Descriptions

The AMP-activated protein kinase (AMPK) is characterized by its ability to bind to AMP, which enables it to adjust enzymatic activity by sensing the cellular energy status and maintain the balance between ATP production and consumption in eukaryotic cells. AMPKs are highly conserved heterotrimeric enzymes found in most eukaryotic species. The catalytic α-subunit contains a conventional Ser/Thr kinase domain, followed by an autoinhibitory sequence and a C-terminal segment for interacting with the β-subunit. The autoinhibitory sequence binds to the hinge region of its kinase domain, forming contacts with both amino-terminal and carboxy-terminal lobes. AMP activates AMPK both allosterically and by inhibiting dephosphorylation.

Autoinhibitory domains (AIDs)

Target domain

34-285 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Structural analysis, Mutagenesis experiment

Accessory elements

173-195 (Activation loop from InterPro)

Target domain

34-285 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

8 structures for O74536

Entry ID Method Resolution Chain Position Source
2OOX X-ray 260 A A/C 440-576 PDB
2OOY X-ray 288 A A/C 440-576 PDB
2QR1 X-ray 270 A A/C 440-576 PDB
2QRC X-ray 270 A A/C 440-576 PDB
2QRD X-ray 241 A A/C 440-576 PDB
2QRE X-ray 301 A A/C 440-576 PDB
3H4J X-ray 280 A A/B 25-351 PDB
AF-O74536-F1 Predicted AlphaFoldDB

No variants for O74536

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O74536

No associated diseases with O74536

6 regional properties for O74536

Type Name Position InterPro Accession
domain Protein kinase domain 34 - 285 IPR000719
active_site Serine/threonine-protein kinase, active site 152 - 164 IPR008271
domain Carbon catabolite-derepressing protein kinase, ubiquitin-associated domain 305 - 351 IPR013896
domain Ubiquitin-associated domain 316 - 345 IPR015940
binding_site Protein kinase, ATP binding site 40 - 63 IPR017441
domain AMPK, C-terminal adenylate sensor domain 451 - 573 IPR032270

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Nuclear translocation occurs under nitrogen and glucose starvation conditions and depends on Thr-189 phosphorylation by ssp1 (PubMed:22375066)
PANTHER Family PTHR24346 MAP/MICROTUBULE AFFINITY-REGULATING KINASE
PANTHER Subfamily PTHR24346:SF82 SERINE_THREONINE-PROTEIN KINASE MARK-A-RELATED
PANTHER Protein Class non-receptor serine/threonine protein kinase
protein modifying enzyme
PANTHER Pathway Category p53 pathway by glucose deprivation
AMPK

5 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
mitotic spindle pole body The microtubule organizing center that forms as part of the mitotic cell cycle; functionally homologous to the animal cell centrosome.
nucleotide-activated protein kinase complex A protein complex that possesses nucleotide-dependent protein kinase activity. The nucleotide can be AMP (in S. pombe and human) or ADP (in S. cerevisiae).
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

11 GO annotations of biological process

Name Definition
CAMKK-AMPK signaling cascade The series of molecular signals in which calmodulin-dependent protein kinase activity enabled by a CAMKK directly activates an AMPK. The cascade begins with calmodulin binding calcium which in turn binds CAMKK enabling its calmodulin-dependent protein kinase activity. The cascade ends with AMP-activated protein kinase activity.
carbohydrate metabolic process The chemical reactions and pathways involving carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y.
induction of conjugation with cellular fusion The process in which a cell initiates conjugation with cellular fusion. Conjugation with cellular fusion is the process that results in the union of cellular and genetic information from compatible mating types.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cytoplasmic translation Any process that stops, prevents or reduces the frequency, rate or extent of cytoplasmic translation.
negative regulation of TORC1 signaling Any process that stops, prevents or reduces the frequency, rate or extent of TORC1 signaling.
positive regulation of ascus development Any process that activates, maintains or increases the frequency, rate or extent of ascus development, a saclike structure produced by fungi of the phylum Ascomycota (sac fungi) in which sexually produced spores (ascospores), usually four or eight in number, are formed.
positive regulation of cell cycle switching, mitotic to meiotic cell cycle Any process that activates or increases the frequency, rate or extent of mitotic to meiotic cell cycle switching, the process in which a cell switches cell cycle mode from mitotic to meiotic division.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
protein phosphorylation The process of introducing a phosphate group on to a protein.
SREBP signaling pathway The series of molecular signals from the endoplasmic reticulum to the nucleus generated as a consequence of decreased levels of one or more sterols (and in some yeast, changes in oxygen levels) and which proceeds through activation of a sterol response element binding transcription factor (SREBP) to result in up-regulation of target gene transcription.

No homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
No homologous proteins
10 20 30 40 50 60
MQPQEVDLME NSTMRNGARV LPPEAISKRH IGPYIIRETL GEGSFGKVKL ATHYKTQQKV
70 80 90 100 110 120
ALKFISRQLL KKSDMHMRVE REISYLKLLR HPHIIKLYDV ITTPTDIVMV IEYAGGELFD
130 140 150 160 170 180
YIVEKKRMTE DEGRRFFQQI ICAIEYCHRH KIVHRDLKPE NLLLDDNLNV KIADFGLSNI
190 200 210 220 230 240
MTDGNFLKTS CGSPNYAAPE VINGKLYAGP EVDVWSCGIV LYVMLVGRLP FDDEFIPNLF
250 260 270 280 290 300
KKVNSCVYVM PDFLSPGAQS LIRRMIVADP MQRITIQEIR RDPWFNVNLP DYLRPMEEVQ
310 320 330 340 350 360
GSYADSRIVS KLGEAMGFSE DYIVEALRSD ENNEVKEAYN LLHENQVIQE KSHLSKSKRV
370 380 390 400 410 420
DSFLSVSPPA FSEYTSELQK KSKQELIDPT LEGPRWTVSD PPTYAKQTID SNICVLVPTA
430 440 450 460 470 480
EKNKLEMRTL ADAASAVDTS QSTRKKSRRN KWHFGVRCRG DAPEILLAVY RALQRAGAQF
490 500 510 520 530 540
TVPKPVNGKY RSDMYTIKSR WEIPHCKREG KNTYAYIELQ LYEVMPGCFM LDVKSNGYKD
550 560 570
IYSHPERTAD HGMDDLKSSF PFLDLCAMLV CKLFSA