AAKG2_PONAB
ID AAKG2_PONAB Reviewed; 524 AA.
AC Q5R4S0;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-2;
DE Short=AMPK gamma2;
DE Short=AMPK subunit gamma-2;
GN Name=PRKAG2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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; leading to negatively regulate AMPK
CC activity and suggesting the existence of a regulatory feedback loop
CC between ULK1 and AMPK.
CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma
CC subunit family. {ECO:0000305}.
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DR EMBL; CR861174; CAH93246.1; -; mRNA.
DR RefSeq; NP_001126909.1; NM_001133437.1.
DR AlphaFoldDB; Q5R4S0; -.
DR SMR; Q5R4S0; -.
DR STRING; 9601.ENSPPYP00000020405; -.
DR GeneID; 100173926; -.
DR KEGG; pon:100173926; -.
DR CTD; 51422; -.
DR eggNOG; KOG1764; Eukaryota.
DR InParanoid; Q5R4S0; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IEA:InterPro.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR039170; AMPKG-2.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR PANTHER; PTHR13780:SF122; PTHR13780:SF122; 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..524
FT /note="5'-AMP-activated protein kinase subunit gamma-2"
FT /id="PRO_0000204383"
FT DOMAIN 230..290
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 312..370
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 385..447
FT /note="CBS 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 459..517
FT /note="CBS 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 325..346
FT /note="AMPK pseudosubstrate"
FT COMPBIAS 35..51
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..173
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 257
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 257
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 272..277
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 272..277
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 272..277
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 317
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 338..339
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 338..339
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 338..339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 338
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 339
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 357
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 357
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 357
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 387
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 392
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 413..414
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 429..432
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 429..432
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 429..432
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 456
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 456
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 456
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 485..486
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 485..486
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 485..486
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 485
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT BINDING 501..504
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P80385"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UGJ0"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 121
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91WG5"
SQ SEQUENCE 524 AA; 58316 MW; 35C76FC591B4DFBB CRC64;
MPLLDGDLEG SGKHSSRKVD SPFGPGSPSK GFFSRGPQPR PPSPMSAPVR PKTSPGSPKT
VFPFSYQESP PRSPRRMSFS GIFRSSSKES SPNSNPATSP GGIRFFSRSR KTSGLSSSPS
TPTQVTKQHT FPLESYKHEP ERLENRIYAS SSPPDTGQRF CPSSFQSPTR PPLASPTHYA
PSKAAALAAA LGPAEAGMLE KLEFEDEVED SESGVYMRFM RSHKCYDIVP TSSKLVVFDT
TLQVKKAFFA LVANGVRAAP LWESKKQSFV GMLTITDFIN ILHRYYKSPM VQIYELEEHK
IETWRELYLQ ETFKPLVNIS PDASLLDAVY SLIKNKIHRL PVIDPISGNA LYILTHKRIL
KFLQLFMSDM PKPAFMKQNL DELGIGTYHN IAFIHPDTPI IKALNIFVER RISALPVVDE
SGKVVDIYSK FDVINLAAEK TYNNLDITVT QALQHRSQYF EGVVKCNKLE ILETIVDRIV
RAEVHRLVVA NEADSIVGII SLSDILQALI LTPAGAKQKE TETE
