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Protein

Calcium/calmodulin-dependent protein kinase type 1

Gene

Camk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca2+ elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-516', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation (By similarity). Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-275' and 'Ser-294'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.By similarity8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca2+/calmodulin activation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1
Active sitei141Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calmodulin-dependent protein kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type 1 (EC:2.7.11.17)
Alternative name(s):
CaM kinase I
Short name:
CaM-KI
CaM kinase I alpha
Short name:
CaMKI-alpha
Gene namesi
Name:Camk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi629473. Camk1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi177T → A: Loss of activation by CaMKK1 and CaMKK2. 1 Publication1
Mutagenesisi263 – 264KR → AA: Partially excluded from the nucleus; when associated with 319-AQA-321. 1 Publication2
Mutagenesisi319 – 321LQL → AQA: Retention in the nucleus. Partially excluded from the nucleus; when associated with 263-AA-264. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860781 – 374Calcium/calmodulin-dependent protein kinase type 1Add BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei177Phosphothreonine; by CaMKK1 and CaMKK21 Publication1

Post-translational modificationi

Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.1 Publication
Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ63450.
PRIDEiQ63450.

PTM databases

iPTMnetiQ63450.
PhosphoSitePlusiQ63450.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSRNOG00000021781.
GenevisibleiQ63450. RN.

Interactioni

Subunit structurei

Monomer. Interacts with XPO1.2 Publications

Protein-protein interaction databases

BioGridi251279. 3 interactors.
IntActiQ63450. 5 interactors.
MINTiMINT-3375300.
STRINGi10116.ENSRNOP00000033456.

Structurei

Secondary structure

1374
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi16 – 18Combined sources3
Beta strandi20 – 28Combined sources9
Helixi29 – 33Combined sources5
Beta strandi34 – 39Combined sources6
Turni40 – 42Combined sources3
Beta strandi45 – 52Combined sources8
Helixi65 – 71Combined sources7
Beta strandi81 – 86Combined sources6
Beta strandi88 – 95Combined sources8
Helixi103 – 108Combined sources6
Helixi115 – 134Combined sources20
Helixi144 – 146Combined sources3
Beta strandi147 – 153Combined sources7
Beta strandi158 – 160Combined sources3
Helixi187 – 190Combined sources4
Helixi198 – 213Combined sources16
Helixi223 – 231Combined sources9
Turni239 – 244Combined sources6
Helixi247 – 256Combined sources10
Helixi261 – 263Combined sources3
Helixi267 – 272Combined sources6
Turni274 – 276Combined sources3
Beta strandi277 – 279Combined sources3
Helixi287 – 297Combined sources11
Helixi298 – 317Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A06X-ray2.50A1-329[»]
1MXEX-ray1.70E/F294-318[»]
2L7LNMR-B299-320[»]
ProteinModelPortaliQ63450.
SMRiQ63450.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ63450.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 276Protein kinasePROSITE-ProRule annotationAdd BLAST257

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni276 – 316Autoinhibitory domainAdd BLAST41
Regioni296 – 317Calmodulin-bindingAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi263 – 264Involved in nuclear importCurated2
Motifi315 – 321Nuclear export signal7

Domaini

The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.1 Publication

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118944.
HOVERGENiHBG108055.
InParanoidiQ63450.
KOiK08794.
OMAiVTVEKRY.
OrthoDBiEOG091G0HK9.
PhylomeDBiQ63450.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63450-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC
60 70 80 90 100
IAKKALEGKE GSMENEIAVL HKIKHPNIVA LDDIYESGGH LYLIMQLVSG
110 120 130 140 150
GELFDRIVEK GFYTERDASR LIFQVLDAVK YLHDLGIVHR DLKPENLLYY
160 170 180 190 200
SLDEDSKIMI SDFGLSKMED PGSVLSTACG TPGYVAPEVL AQKPYSKAVD
210 220 230 240 250
CWSIGVIAYI LLCGYPPFYD ENDAKLFEQI LKAEYEFDSP YWDDISDSAK
260 270 280 290 300
DFIRHLMEKD PEKRFTCEQA LQHPWIAGDT ALDKNIHQSV SEQIKKNFAK
310 320 330 340 350
SKWKQAFNAT AVVRHMRKLQ LGTSQEGQGQ TASHGELLTP TAGGPAAGCC
360 370
CRDCCVEPGS ELPPAPPPSS RAMD
Length:374
Mass (Da):41,638
Last modified:July 15, 1998 - v2
Checksum:i37889B3DEF033AB2
GO

Sequence cautioni

The sequence AAA19670 differs from that shown. Reason: Frameshift at positions 321 and 363.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37A → T AA sequence (PubMed:8386178).Curated1
Sequence conflicti112F → G in AAA19670 (PubMed:8253780).Curated1
Sequence conflicti118A → R in AAA19670 (PubMed:8253780).Curated1
Sequence conflicti239S → V AA sequence (PubMed:8386178).Curated1
Sequence conflicti309A → R in AAA19670 (PubMed:8253780).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24907 mRNA. Translation: AAA19670.1. Frameshift.
L26288 mRNA. Translation: AAA66944.1.
BC071177 mRNA. Translation: AAH71177.1.
PIRiS50193.
RefSeqiNP_604463.1. NM_134468.1.
XP_006237065.1. XM_006237003.3.
UniGeneiRn.11018.

Genome annotation databases

EnsembliENSRNOT00000029728; ENSRNOP00000033456; ENSRNOG00000021781.
GeneIDi171503.
KEGGirno:171503.
UCSCiRGD:629473. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24907 mRNA. Translation: AAA19670.1. Frameshift.
L26288 mRNA. Translation: AAA66944.1.
BC071177 mRNA. Translation: AAH71177.1.
PIRiS50193.
RefSeqiNP_604463.1. NM_134468.1.
XP_006237065.1. XM_006237003.3.
UniGeneiRn.11018.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A06X-ray2.50A1-329[»]
1MXEX-ray1.70E/F294-318[»]
2L7LNMR-B299-320[»]
ProteinModelPortaliQ63450.
SMRiQ63450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi251279. 3 interactors.
IntActiQ63450. 5 interactors.
MINTiMINT-3375300.
STRINGi10116.ENSRNOP00000033456.

PTM databases

iPTMnetiQ63450.
PhosphoSitePlusiQ63450.

Proteomic databases

PaxDbiQ63450.
PRIDEiQ63450.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000029728; ENSRNOP00000033456; ENSRNOG00000021781.
GeneIDi171503.
KEGGirno:171503.
UCSCiRGD:629473. rat.

Organism-specific databases

CTDi8536.
RGDi629473. Camk1.

Phylogenomic databases

eggNOGiKOG0032. Eukaryota.
ENOG410XRMJ. LUCA.
GeneTreeiENSGT00760000118944.
HOVERGENiHBG108055.
InParanoidiQ63450.
KOiK08794.
OMAiVTVEKRY.
OrthoDBiEOG091G0HK9.
PhylomeDBiQ63450.

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Miscellaneous databases

EvolutionaryTraceiQ63450.
PROiQ63450.

Gene expression databases

BgeeiENSRNOG00000021781.
GenevisibleiQ63450. RN.

Family and domain databases

InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKCC1A_RAT
AccessioniPrimary (citable) accession number: Q63450
Secondary accession number(s): Q63084
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Dendrite development is blocked in hippocampal neurons silencing CAKM1.

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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.