ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae ubiquitin-like protein Smt3p and similar proteins; Smt3 (Suppressor of Mif Two 3) was originally isolated as a high-copy suppressor of a mutation in MIF2, the gene of a centromere binding protein in S. cerevisiae. Smt3p is the yeast homolog of small ubiquitin-related modifier (SUMO) proteins that are involved in post-translational protein modification called SUMOylation, covalently attaching to and detaching from other proteins in cells to modify their function. SUMO resembles ubiquitin (Ub) in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. Smt3p plays essential roles in cell-cycle regulation and chromosome segregation in budding yeast. It interacts with different modification enzymes, and regulates their functions through linking covalently to its targets.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 257708841  34 EHINLKVVGQDNNEVFFKIKKTTEFSKLMKIYCARQGKSMNSLRFLVDGERIRPDQTPAELDMEDGDQIEAVLE 107
Cdd:cd16116    1 EHINLKVKDQDGNEVFFKIKRTTPLRKLMEAYCKRQGKSMDSVRFLFDGERIREDQTPEDLGMEDGDEIDAMVE 74

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae ubiquitin-like protein Smt3p and similar proteins; Smt3 (Suppressor of Mif Two 3) was originally isolated as a high-copy suppressor of a mutation in MIF2, the gene of a centromere binding protein in S. cerevisiae. Smt3p is the yeast homolog of small ubiquitin-related modifier (SUMO) proteins that are involved in post-translational protein modification called SUMOylation, covalently attaching to and detaching from other proteins in cells to modify their function. SUMO resembles ubiquitin (Ub) in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. Smt3p plays essential roles in cell-cycle regulation and chromosome segregation in budding yeast. It interacts with different modification enzymes, and regulates their functions through linking covalently to its targets.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 257708841  34 EHINLKVVGQDNNEVFFKIKKTTEFSKLMKIYCARQGKSMNSLRFLVDGERIRPDQTPAELDMEDGDQIEAVLE 107
Cdd:cd16116    1 EHINLKVKDQDGNEVFFKIKRTTPLRKLMEAYCKRQGKSMDSVRFLFDGERIREDQTPEDLGMEDGDEIDAMVE 74

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO-1) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. Four SUMO paralogs exist in mammals, SUMO1 through SUMO4. SUMO2-SUMO4 are more closely related to each other than they are to SUMO1. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange. SUMO1 conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257708841  35 HINLKVVGQDNNEVFFKIKKTTEFSKLMKIYCARQGKSMNSLRFLVDGERIRPDQTPAELDMEDGDQIEAVLEQLG 110
Cdd:cd16114    1 YIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVYQEQTG 76

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 257708841   36 INLKVVGQDNNEVFFKIKKTTEFSKLMKIYCARQGKSM-NSLRFLVDGERIRPDQTPAELDMEDGDQIEAVL 106
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPsQQVRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in nuclear factor of activated T-cells 2 interacting protein (NFATC2ip) and similar proteins; NFATC2ip, also termed nuclear factor of activated T cells (NFAT), cytoplasmic, calcineurin dependent 2 interacting protein, or 45 kDa NF-AT-interacting protein, or 45 kDa NFAT-interacting protein (Nip45), or nuclear factor of activated T-cells, or cytoplasmic 2-interacting protein, belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family. The family members may act as factors in transcriptional regulation, chromatin silencing and genomic stability, and typically contain an N-terminal polar/charged low-complexity segment and two C-terminal consecutive unique small ubiquitin-related modifier (SUMO)-like domains (SLD1 and SLD2) with beta-grasp fold. NFATC2ip was firstly identified as a co-regulator with NFAT and the T helper 2 (Th2)-specific transcription factor, c-Maf, to induce IL-4 production. NFATC2ip has also been involved in cellular differentiation and coordination of the immune response in humans and mice. NFATC2ip SLD2 domain binds to E2 SUMOylation enzyme, Ubc9, in an almost identical manner to that of SUMO and thereby inhibits elongation of poly-SUMO chains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 257708841  34 EHINLKVVGQDNNEVF-FKIKKTTEFSKLMKIYCARQGKSMNSLRFLVDGERIRPDQTPAELDMEDGDQIEA 104
Cdd:cd17079    1 DEICLRVQGKEKHSQLeVSVSKTAPLKSLMSQYEEAMGLSGRKLSFFFDGTKLSGKETPADLGMESGDVIEV 72

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257708841  38 LKVVGQDNNEVFFKIKKTTEFSKLMKIYCARQGKSMNSLRFLVDGERIRPDQTPAELDMEDGDQIE 103
Cdd:cd00196    1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELH 66