AAKG3_PIG
ID AAKG3_PIG Reviewed; 514 AA.
AC Q9MYP4; Q53ZT5; Q6WZ89;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-3;
DE Short=AMPK gamma3;
DE Short=AMPK subunit gamma-3;
GN Name=PRKAG3;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN RN(-),
RP AND VARIANT RN(-) GLN-250.
RC TISSUE=Skeletal muscle;
RX PubMed=10818001; DOI=10.1126/science.288.5469.1248;
RA Milan D., Jeon J.-T., Looft C., Amarger V., Robic A., Thelander M.,
RA Rogel-Gaillard C., Paul S., Iannuccelli N., Rask L., Ronne H.,
RA Lundstroem K., Reinsch N., Gellin J., Kalm E., Le Roy P., Chardon P.,
RA Andersson L.;
RT "A mutation in PRKAG3 associated with excess glycogen content in pig
RT skeletal muscle.";
RL Science 288:1248-1251(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2).
RC TISSUE=Skeletal muscle;
RA Milan D., Jeon J.-T., Looft C., Amarger V., Robic A., Rogel-Gaillard C.,
RA Paul S., Gellin J., Lundstroem K., Reinsch N., Kalm E., Le Roy P.,
RA Chardon P., Andersson L.;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=14970697; DOI=10.1159/000075743;
RA Amarger V., Erlandsson R., Pielberg G., Jeon J.-T., Andersson L.;
RT "Comparative sequence analysis of the PRKAG3 region between human and pig:
RT evolution of repetitive sequences and potential new exons.";
RL Cytogenet. Genome Res. 102:163-172(2003).
CC -!- FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase
CC (AMPK), an energy sensor protein kinase that plays a key role in
CC regulating cellular energy metabolism. In response to reduction of
CC intracellular ATP levels, AMPK activates energy-producing pathways and
CC inhibits energy-consuming processes: inhibits protein, carbohydrate and
CC lipid biosynthesis, as well as cell growth and proliferation. AMPK acts
CC via direct phosphorylation of metabolic enzymes, and by longer-term
CC effects via phosphorylation of transcription regulators. AMPK also acts
CC as a regulator of cellular polarity by remodeling the actin
CC cytoskeleton; probably by indirectly activating myosin. The AMPK gamma3
CC subunit is a non-catalytic subunit with a regulatory role in muscle
CC energy metabolism. It mediates binding to AMP, ADP and ATP, leading to
CC AMPK activation or inhibition: AMP-binding results in allosteric
CC activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by
CC inducing phosphorylation and preventing dephosphorylation of catalytic
CC subunits. ADP also stimulates phosphorylation, without stimulating
CC already phosphorylated catalytic subunit. ATP promotes
CC dephosphorylation of catalytic subunit, rendering the AMPK enzyme
CC inactive. {ECO:0000250|UniProtKB:Q9UGI9}.
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1
CC or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic
CC subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=Q9MYP4-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9MYP4-2; Sequence=VSP_008059;
CC -!- TISSUE SPECIFICITY: Muscle.
CC -!- DOMAIN: The AMPK pseudosubstrate motif resembles the sequence around
CC sites phosphorylated on target proteins of AMPK, except the presence of
CC a non-phosphorylatable residue in place of Ser. In the absence of AMP
CC this pseudosubstrate sequence may bind to the active site groove on the
CC alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the
CC upstream activating kinase STK11/LKB1 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The 4 CBS domains mediate binding to nucleotides. Of the 4
CC potential nucleotide-binding sites, 3 are occupied, designated as sites
CC 1, 3, and 4 based on the CBS modules that provide the acidic residue
CC for coordination with the 2'- and 3'-hydroxyl groups of the ribose of
CC AMP. Of these, site 4 appears to be a structural site that retains a
CC tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can
CC bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-
CC affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP,
CC ADP or ATP 2) is the weakest nucleotide-binding site on the gamma
CC subunit, yet it is exquisitely sensitive to changes in nucleotide
CC levels and this allows AMPK to respond rapidly to changes in cellular
CC energy status. Site 3 is likely to be responsible for protection of a
CC conserved threonine in the activation loop of the alpha catalytic
CC subunit through conformational changes induced by binding of AMP or
CC ADP. {ECO:0000250|UniProtKB:P80385}.
CC -!- PTM: Phosphorylated by ULK1; leading to negatively regulate AMPK
CC activity and suggesting the existence of a regulatory feedback loop
CC between ULK1 and AMPK. {ECO:0000250|UniProtKB:Q9UGI9}.
CC -!- DISEASE: Note=Defects in PRKAG3 are the cause of the RN- phenotype
CC which is associated with excess glycogen content (about 70%) in
CC skeletal muscle. This mutation originated in the hampshire breed pigs
CC and has beneficial effects on meat content but detrimental effects on
CC processing yield. {ECO:0000269|PubMed:10818001}.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
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DR EMBL; AF214520; AAF73988.2; -; mRNA.
DR EMBL; AF214521; AAF73989.1; -; Genomic_DNA.
DR EMBL; AY263454; AAP14907.1; -; Genomic_DNA.
DR EMBL; AY264345; AAP12533.1; -; mRNA.
DR RefSeq; NP_999242.1; NM_214077.1. [Q9MYP4-1]
DR AlphaFoldDB; Q9MYP4; -.
DR SMR; Q9MYP4; -.
DR STRING; 9823.ENSSSCP00000017163; -.
DR PaxDb; Q9MYP4; -.
DR PeptideAtlas; Q9MYP4; -.
DR GeneID; 397149; -.
DR KEGG; ssc:397149; -.
DR CTD; 53632; -.
DR eggNOG; KOG1764; Eukaryota.
DR InParanoid; Q9MYP4; -.
DR OrthoDB; 631088at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0019887; F:protein kinase regulator activity; IBA:GO_Central.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0050790; P:regulation of catalytic activity; IBA:GO_Central.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IEA:InterPro.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR039168; AMPKG-3.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR PANTHER; PTHR13780:SF31; PTHR13780:SF31; 1.
DR Pfam; PF00571; CBS; 3.
DR SMART; SM00116; CBS; 4.
DR SUPFAM; SSF54631; SSF54631; 2.
DR PROSITE; PS51371; CBS; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; CBS domain; Disease variant;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..514
FT /note="5'-AMP-activated protein kinase subunit gamma-3"
FT /id="PRO_0000204386"
FT DOMAIN 222..283
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 305..363
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 380..440
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 452..511
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 134..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 318..339
FT /note="AMPK pseudosubstrate"
FT COMPBIAS 55..76
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 250
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 250
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 250
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 250
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 265..270
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 265..270
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 265..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 310
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 310
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 310
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 331..332
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 331..332
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 331..332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 331
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 350
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 350
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 350
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 380
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 385
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 406..407
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 422..425
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 422..425
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 422..425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 449
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 449
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 449
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 457
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 457
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 457
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 478..479
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 478..479
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 478..479
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 478
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 494..497
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10818001"
FT /id="VSP_008059"
FT VARIANT 250
FT /note="R -> Q (in RN-)"
FT /evidence="ECO:0000269|PubMed:10818001"
FT CONFLICT 418
FT /note="V -> E (in Ref. 3; AAP14907)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="N -> S (in Ref. 3; AAP14907)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 56790 MW; 8CE025FBBF93E4AE CRC64;
MELAELEQAL RRVPGSRGGW ELEQLRPEGR GPTTADTPSW SSLGGPKHQE MSFLEQGESR
SWPSRAVTTS SERSHGDQGN KASRWTRQED VEEGGPPGPR EGPQSRPVAE STGQEATFPK
ATPLAQAAPL AEVDNPPTER DILPSDCAAS ASDSNTDHLD LGIEFSASAA SGDELGLVEE
KPAPCPSPEV LLPRLGWDDE LQKPGAQVYM HFMQEHTCYD AMATSSKLVI FDTMLEIKKA
FFALVANGVR AAPLWDSKKQ SFVGMLTITD FILVLHRYYR SPLVQIYEIE EHKIETWREI
YLQGCFKPLV SISPNDSLFE AVYALIKNRI HRLPVLDPVS GAVLHILTHK RLLKFLHIFG
TLLPRPSFLY RTIQDLGIGT FRDLAVVLET APILTALDIF VDRRVSALPV VNETGQVVGL
YSRFDVIHLA AQQTYNHLDM NVGEALRQRT LCLEGVLSCQ PHETLGEVID RIVREQVHRL
VLVDETQHLL GVVSLSDILQ ALVLSPAGID ALGA
