Q9Y478 (AAKB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5'-AMP-activated protein kinase subunit beta-1
Short name=AMPK subunit beta-1
Short name=AMPKb

Gene names

Name:	PRKAB1
Synonyms:	AMPK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	270 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non-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. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
Subunit structure	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. Ref.7 Ref.8 Ref.18
Domain	The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity By similarity.
Post-translational modification	Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Ref.15
Sequence similarities	Belongs to the 5'-AMP-activated protein kinase beta subunit family.
Sequence caution	The sequence AAB71326.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAC98897.1 differs from that shown. Reason: Frameshift at position 245.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle arrest Traceable author statement. Source: Reactome fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of gene expression Inferred from direct assay Ref.7. Source: UniProtKB protein heterooligomerization Inferred from electronic annotation. Source: Compara regulation of catalytic activity Inferred from electronic annotation. Source: Compara regulation of fatty acid oxidation Traceable author statement. Source: Reactome
Cellular_component	AMP-activated protein kinase complex Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	protein kinase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	2	EBI-719769,EBI-401755
PRKAG1	P54619	3	EBI-719769,EBI-1181439

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 270	270	5'-AMP-activated protein kinase subunit beta-1		PRO_0000204363
Regions
	Region	68 – 163	96	Glycogen-binding domain By similarity
Amino acid modifications
	Modified residue	4	1	Phosphothreonine Ref.9
	Modified residue	5	1	Phosphoserine Ref.9
	Modified residue	6	1	Phosphoserine Ref.9
	Modified residue	19	1	Phosphothreonine Ref.10 Ref.12
	Modified residue	24	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	25	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	40	1	Phosphoserine Ref.10 Ref.12 Ref.14
	Modified residue	96	1	Phosphoserine Ref.13
	Modified residue	101	1	Phosphoserine By similarity
	Modified residue	108	1	Phosphoserine Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17
	Modified residue	148	1	Phosphothreonine Ref.12
	Modified residue	182	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine
Experimental info
	Mutagenesis	2	1	G → A: Abolishes myristoylation and AMP-enhanced phosphorylation of PRKAA1 or PRKAA2. Ref.18
	Sequence conflict	10	1	A → G in CAA73146. Ref.2
	Sequence conflict	10	1	A → G in AAC98897. Ref.4
	Sequence conflict	15	1	G → A in CAA12024. Ref.1
	Sequence conflict	20	1	P → A in CAA73146. Ref.2
	Sequence conflict	20	1	P → A in AAC98897. Ref.4
	Sequence conflict	22	1	R → K in AAD09237. Ref.3
	Sequence conflict	22	1	R → K in AAD00625. Ref.3
	Sequence conflict	56	1	E → Y in AAD09237. Ref.3
	Sequence conflict	56	1	E → Y in AAD00625. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9Y478 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: F0BCAA94D5BC15FC	FASTA	270	30,382
	10 20 30 40 50 60 MGNTSSERAA LERHGGHKTP RRDSSGGTKD GDRPKILMDS PEDADLFHSE EIKAPEKEEF 70 80 90 100 110 120 LAWQHDLEVN DKAPAQARPT VFRWTGGGKE VYLSGSFNNW SKLPLTRSHN NFVAILDLPE 130 140 150 160 170 180 GEHQYKFFVD GQWTHDPSEP IVTSQLGTVN NIIQVKKTDF EVFDALMVDS QKCSDVSELS 190 200 210 220 230 240 SSPPGPYHQE PYVCKPEERF RAPPILPPHL LQVILNKDTG ISCDPALLPE PNHVMLNHLY 250 260 270 ALSIKDGVMV LSATHRYKKK YVTTLLYKPI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Non-catalytic beta and gamma subunits isoforms of the AMP-activated protein kinase." Carling D. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location." Stapleton D., Woollatt E., Mitchelhill K., Nicholl J.K., Fernandez C.S., Michell B.J., Witters L.A., Power D.A., Sutherland G.R., Kemp B.E. FEBS Lett. 409:452-456(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Transcription map of the 5cM region surrounding the hepatocyte nuclear factor-1a/MODY3 gene on chromosome 12." Yamagata K., Oda N., Furuta H., Vaxillaire M., Southam L., Boriraj V., Chen X., Oda Y., Takeda J., Yamada S., Nishigori H., Lebeau M.M., Lathrop M., Cox R.D., Bell G.I. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Cloning and expression of the complete mRNA coding human AMP-activated protein kinase." Wang X., Yu L., Tu Q. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Lung and Muscle.
[7]	"Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling." Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B. Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FNIP1.
[8]	"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.
[9]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4; SER-5; SER-6 AND SER-108, MASS SPECTROMETRY. Tissue: Platelet.
[10]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40 AND SER-108, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-19; SER-40; SER-108 AND THR-148, MASS SPECTROMETRY.
[13]	"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 SER-96 AND SER-108, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40 AND SER-108, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, MASS SPECTROMETRY.
[18]	"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 PRKAA1 AND PRKAG1, MUTAGENESIS OF GLY-2.
[19]	"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.
[20]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ224515 mRNA. Translation: CAA12024.1. Y12556 mRNA. Translation: CAA73146.1. U83994 mRNA. Translation: AAD09237.1. U87276 , U87271, U87272, U87273, U87274, U87275 Genomic DNA. Translation: AAD00625.1. AF022116 mRNA. Translation: AAC98897.1. Frameshift. AC002563 Genomic DNA. Translation: AAB71326.1. Sequence problems. BC001007 mRNA. Translation: AAH01007.1. BC001056 mRNA. Translation: AAH01056.1. BC001823 mRNA. Translation: AAH01823.1. BC017671 mRNA. Translation: AAH17671.1.
IPI	IPI00220409.
PIR	T09514.
RefSeq	NP_006244.2. NM_006253.4.
UniGene	Hs.741184.
3D structure databases
ProteinModelPortal	Q9Y478.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y478. 13 interactions.
MINT	MINT-1400840.
STRING	9606.ENSP00000229328.
Protein family/group databases
CAZy	CBM48. Carbohydrate-Binding Module Family 48.
PTM databases
PhosphoSite	Q9Y478.
Polymorphism databases
DMDM	14194425.
Proteomic databases
PaxDb	Q9Y478.
PRIDE	Q9Y478.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000229328; ENSP00000229328; ENSG00000111725. ENST00000541640; ENSP00000441369; ENSG00000111725.
GeneID	5564.
KEGG	hsa:5564.
UCSC	uc001txg.3. human.
Organism-specific databases
CTD	5564.
GeneCards	GC12P120105.
HGNC	HGNC:9378. PRKAB1.
HPA	CAB005058. HPA004247.
MIM	602740. gene.
neXtProt	NX_Q9Y478.
PharmGKB	PA33746.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238368.
HOGENOM	HOG000230597.
HOVERGEN	HBG050430.
InParanoid	Q9Y478.
KO	K07199.
OMA	PYICKPE.
OrthoDB	EOG4G1MH4.
PhylomeDB	Q9Y478.
Enzyme and pathway databases
Pathway_Interaction_DB	mtor_4pathway. mTOR signaling pathway.
Reactome	REACT_111102. Signal Transduction. REACT_11123. Membrane Trafficking. REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
Gene expression databases
ArrayExpress	Q9Y478.
Bgee	Q9Y478.
CleanEx	HS_PRKAB1.
Genevestigator	Q9Y478.
GermOnline	ENSG00000111725. Homo sapiens.
Family and domain databases
InterPro	IPR006828. AMP_prot_kin_bsu_interact-dom. [Graphical view]
Pfam	PF04739. AMPKBI. 1 hit. [Graphical view]
SMART	SM01010. AMPKBI. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y478.
ChEMBL	CHEMBL3847.
DrugBank	DB00131. Adenosine monophosphate. DB00331. Metformin.
GenomeRNAi	5564.
NextBio	21556.
SOURCE	Search...

Entry information

Entry name

AAKB1_HUMAN

Accession

Primary (citable) accession number: Q9Y478
Secondary accession number(s): Q9UBV0 , Q9UE20, Q9UEX2, Q9Y6V8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 126 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.