AAKG1_BOVIN
ID AAKG1_BOVIN Reviewed; 330 AA.
AC P58108; Q29RZ6;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-1;
DE Short=AMPK gamma1;
DE Short=AMPK subunit gamma-1;
DE Short=AMPKg;
GN Name=PRKAG1;
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].
RA Benkel B., Kollers S., Fries R., Sazanov A., Yoshida E., Davoren J.,
RA Hickey D.;
RT "Characterization of the bovine AMPK gamma-1 gene.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
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. Also acts as a
CC regulator of cellular polarity by remodeling the actin cytoskeleton;
CC probably by indirectly activating myosin. Gamma non-catalytic subunit
CC mediates binding to AMP, ADP and ATP, leading to activate or inhibit
CC AMPK: AMP-binding results in allosteric activation of alpha catalytic
CC subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and
CC preventing dephosphorylation of catalytic subunits. ADP also stimulates
CC phosphorylation, without stimulating already phosphorylated catalytic
CC subunit. ATP promotes dephosphorylation of catalytic subunit, rendering
CC the AMPK enzyme inactive (By similarity). {ECO:0000250}.
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 -!- 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 and ULK2; leading to negatively regulate
CC AMPK activity and suggesting the existence of a regulatory feedback
CC loop between ULK1, ULK2 and AMPK. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
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DR EMBL; AF329081; AAK19307.1; -; Genomic_DNA.
DR EMBL; BT025456; ABF57412.1; -; mRNA.
DR EMBL; BC113296; AAI13297.1; -; mRNA.
DR RefSeq; NP_777011.2; NM_174586.2.
DR AlphaFoldDB; P58108; -.
DR SMR; P58108; -.
DR STRING; 9913.ENSBTAP00000043459; -.
DR PaxDb; P58108; -.
DR PRIDE; P58108; -.
DR Ensembl; ENSBTAT00000046133; ENSBTAP00000043459; ENSBTAG00000014426.
DR GeneID; 282324; -.
DR KEGG; bta:282324; -.
DR CTD; 5571; -.
DR VEuPathDB; HostDB:ENSBTAG00000014426; -.
DR VGNC; VGNC:33322; PRKAG1.
DR eggNOG; KOG1764; Eukaryota.
DR GeneTree; ENSGT00950000183019; -.
DR InParanoid; P58108; -.
DR OMA; ACVKMLE; -.
DR OrthoDB; 631088at2759; -.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000014426; Expressed in myometrium and 103 other tissues.
DR ExpressionAtlas; P58108; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0016208; F:AMP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0019887; F:protein kinase regulator activity; ISS:UniProtKB.
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; IPR039166; AMPKG-1.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR PANTHER; PTHR13780:SF38; PTHR13780:SF38; 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 ATP-binding; CBS domain; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..330
FT /note="5'-AMP-activated protein kinase subunit gamma-1"
FT /id="PRO_0000204376"
FT DOMAIN 43..103
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 125..187
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 198..260
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 272..329
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 138..159
FT /note="AMPK pseudosubstrate"
FT BINDING 70
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 70
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 85..90
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 85..90
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 85..90
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 130
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 130
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 151..152
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 151..152
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 151..152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 151
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 170
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 170
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 170
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 200
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 205
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 226..227
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 242..245
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 242..245
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 242..245
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 269
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 269
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 277
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 277
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 277
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 298..299
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 298..299
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 298..299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 298
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 314..317
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 261
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 263
FT /note="Phosphothreonine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 270
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT CONFLICT 121
FT /note="Y -> F (in Ref. 1; AAK19307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37497 MW; 40C9C8D5B1798FDA CRC64;
MEAVPSSDSY PAVENEHLQE TPESNNSVYT SFMKSHRCYD LIPTSSKLVV FDTSLQVKKA
FFALVTNGVR AAPLWDSKKQ SFVGMLTITD FINILHRYYK SALVQIYELE EHKIETWREV
YLQDSFKPLV CISPNASLFD AVSSLIRNKI HRLPVIDPES GNTLYILTHK RILKFLKLFI
TEFPKPEFMS KSLEELQIGT YANIAMVRTT TPVYVALGIF VQHRVSALPV VDEKGRVVDI
YSKFDVINLA AEKTYNNLDV SVTKALQHRS HYFEGVLKCY LHETLETIIN RLVEAEVHRL
VVVDENDVVK GIVSLSDILQ ALVLTGGEKP
