AAKG3_BOVIN
ID AAKG3_BOVIN Reviewed; 497 AA.
AC Q2LL38; Q2LL34; Q2LL35; Q2LL36; Q2LL37; Q2LL39; Q2LL40; Q2LL41;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 88.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3 AND 4), AND
RP VARIANTS SER-127; SER-153; TRP-262; TYR-358 AND MET-373.
RX PubMed=16416094; DOI=10.1007/s00335-005-0093-0;
RA Roux M., Nizou A., Forestier L., Ouali A., Leveziel H., Amarger V.;
RT "Characterization of the bovine PRKAG3 gene: structure, polymorphism, and
RT alternative transcripts.";
RL Mamm. Genome 17:83-92(2006).
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=4;
CC Name=1;
CC IsoId=Q2LL38-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2LL38-2; Sequence=VSP_019297;
CC Name=3;
CC IsoId=Q2LL38-3; Sequence=VSP_019298;
CC Name=4;
CC IsoId=Q2LL38-4; Sequence=VSP_019297, VSP_019298;
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 -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
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DR EMBL; DQ082732; AAZ31228.1; -; mRNA.
DR EMBL; DQ082733; AAZ31229.1; -; mRNA.
DR EMBL; DQ082734; AAZ31230.1; -; mRNA.
DR EMBL; DQ082735; AAZ31231.1; -; mRNA.
DR EMBL; DQ082736; AAZ31232.1; -; Genomic_DNA.
DR EMBL; DQ082736; AAZ31233.1; -; Genomic_DNA.
DR EMBL; DQ082736; AAZ31234.1; -; Genomic_DNA.
DR EMBL; DQ082736; AAZ31235.1; -; Genomic_DNA.
DR RefSeq; NP_001025473.2; NM_001030302.2. [Q2LL38-1]
DR RefSeq; NP_001155891.1; NM_001162419.1. [Q2LL38-3]
DR RefSeq; NP_001155892.1; NM_001162420.1. [Q2LL38-2]
DR RefSeq; NP_001155893.1; NM_001162421.1. [Q2LL38-4]
DR AlphaFoldDB; Q2LL38; -.
DR SMR; Q2LL38; -.
DR STRING; 9913.ENSBTAP00000017940; -.
DR PaxDb; Q2LL38; -.
DR PRIDE; Q2LL38; -.
DR Ensembl; ENSBTAT00000017940; ENSBTAP00000017940; ENSBTAG00000013492. [Q2LL38-1]
DR GeneID; 511961; -.
DR KEGG; bta:511961; -.
DR CTD; 53632; -.
DR VEuPathDB; HostDB:ENSBTAG00000013492; -.
DR eggNOG; KOG1764; Eukaryota.
DR GeneTree; ENSGT00950000183019; -.
DR HOGENOM; CLU_021740_6_0_1; -.
DR InParanoid; Q2LL38; -.
DR OMA; DFIMVLM; -.
DR OrthoDB; 631088at2759; -.
DR TreeFam; TF313247; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000013492; Expressed in choroid plexus and 95 other tissues.
DR ExpressionAtlas; Q2LL38; baseline.
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:0004679; F:AMP-activated protein kinase activity; IEA:Ensembl.
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:0005978; P:glycogen biosynthetic process; IEA:Ensembl.
DR GO; GO:0006096; P:glycolytic process; IEA:Ensembl.
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 GO; GO:0014873; P:response to muscle activity involved in regulation of muscle adaptation; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; CBS domain; Fatty acid biosynthesis;
KW Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..497
FT /note="5'-AMP-activated protein kinase subunit gamma-3"
FT /id="PRO_0000240150"
FT DOMAIN 204..265
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 287..345
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 363..423
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 435..494
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 16..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 300..321
FT /note="AMPK pseudosubstrate"
FT COMPBIAS 35..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..81
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 232
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 232
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 247..252
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 247..252
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 247..252
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 292
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 292
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 292
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 313..314
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 313..314
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 313..314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 313
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 314
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 332
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 332
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
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 363
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 368
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 389..390
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 405..408
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 405..408
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 405..408
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 432
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 432
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 432
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 440
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 440
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 440
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 461..462
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 461..462
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 461..462
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 461
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 477..480
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT VAR_SEQ 13..18
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16416094"
FT /id="VSP_019297"
FT VAR_SEQ 342
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16416094"
FT /id="VSP_019298"
FT VARIANT 127
FT /note="A -> S (in strain: Charolais, Holstein and
FT Limousin)"
FT /evidence="ECO:0000269|PubMed:16416094"
FT VARIANT 153
FT /note="W -> S (in strain: Charolais and Limousin)"
FT /evidence="ECO:0000269|PubMed:16416094"
FT VARIANT 262
FT /note="R -> W (in strain: Charolais, Holstein and
FT Limousin)"
FT /evidence="ECO:0000269|PubMed:16416094"
FT VARIANT 358
FT /note="D -> Y (in strain: Charolais)"
FT /evidence="ECO:0000269|PubMed:16416094"
FT VARIANT 373
FT /note="T -> M (in strain: Limousin)"
FT /evidence="ECO:0000269|PubMed:16416094"
FT CONFLICT 455
FT /note="I -> F (in Ref. 1; AAZ31228/AAZ31229/AAZ31230/
FT AAZ31231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 497 AA; 54920 MW; A0D7B696B8681530 CRC64;
MEPAELEHAL CGSLFSTQTP SWSSFGGPEH QEMSFLEQGD STSWPSPAMT TSAEISLGEQ
RTKVSRWKSQ EDVEERELPG LEGGPQSRAA AESTGLEATF PKATPLAQAT PLSAVGTPTT
ERDSLPADCT ASASSSSTDD LDQGIEFSAP AAWGDELGLV EERPAQCPSP QVPVLRLGWD
DELRKPGAQV YMHFMQEHTC YDAMATSSKL VIFDTMLQIK KAFFALVANG VRAAPLWDSK
KQSFVGMLTI TDFILVLHRY YRSPLVQIYE IEEHKIETWR EIYLQGCFKP LVSISPSDSL
FEAVYTLIKN RIHRLPVLDP VSGAVLHILT HKRLLKFLHI FQRTLLPRPS FLYRTIQDLG
IGTFRDLAVV LETAPILTAL DIFVDRRVSA LPVINEAGQV VGLYSRFDVI HLAAQQTYNH
LDISVGEALR RRTLCLEGVL SCQPHETLGE VIDRIAREQV HRLVLVDETQ HLLGVVSLSD
ILQALVLSPA GIDALGA
