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

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Reviewed, UniProtKB/Swiss-Prot P54645 (AAPK1_RAT)

Last modified November 25, 2008. Version 80. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-1
      Short name=AMPK alpha-1 chain
    EC=2.7.11.1

Gene names

Name:	Prkaa1
Synonyms:	Ampk1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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Protein attributes

Sequence length	548 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase. It also regulates cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Appears to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia. This is a catalytic subunit.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-172 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Also activated by phosphorylation by CAMKK2 triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio.
Subunit structure	Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 By similarity.
Tissue specificity	Low expression in kidney, liver, lung, heart and brain.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain.

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Ontologies

Keywords
Biological process	Cholesterol biosynthesis Fatty acid biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of translation Non-traceable author statement. Source: UniProtKB positive regulation of fatty acid oxidation Non-traceable author statement. Source: UniProtKB positive regulation of gluconeogenesis Non-traceable author statement. Source: UniProtKB positive regulation of glucose import Non-traceable author statement. Source: UniProtKB protein amino acid phosphorylation Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro eukaryotic elongation factor-2 kinase activator activity Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 548

548

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

PRO_0000085593

Regions

Domain

16 – 268

253

Protein kinase

Nucleotide binding

22 – 30

ATP By similarity

Sites

Active site

139

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

172

Phosphothreonine; by STK11

Modified residue

173

Phosphoserine By similarity

Modified residue

258

Phosphothreonine

Modified residue

345

Phosphoserine By similarity

Modified residue

371

Phosphothreonine By similarity

Modified residue

431

Phosphotyrosine By similarity

Modified residue

475

Phosphoserine By similarity

Modified residue

479

Phosphothreonine By similarity

Modified residue

485

Phosphoserine

Modified residue

497

Phosphoserine By similarity

Experimental info

Mutagenesis

172

T → E: Hinders activation

Mutagenesis

258

T → A: Hinders activation

Mutagenesis

258

T → D: Retains activation ability

Mutagenesis

485

S → A: Hinders activation

Mutagenesis

485

S → D: Retains activation ability

Sequence conflict

462

D → L protein sequence Ref.1

Secondary structure

548

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P54645-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5CCA3281C195F867
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FASTA

548

62,600

        10         20         30         40         50         60 
MAEKQKHDGR VKIGHYILGD TLGVGTFGKV KVGKHELTGH KVAVKILNRQ KIRSLDVVGK 

        70         80         90        100        110        120 
IRREIQNLKL FRHPHIIKLY QVISTPSDIF MVMEYVSGGE LFDYICKNGR LDEKESRRLF 

       130        140        150        160        170        180 
QQILSGVDYC HRHMVVHRDL KPENVLLDAH MNAKIADFGL SNMMSDGEFL RTSCGSPNYA 

       190        200        210        220        230        240 
APEVISGRLY AGPEVDIWSS GVILYALLCG TLPFDDDHVP TLFKKICDGI FYTPQYLNPS 

       250        260        270        280        290        300 
VISLLKHMLQ VDPMKRATIK DIREHEWFKQ DLPKYLFPED PSYSSTMIDD EALKEVCEKF 

       310        320        330        340        350        360 
ECSEEEVLSC LYNRNHQDPL AVAYHLIIDN RRIMNEAKDF YLATSPPDSF LDDHHLTRPH 

       370        380        390        400        410        420 
PERVPFLVAE TPRARHTLDE LNPQKSKHQG VRKAKWHLGI RSQSRPNDIM AEVCRAIKQL 

       430        440        450        460        470        480 
DYEWKVVNPY YLRVRRKNPV TSTFSKMSLQ LYQVDSRTYL LDFRSIDDEI TEAKSGTATP 

       490        500        510        520        530        540 
QRSGSISNYR SCQRSDSDAE AQGKPSEVSL TSSVTSLDSS PVDVAPRPGS HTIEFFEMCA 


NLIKILAQ

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References

[1]	"Mammalian AMP-activated protein kinase subfamily." Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E. J. Biol. Chem. 271:611-614(1996) [PubMed: 8557660] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 13-29; 79-104; 118-129; 139-149; 155-171; 225-246; 261-265; 275-294; 315-330; 339-356; 364-373; 396-415; 426-435; 447-464 AND 496-506. Strain: Sprague-Dawley. Tissue: Hypothalamus and Liver.
[2]	"Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase." Stapleton D., Gao G., Michell B.J., Widmer J., Mitchelhill K.I., Teh T., House C.M., Witters L.A., Kemp B.E. J. Biol. Chem. 269:29343-29346(1994) [PubMed: 7961907] [Abstract] Cited for: INTERACTION WITH SUBUNITS BETA AND GAMMA. Strain: Sprague-Dawley. Tissue: Hypothalamus and Liver.
[3]	"Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade." Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P., Alessi D.R., Hardie D.G. J. Biol. 2:28.1-28.16(2003) [PubMed: 14511394] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-172.
[4]	"Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis." Woods A., Vertommen D., Neumann D., Turk R., Bayliss J., Schlattner U., Wallimann T., Carling D., Rider M.H. J. Biol. Chem. 278:28434-28442(2003) [PubMed: 12764152] [Abstract] Cited for: PHOSPHORYLATION AT THR-258 AND SER-485, MUTAGENESIS OF THR-172; THR-258 AND SER-485, MASS SPECTROMETRY.
[5]	"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: 16054095] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

U40819 mRNA. Translation: AAC52355.1.

RefSeq

NP_062015.1.

UniGene

Rn.87789

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V8Q	X-ray	2.10	A	396-548	[»]
2V92	X-ray	2.40	A	396-548	[»]
2V9J	X-ray	2.53	A	396-548	[»]

SMR

P54645. Positions 10-278.

ModBase

Search...

PTM databases

PhosphoSite

P54645.

Genome annotation databases

Ensembl

ENSRNOG00000012799. Rattus norvegicus. [Contig view]

GeneID

65248.

KEGG

rno:65248.

Organism-specific databases

RGD

3387. Prkaa1.

Phylogenomic databases

HOVERGEN

P54645.

Gene expression databases

ArrayExpress

P54645.

GermOnline

ENSRNOG00000012799. Rattus norvegicus.

Family and domain databases

InterPro

IPR015741. AMPK.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

PANTHER

PTHR22982:SF61. AMPK. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

614203.

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Entry information

Entry name

AAPK1_RAT

Accession

Primary (citable) accession number: P54645

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents