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Protein

5'-AMP-activated protein kinase catalytic subunit alpha-1

Gene

PRKAA1

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

Functioni

Catalytic 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/ULK1: 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 ATG1/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 SLC12A1.12 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + [tau protein] = ADP + [tau protein] phosphate.
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate.
ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate.

Cofactori

Enzyme regulationi

Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol.5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei56 – 561ATPPROSITE-ProRule annotation
Active sitei150 – 1501Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi33 – 419ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Autophagy, Biological rhythms, Cholesterol biosynthesis, Cholesterol metabolism, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism, Transcription, Transcription regulation, Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_21285. Regulation of AMPK activity via LKB1.
REACT_21393. Regulation of Rheb GTPase activity by AMPK.
REACT_355377. TP53 Regulates Metabolic Genes.
SignaLinkiQ13131.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-1 (EC:2.7.11.1)
Short name:
AMPK subunit alpha-1
Alternative name(s):
Acetyl-CoA carboxylase kinase (EC:2.7.11.27)
Short name:
ACACA kinase
Hydroxymethylglutaryl-CoA reductase kinase (EC:2.7.11.31)
Short name:
HMGCR kinase
Tau-protein kinase PRKAA1 (EC:2.7.11.26)
Gene namesi
Name:PRKAA1
Synonyms:AMPK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:9376. PRKAA1.

Subcellular locationi

GO - Cellular componenti

  • AMP-activated protein kinase complex Source: UniProtKB
  • apical plasma membrane Source: Ensembl
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • intracellular Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi307 – 3071V → G or Q: Activates the kinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA33744.

Chemistry

DrugBankiDB00945. Acetylsalicylic acid.
DB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.
DB00914. Phenformin.

Polymorphism and mutation databases

BioMutaiPRKAA1.
DMDMi254763436.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5595595'-AMP-activated protein kinase catalytic subunit alpha-1PRO_0000085589Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei32 – 321Phosphothreonine1 Publication
Modified residuei183 – 1831Phosphothreonine; by LKB1 and CaMKK2By similarity
Modified residuei269 – 2691PhosphothreonineBy similarity
Modified residuei355 – 3551Phosphothreonine1 Publication
Modified residuei356 – 3561Phosphoserine1 Publication
Modified residuei360 – 3601Phosphoserine; by ULK1By similarity
Modified residuei368 – 3681Phosphothreonine; by ULK1By similarity
Modified residuei382 – 3821Phosphothreonine2 Publications
Modified residuei397 – 3971Phosphoserine; by ULK11 Publication
Modified residuei467 – 4671Phosphoserine1 Publication
Modified residuei486 – 4861Phosphoserine1 Publication
Modified residuei488 – 4881Phosphothreonine; by ULK11 Publication
Modified residuei490 – 4901Phosphothreonine1 Publication
Modified residuei496 – 4961Phosphoserine2 Publications
Modified residuei508 – 5081Phosphoserine1 Publication
Modified residuei524 – 5241Phosphoserine1 Publication
Modified residuei527 – 5271Phosphoserine1 Publication

Post-translational modificationi

Ubiquitinated.By similarity
Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.4 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ13131.
PaxDbiQ13131.
PRIDEiQ13131.

PTM databases

PhosphoSiteiQ13131.

Expressioni

Gene expression databases

BgeeiQ13131.
CleanExiHS_PRKAA1.
ExpressionAtlasiQ13131. baseline and differential.
GenevisibleiQ13131. HS.

Organism-specific databases

HPAiCAB005050.
HPA035409.

Interactioni

Subunit structurei

AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABI2Q9NYB93EBI-1181405,EBI-743598
AESQ081173EBI-1181405,EBI-717810
BHLHE40O145033EBI-1181405,EBI-711810
CDX4O146273EBI-1181405,EBI-10181162
CTBP1Q13363-23EBI-1181405,EBI-10171858
FSBPO950733EBI-1181405,EBI-1059030
GOLGA2Q083793EBI-1181405,EBI-618309
HMBOX1Q6NT763EBI-1181405,EBI-2549423
HOMEZQ8IX15-33EBI-1181405,EBI-10172004
HSP90AB1P082382EBI-1181405,EBI-352572
IKZF3Q9UKT93EBI-1181405,EBI-747204
INO80EQ8NBZ03EBI-1181405,EBI-769401
KRT40Q6A1623EBI-1181405,EBI-10171697
L3MBTL3Q96JM73EBI-1181405,EBI-2686809
MTUS2Q5JR593EBI-1181405,EBI-742948
PHC2Q8IXK03EBI-1181405,EBI-713786
PNMA5Q96PV43EBI-1181405,EBI-10171633
PRKAB1Q9Y4786EBI-1181405,EBI-719769
PRKAB2O4374112EBI-1181405,EBI-1053424
PRKAG1P5461910EBI-1181405,EBI-1181439
RBPMSQ930623EBI-1181405,EBI-740322
RFX6Q8HWS33EBI-1181405,EBI-746118
RIMBP3Q9UFD93EBI-1181405,EBI-10182375
ROPN1Q9HAT03EBI-1181405,EBI-1378139
SSX2IPQ9Y2D83EBI-1181405,EBI-2212028
THAP1Q9NVV93EBI-1181405,EBI-741515
TRIM27P143733EBI-1181405,EBI-719493
TRIP6Q156543EBI-1181405,EBI-742327
TSC22D4Q9Y3Q83EBI-1181405,EBI-739485
UBXN11Q5T1243EBI-1181405,EBI-746004
VPS37BQ9H9H43EBI-1181405,EBI-4400866
VPS52Q8N1B43EBI-1181405,EBI-2799833
ZBED1O960063EBI-1181405,EBI-740037

Protein-protein interaction databases

BioGridi111549. 140 interactions.
DIPiDIP-39973N.
IntActiQ13131. 93 interactions.
MINTiMINT-6771251.
STRINGi9606.ENSP00000346148.

Structurei

Secondary structure

1
559
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi27 – 359Combined sources
Beta strandi40 – 4910Combined sources
Beta strandi52 – 598Combined sources
Helixi60 – 667Combined sources
Beta strandi68 – 703Combined sources
Helixi71 – 777Combined sources
Beta strandi90 – 956Combined sources
Beta strandi97 – 1059Combined sources
Helixi112 – 1187Combined sources
Helixi124 – 14421Combined sources
Helixi153 – 1553Combined sources
Beta strandi156 – 1583Combined sources
Beta strandi164 – 1674Combined sources
Beta strandi169 – 1713Combined sources
Helixi193 – 1964Combined sources
Helixi204 – 22017Combined sources
Beta strandi227 – 2293Combined sources
Helixi231 – 2333Combined sources
Helixi250 – 25910Combined sources
Helixi264 – 2663Combined sources
Helixi270 – 2745Combined sources
Helixi277 – 2804Combined sources
Turni296 – 2983Combined sources
Helixi301 – 31010Combined sources
Helixi315 – 3239Combined sources
Helixi330 – 34011Combined sources
Turni347 – 3515Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4REDX-ray2.95A/B22-362[»]
4RERX-ray4.05A20-559[»]
4REWX-ray4.58A20-559[»]
ProteinModelPortaliQ13131.
SMRiQ13131. Positions 20-559.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 279253Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni302 – 38180AISAdd
BLAST

Domaini

The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.2 Publications

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122960.
HOGENOMiHOG000233016.
HOVERGENiHBG050432.
KOiK07198.
OMAiMKRATIR.
OrthoDBiEOG7RRF6K.
PhylomeDBiQ13131.
TreeFamiTF314032.

Family and domain databases

InterProiIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24343:SF81. PTHR24343:SF81. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13131-1) [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
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG
60 70 80 90 100
HKVAVKILNR QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI
110 120 130 140 150
FMVMEYVSGG ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD
160 170 180 190 200
LKPENVLLDA HMNAKIADFG LSNMMSDGEF LRTSCGSPNY AAPEVISGRL
210 220 230 240 250
YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG IFYTPQYLNP
260 270 280 290 300
SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID
310 320 330 340 350
DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD
360 370 380 390 400
FYLATSPPDS FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ
410 420 430 440 450
GVRKAKWHLG IRSQSRPNDI MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP
460 470 480 490 500
VTSTYSKMSL QLYQVDSRTY LLDFRSIDDE ITEAKSGTAT PQRSGSVSNY
510 520 530 540 550
RSCQRSDSDA EAQGKSSEVS LTSSVTSLDS SPVDLTPRPG SHTIEFFEMC

ANLIKILAQ
Length:559
Mass (Da):64,009
Last modified:July 28, 2009 - v4
Checksum:iABAE71FBF912947A
GO
Isoform 2 (identifier: Q13131-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     121-121: R → RKSDVPGVVKTGSTKE

Show »
Length:574
Mass (Da):65,523
Checksum:i8EA8B85393F48DAA
GO

Sequence cautioni

The sequence AAA64850.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD43027.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH37303.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA36547.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG35788.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51S → C in BAG35788 (PubMed:14702039).Curated
Sequence conflicti9 – 91K → S in AAD43027 (PubMed:11042152).Curated
Sequence conflicti37 – 371T → A in AAA64850 (Ref. 6) Curated
Sequence conflicti202 – 2021A → V in AAA64850 (Ref. 6) Curated
Sequence conflicti208 – 2081I → L in AAA64850 (Ref. 6) Curated
Sequence conflicti269 – 2691T → S in BAA36547 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101M → L.1 Publication
Corresponds to variant rs17855679 [ dbSNP | Ensembl ].
VAR_058401
Natural varianti16 – 161Q → R in a breast cancer sample; somatic mutation. 1 Publication
VAR_035622

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei121 – 1211R → RKSDVPGVVKTGSTKE in isoform 2. 1 PublicationVSP_035431

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC008810 Genomic DNA. No translation available.
BC048980 mRNA. Translation: AAH48980.1.
AB022017 mRNA. Translation: BAA36547.1. Different initiation.
AK312947 mRNA. Translation: BAG35788.1. Different initiation.
BC037303 mRNA. Translation: AAH37303.1. Different initiation.
AF100763 mRNA. Translation: AAD43027.1. Different initiation.
U22456 mRNA. Translation: AAA64850.1. Different initiation.
Y12856 mRNA. Translation: CAA73361.1.
CCDSiCCDS3932.2. [Q13131-1]
CCDS3933.2. [Q13131-2]
PIRiG01743.
RefSeqiNP_006242.5. NM_006251.5. [Q13131-1]
NP_996790.3. NM_206907.3. [Q13131-2]
UniGeneiHs.43322.

Genome annotation databases

EnsembliENST00000354209; ENSP00000346148; ENSG00000132356. [Q13131-2]
ENST00000397128; ENSP00000380317; ENSG00000132356. [Q13131-1]
GeneIDi5562.
KEGGihsa:5562.
UCSCiuc003jmb.3. human. [Q13131-2]
uc003jmc.3. human. [Q13131-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC008810 Genomic DNA. No translation available.
BC048980 mRNA. Translation: AAH48980.1.
AB022017 mRNA. Translation: BAA36547.1. Different initiation.
AK312947 mRNA. Translation: BAG35788.1. Different initiation.
BC037303 mRNA. Translation: AAH37303.1. Different initiation.
AF100763 mRNA. Translation: AAD43027.1. Different initiation.
U22456 mRNA. Translation: AAA64850.1. Different initiation.
Y12856 mRNA. Translation: CAA73361.1.
CCDSiCCDS3932.2. [Q13131-1]
CCDS3933.2. [Q13131-2]
PIRiG01743.
RefSeqiNP_006242.5. NM_006251.5. [Q13131-1]
NP_996790.3. NM_206907.3. [Q13131-2]
UniGeneiHs.43322.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4REDX-ray2.95A/B22-362[»]
4RERX-ray4.05A20-559[»]
4REWX-ray4.58A20-559[»]
ProteinModelPortaliQ13131.
SMRiQ13131. Positions 20-559.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111549. 140 interactions.
DIPiDIP-39973N.
IntActiQ13131. 93 interactions.
MINTiMINT-6771251.
STRINGi9606.ENSP00000346148.

Chemistry

BindingDBiQ13131.
ChEMBLiCHEMBL3038452.
DrugBankiDB00945. Acetylsalicylic acid.
DB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.
DB00914. Phenformin.
GuidetoPHARMACOLOGYi1541.

PTM databases

PhosphoSiteiQ13131.

Polymorphism and mutation databases

BioMutaiPRKAA1.
DMDMi254763436.

Proteomic databases

MaxQBiQ13131.
PaxDbiQ13131.
PRIDEiQ13131.

Protocols and materials databases

DNASUi5562.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000354209; ENSP00000346148; ENSG00000132356. [Q13131-2]
ENST00000397128; ENSP00000380317; ENSG00000132356. [Q13131-1]
GeneIDi5562.
KEGGihsa:5562.
UCSCiuc003jmb.3. human. [Q13131-2]
uc003jmc.3. human. [Q13131-1]

Organism-specific databases

CTDi5562.
GeneCardsiGC05M040759.
H-InvDBHIX0004832.
HGNCiHGNC:9376. PRKAA1.
HPAiCAB005050.
HPA035409.
MIMi602739. gene.
neXtProtiNX_Q13131.
PharmGKBiPA33744.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122960.
HOGENOMiHOG000233016.
HOVERGENiHBG050432.
KOiK07198.
OMAiMKRATIR.
OrthoDBiEOG7RRF6K.
PhylomeDBiQ13131.
TreeFamiTF314032.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_21285. Regulation of AMPK activity via LKB1.
REACT_21393. Regulation of Rheb GTPase activity by AMPK.
REACT_355377. TP53 Regulates Metabolic Genes.
SignaLinkiQ13131.

Miscellaneous databases

ChiTaRSiPRKAA1. human.
GeneWikiiProtein_kinase,_AMP-activated,_alpha_1.
GenomeRNAii5562.
NextBioi21546.
PROiQ13131.
SOURCEiSearch...

Gene expression databases

BgeeiQ13131.
CleanExiHS_PRKAA1.
ExpressionAtlasiQ13131. baseline and differential.
GenevisibleiQ13131. HS.

Family and domain databases

InterProiIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24343:SF81. PTHR24343:SF81. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "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] (ISOFORMS 1 AND 2), VARIANT LEU-10.
    Tissue: Brain and Testis.
  3. "Nucleotide sequence of cDNA for human AMP-activated protein kinase alpha-1."
    Yano K.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-559 (ISOFORM 1).
    Tissue: Mammary gland.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-559 (ISOFORM 1).
    Tissue: Trachea.
  5. "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
    Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X.
    , Gu J., Chen S.-J., Chen Z.
    Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-559 (ISOFORM 1).
    Tissue: Umbilical cord blood.
  6. Taboada E.N., Hickey D.A.
    Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-209 (ISOFORM 1).
    Tissue: Intestine.
  7. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 303-559 (ISOFORMS 1/2).
    Tissue: Liver.
  8. "Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase."
    Crute B.E., Seefeld K., Gamble J., Kemp B.E., Witters L.A.
    J. Biol. Chem. 273:35347-35354(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN AIS.
  9. "Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line."
    Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.
    Biochem. Biophys. Res. Commun. 287:562-567(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors."
    Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.
    J. Biol. Chem. 276:38341-38344(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF EP300.
  11. Cited for: ENZYME REGULATION.
  12. "Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells."
    Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.
    Am. J. Physiol. 284:C1297-C1308(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF CFTR.
  13. "TSC2 mediates cellular energy response to control cell growth and survival."
    Inoki K., Zhu T., Guan K.L.
    Cell 115:577-590(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
  14. "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
    Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
    EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
  15. "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase."
    Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G.
    Cell Metab. 2:9-19(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
  16. "The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases."
    Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., Witters L.A.
    J. Biol. Chem. 280:29060-29066(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
  17. "AMP-activated protein kinase induces a p53-dependent metabolic checkpoint."
    Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., Birnbaum M.J., Thompson C.B.
    Mol. Cell 18:283-293(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  18. Cited for: INTERACTION WITH FNIP1.
  19. "Conserved alpha-helix acts as autoinhibitory sequence in AMP-activated protein kinase alpha subunits."
    Pang T., Xiong B., Li J.Y., Qiu B.Y., Jin G.Z., Shen J.K., Li J.
    J. Biol. Chem. 282:495-506(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN AIS, MUTAGENESIS OF VAL-307.
  20. "The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor."
    Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., Gygi S.P., Brunet A.
    J. Biol. Chem. 282:30107-30119(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO3.
  21. "Energy-dependent regulation of cell structure by AMP-activated protein kinase."
    Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., Shong M., Kim J.M., Kim J., Chung J.
    Nature 447:1017-1020(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL POLARITY.
  22. "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5."
    McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., Schertzer J.D., Kemp B.E., Hargreaves M.
    Diabetes 57:860-867(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5.
  23. "Identification and characterization of a novel folliculin-interacting protein FNIP2."
    Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A., Linehan W.M., Schmidt L.S.
    Gene 415:60-67(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FNIP2.
  24. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
    Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
    J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Platelet.
  26. Cited for: FUNCTION IN PHOSPHORYLATION OF RPTOR.
  27. "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.
  28. "Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein."
    Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., Zhang D., Abe M., Hagiwara Y., Takahashi K., Hino O.
    Oncogene 27:5339-5347(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FNIP2.
  29. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-486; THR-490 AND SER-496, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  30. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  31. "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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  32. "Cell-wide analysis of secretory granule dynamics in three dimensions in living pancreatic beta-cells: evidence against a role for AMPK-dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin granule movement."
    McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., Rutter G.A.
    Biochem. Soc. Trans. 38:205-208(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF KLC1.
  33. Cited for: FUNCTION.
  34. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  35. "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop."
    Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.
    Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY ULK1 AND ULK2.
  36. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  37. Cited for: FUNCTION IN PHOSPHORYLATION OF ULK1.
  38. "AMPK is a direct adenylate charge-regulated protein kinase."
    Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S., Kemp B.E.
    Science 332:1433-1435(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRKAB1 AND PRKAG1, ENZYME REGULATION.
  39. "AMP-activated protein kinase in metabolic control and insulin signaling."
    Towler M.C., Hardie D.G.
    Circ. Res. 100:328-341(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  40. "AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy."
    Hardie D.G.
    Nat. Rev. Mol. Cell Biol. 8:774-785(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  41. "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells."
    Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T., Tamura S., Kobayashi T.
    Biochem. J. 449:741-749(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEPHOSPHORYLATION.
  42. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-355; SER-496; SER-508; SER-524 AND SER-527, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  43. Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-16.

Entry informationi

Entry nameiAAPK1_HUMAN
AccessioniPrimary (citable) accession number: Q13131
Secondary accession number(s): A8MTQ6
, B2R7E1, O00286, Q5D0E1, Q86VS1, Q9UNQ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 28, 2009
Last modified: June 24, 2015
This is version 168 of the entry and version 4 of the sequence. [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 5
    Human chromosome 5: 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

External Data

Dasty 3

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 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.