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Protein

5'-AMP-activated protein kinase subunit gamma-3

Gene

PRKAG3

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

AMP/ATP-binding 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. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei250AMP, ADP or ATP 2By similarity1
Binding sitei310AMP, ADP or ATP 1; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei331AMP 3By similarity1
Binding sitei350AMP, ADP or ATP 2By similarity1
Binding sitei380AMP 3By similarity1
Binding sitei385AMP 3; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei449AMP, ADP or ATP 2By similarity1
Binding sitei457AMP, ADP or ATP 2; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei478AMP 3By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi267 – 270AMP, ADP or ATP 1By similarity4
Nucleotide bindingi331 – 332AMP, ADP or ATP 1By similarity2
Nucleotide bindingi406 – 407AMP 3By similarity2
Nucleotide bindingi422 – 425AMP, ADP or ATP 2By similarity4
Nucleotide bindingi478 – 479AMP, ADP or ATP 2By similarity2
Nucleotide bindingi494 – 497AMP 3By similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase subunit gamma-3
Short name:
AMPK gamma3
Short name:
AMPK subunit gamma-3
Gene namesi
Name:PRKAG3
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Pathology & Biotechi

Involvement in diseasei

Defects in PRKAG3 are the cause of the RN- phenotype which is associated with excess glycogen content (about 70%) in skeletal muscle. This mutation originated in the hampshire breed pigs and has beneficial effects on meat content but detrimental effects on processing yield.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002043861 – 5145'-AMP-activated protein kinase subunit gamma-3Add BLAST514

Post-translational modificationi

Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9MYP4.
PeptideAtlasiQ9MYP4.
PRIDEiQ9MYP4.

Expressioni

Tissue specificityi

Muscle.

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000017163.

Structurei

3D structure databases

ProteinModelPortaliQ9MYP4.
SMRiQ9MYP4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini222 – 283CBS 1PROSITE-ProRule annotationAdd BLAST62
Domaini305 – 363CBS 2PROSITE-ProRule annotationAdd BLAST59
Domaini380 – 440CBS 3PROSITE-ProRule annotationAdd BLAST61
Domaini452 – 511CBS 4PROSITE-ProRule annotationAdd BLAST60

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi318 – 339AMPK pseudosubstrateAdd BLAST22

Domaini

The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity).By similarity
The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.By similarity

Sequence similaritiesi

Keywords - Domaini

CBS domain, Repeat

Phylogenomic databases

eggNOGiKOG1764. Eukaryota.
COG0517. LUCA.
HOGENOMiHOG000176880.
HOVERGENiHBG050431.
InParanoidiQ9MYP4.
KOiK07200.

Family and domain databases

InterProiView protein in InterPro
IPR000644. CBS_dom.
PfamiView protein in Pfam
PF00571. CBS. 3 hits.
SMARTiView protein in SMART
SM00116. CBS. 4 hits.
PROSITEiView protein in PROSITE
PS51371. CBS. 4 hits.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 2 (identifier: Q9MYP4-1) [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
MELAELEQAL RRVPGSRGGW ELEQLRPEGR GPTTADTPSW SSLGGPKHQE
60 70 80 90 100
MSFLEQGESR SWPSRAVTTS SERSHGDQGN KASRWTRQED VEEGGPPGPR
110 120 130 140 150
EGPQSRPVAE STGQEATFPK ATPLAQAAPL AEVDNPPTER DILPSDCAAS
160 170 180 190 200
ASDSNTDHLD LGIEFSASAA SGDELGLVEE KPAPCPSPEV LLPRLGWDDE
210 220 230 240 250
LQKPGAQVYM HFMQEHTCYD AMATSSKLVI FDTMLEIKKA FFALVANGVR
260 270 280 290 300
AAPLWDSKKQ SFVGMLTITD FILVLHRYYR SPLVQIYEIE EHKIETWREI
310 320 330 340 350
YLQGCFKPLV SISPNDSLFE AVYALIKNRI HRLPVLDPVS GAVLHILTHK
360 370 380 390 400
RLLKFLHIFG TLLPRPSFLY RTIQDLGIGT FRDLAVVLET APILTALDIF
410 420 430 440 450
VDRRVSALPV VNETGQVVGL YSRFDVIHLA AQQTYNHLDM NVGEALRQRT
460 470 480 490 500
LCLEGVLSCQ PHETLGEVID RIVREQVHRL VLVDETQHLL GVVSLSDILQ
510
ALVLSPAGID ALGA
Length:514
Mass (Da):56,790
Last modified:August 22, 2003 - v2
Checksum:i8CE025FBBF93E4AE
GO
Isoform 1 (identifier: Q9MYP4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:464
Mass (Da):51,309
Checksum:i17638CB12A2BA9DF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti418V → E in AAP14907 (PubMed:14970697).Curated1
Sequence conflicti441N → S in AAP14907 (PubMed:14970697).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti250R → Q in RN-. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0080591 – 50Missing in isoform 1. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF214520 mRNA. Translation: AAF73988.2.
AF214521 Genomic DNA. Translation: AAF73989.1.
AY263454 Genomic DNA. Translation: AAP14907.1.
AY264345 mRNA. Translation: AAP12533.1.
RefSeqiNP_999242.1. NM_214077.1. [Q9MYP4-1]
UniGeneiSsc.287.

Genome annotation databases

GeneIDi397149.
KEGGissc:397149.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAAKG3_PIG
AccessioniPrimary (citable) accession number: Q9MYP4
Secondary accession number(s): Q53ZT5, Q6WZ89
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: August 22, 2003
Last modified: March 15, 2017
This is version 79 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families