C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK) alpha 1 catalytic subunit; AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma. Co-expression of the three subunits is required for kinase activity; in the absence of one, the other two subunits get degraded. The AMPK alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain and a C-terminal regulatory domain (RD). Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation. It is selectively regulated by nucleoside diphosphate kinase (NDPK)-A in an AMP-independent manner. AMPKalpha1 impacts the regulation of fat metabolism through its in vivo target, acetyl coenzyme A carboxylase (ACC). It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA. The C-terminal RD of the AMPK alpha 1 subunit is involved in AMPK heterotrimer formation. It mainly interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit RD also contains an auto-inhibitory region that interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4EAK_A        6 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDggggG 85
Cdd:cd12199   2 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDD----E 77

                        90
                ....*....|....*....
4EAK_A       86 GGSHTIEFFEMCANLIKIL 104
Cdd:cd12199  78 ITSHTIEFFEMCANLIKIL 96

C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK) alpha 1 catalytic subunit; AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma. Co-expression of the three subunits is required for kinase activity; in the absence of one, the other two subunits get degraded. The AMPK alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain and a C-terminal regulatory domain (RD). Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation. It is selectively regulated by nucleoside diphosphate kinase (NDPK)-A in an AMP-independent manner. AMPKalpha1 impacts the regulation of fat metabolism through its in vivo target, acetyl coenzyme A carboxylase (ACC). It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA. The C-terminal RD of the AMPK alpha 1 subunit is involved in AMPK heterotrimer formation. It mainly interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit RD also contains an auto-inhibitory region that interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4EAK_A        6 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDggggG 85
Cdd:cd12199   2 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDD----E 77

                        90
                ....*....|....*....
4EAK_A       86 GGSHTIEFFEMCANLIKIL 104
Cdd:cd12199  78 ITSHTIEFFEMCANLIKIL 96

C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK) alpha 1 catalytic subunit; AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma. Co-expression of the three subunits is required for kinase activity; in the absence of one, the other two subunits get degraded. The AMPK alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain and a C-terminal regulatory domain (RD). Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation. It is selectively regulated by nucleoside diphosphate kinase (NDPK)-A in an AMP-independent manner. AMPKalpha1 impacts the regulation of fat metabolism through its in vivo target, acetyl coenzyme A carboxylase (ACC). It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA. The C-terminal RD of the AMPK alpha 1 subunit is involved in AMPK heterotrimer formation. It mainly interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit RD also contains an auto-inhibitory region that interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4EAK_A        6 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDggggG 85
Cdd:cd12199   2 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDD----E 77

                        90
                ....*....|....*....
4EAK_A       86 GGSHTIEFFEMCANLIKIL 104
Cdd:cd12199  78 ITSHTIEFFEMCANLIKIL 96

C-terminal regulatory domain of 5'-AMP-activated serine/threonine kinase, subunit alpha; AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma. Co-expression of the three subunits is required for kinase activity; in the absence of one, the other two subunits get degraded. The AMPK alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain and a C-terminal regulatory domain (RD). Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha2 shows cytoplasmic and nuclear localization, whereas AMPKalpha1 is localized only in the cytoplasm. The C-terminal RD of the AMPK alpha 1 subunit is involved in AMPK heterotrimer formation. It mainly interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit RD also contains an auto-inhibitory region that interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4EAK_A        6 AKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDggGGG 85
Cdd:cd12200   6 AKWHLGIRSQSKPYDIMAEVYRAMKQLDFEWKVVNPYHLRVRRKNPVTGNYVKMSLQLYQVDNRSYLLDFKSIDD--EPR 83

                        90
                ....*....|....*....
4EAK_A       86 GGSHTIEFFEMCANLIKIL 104
Cdd:cd12200  84 LGSHTMDFFEMCASLITTL 102

C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK) alpha subunit and similar domains; This family is composed of AMPKs, microtubule-associated protein/microtubule affinity regulating kinases (MARKs), yeast Kcc4p-like proteins, plant calcineurin B-Like (CBL)-interacting protein kinases (CIPKs), and similar proteins. They are serine/threonine protein kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. AMPKs act as sensors for the energy status of the cell and are activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. MARKs phosphorylate the tau protein and related microtubule-associated proteins (MAPs) on tubulin binding sites to induce detachment from microtubules, and are involved in the regulation of cell shape and polarity, cell cycle control, transport, and the cytoskeleton. Kcc4p and related proteins are septin-associated proteins that are involved in septin organization and in the yeast morphogenesis checkpoint coordinating the cell cycle with bud formation. CIPKs interact with the calcineurin B-like (CBL) calcium sensors to form a signaling network that decode specific calcium signals triggered by a variety of environmental stimuli including salinity, drought, cold, light, and mechanical perturbation, among others. All members of this family contain an N-terminal catalytic kinase domain and a C-terminal regulatory domain which is also called kinase associated domain 1 (KA1) in some cases. The C-terminal regulatory domain serves as a protein interaction domain in AMPKs and CIPKs. In MARKs and Kcc4p-like proteins, this domain binds phospholipids and may be involved in membrane localization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4EAK_A        5 GAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYY-LRVRRKNP--VTSTFSKMSLQLYQVDSRTYLLDFRSIddg 81
Cdd:cd12120   1 RKKWELEIHSRIDPSEIYEGIHKVLEGWGKNLVFRITNFiITGKLVNDhiLFLRSTLFEIEVYEVGPGLFMVDFKKK--- 77

                        90       100
                ....*....|....*....|...
4EAK_A       82 gggggGSHTIEFFEMCANLIKIL 104
Cdd:cd12120  78 -----TGSTKTFTKLATKIQIKL 95