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 111162657   2 HKLKSAQKDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNP 48
Cdd:cd14412    1 HKLKSSQKDKVRQFMAFTQAGERTAIYCLTQNEWKLEVATDNYFQNP 47

UBA-like domain found in DCN1-like protein 2 (DCNL2) and similar proteins; DCNL2 (defective in cullin neddylation protein 1-like protein 2), also called DCUN1 domain-containing protein 2, is encoded by gene DCUN1D2. Although its biological function remains unclear, DCNL2 shows high sequence similarity with DCNL1, a protein that plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. At this point, DCNL2 may also contribute to neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Like DCNL1, DCNL2 contains an N-terminal ubiquitin-associated (UBA)-like domain and a C-terminal cullin binding domain that is responsible for the binding to cullins and Rbx-1, components of an E3 ubiquitin ligase complex for neddylation.

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                 ....*....|....*....|....*....|....*....|....*..
gi 111162657   2 HKLKSAQKDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNP 48
Cdd:cd14412    1 HKLKSSQKDKVRQFMAFTQAGERTAIYCLTQNEWKLEVATDNYFQNP 47

UBA-like domain;

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                  ....*....|....*....|....*....|....*....|..
gi 111162657    9 KDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNPEA 50
Cdd:pfam14555   1 DELIAQFQAITGADEEVARQYLEAHNWDLEAAVNAFFDDGEA 42

UBA-like domain found in DCN1-like protein 2 (DCNL2) and similar proteins; DCNL2 (defective in cullin neddylation protein 1-like protein 2), also called DCUN1 domain-containing protein 2, is encoded by gene DCUN1D2. Although its biological function remains unclear, DCNL2 shows high sequence similarity with DCNL1, a protein that plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. At this point, DCNL2 may also contribute to neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Like DCNL1, DCNL2 contains an N-terminal ubiquitin-associated (UBA)-like domain and a C-terminal cullin binding domain that is responsible for the binding to cullins and Rbx-1, components of an E3 ubiquitin ligase complex for neddylation.

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                 ....*....|....*....|....*....|....*....|....*..
gi 111162657   2 HKLKSAQKDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNP 48
Cdd:cd14412    1 HKLKSSQKDKVRQFMAFTQAGERTAIYCLTQNEWKLEVATDNYFQNP 47

UBA-like domain found in DCN1-like protein DCNL1, DCNL2 and similar proteins; DCNL1 (defective in cullin neddylation protein 1-like protein 1), also called DCUN1 domain-containing protein 1, is encoded by squamous cell carcinoma-related oncogene SCCRO (DCUN1D1). It interacts with known cullin isoforms as well as ROC1, Ubc12 and CAND1, the components of the neddylation pathway. It plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. DCNL1 contains an N-terminal ubiquitin-associated (UBA)-like domain and a C-terminal cullin binding domain that binds to cullins and Rbx-1, components of an E3 ubiquitin ligase complex for neddylation. DCNL2 (defective in cullin neddylation protein 1-like protein 2), also called DCUN1 domain-containing protein 2, is encoded by gene DCUN1D2. Although its biological function remains unclear, DCNL2 shows high sequence similarity with DCNL1 and may also contribute to neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Like DCNL1, DCNL2 contains an N-terminal UBA-like domain and a C-terminal cullin binding domain.

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                 ....*....|....*....|....*....|....*....|..
gi 111162657   7 AQKDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNP 48
Cdd:cd14350    1 SQKDKVRQFMSITQANEKTAIQCLKDADWNLELAVDAYFQNP 42

UBA-like domain;

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                  ....*....|....*....|....*....|....*....|..
gi 111162657    9 KDKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFFQNPEA 50
Cdd:pfam14555   1 DELIAQFQAITGADEEVARQYLEAHNWDLEAAVNAFFDDGEA 42

UBA-like domain found in yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins; DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity. It contains an N-terminal ubiquitin-associated (UBA)-like domain and a unique C-terminal PONY domain that is essential for the neddylation function of DCN1.

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                 ....*....|....*....|....*....|....
gi 111162657  12 VRQFMACTQASERTAIYCLTQNEWKLDEATDSFF 45
Cdd:cd14352    3 IKQFREITATSPEVARDYLQRSNWNLNYAVDDFY 36

UBA-like domain found in yeast UBX domain-containing protein 1 (Ubx1) and similar proteins; Ubx1, also called suppressor of high-copy PP1 protein (Shp1), is the substrate-recruiting cofactor of AAA-adenosine triphosphatase Cdc48 in Saccharomyces cerevisiae. In concert with ubiquitin-like Atg8, Cdc48 and Ubx1 are involved in the regulation of autophagosome biogenesis. Ubx1 also functions as a regulator of phosphoprotein phosphatase 1 (PP1) with differential effects on glycogen metabolism, meiotic differentiation, and mitotic cell cycle progression. All family members contain an N-terminal ubiquitin-associated (UBA)-like domain.

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                 ....*....|....*....|....*....|....*.
gi 111162657  10 DKVRQFMACTQASERTAIYCLTQNEWKLDEATDSFF 45
Cdd:cd14351    2 EAIQQFMELTGASPEVAQQYLEEYGGDLNDAINAYF 37