ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier SUMO-2, SUMO-3, SUMO-4, 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. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4. SUMO2 and SUMO3 are more closely related to each other than they are to SUMO1. SUMO2/3 are capable of forming chains on substrate proteins through internal lysine residues. The basic biology of SUMO4 remains unclear. A M55V polymorphism in SUMO4 has been associated with susceptibility to type I diabetes in some genetic studies.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 23503102  16 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 87
Cdd:cd16115   1 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCDRQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 72

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier SUMO-2, SUMO-3, SUMO-4, 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. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4. SUMO2 and SUMO3 are more closely related to each other than they are to SUMO1. SUMO2/3 are capable of forming chains on substrate proteins through internal lysine residues. The basic biology of SUMO4 remains unclear. A M55V polymorphism in SUMO4 has been associated with susceptibility to type I diabetes in some genetic studies.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 23503102  16 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 87
Cdd:cd16115   1 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCDRQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 72

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 23503102    17 INLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSM-RQIRFRFDGQPINETDTPAQLEMEDEDTIDV 85
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPsQQVRLIFDGERLDPNSTVEDLDIEDGDTIDV 70

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier SUMO-2, SUMO-3, SUMO-4, 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. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4. SUMO2 and SUMO3 are more closely related to each other than they are to SUMO1. SUMO2/3 are capable of forming chains on substrate proteins through internal lysine residues. The basic biology of SUMO4 remains unclear. A M55V polymorphism in SUMO4 has been associated with susceptibility to type I diabetes in some genetic studies.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 23503102  16 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 87
Cdd:cd16115   1 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCDRQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 72

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 23503102  16 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQQQTG 91
Cdd:cd16114   1 YIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVYQEQTG 76

Ubiquitin-like protein (sentrin) [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23503102   2 SEEKPKEG--VKTENDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMED 79
Cdd:COG5227   8 SEFKTNENplVKPITKHINLKVVDQDGTELFFKIKKTTTFKKLMDAFSRRQGKNMSSLRFLFDGKRIDLDQTPGDLDMED 87

                        90
                ....*....|...
gi 23503102  80 EDTIDVFQQQTGG 92
Cdd:COG5227  88 NDEIEAVTEQVGG 100

SUMO-like domain 2 (SLD2), structurally similar to a beta-grasp ubiquitin-like fold, found in Saccharomyces cerevisiae establishes silent chromatin protein 2 (Esc2p) and similar proteins; Protein Esc2p belongs to the eukaryotic-specific Rad60-Esc2-Nip45 (RENi) protein family, whose 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. Yeast Esc2p was identified as a factor promoting gene silencing. It is also required for genome integrity during DNA replication and sister chromatid cohesion in Saccharomyces cerevisiae. Esc2p promotes Mus81p complex-activity via its SUMO-like and DNA binding domains. It also acts as a novel structure-specific DNA-binding factor implicated in the local regulation of the Srs2p helicase through promoting recombination at sites of stalled replication. In addition, Esc2p specifically promotes the accumulation of SUMOylated Mms21-specific substrates and functions with Mms21p to suppress gross chromosomal rearrangements (GCRs). This family also includes DNA repair protein Rad60p from Schizosaccharomyces pombe. It is a SUMO mimetic and SUMO-targeted ubiquitin ligase (STUbL)-interacting protein that is required for the repair of DNA double strand breaks, recovery from S phase replication arrest, and plays an essential role in cell viability. Like other RENi family members, Rad60p has two SLD domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 23503102  17 INLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMR--QIRFRFDGQPINETDTPAQLEMEDEDTIDVF 86
Cdd:cd17080   3 IKLKLRGKDNKRLSLKVKPSTTLSDLVEAYKIKKKLSLAaaKVKLEFDGEPLDLSETVEDLDLEDEDMLEVV 74

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 23503102     17 INLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDV 85
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHL 69

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 23503102  19 LKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDV 85
Cdd:cd00196   1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHF 67