EKS-MUM-00254
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-MUM-00254
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
CAMK/CAMKL337.98.0E-10127279253
StatusReviewed
Ensembl ProteinENSMUSP00000063166
UniProt AccessionQ5EG47;
Protein Name5'-AMP-activated protein kinase catalytic subunit alpha-1
Protein Synonyms/Alias AMPK subunit alpha-1; Acetyl-CoA carboxylase kinase; ACACA kinase; Hydroxymethylglutaryl-CoA reductase kinase; HMGCR kinase; Tau-protein kinase PRKAA1;
Gene NamePrkaa1
Gene Synonyms/Alias Prkaa1;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSMUSG00000050697ENSMUSP00000063166ENSMUST00000051186
OrganismMus musculus
Functional DescriptionCatalytic subunit of AMP-activated protein kinase(AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.
Protein Length559
Protein Sequence
(FASTA)
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR 60
QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG 120
RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF 180
LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG 240
IFYTPQYLNP SVISLLKHML QVDPMKRAAI KDIREHEWFK QDLPKYLFPE DPSYSSTMID 300
DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS 360
FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI 420
MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTFSKMSL QLYQVDSRTY LLDFRSIDDE 480
ITEAKSGTAT PQRSGSISNY RSCQRSDSDA EAQGKPSDVS LTSSVTSLDS SPVDVAPRPG 540
SHTIEFFEMC ANLIKILAQ 559
Nucleotide Sequence
(FASTA)
ATGCGCAGAC TCAGTTCCTG GAGAAAGATG GCGACGGCCG AGAAGCAGAA GCACGACGGG 60
CGGGTGAAGA TCGGCCACTA CATCCTGGGG GACACGCTTG GTGTCGGCAC CTTCGGGAAA 120
GTGAAGGTGG GCAAGCACGA GTTGACCGGA CATAAAGTGG CTGTGAAGAT ACTCAACCGG 180
CAGAAGATTC GGAGCCTTGA CGTGGTGGGA AAAATCCGCC GGGAGATTCA GAACCTGAAG 240
CTGTTCAGGC ACCCTCACAT CATCAAACTG TACCAGGTCA TCAGTACACC ATCTGATATT 300
TTCATGGTGA TGGAATATGT CTCTGGAGGA GAGCTATTTG ATTATATCTG TAAAAATGGA 360
AGGTTGGACG AAAAGGAAAG CCGCCGTCTG TTCCAGCAGA TCCTTTCCGG TGTGGATTAT 420
TGTCACAGGC ATATGGTGGT CCACAGAGAT TTGAAACCTG AGAACGTCCT GCTTGATGCA 480
CACATGAATG CAAAGATAGC CGACTTTGGT CTTTCAAACA TGATGTCAGA TGGTGAATTT 540
TTAAGAACAA GCTGTGGCTC ACCCAATTAT GCCGCACCAG AAGTCATTTC AGGAAGATTG 600
TACGCAGGCC CCGAGGTGGA CATCTGGAGC AGCGGGGTCA TTCTCTATGC TTTGCTGTGT 660
GGAACCCTCC CTTTTGATGA TGACCATGTG CCAACTCTTT TTAAGAAGAT ATGTGATGGG 720
ATCTTTTATA CCCCTCAGTA CTTAAACCCT TCAGTAATCA GCCTTTTGAA ACATATGCTG 780
CAGGTGGATC CCATGAAGAG GGCCGCAATA AAAGATATCA GGGAACACGA GTGGTTTAAA 840
CAGGACCTTC CGAAGTATCT CTTTCCTGAG GACCCATCTT ATAGTTCAAC CATGATCGAT 900
GACGAAGCCT TGAAAGAAGT GTGTGAGAAG TTCGAGTGTT CGGAGGAGGA GGTCCTCAGC 960
TGCCTGTACA ACAGAAACCA CCAGGACCCA CTAGCCGTCG CCTACCACCT CATCATAGAC 1020
AACAGGAGAA TAATGAATGA AGCCAAAGAT TTCTACCTAG CAACCAGCCC ACCTGACTCT 1080
TTCCTGGACG ACCACCATTT AACTCGGCCT CACCCTGAAA GAGTACCGTT CTTGGTTGCC 1140
GAAACACCAC GGGCCCGGCA CACCCTGGAT GAATTAAACC CACAGAAATC CAAACACCAA 1200
GGTGTACGGA AGGCAAAATG GCATTTGGGA ATTCGAAGTC AAAGCCGACC CAATGATATC 1260
ATGGCAGAAG TTTGTAGAGC AATCAAGCAG TTGGATTATG AATGGAAGGT TGTAAACCCC 1320
TATTATTTGC GTGTACGAAG GAAGAATCCT GTGACAAGCA CATTTTCCAA AATGAGTCTA 1380
CAGCTATACC AAGTGGATAG TAGGACTTAC TTGTTGGATT TCCGTAGTAT TGATGATGAG 1440
ATTACAGAAG CCAAATCAGG GACTGCTACT CCACAGAGAT CGGGATCCAT CAGCAACTAT 1500
CGATCTTGCC AAAGGAGTGA CTCTGATGCC GAAGCTCAAG GAAAGCCCTC AGACGTCTCC 1560
CTTACCTCAT CTGTCACCTC CCTCGACTCC TCCCCTGTCG ACGTAGCTCC AAGACCAGGA 1620
AGTCATACAA TAGAATTTTT TGAAATGTGT GCAAATCTAA TTAAAATTCT TGCACAGTAA 1680
Domain Profile
S: 1     ykllktlGegsfgkVklakhketkekvavKiikkkkl.seeslekikrEieilkklkhpn  59
         y l++tlG g+fgkVk+ kh++t++kvavKi++++k+ s + + ki+rEi+ lk ++hp+
Q: 27    YILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIrSLDVVGKIRREIQNLKLFRHPH  86
         8899********************************96667788****************
S: 60    iikllevietkkklylvleyasggeLfdyieekgrlkekearklfkqlvsavkYlhskgi  119
         iikl++vi+t +++++v+ey+sggeLfdyi ++grl+eke+r+lf+q++s+v+Y+h++ +
Q: 87    IIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMV  146
         ************************************************************
S: 120   vHrDlKpeNllldkkenikiaDFGlanlfkegklletfcGsppYaaPellkgkkYegpkv  179
         vHrDlKpeN+lld+++n kiaDFGl+n++++g+ l+t+cGsp+YaaPe+++g+ Y gp+v
Q: 147   VHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEV  206
         ************************************************************
S: 180   DvWslGvvLyalvtgklPfdeenlkellekilkgkleipkklskelesLlrklLvvdpek  239
         D+Ws Gv+Lyal++g+lPfd++++ +l++ki +g + +p++l+++++sLl+++L+vdp k
Q: 207   DIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMK  266
         ************************************************************
S: 240   Ratieeilkhewl  252
         Ra i++i++hew+
Q: 267   RAAIKDIREHEWF  279
         ************7
Domain Sequence
(FASTA)
YILGDTLGVG TFGKVKVGKH ELTGHKVAVK ILNRQKIRSL DVVGKIRREI QNLKLFRHPH 60
IIKLYQVIST PSDIFMVMEY VSGGELFDYI CKNGRLDEKE SRRLFQQILS GVDYCHRHMV 120
VHRDLKPENV LLDAHMNAKI ADFGLSNMMS DGEFLRTSCG SPNYAAPEVI SGRLYAGPEV 180
DIWSSGVILY ALLCGTLPFD DDHVPTLFKK ICDGIFYTPQ YLNPSVISLL KHMLQVDPMK 240
RAAIKDIREH EWF 253
KeywordATP-binding; Autophagy; Biological rhythms; Cholesterol biosynthesis; Cholesterol metabolism; Chromatin regulator; Complete proteome; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Kinase; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transcription; Transcription regulation; Transferase; Ubl conjugation; Wnt signaling pathway.
Sequence SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Choloepus hoffmanni"; ?>Danio rerio"; ?>Echinops telfairi"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>
EKS-AIM-00227
EKS-ANC-00241
EKS-BOT-00244
EKS-CAJ-00254
EKS-CAF-00257
EKS-CAP-00269
EKS-CHH-00009
EKS-DAR-00564
EKS-ECT-00008
EKS-EQC-00243
EKS-FEC-00232
EKS-GAM-00145
EKS-GAG-00212
EKS-GAA-00302
EKS-GOG-00243
EKS-HOS-00256
EKS-ICT-00235
EKS-LAC-00255
EKS-LOA-00248
EKS-MAM-00244
EKS-MEG-00198
EKS-MOD-00245
EKS-MUP-00247
EKS-MYL-00250
EKS-NOL-00227
EKS-OCP-00014
EKS-ORN-00319
EKS-ORA-00216
EKS-ORC-00218
EKS-ORL-00299
EKS-OTG-00251
EKS-PAT-00234
EKS-PES-00217
EKS-POA-00241
EKS-RAN-00244
EKS-SAH-00229
EKS-SUS-00212
EKS-TAG-00260
EKS-TAR-00312
EKS-TEN-00307
EKS-TUT-00024
EKS-XET-00319
EKS-XIM-00310
Gene Ontology
GO:0031588; C:AMP-activated protein kinase complex
GO:0016324; C:apical plasma membrane
GO:0005737; C:cytoplasm
GO:0005634; C:nucleus
GO:0050405; F:[acetyl-CoA carboxylase] kinase activity
GO:0047322; F:[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
GO:0004679; F:AMP-activated protein kinase activity
GO:0005524; F:ATP binding
GO:0003682; F:chromatin binding
GO:0035174; F:histone serine kinase activity
GO:0046872; F:metal ion binding
GO:0050321; F:tau-protein kinase activity
GO:0006914; P:autophagy
GO:0071361; P:cellular response to ethanol
GO:0042149; P:cellular response to glucose starvation
GO:0070301; P:cellular response to hydrogen peroxide
GO:0071456; P:cellular response to hypoxia
GO:0071417; P:cellular response to organic nitrogen
GO:0006695; P:cholesterol biosynthetic process
GO:0006633; P:fatty acid biosynthetic process
GO:0055089; P:fatty acid homeostasis
GO:0019395; P:fatty acid oxidation
GO:0042593; P:glucose homeostasis
GO:0006006; P:glucose metabolic process
GO:0008610; P:lipid biosynthetic process
GO:0043066; P:negative regulation of apoptotic process
GO:0050995; P:negative regulation of lipid catabolic process
GO:0032007; P:negative regulation of TOR signaling cascade
GO:0010508; P:positive regulation of autophagy
GO:0008284; P:positive regulation of cell proliferation
GO:0045821; P:positive regulation of glycolysis
GO:0051291; P:protein heterooligomerization
GO:0042752; P:regulation of circadian rhythm
GO:2000505; P:regulation of energy homeostasis
GO:0006355; P:regulation of transcription, DNA-dependent
GO:0060627; P:regulation of vesicle-mediated transport
GO:0014823; P:response to activity
GO:0031000; P:response to caffeine
GO:0048511; P:rhythmic process
GO:0006351; P:transcription, DNA-dependent
GO:0016055; P:Wnt receptor signaling pathway
KEGG
mmu:105787;
InterPros
IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR002290; Ser/Thr_dual-sp_kinase_dom.
IPR008271; Ser/Thr_kinase_AS.
Pfam
PF00069; Pkinase; 1.
SMARTs
SM00220; S_TKc; 1.
Prosites
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
Prints
Created Date20-Feb-2013