P78368 (KC1G2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Casein kinase I isoform gamma-2
Short name=CKI-gamma 2
EC=2.7.11.1

Gene names

Name:	CSNK1G2
Synonyms:	CK1G2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	415 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase. 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 By similarity. Phosphorylates COL4A3BP/CERT, MTA1 and SMAD3. Involved in brain development and vesicular trafficking and neurotransmitter releasing from small synaptic vesicles. Regulates fast synaptic transmission mediated by glutamate. SMAD3 phosphorylation promotes its ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Hyperphosphorylation of the serine-repeat motif of COL4A3BP/CERT leads to its inactivation by dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis. Ref.7 Ref.8 Ref.11 Ref.12
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Stimulated by estrogen. Repressed by 5-iodotubercidin (DB04604). Ref.8
Subunit structure	Monomer By similarity. Interacts with MTA1 (short isoform) in the cytoplasm. Binds to PER1 and triggers its proteasomal degradation. Interacts with SMAD3. Ref.8 Ref.9 Ref.11
Subcellular location	Cytoplasm Ref.8.
Tissue specificity	Testis.
Post-translational modification	Autophosphorylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Traceable author statement. Source: Reactome protein autophosphorylation Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome sphingolipid biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: Compara peptide binding Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 415

415

Casein kinase I isoform gamma-2

PRO_0000192842

Regions

Domain

46 – 316

271

Protein kinase

Nucleotide binding

52 – 60

9

ATP By similarity

Sites

Active site

165

1

Proton acceptor By similarity

Binding site

75

1

ATP By similarity

Natural variations

Natural variant

189

1

F → L. Ref.16

VAR_042086

Natural variant

194

1

E → G. Ref.16

VAR_042087

Natural variant

196

1

I → T. Ref.16

VAR_042088

Natural variant

206

1

Y → C. Ref.16

VAR_042089

Natural variant

206

1

Y → H. Ref.16

VAR_042090

Natural variant

207

1

R → S. Ref.16

VAR_042091

Natural variant

208

1

E → Q. Ref.16

VAR_042092

Natural variant

217

1

R → C. Ref.16

VAR_042093

Natural variant

223

1

T → M. Ref.16

VAR_042094

Experimental info

Sequence conflict

113

1

K → N in AAP88924. Ref.2

Sequence conflict

113

1

K → N in AAH20972. Ref.6

Secondary structure

1

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415

Helix Strand Turn

Details...

Beta strand

46 – 51

6

Beta strand

60 – 65

6

Turn

66 – 68

3

Beta strand

71 – 78

8

Helix

86 – 95

10

Turn

96 – 98

3

Beta strand

105 – 111

7

Beta strand

114 – 120

7

Helix

126 – 132

7

Turn

133 – 135

3

Helix

139 – 158

20

Helix

168 – 170

3

Beta strand

171 – 173

3

Turn

179 – 182

4

Beta strand

183 – 186

4

Beta strand

193 – 196

4

Turn

198 – 200

3

Turn

216 – 218

3

Helix

221 – 224

4

Helix

231 – 247

17

Turn

251 – 254

4

Beta strand

257 – 259

3

Helix

260 – 272

13

Helix

276 – 279

4

Turn

280 – 282

3

Helix

285 – 295

11

Helix

305 – 318

14

Turn

328 – 331

4

Sequences

	Sequence		Length	Mass (Da)
	P78368 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 036A39148A1DA038	FASTA	415	47,457
	10 20 30 40 50 60 MDFDKKGGKG ETEEGRRMSK AGGGRSSHGI RSSGTSSGVL MVGPNFRVGK KIGCGNFGEL 70 80 90 100 110 120 RLGKNLYTNE YVAIKLEPIK SRAPQLHLEY RFYKQLSATE GVPQVYYFGP CGKYNAMVLE 130 140 150 160 170 180 LLGPSLEDLF DLCDRTFTLK TVLMIAIQLI TRMEYVHTKS LIYRDVKPEN FLVGRPGTKR 190 200 210 220 230 240 QHAIHIIDFG LAKEYIDPET KKHIPYREHK SLTGTARYMS INTHLGKEQS RRDDLEALGH 250 260 270 280 290 300 MFMYFLRGSL PWQGLKADTL KERYQKIGDT KRATPIEVLC ENFPEEMATY LRYVRRLDFF 310 320 330 340 350 360 EKPDYDYLRK LFTDLFDRSG FVFDYEYDWA GKPLPTPIGT VHTDLPSQPQ LRDKTQPHSK 370 380 390 400 410 NQALNSTNGE LNADDPTAGH SNAPITAPAE VEVADETKCC CFFKRRKRKS LQRHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and chromosomal mapping of human casein kinase I gamma 2 (CSNK1G2)." Kitabayashi A.N., Kusuda J., Hirai M., Hashimoto K. Genomics 46:133-137(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Colon and Muscle.
[7]	"Polymorphisms of casein kinase I gamma 2 gene associated with simple febrile seizures in Chinese Han population." Yinan M., Yu Q., Zhiyue C., Jianjun L., Lie H., Liping Z., Jianhui Z., Fang S., Dingfang B., Qing L., Xiru W. Neurosci. Lett. 368:2-6(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BRAIN DEVELOPMENT.
[8]	"Metastatic tumor antigen 1 short form (MTA1s) associates with casein kinase I-gamma2, an estrogen-responsive kinase." Mishra S.K., Yang Z., Mazumdar A., Talukder A.H., Larose L., Kumar R. Oncogene 23:4422-4429(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS MTA1 KINASE, INTERACTION WITH MTA1, SUBCELLULAR LOCATION, ENZYME REGULATION.
[9]	"SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein." Shirogane T., Jin J., Ang X.L., Harper J.W. J. Biol. Chem. 280:26863-26872(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PER1.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling." Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S., Liu X., Wang X.-F. Oncogene 27:7235-7247(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SMAD3 KINASE, INTERACTION WITH SMAD3.
[12]	"Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin." Tomishige N., Kumagai K., Kusuda J., Nishijima M., Hanada K. Mol. Biol. Cell 20:348-357(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS COL4A3BP/CERT KINASE.
[13]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[15]	"The structure of casein kinase 1 gamma 2." Bunkoczi G., Rellos P., Das S., Ugochukwu E., Fedorov O., Sobott F., Eswaran J., Amos A., Ball L., Von Delft F., Bullock A., Debreczeni J., Turnbull A., Sundstrom M., Weigelt J., Arrowsmith C., Edwards A., Knapp S. Submitted (JUL-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 43-353 IN COMPLEX WITH 5-IODOTUBERCIDIN.
[16]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-189; GLY-194; THR-196; CYS-206; HIS-206; SER-207; GLN-208; CYS-217 AND MET-223.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U89896 mRNA. Translation: AAB88627.1.
BT009922 mRNA. Translation: AAP88924.1.
AF001177 Transcribed RNA. Translation: AAC00212.1.
AB451278 mRNA. Translation: BAG70092.1.
AB451410 mRNA. Translation: BAG70224.1.
AC005306 Genomic DNA. Translation: AAC26983.1.
CH471139 Genomic DNA. Translation: EAW69430.1.
BC018693 mRNA. Translation: AAH18693.1.
BC018699 mRNA. Translation: AAH18699.1.
BC020972 mRNA. Translation: AAH20972.1.

IPI

IPI00297767.

RefSeq

NP_001310.3. NM_001319.6.

UniGene

Hs.651905.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C47	X-ray	2.40	A/B/C/D	43-353	[»]

ProteinModelPortal

P78368.

ModBase

Search...

Protein-protein interaction databases

IntAct

P78368. 2 interactions.

MINT

MINT-1473562.

STRING

9606.ENSP00000255641.

PTM databases

PhosphoSite

P78368.

Polymorphism databases

DMDM

3024060.

Proteomic databases

PaxDb

P78368.

PRIDE

P78368.

Protocols and materials databases

DNASU

1455.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000255641; ENSP00000255641; ENSG00000133275.

GeneID

1455.

KEGG

hsa:1455.

UCSC

uc002lul.4. human.

Organism-specific databases

CTD

1455.

GeneCards

GC19P001941.

HGNC

HGNC:2455. CSNK1G2.

HPA

HPA034868.

MIM

602214. gene.

neXtProt

NX_P78368.

PharmGKB

PA26955.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000182054.

HOVERGEN

HBG000176.

InParanoid

P78368.

KO

K08958.

OMA

FDICGRR.

OrthoDB

EOG4GHZP4.

PhylomeDB

P78368.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

foxopathway. FoxO family signaling.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P78368.

CleanEx

HS_CSNK1G2.

Genevestigator

P78368.

GermOnline

ENSG00000133275. Homo sapiens.

Family and domain databases

InterPro

IPR022247. Casein_kinase-1_gamma_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF12605. CK1gamma_C. 1 hit.
PF00069. Pkinase. 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

BindingDB

P78368.

ChEMBL

CHEMBL2543.

ChiTaRS

CSNK1G2. human.

EvolutionaryTrace

P78368.

GenomeRNAi

1455.

NextBio

5975.

SOURCE

Search...

Entry information

Entry name

KC1G2_HUMAN

Accession

Primary (citable) accession number: P78368
Secondary accession number(s): B5BU42, O00704, Q8WUB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.