UBA domain-like superfamily; The ubiquitin-associated (UBA) domain-like superfamily contains alpha-helical structural homology ubiquitin-binding domains, including UBA domains and coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) domains which share a common three-helical bundle architecture. UBA domains are commonly occurring sequence motifs found in proteins involved in ubiquitin-mediated proteolysis. They contribute to ubiquitin (Ub) binding or ubiquitin-like (UbL) domain binding. However, some kinds of UBA domains can only bind the UbL domain, but not the Ub domain. UBA domains are normally comprised of compact three-helix bundles which contain a conserved GF/Y-loop. They can bind polyubiquitin with high affinity. They also bind monoubiquitin and other proteins. Most UBA domain-containing proteins have one UBA domain, but some harbor two or three UBA domains. CUE domain containing proteins are characterized by an FP and a di-leucine-like sequence and bind to monoubiquitin with varying affinities. Some higher eukaryotic CUE domain proteins do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains. This superfamily also includes many UBA-like domains found in AMP-activated protein kinase (AMPK) related kinases, the NXF family of mRNA nuclear export factors, elongation factor Ts (EF-Ts), nascent polypeptide-associated complex subunit alpha (NACA) and similar proteins. Although many UBA-like domains may have a conserved TG but not GF/Y-loop, they still show a high level of structural and sequence similarity with three-helical ubiquitin binding domains.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLLERLKEHR 33
Cdd:cd14408  18 IDRQRTVESLQNSSYNHFAAIYYLLLERLKEYR 50

UBA domain found in salt-inducible kinase 1 (SIK1); SIK1, also called serine/threonine-protein kinase SNF1-like kinase 1 (SNF1LK), is a serine/threonine kinase abundant in adrenal glands. It belongs to the AMP-activated protein kinases (AMPK) family involved in the regulation of metabolism during energy stress. SIK1 is required for myogenic differentiation. It is degraded by the proteasome in myoblasts which is regulated by cAMP signaling. Moreover, SIK1 acts as a class II histone deacetylase (HDAC) kinase, triggering the cytoplasmic export of the HDACs and activation of myocyte enhancer factor 2 (MEF2)-dependent transcription. It also regulates transcription through inhibitory phosphorylation of a family of cAMP responsive element binding protein (CREB) coactivators, called TORCs/CRTCs. In addition, SIK1 links LKB1 to p53-dependent anoikis and suppresses metastasis. It is also involved in a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process. SIK1 contains an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain and a putative PEST domain.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLLERLKEHR 33
Cdd:cd14408  18 IDRQRTVESLQNSSYNHFAAIYYLLLERLKEYR 50

UBA domain found in salt-inducible kinase 1 (SIK1); SIK1, also called serine/threonine-protein kinase SNF1-like kinase 1 (SNF1LK), is a serine/threonine kinase abundant in adrenal glands. It belongs to the AMP-activated protein kinases (AMPK) family involved in the regulation of metabolism during energy stress. SIK1 is required for myogenic differentiation. It is degraded by the proteasome in myoblasts which is regulated by cAMP signaling. Moreover, SIK1 acts as a class II histone deacetylase (HDAC) kinase, triggering the cytoplasmic export of the HDACs and activation of myocyte enhancer factor 2 (MEF2)-dependent transcription. It also regulates transcription through inhibitory phosphorylation of a family of cAMP responsive element binding protein (CREB) coactivators, called TORCs/CRTCs. In addition, SIK1 links LKB1 to p53-dependent anoikis and suppresses metastasis. It is also involved in a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process. SIK1 contains an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain and a putative PEST domain.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLLERLKEHR 33
Cdd:cd14408  18 IDRQRTVESLQNSSYNHFAAIYYLLLERLKEYR 50

UBA domain found in salt-inducible kinase 2 (SIK2); SIK2, also called Qin-induced kinase or serine/threonine-protein kinase SNF1-like kinase 2 (SNF1LK2), is a serine/threonine kinase highly expressed in adipocytes. It belongs to the AMP-activated protein kinases (AMPK) family involved in the regulation of metabolism during energy stress. It plays an important role in the insulin-signaling pathway during adipocyte differentiation, as well as in autophagy progression. Moreover, SIK2 plays a critical role in neuronal survival and modulates cAMP responsive element binding protein (CREB)-mediated gene expression in response to hormones and nutrients. SIK2 acts as a critical determinant in autophagy progression. In addition, SIK2 localizes at the centrosome and functions as a centrosome kinase required for bipolar mitotic spindle formation. It is involved in the initiation of mitosis, and regulates the localization of the centrosome linker protein, C-Nap1, through S2392 phosphorylation. SIK2 contains an N-terminal protein kinase catalytic domain followed by an ubiquitin-associated (UBA) domain.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLLERLKEHR 33
Cdd:cd14409  13 IDQQKTIESLQNKSYNHFAAIYYLLVERLKSHR 45

UBA domain of AMPK related kinases; The AMPK-RK family comprises AMP-activated protein kinases (AMPKs), MAP/microtubule affinity-regulating kinases (MARKs), Brain-specific kinases (BRSKs), Salt inducible kinases (SIKs), maternal embryonic leucine zipper kinase (MELK), and SNF-related serine/threonine-protein kinase (SNRK). It is the only kinase family in the human genome containing an ubiquitin-associated (UBA) or UBA-like domain which is located immediately C-terminal to their N-terminal protein kinase catalytic domain. In addition, most of family members contain a C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK), but some are lack of this region. AMPK-RKs play central roles in metabolic control, energy homeostasis and stress responses in eukaryotes. They require phosphorylation by liver kinase B1 (LKB1) for full activity. Normally, AMPK-RKs appear to exist as heterotrimeric complexes consisting of a catalytic alpha-subunit and regulatory beta- and gamma-subunits. This model corresponds to the catalytic subunit. The UBA domain, previously called SNF1 homology (SNH) domain, regulates the conformation, LKB1-mediated phosphorylation and activation, and localization of the AMPK-RKs, but does not interact with ubiquitin-like molecules. In AMPKalpha subunits, the UBA-like autoinhibitory domain (AID) is responsible for AMPKalpha subunit autoinhibition. Due to the lack of UBA domain, NUAK1 kinase, also called ARK5 (AMPK-related kinase 5), and NUAK2 kinase, also called SNARK (SNF1/AMPK-related kinase), are not included in this family.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLL 26
Cdd:cd14272  13 YDREEIVESLRNNRYNDLAATYYLLL 38

UBA domain found in the plant sucrose nonfermenting-1-related kinase (SnRK1) proteins; The plant SnRK1 proteins (also known as AKIN10/11) family contains plant orthologs of the yeast sucrose non-fermenting (Snf1) kinase and mammalian AMP-activated protein kinase (AMPK), including two catalytic alpha-subunits of plant Snf1-related kinases (SnRKs): SNF1-related protein kinase catalytic subunit alpha KIN10 (also called AKIN10 or AKIN alpha2) and SNF1-related protein kinase catalytic subunit alpha KIN11 (also called AKIN11 or AKIN alpha1). AKIN10 and AKIN11 function as central integrators of sugar, metabolic, stress, and developmental signals in plants. They form different complexes with the regulatory AKINbeta2, a plant ortholog of conserved Snf1/AMPK beta-subunits. In addition to an N-terminal protein kinase domain and a C-terminal regulatory domain of 5'-AMP-activated protein kinase (AMPK), Snf1 contains an ubiquitin-associated (UBA) domain, previously called SNF1 homology (SNH) domain, in the middle region.

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gi 26352430   1 IDRQRTIESLQNSSYNHFAAIYYLLLE 27
Cdd:cd14335  14 FDREYLVESLRNRKQNHATVTYYLLLD 40