O43741 (AAKB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5'-AMP-activated protein kinase subunit beta-2
Short name=AMPK subunit beta-2

Gene names

Name:

PRKAB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	272 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).
Post-translational modification	Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the 5'-AMP-activated protein kinase beta subunit family.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carnitine shuttle Traceable author statement. Source: Reactome cell cycle arrest Traceable author statement. Source: Reactome energy reserve metabolic process 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 regulation of fatty acid biosynthetic process Traceable author statement. Source: Reactome regulation of fatty acid oxidation Traceable author statement. Source: Reactome
Cellular component	AMP-activated protein kinase complex Inferred from direct assay Ref.17Ref.18. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	cAMP-dependent protein kinase activity Traceable author statement. Source: Reactome identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1053424,EBI-1053424
PRKAA1	Q13131	5	EBI-1053424,EBI-1181405
PRKAG1	P54619	3	EBI-1053424,EBI-1181439

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 272

272

5'-AMP-activated protein kinase subunit beta-2

PRO_0000204368

Amino acid modifications

Modified residue

39

1

Phosphoserine; by ULK1 Probable

Modified residue

40

1

Phosphothreonine; by ULK1 Probable

Modified residue

69

1

Phosphoserine; by ULK1 By similarity

Modified residue

108

1

Phosphoserine Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Modified residue

182

1

Phosphoserine Ref.12

Modified residue

183

1

Phosphoserine Ref.12

Modified residue

184

1

Phosphoserine Ref.7 Ref.9 Ref.10 Ref.12

Experimental info

Mutagenesis

235

1

H → A: Results in an AMPK enzyme that is activable by phosphorylation but has significantly increased rate of dephosphorylation in phosphatase assays. Ref.18

Secondary structure

1

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272

Helix Strand Turn

Details...

Beta strand

76 – 83

8

Beta strand

90 – 94

5

Helix

95 – 97

3

Beta strand

112 – 129

18

Beta strand

132 – 134

3

Beta strand

141 – 143

3

Beta strand

149 – 155

7

Turn

159 – 162

4

Beta strand

201 – 204

4

Beta strand

214 – 217

4

Beta strand

250 – 259

10

Beta strand

262 – 271

10

Sequences

	Sequence		Length	Mass (Da)
	O43741 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 42B23BD70B92519C	FASTA	272	30,302
	10 20 30 40 50 60 MGNTTSDRVS GERHGAKAAR SEGAGGHAPG KEHKIMVGST DDPSVFSLPD SKLPGDKEFV 70 80 90 100 110 120 SWQQDLEDSV KPTQQARPTV IRWSEGGKEV FISGSFNNWS TKIPLIKSHN DFVAILDLPE 130 140 150 160 170 180 GEHQYKFFVD GQWVHDPSEP VVTSQLGTIN NLIHVKKSDF EVFDALKLDS MESSETSCRD 190 200 210 220 230 240 LSSSPPGPYG QEMYAFRSEE RFKSPPILPP HLLQVILNKD TNISCDPALL PEPNHVMLNH 250 260 270 LYALSIKDSV MVLSATHRYK KKYVTTLLYK PI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle." Thornton C., Snowden M.A., Carling D. J. Biol. Chem. 273:12443-12450(1998) [PubMed: 9575201] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians." Prochazka M., Farook V.S., Ossowski V., Wolford J.K., Bogardus C. Mol. Cell. Probes 16:421-427(2002) [PubMed: 12490143] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[7]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108 AND SER-184, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, MASS SPECTROMETRY. Tissue: Liver.
[9]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; SER-108 AND SER-184, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; THR-40 AND SER-184, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; SER-108; SER-182; SER-183 AND SER-184, MASS SPECTROMETRY.
[13]	"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: 21460634] [Abstract] Cited for: PHOSPHORYLATION BY ULK1 AND ULK2.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"AMP-activated protein kinase in metabolic control and insulin signaling." Towler M.C., Hardie D.G. Circ. Res. 100:328-341(2007) [PubMed: 17307971] [Abstract] Cited for: REVIEW ON FUNCTION.
[16]	"AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy." Hardie D.G. Nat. Rev. Mol. Cell Biol. 8:774-785(2007) [PubMed: 17712357] [Abstract] Cited for: REVIEW ON FUNCTION.
[17]	"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 187-272 IN COMPLEX WITH PRKAA1 AND PRKAG1.
[18]	"Structure of mammalian AMPK and its regulation by ADP." Xiao B., Sanders M.J., Underwood E., Heath R., Mayer F.V., Carmena D., Jing C., Walker P.A., Eccleston J.F., Haire L.F., Saiu P., Howell S.A., Aasland R., Martin S.R., Carling D., Gamblin S.J. Nature 472:230-233(2011) [PubMed: 21399626] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 187-272 IN COMPLEX WITH PRKAA1 AND PRKAG1, MUTAGENESIS OF HIS-235.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ224538 mRNA. Translation: CAA12030.1.
AF504543 , AF504538, AF504539, AF504540, AF504541, AF504542 Genomic DNA. Translation: AAM74153.1.
AK292820 mRNA. Translation: BAF85509.1.
AL356378 Genomic DNA. Translation: CAH72644.1.
CH471223 Genomic DNA. Translation: EAW50945.1.
BC053610 mRNA. Translation: AAH53610.1.

IPI

IPI00013905.

RefSeq

NP_005390.1. NM_005399.3.

UniGene

Hs.50732.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F15	X-ray	2.00	A	69-163	[»]
2V8Q	X-ray	2.10	B	187-272	[»]
2V92	X-ray	2.40	B	187-272	[»]
2V9J	X-ray	2.53	B	187-272	[»]
2Y8L	X-ray	2.50	B	187-272	[»]
2Y8Q	X-ray	2.80	B	187-272	[»]
2Y94	X-ray	3.24	B	187-272	[»]
2YA3	X-ray	2.51	B	187-272	[»]

ProteinModelPortal

O43741.

SMR

O43741. Positions 75-272.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43741. 30 interactions.

STRING

O43741.

Protein family/group databases

CAZy

CBM48. Carbohydrate-Binding Module Family 48.

PTM databases

PhosphoSite

O43741.

Proteomic databases

PeptideAtlas

O43741.

PRIDE

O43741.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000254101; ENSP00000254101; ENSG00000131791.

GeneID

5565.

KEGG

hsa:5565.

UCSC

uc001epe.1. human.

Organism-specific databases

CTD

5565.

GeneCards

GC01M146627.

H-InvDB

HIX0199829.

HGNC

HGNC:9379. PRKAB2.

HPA

HPA044342.

MIM

602741. gene.

neXtProt

NX_O43741.

PharmGKB

PA33747.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17994.

GeneTree

ENSGT00390000001416.

HOGENOM

HBG623595.

HOVERGEN

HBG050430.

InParanoid

O43741.

OMA

EDECPVQ.

OrthoDB

EOG4W9J4H.

PhylomeDB

O43741.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

O43741.

Bgee

O43741.

CleanEx

HS_PRKAB2.

Genevestigator

O43741.

GermOnline

ENSG00000131791. Homo sapiens.

Family and domain databases

InterPro

IPR006828. AMP_prot_kin_bsu_interact-dom.
[Graphical view]

KO

K07199.

Pfam

PF04739. AMPKBI. 1 hit.
[Graphical view]

SMART

SM01010. AMPKBI. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00131. Adenosine monophosphate.

NextBio

21560.

SOURCE

Search...

Entry information

Entry name

AAKB2_HUMAN

Accession

Primary (citable) accession number: O43741
Secondary accession number(s): A8K9V5, Q5VXY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	June 1, 1998
Last modified:	January 25, 2012
This is version 106 of the entry and version 1 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.