Phospho-AMPK alpha (Thr172) Antibody - #AF3423

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产品: 磷酸化 AMPK alpha (Thr172) 抗体
货号: AF3423
描述: Rabbit polyclonal antibody to Phospho-AMPK alpha (Thr172)
应用: WB IHC IF/ICC
反应: Human, Mouse, Rat
预测: Pig, Zebrafish, Bovine, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 62kDa; 64kD,62kD(Calculated).
蛋白号: Q13131 | P54646
RRID: AB_2834865

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 50ul RMB¥ 1300 现货
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 200ul RMB¥ 3200 现货

货期: 当天发货

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说明书
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实验方案
WB Handbook
IHC Protocol
IF/ICC Protocol

产品描述

来源:
Rabbit
应用:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Pig(100%), Zebrafish(100%), Bovine(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
克隆:
Polyclonal
特异性:
Phospho-AMPK alpha (Thr172) Antibody detects endogenous levels of AMPK alpha 1 when phosphorylated at Thr183, or AMPK alpha 2 when phosphorylated at Thr172.
RRID:
AB_2834865
引用格式: Affinity Biosciences Cat# AF3423, RRID:AB_2834865.
偶联:
Unconjugated.
纯化:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

5 AMP activated protein kinase alpha 1catalytic subunit; 5 AMP activated protein kinase catalytic alpha 1 chain; 5' AMP activated protein kinase catalytic subunit alpha 1; 5'-AMP-activated protein kinase catalytic subunit alpha-1; AAPK1; AAPK1_HUMAN; ACACA kinase; acetyl CoA carboxylase kinase; AI194361; AI450832; AL024255; AMP -activate kinase alpha 1 subunit; AMP-activated protein kinase, catalytic, alpha -1; AMPK 1; AMPK alpha 1; AMPK alpha 1 chain; AMPK; AMPK subunit alpha-1; AMPK1; AMPKa1; AMPKalpha1; C130083N04Rik; cb116; EC 2.7.11.1; HMG CoA reductase kinase; HMGCR kinase; hormone sensitive lipase kinase; Hydroxymethylglutaryl CoA reductase kinase; im:7154392; kinase AMPK alpha1; MGC33776; MGC57364; OTTHUMP00000161795; OTTHUMP00000161796; PRKAA 1; PRKAA1; Protein kinase AMP activated alpha 1 catalytic subunit; SNF1-like protein AMPK; SNF1A; Tau protein kinase PRKAA1; wu:fa94c10; 5'-AMP-activated protein kinase catalytic subunit alpha-2; AAPK2_HUMAN; ACACA kinase; Acetyl-CoA carboxylase kinase; AMPK alpha 2 chain; AMPK subunit alpha-2; AMPK2; AMPKa2; AMPKalpha2; HMGCR kinase; Hydroxymethylglutaryl-CoA reductase kinase; PRKAA; PRKAA2; Protein kinase AMP activated alpha 2 catalytic subunit; Protein kinase AMP activated catalytic subunit alpha 2;

抗原和靶标

免疫原:
Uniprot:

Q13131(AAPK1_HUMAN) >>Visit HPA database.

P54646(AAPK2_HUMAN) >>Visit HPA database.

基因/基因ID:
PRKAA1(5562) | PRKAA2(5563)
序列:
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMIDDEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDSFLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDEITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPGSHTIEFFEMCANLIKILAQ

MAEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLDVVGKIKREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRVEEMEARRLFQQILSAVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPTLFKKIRGGVFYIPEYLNRSVATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYLFPEDPSYDANVIDDEAVKEVCEKFECTESEVMNSLYSGDPQDQLAVAYHLIIDNRRIMNQASEFYLASSPPSGSFMDDSAMHIPPGLKPHPERMPPLIADSPKARCPLDALNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNAYHLRVRRKNPVTGNYVKMSLQLYLVDNRSYLLDFKSIDDEVVEQRSGSSTPQRSCSAAGLHRPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTMDFFEMCASLITTLAR

种属预测

种属预测:

score>80的预测可信度较高，可尝试用于WB检测。*预测模型主要基于免疫原序列比对，结果仅作参考，不作为质保凭据。

Species
Results
Score
Pig
100
Bovine
100
Sheep
100
Dog
100
Xenopus
100
Zebrafish
100
Chicken
100
Rabbit
100
Horse
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - Q13131/P54646 作为底物

Site PTM Type Enzyme
S6 Phosphorylation
T32 Phosphorylation
K40 Ubiquitination
K45 Ubiquitination
K52 Ubiquitination
K56 Ubiquitination
K71 Ubiquitination
K80 Acetylation
K80 Ubiquitination
K152 Ubiquitination
S172 Phosphorylation
S176 Phosphorylation
T183 Phosphorylation Q8TDC3-2 (BRSK1) , Q16584 (MAP3K11) , Q15831 (STK11) , Q13554 (CAMK2B) , Q8N5S9 (CAMKK1) , Q13131 (PRKAA1) , Q96RR4 (CAMKK2) , Q8IWQ3 (BRSK2)
S184 Phosphorylation
C185 S-Nitrosylation
S187 Phosphorylation
Y190 Phosphorylation
Y247 Phosphorylation
K266 Ubiquitination
K271 Ubiquitination
K280 Ubiquitination
K285 Ubiquitination
S293 Phosphorylation
Y294 Phosphorylation
T355 Phosphorylation
S356 Phosphorylation
S360 Phosphorylation Q13131 (PRKAA1) , O75385 (ULK1)
T368 Phosphorylation O75385 (ULK1)
T382 Phosphorylation
T388 Phosphorylation Q13131 (PRKAA1)
K396 Ubiquitination
S397 Phosphorylation O75385 (ULK1)
K406 Sumoylation
K406 Ubiquitination
K429 Ubiquitination
Y441 Phosphorylation
Y442 Phosphorylation
K448 Ubiquitination
Y463 Phosphorylation
S467 Phosphorylation
T482 Phosphorylation
K485 Ubiquitination
S486 Phosphorylation P49841 (GSK3B) , O75385 (ULK1) , Q13131 (PRKAA1) , P17612 (PRKACA)
T488 Phosphorylation O75385 (ULK1)
T490 Phosphorylation P49841 (GSK3B)
S494 Phosphorylation Q13131 (PRKAA1)
S496 Phosphorylation Q13131 (PRKAA1) , P31749 (AKT1)
S498 Phosphorylation
Y500 Phosphorylation
S506 Phosphorylation
S508 Phosphorylation
K515 Ubiquitination
S520 Phosphorylation
T522 Phosphorylation
S523 Phosphorylation
S524 Phosphorylation
T526 Phosphorylation
S527 Phosphorylation
S531 Phosphorylation
Site PTM Type Enzyme
K41 Ubiquitination
K45 Ubiquitination
K69 Acetylation
K69 Ubiquitination
K141 Ubiquitination
S161 Phosphorylation
S165 Phosphorylation
T172 Phosphorylation Q96RR4 (CAMKK2) , O43318 (MAP3K7) , Q15831 (STK11)
S173 Phosphorylation P17612 (PRKACA)
C174 S-Nitrosylation
S176 Phosphorylation
Y179 Phosphorylation
R227 Methylation
Y232 Phosphorylation
K260 Ubiquitination
K269 Ubiquitination
Y324 Phosphorylation
S377 Phosphorylation
K391 Ubiquitination
K401 Sumoylation
K401 Ubiquitination
Y436 Phosphorylation
S481 Phosphorylation
S483 Phosphorylation
T485 Phosphorylation Q15831 (STK11)
S489 Phosphorylation
S491 Phosphorylation P31749 (AKT1)
S500 Phosphorylation
S501 Phosphorylation
S509 Phosphorylation
S511 Phosphorylation
S515 Phosphorylation
T521 Phosphorylation
T524 Phosphorylation
S527 Phosphorylation
S534 Phosphorylation

翻译修饰 - Q13131/P54646 作为激酶

Substrate Site Source
O00418 (EEF2K) S78 Uniprot
O00418 (EEF2K) S366 Uniprot
O00418 (EEF2K) S398 Uniprot
O00429 (DNM1L) S637 Uniprot
O00763 (ACACB) S222 Uniprot
O15350 (TP73) S426 Uniprot
O15360 (FANCA) S347 Uniprot
O43524 (FOXO3) T179 Uniprot
O43524 (FOXO3) S399 Uniprot
O43524 (FOXO3) S413 Uniprot
O43524 (FOXO3) S555 Uniprot
O43524 (FOXO3) S588 Uniprot
O43524 (FOXO3) S626 Uniprot
O60825 (PFKFB2) S466 Uniprot
O75385 (ULK1) S317 Uniprot
O75385 (ULK1) S638 Uniprot
O95278 (EPM2A) S25 Uniprot
O95863 (SNAI1) S11 Uniprot
O95863 (SNAI1) S92 Uniprot
P00533 (EGFR) T892 Uniprot
P04049 (RAF1) S259 Uniprot
P04049 (RAF1) S621 Uniprot
P04406 (GAPDH) S122 Uniprot
P04626 (ERBB2) T900 Uniprot
P04637 (TP53) S15 Uniprot
P04637 (TP53) T18 Uniprot
P04637 (TP53) S20 Uniprot
P06400 (RB1) S811 Uniprot
P10636-8 (MAPT) S214 Uniprot
P10636-8 (MAPT) T231 Uniprot
P10636 (MAPT) S255 Uniprot
P10636-8 (MAPT) S262 Uniprot
P10636 (MAPT) S355 Uniprot
P10636-8 (MAPT) S356 Uniprot
P10636 (MAPT) S396 Uniprot
P10636-8 (MAPT) S422 Uniprot
P13569 (CFTR) S737 Uniprot
P13569 (CFTR) S768 Uniprot
P13569 (CFTR) S813 Uniprot
P14859 (POU2F1) S335 Uniprot
P14859 (POU2F1) S385 Uniprot
P15056 (BRAF) S729 Uniprot
P15531 (NME1) S122 Uniprot
P15531 (NME1) S144 Uniprot
P17600 (SYN1) S9 Uniprot
P19429 (TNNI3) S23 Uniprot
P19429 (TNNI3) S24 Uniprot
P19429 (TNNI3) S150 Uniprot
P29474 (NOS3) T495 Uniprot
P29474 (NOS3) S633 Uniprot
P29474 (NOS3) S1177 Uniprot
P36956-3 (SREBF1) S372 Uniprot
P41235 (HNF4A) S303 Uniprot
P41235 (HNF4A) S313 Uniprot
P42345 (MTOR) T2446 Uniprot
P43405 (SYK) S178 Uniprot
P46527 (CDKN1B) T198 Uniprot
P46937 (YAP1) S61 Uniprot
P46937 (YAP1) S94 Uniprot
P49116 (NR2C2) S351 Uniprot
P49674 (CSNK1E) S389 Uniprot
P50552 (VASP) T278 Uniprot
P52292 (KPNA2) S105 Uniprot
P54840 (GYS2) S8 Uniprot
P55011 (SLC12A2) S77 Uniprot
P63244 (RACK1) T50 Uniprot
Q04759 (PRKCQ) T538 Uniprot
Q05469 (LIPE) S855 Uniprot
Q06210 (GFPT1) S242 Uniprot
Q06210-2 (GFPT1) S243 Uniprot
Q06210 (GFPT1) S261 Uniprot
Q07866 (KLC1) S521 Uniprot
Q09472 (EP300) S89 Uniprot
Q12778 (FOXO1) T649 Uniprot
Q13002-1 (GRIK2) S715 Uniprot
Q13085-2 (ACACA) S22 Uniprot
Q13085 (ACACA) S80 Uniprot
Q13085-4 (ACACA) S117 Uniprot
Q13085-1 (ACACA) S1201 Uniprot
Q13085-4 (ACACA) S1238 Uniprot
Q13131 (PRKAA1) T183 Uniprot
Q13131 (PRKAA1) S360 Uniprot
Q13131 (PRKAA1) T388 Uniprot
Q13131 (PRKAA1) S486 Uniprot
Q13131 (PRKAA1) S494 Uniprot
Q13131 (PRKAA1) S496 Uniprot
Q13362 (PPP2R5C) S298 Uniprot
Q13362 (PPP2R5C) S336 Uniprot
Q13363 (CTBP1) S158 Uniprot
Q13621 (SLC12A1) S122 Uniprot
Q13621 (SLC12A1) S130 Uniprot
Q15036 (SNX17) S437 Uniprot
Q16526 (CRY1) S71 Uniprot
Q16875 (PFKFB3) S461 Uniprot
Q53ET0 (CRTC2) S170 Uniprot
Q6N021 (TET2) S99 Uniprot
Q7Z3C6 (ATG9A) S761 Uniprot
Q7Z628 (NET1) S100 Uniprot
Q86TI0 (TBC1D1) S237 Uniprot
Q86TI0 (TBC1D1) T596 Uniprot
Q8IXJ6 (SIRT2) T101 Uniprot
Q8N122 (RPTOR) S722 Uniprot
Q8N122 (RPTOR) S792 Uniprot
Q8WUI4 (HDAC7) S155 Uniprot
Q8WUI4 (HDAC7) S358 Uniprot
Q92538 (GBF1) T1337 Uniprot
Q9BU19 (ZNF692) S470 Uniprot
Q9BZL4 (PPP1R12C) S452 Uniprot
Q9GZY8 (MFF) S155 Uniprot
Q9GZY8 (MFF) S172 Uniprot
Q9H0B6 (KLC2) S539 Uniprot
Q9H0B6 (KLC2) S545 Uniprot
Q9H0B6 (KLC2) S581 Uniprot
Q9H0B6 (KLC2) S582 Uniprot
Q9NYV6 (RRN3) S635 Uniprot
Q9P2M7 (CGN) S131 Uniprot
Q9UBK2 (PPARGC1A) T178 Uniprot
Q9UQK1 (PPP1R3C) S33 Uniprot
Q9UQK1 (PPP1R3C) S293 Uniprot
Q9UQL6 (HDAC5) S259 Uniprot
Q9UQL6 (HDAC5) S498 Uniprot
Q9Y478 (PRKAB1) S24 Uniprot
Q9Y478 (PRKAB1) T80 Uniprot
Q9Y478 (PRKAB1) S108 Uniprot
Q9Y478 (PRKAB1) T148 Uniprot
Q9Y478 (PRKAB1) T158 Uniprot
Q9Y478 (PRKAB1) S174 Uniprot
Q9Y478 (PRKAB1) S177 Uniprot
Substrate Site Source
F1D8S2 (NR2A1) S313 Uniprot
O00418 (EEF2K) S78 Uniprot
O00418 (EEF2K) S366 Uniprot
O00418 (EEF2K) S398 Uniprot
O00763-1 (ACACB) S222 Uniprot
O14920 (IKBKB) S177 Uniprot
O14920 (IKBKB) S181 Uniprot
O15151 (MDM4) S342 Uniprot
O43524 (FOXO3) T179 Uniprot
O43524 (FOXO3) S399 Uniprot
O43524 (FOXO3) S413 Uniprot
O43524 (FOXO3) S555 Uniprot
O43524 (FOXO3) S588 Uniprot
O43524 (FOXO3) S626 Uniprot
O60825 (PFKFB2) S466 Uniprot
O75385 (ULK1) S317 Uniprot
O75385 (ULK1) S556 Uniprot
O75385 (ULK1) S638 Uniprot
P05549 (TFAP2A) S219 Uniprot
P06241 (FYN) T12 Uniprot
P08151 (GLI1) S102 Uniprot
P08151 (GLI1) S408 Uniprot
P08151 (GLI1) T1074 Uniprot
P09874 (PARP1) S177 Uniprot
P28562 (DUSP1) S334 Uniprot
P29474 (NOS3) S633 Uniprot
P29474 (NOS3) S1177 Uniprot
P30260 (CDC27) S379 Uniprot
P35222 (CTNNB1) S552 Uniprot
P36956 (SREBF1) S396 Uniprot
P41235-3 (HNF4A) S313 Uniprot
P49815 (TSC2) S1387 Uniprot
P50552 (VASP) T278 Uniprot
P50552 (VASP) S322 Uniprot
P55011 (SLC12A2) S77 Uniprot
P55011 (SLC12A2) S242 Uniprot
Q13085-2 (ACACA) S22 Uniprot
Q13085 (ACACA) S78 Uniprot
Q13085 (ACACA) S80 Uniprot
Q13085-4 (ACACA) S117 Uniprot
Q13177 (PAK2) S20 Uniprot
Q13393 (PLD1) S505 Uniprot
Q15121 (PEA15) S116 Uniprot
Q53ET0 (CRTC2) S171 Uniprot
Q86TI0 (TBC1D1) S237 Uniprot
Q8IY63 (AMOTL1) S793 Uniprot
Q8N122 (RPTOR) S863 Uniprot
Q8NFG4 (FLCN) S62 Uniprot
Q92819 (HAS2) T110 Uniprot
Q96EB6 (SIRT1) T344 Uniprot
Q9BZL4 (PPP1R12C) S452 Uniprot
Q9UQB8 (BAIAP2) S366 Uniprot
Q9UQL6 (HDAC5) S259 Uniprot
Q9UQL6 (HDAC5) S498 Uniprot
Q9Y2I7 (PIKFYVE) S307 Uniprot

研究背景

功能:

Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.

翻译修饰:

Ubiquitinated.

Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.

细胞定位:

Cytoplasm. Nucleus.
Note: In response to stress, recruited by p53/TP53 to specific promoters.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
亚基结构:

AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.

蛋白家族:

The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

功能:

Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. Involved in insulin receptor/INSR internalization. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. In that process also activates WDR45. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity).

翻译修饰:

Ubiquitinated.

Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1).

细胞定位:

Cytoplasm. Nucleus.
Note: In response to stress, recruited by p53/TP53 to specific promoters.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
亚基结构:

AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2. Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; PRKAA2/AMPK2 together with ATIC and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis.

蛋白家族:

The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

研究领域

· Cellular Processes > Transport and catabolism > Autophagy - animal.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Tight junction.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > mTOR signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > AMPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Apelin signaling pathway.   (View pathway)

· Human Diseases > Endocrine and metabolic diseases > Insulin resistance.

· Human Diseases > Endocrine and metabolic diseases > Non-alcoholic fatty liver disease (NAFLD).

· Human Diseases > Cardiovascular diseases > Hypertrophic cardiomyopathy (HCM).

· Organismal Systems > Aging > Longevity regulating pathway.   (View pathway)

· Organismal Systems > Aging > Longevity regulating pathway - multiple species.   (View pathway)

· Organismal Systems > Environmental adaptation > Circadian rhythm.   (View pathway)

· Organismal Systems > Endocrine system > Insulin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Adipocytokine signaling pathway.

· Organismal Systems > Endocrine system > Oxytocin signaling pathway.

· Organismal Systems > Endocrine system > Glucagon signaling pathway.

文献引用

1). Heat shock protein 22 modulates NRF1/TFAM-dependent mitochondrial biogenesis and DRP1-sparked mitochondrial apoptosis through AMPK-PGC1α signaling pathway to alleviate the early brain injury of subarachnoid hemorrhage in rats. Redox Biology, 2021 (PubMed: 33472123) [IF=11.4]

Application: WB    Species: rat    Sample: brain

Fig. 6. Hsp22 regulates PGC1α via AMPK signaling pathway in rats after SAH Beam balance scores, Modified Garcia scores and Brainwater content in various groups. n = 6 per group. (B) Representative photomicrographs of TUNEL staining and quantitative analyses in the indicated groups. n = 4 per group. Scale bar = 100 μm. (C) Typical photomicrographs showing double immunofluorescence staining of PGC1α (green) and NeuN (red) in diverse experimental groups. n = 4 per group. Scale bar = 50 μm. (D) Western blot images and quantitative analyses of p-AMPK/AMPK, PGC1α, Drp1, Nrf1, TFAM, UCP2, Cleaved caspase-3/Caspase-3, Bcl2, Bax, Cytosolic and mitochondrial cytochrome c. n = 6 per group. Bars represent mean ± SD. **P < 0.01, *P < 0.05 vs. Sham group. ##P < 0.01, #P < 0.05 vs. SAH + Vehicle group. &&P < 0.01, &P < 0.05 vs. SAH + hsp22+scramble siRNA. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
2). Regulatory effects mediated by ulvan oligosaccharide and its zinc complex on lipid metabolism in high-fat diet-fed mice. Carbohydrate Polymers, 2023 (PubMed: 36372481) [IF=11.2]
3). NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer. CANCER LETTERS, 2021 (PubMed: 34229059) [IF=9.7]

Application: WB    Species: Human    Sample: CRC cells

Fig. 2. NCAPD2 inhibited cell autophagy and disrupted autophagic flux via Ca2+/CAMKK2/AMPK/mTORC1 pathway. (A) Western blot analyses for phosphorylated mTOR (p-mTOR, S2448), phosphorylated p70S6K (p-p70S6K, T389/412), phosphorylated 4E-BP1 (p-4E-BP1, T70) and phosphorylated AKT (p-AKT, S473) in CRCC cells with different treatments as indicated. (B) Western blot of indicated proteins in cells treated with mTORC1 inhibitor Rapamycin (3 nM, 24h). (C) Immunofluorescence staining of LC3II (red) and P62 (red) in CRC cells with different treatments as indicated. Merged images represented overlays of LC3II or P62 and nuclear staining by DAPI (blue). (D) Intracellular Ca2+ levels were analyzed by flow cytometry after staining with the fluorescent probe Fluo-3, AM in CRC cells. (E) Representative Western blot gel documents of phosphorylated CAMKK2(S511), phosphorylated AMPK(T172), phosphorylated mTOR(S2448), Beclin, ATG5, P62, LC3II in CRC cells with different treatments. (F) Western blots of indicated proteins in cells treated with an inhibitor of microsomal Ca2+-ATPase Thapsigargin (1 μM, 6h) and Ca2+ chelator BAPTA-AM (10 μM, 12h) respectively. Results are shown as mean ± s.d, *P < 0.05, **P < 0.01, ***P < 0.001, based on Student’s t-test. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
4). Amelioration action of gastrodigenin rhamno-pyranoside from Moringa seeds on non-alcoholic fatty liver disease. Food Chemistry, 2022 (PubMed: 35086000) [IF=8.8]
5). Osthole: A potential AMPK agonist that inhibits NLRP3 inflammasome activation by regulating mitochondrial homeostasis for combating rheumatoid arthritis. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2023 (PubMed: 36608498) [IF=7.9]

Application: WB    Species: Mouse    Sample: adipose tissue

Fig. 2 Effects of DAPA on “browning” of HFD-induced C57BL/6 mouse adipose tissue. After being fed a high-fat diet for 4 weeks, mice were injected with or without DAPA, and adipose tissue was collected after euthanasia to measure: A eWAT, B iWAT, and C BAT expression of thermogenic proteins; and D UCP1 immunoreactivity signals in eWAT, iWAT, and BAT tissues (brown color, magnification: 200 × , scale bar: 100 μm). E quantification of IHC. Additionally, qPCR was used to measure F thermogenic and lipogenic gene mRNA expression in eWAT, G iWAT, and H BAT. β-actin was used for normalization. The data are presented as mean ± SD; **P 
6). Podophyllotoxin via SIRT1/PPAR /NF-κB axis induced cardiac injury in rats based on the toxicological evidence chain (TEC) concept. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2024 (PubMed: 38838636) [IF=7.9]
7). Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK activation. PHYTOMEDICINE, 2021 (PubMed: 33296813) [IF=7.9]

Application: WB    Species: Mice    Sample: colon tissues

Fig. 3. Mogrol improved the colonic mucosal integrity in vivo. Colitis was induced by orally administering 4% DSS fromd ay 1 to day 7. Mice received a gavage of vehicle (0.5% CMC-Na) or mogrol (MG, 1 or 5 mg/kg body weight) or mesalazine (Mes, 100 mg/kg body weight) each day from day 1 to day 8, and they were euthanized on day 8. The levels of ZO-1 (A) and occludin (C) expression in colonic homogenates were detected by western blot. The mRNA levels of ZO-1 (B) andoccludin (D), SIRT1 (G) were detected by quantitative real-time PCR assay. The protein expression of p-AMPK/AMPK (E) and SIRT1 (F) in colon tissues were determined by western blot analysis. All data are expressed as the mean ± S.D. (n = 5). * p < 0.05, ** p < 0.01, *** p < 0.001, ns: non-significant.
8). Insights into the mechanism of action of pterostilbene against influenza A virus-induced acute lung injury. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2024 (PubMed: 38583346) [IF=7.9]
9). β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway. BIOMEDICINE & PHARMACOTHERAPY, 2021 (PubMed: 33341045) [IF=7.5]

Application: WB    Species: Human    Sample: L02 cell

Fig. 7. β-PAE ameliorates hepatic lipid synthesis and lipid oxidation via the AMPK pathway. (A and B) Western blot analysis on the expression of AMPKα and pAMPKα in vivo; (C) The mRNA expression of AMPKα in vivo; (D) Cell Oil red O staining (400 ×); (E) Cell TG; (F–J) Western blot analysis of AMPK, p-AMPK, SREBP- 1c, HMG-CR and SIRT1 in vitro. Data are presented as the mean ± SD (n = 5~6). ##p < 0.01 vs. NC group; *p < 0.05, **p < 0.01 vs. Model group.
10). Stigmasterol attenuates inflammatory response of microglia via NF-κB and NLRP3 signaling by AMPK activation. Biomedicine & Pharmacotherapy, 2022 (PubMed: 35772378) [IF=7.5]

Application: WB    Species: Mouse    Sample: BV2 cells

Fig. 5. Effects of stigmasterol treatment on inflammatory pathways in Aβ42 oligomers induced BV2 cells when treated with AMPK inhibitor. Cells were pretreated with Compound C (10 μM) for 4 h, and then treated with Aβ42 oligomers (1 μM) for 24 h, followed by treatment with stigmasterol (20 μM) for 4 h. (A,B) Representative western blot analysis of AMPK signaling. GAPDH immunoreactivity was used as a loading control. (C-E) Representative western blot analysis of NF-κB signaling. The cytosolic and nuclear fractions were prepared and analyzed with total NF-κB p65. α-Tubulin immunoreactivity was used as a loading control in the cytosolic fraction, Histone H3 was used as the loading control in the nuclear fraction. (F-H) Representative western blot analysis of NLRP3 signaling, including NLRP3 and Caspase-1, p20. GAPDH immunoreactivity was used as a loading control (I, J) Concentration of TNFα and IL-1β. Data were presented as the mean ± SEM from three independent experiments. One-way ANOVA with Tukey’s multiple comparison test revealed a difference between groups.
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