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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332027276 114 YIKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQEQTG 189
Cdd:cd16114    1 YIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVYQEQTG 76

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332027276 114 YIKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQEQTG 189
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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 332027276  115 IKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPM-TSLRFLFDGKRINDDETPKQLEMENDDVIEVY 184
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPsQQVRLIFDGERLDPNSTVEDLDIEDGDTIDVV 71

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 332027276 114 YIKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQEQTG 189
Cdd:cd16114    1 YIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVIEVYQEQTG 76

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 332027276 114 YIKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQ 185
Cdd:cd16115    1 HINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCDRQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQ 72

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier (SUMO) 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, which all regulate different cellular functions by conjugating to different proteins. SUMO2-4 are more closely related to each other than to SUMO1.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 332027276 114 YIKLKVVGND-SNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVY 184
Cdd:cd01763    1 KITIKVRGQDgGKKVRFKVKKTTKLKKLFDAYAEKKGLDPDSLRFTFDGERISPNDTPESLGLEDGDIIDVV 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 332027276  115 IKLKVvgNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQEQT 188
Cdd:pfam00240   1 ITVKT--LDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 332027276 117 LKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVY 184
Cdd:cd00196    1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 332027276 115 IKLKVVGNDSNEIHFRVKMTTQMGKLKKSYSDRVGVPMTS--LRFLFDGKRINDDETPKQLEMENDDVIEV 183
Cdd:cd17080    3 IKLKLRGKDNKRLSLKVKPSTTLSDLVEAYKIKKKLSLAAakVKLEFDGEPLDLSETVEDLDLEDEDMLEV 73

ubiquitin-like (Ubl) domain found in IQ and ubiquitin-like domain-containing protein (IQUB) and similar proteins; IQUB is an IQ motif and ubiquitin domain-containing protein that may play roles in cilia formation and/or maintenance. It contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 332027276 135 TQMGKLKKSYSDRVGVPMTSLRFLFDGKRINDDETPK----------QLEMENDD 179
Cdd:cd17061   24 QTIGELKEHFSSELKIPPDVLQIMFDGKLVEDNTTLVdlgvrpngtiQLEMSSLD 78

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 332027276 139 KLKKSYSDRVGVPMTSLRFLFDGKRINDDETPKQLEMENDDVIEVYQ 185
Cdd:cd01798   23 QLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQ 69