Reviewed, UniProtKB/Swiss-Prot P54645 (AAPK1_RAT)

Names and origin

Protein names

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

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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. Ref.4 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-183 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. Ref.4 Ref.6
Subunit structure	Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 By similarity. Ref.3
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.

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 protein heterooligomerization Ref.4 Inferred from direct assay. Source: RGD
Cellular component	AMP-activated protein kinase complex Inferred from direct assay. Source: RGD
Molecular function	AMP-activated protein kinase activity Ref.4 Inferred from direct assay. Source: RGD ATP binding Inferred from direct assay. Source: RGD eukaryotic elongation factor-2 kinase activator activity Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein C-terminus binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 559

559

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

PRO_0000085593

Regions

Domain

27 – 279

253

Protein kinase

Nucleotide binding

33 – 41

9

ATP By similarity

Sites

Active site

150

1

Proton acceptor By similarity

Binding site

56

1

ATP By similarity

Amino acid modifications

Modified residue

32

1

Phosphothreonine By similarity

Modified residue

183

1

Phosphothreonine; by STK11 Ref.4

Modified residue

184

1

Phosphoserine By similarity

Modified residue

187

1

Phosphoserine By similarity

Modified residue

269

1

Phosphothreonine Ref.5

Modified residue

355

1

Phosphothreonine By similarity

Modified residue

356

1

Phosphoserine By similarity

Modified residue

382

1

Phosphothreonine By similarity

Modified residue

397

1

Phosphoserine By similarity

Modified residue

441

1

Phosphotyrosine By similarity

Modified residue

442

1

Phosphotyrosine By similarity

Modified residue

467

1

Phosphoserine By similarity

Modified residue

476

1

Phosphoserine By similarity

Modified residue

486

1

Phosphoserine By similarity

Modified residue

488

1

Phosphothreonine By similarity

Modified residue

490

1

Phosphothreonine By similarity

Modified residue

496

1

Phosphoserine Ref.5

Modified residue

502

1

Phosphoserine By similarity

Modified residue

506

1

Phosphoserine By similarity

Modified residue

508

1

Phosphoserine By similarity

Modified residue

520

1

Phosphoserine By similarity

Modified residue

522

1

Phosphothreonine By similarity

Modified residue

523

1

Phosphoserine By similarity

Modified residue

524

1

Phosphoserine By similarity

Modified residue

527

1

Phosphoserine By similarity

Experimental info

Mutagenesis

183

1

T → E: Hinders activation. Ref.5

Mutagenesis

269

1

T → A: Hinders activation. Ref.5

Mutagenesis

269

1

T → D: Retains activation ability. Ref.5

Mutagenesis

496

1

S → A: Hinders activation. Ref.5

Mutagenesis

496

1

S → D: Retains activation ability. Ref.5

Sequence conflict

13 – 14

2

Missing in AAC52355. Ref.2

Sequence conflict

473

1

D → L AA sequence Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

559

Helix Strand Turn

Details...

Beta strand

407 – 413

7

Helix

417 – 430

14

Beta strand

434 – 439

6

Beta strand

442 – 448

7

Turn

450 – 452

3

Beta strand

455 – 464

10

Beta strand

466 – 468

3

Beta strand

470 – 477

8

Helix

542 – 555

14

Sequences

	Sequence		Length	Mass (Da)
	P54645-1 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: A869C340A85785ED	FASTA	559	63,973
	10 20 30 40 50 60 MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR 70 80 90 100 110 120 QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG 130 140 150 160 170 180 RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF 190 200 210 220 230 240 LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG 250 260 270 280 290 300 IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID 310 320 330 340 350 360 DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS 370 380 390 400 410 420 FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI 430 440 450 460 470 480 MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTFSKMSL QLYQVDSRTY LLDFRSIDDE 490 500 510 520 530 540 ITEAKSGTAT PQRSGSISNY RSCQRSDSDA EAQGKPSEVS LTSSVTSLDS SPVDVAPRPG 550 SHTIEFFEMC ANLIKILAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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] OF 10-559, PROTEIN SEQUENCE OF 24-40; 90-115; 129-140; 150-160; 166-182; 236-257; 272-276; 286-305; 326-341; 350-367; 375-384; 409-426; 437-446; 458-475 AND 507-517. Strain: Sprague-Dawley. Tissue: Hypothalamus and Liver.
[3]	"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.
[4]	"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-183.
[5]	"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-269 AND SER-496, MUTAGENESIS OF THR-183; THR-269 AND SER-496, MASS SPECTROMETRY.
[6]	"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.
[7]	"Structural basis for AMP binding to mammalian AMP-activated protein kinase." Xiao B., Heath R., Saiu P., Leiper F.C., Leone P., Jing C., Walker P.A., Haire L., Eccleston J.F., Davis C.T., Martin S.R., Carling D., Gamblin S.J. Nature 449:496-500(2007) [PubMed: 17851531] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 405-557.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

CH474048 Genomic DNA. No translation available.
U40819 mRNA. Translation: AAC52355.1.

IPI

IPI00215402.

RefSeq

NP_062015.1.

UniGene

Rn.87789

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V8Q	X-ray	2.10	A	407-559	[»]
2V92	X-ray	2.40	A	407-559	[»]
2V9J	X-ray	2.53	A	407-559	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P54645.

PTM databases

PhosphoSite

P54645.

Proteomic databases

PRIDE

P54645.

Genome annotation databases

Ensembl

ENSRNOT00000017626; ENSRNOP00000017626; ENSRNOG00000012799; Rattus norvegicus. [Genome view]

GeneID

65248.

KEGG

rno:65248.

Organism-specific databases

CTD

65248.

RGD

3387. Prkaa1.

Phylogenomic databases

eggNOG

roNOG12508.

HOVERGEN

P54645.

InParanoid

P54645.

PhylomeDB

P54645.

Enzyme and pathway databases

BRENDA

2.7.11.1. 248.

Gene expression databases

ArrayExpress

P54645.

Genevestigator

P54645.

GermOnline

ENSRNOG00000012799. Rattus norvegicus.

Family and domain databases

InterPro

IPR020636. Ca/CaM-dep_prot_kinase-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR015741. Prot_kinase_Snf1-like_AMPK.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

PANTHER

PTHR22982:SF61. AMPK. 1 hit.
PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

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.

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:	July 28, 2009
Last modified:	February 9, 2010
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)