicti330T → S in AAV38632 (Ref. 6) Curated1
Sequence conflicti330T → S in AAV38633 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042073297D → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035455152K → KCLESPVGKRKRSMTVSTSQ DPSFSGLNQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_055131324 – 335Missing in isoform 3. 2 PublicationsAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80693 mRNA Translation: CAA56710.1
L37042 mRNA Translation: AAC41760.1
AF218004 mRNA Translation: AAG17246.1
AK294942 mRNA Translation: BAG58018.1
CR542206 mRNA Translation: CAG47002.1
BT019829 mRNA Translation: AAV38632.1
BT019830 mRNA Translation: AAV38633.1
DQ082865 mRNA Translation: AAY84562.1
AC021078 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW61767.1
CH471062 Genomic DNA Translation: EAW61769.1
CH471062 Genomic DNA Translation: EAW61773.1
CH471062 Genomic DNA Translation: EAW61774.1
CH471062 Genomic DNA Translation: EAW61776.1
BC008717 mRNA Translation: AAH08717.1
CCDSiCCDS47303.1 [P48729-1]
CCDS47304.1 [P48729-2]
CCDS64291.1 [P48729-3]
PIRiA57011
S46254
RefSeqiNP_001020276.1, NM_001025105.2 [P48729-2]
NP_001258670.1, NM_001271741.1 [P48729-3]
NP_001258671.1, NM_001271742.1
NP_001883.4, NM_001892.5 [P48729-1]
UniGeneiHs.529862
Hs.712555

Genome annotation databases

EnsembliENST00000261798; ENSP00000261798; ENSG00000113712 [P48729-3]
ENST00000377843; ENSP00000367074; ENSG00000113712 [P48729-1]
ENST00000515768; ENSP00000421689; ENSG00000113712 [P48729-2]
GeneIDi1452
KEGGihsa:1452
UCSCiuc003lqw.3 human [P48729-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKC1A_HUMAN
AccessioniPrimary (citable) accession number: P48729
Secondary accession number(s): D3DQG0
, D3DQG1, Q4JJA0, Q5U046, Q5U047, Q6FGA2, Q71TU5, Q96HD2, Q9UDK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 23, 2003
Last modified: March 28, 2018
This is version 189 of the entry and version 2 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, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health