U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 149062427   3 LICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIK 56
Cdd:cd16656    1 MVCAISGEVPEEPVVSPKSGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLIEIK 54

U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 149062427   3 LICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIK 56
Cdd:cd16656    1 MVCAISGEVPEEPVVSPKSGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLIEIK 54

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 149062427    3 LICSISNEVPEHPCVSPvSNHVYERRLIEKYIAENG-TDPINNQPLSEEQLI 53
Cdd:pfam04564   5 FLDPITFELMTDPVILP-SGITYDRSTIERHLLSVDpTDPFTREPLTHDQLI 55

U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 149062427   3 LICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIK 56
Cdd:cd16656    1 MVCAISGEVPEEPVVSPKSGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLIEIK 54

U-box domain, a modified RING finger; The U-box protein family is a family of E3 enzymes that also includes the HECT family and the RING finger family. The E3 enzyme is ubiquitin-protein ligase that cooperates with a ubiquitin-activating enzyme (E1) and a ubiquitin-conjugating enzyme (E2), and plays a central role in determining the specificity of the ubiquitination system. It removes the ubiquitin molecule from the E2 enzyme and attaches it to the target substrate, forming a covalent bond between ubiquitin and the target. U-box proteins are characterized by the presence of a U-box domain of approximately 70 amino acids. The U-box is a modified form of the RING finger domain that lacks metal chelating cysteines and histidines. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 149062427   3 LICSISNEVPEHPCVSPvSNHVYERRLIEKYIAENGTDPINNQPL 47
Cdd:cd16453    1 FLCPISGELMKDPVITP-SGITYDRSAIERWLLSDNTDPFTREPL 44

U-box domain, a modified RING finger, found in carboxyl terminus of HSP70-interacting protein (CHIP) and similar proteins; CHIP, also known as STIP1 homology and U box-containing protein 1 (STUB1), CLL-associated antigen KW-8, or Antigen NY-CO-7, is a multifunctional protein that functions both as a co-chaperone and an E3 ubiquitin-protein ligase. It couples protein folding and proteasome mediated degradation by interacting with heat shock proteins (e.g. HSC70) and ubiquitinating their misfolded client proteins, thereby targeting them for proteasomal degradation. It is also important for cellular differentiation and survival (or apoptosis), as well as susceptibility to stress. It targets a wide range of proteins, such as expanded ataxin-1, ataxin-3, huntingtin, and androgen receptor, which play roles in glucocorticoid response, tau degradation, and both p53 and cAMP signaling. CHIP contains an N-terminal tetratricopeptide repeat (TPR) domain responsible for protein-protein interaction, a highly charged middle coiled-coil (CC), and a C-terminal RING-like U-box domain acting as an ubiquitin ligase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 149062427   3 LICSISNEVPEHPCVSPvSNHVYERRLIEKYIAENG-TDPINNQPLSEEQLI 53
Cdd:cd16654    5 LCCKISFELMRDPVITP-SGITYERKDIEEHLQRVGhFDPITREPLTQDQLI 55

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 149062427    3 LICSISNEVPEHPCVSPvSNHVYERRLIEKYIAENG-TDPINNQPLSEEQLI 53
Cdd:pfam04564   5 FLDPITFELMTDPVILP-SGITYDRSTIERHLLSVDpTDPFTREPLTHDQLI 55

U-box domain, a modified RING finger, found in peptidyl-prolyl cis-trans isomerase-like 2 (PPIL2) and similar proteins; PPIL2 (EC 5.2.1.8), also known as PPIase, CYC4, cyclophilin-60 (Cyp60), cyclophilin-like protein Cyp-60, or Rotamase PPIL2, is a nuclear-specific cyclophilin which interacts with the proteinase inhibitor eglin c and regulates gene expression. PPIL2 belongs to the cyclophilin family of peptidylprolyl isomerases and catalyzes cis-trans isomerization of proline-peptide bonds, which is often a rate-limiting step in protein folding. It positively regulates beta-site amyloid precursor protein cleaving enzyme (BACE1) expression and beta-secretase activity. Moreover, PPIL2 plays an important role in the translocation of CD147 to the cell surface, and thus may present a novel target for therapeutic interventions in diseases where CD147 functions as a pathogenic factor in cancer, human immunodeficiency virus infection, or rheumatoid arthritis. PPIL2 contains an N-terminal RING-like U-box domain and a C-terminal cyclophilin (Cyp)-like chaperone domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 149062427   5 CSISNEVPEHPCVSPvSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIK 56
Cdd:cd16663    5 CALSLQPFENPVCTP-DGIVFDLLNIVPYLKKYGKNPVTGEPLEAKDLIKLN 55

U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 A (UBE4A) and similar proteins; This subfamily includes yeast ubiquitin fusion degradation protein 2 (UFD2p) and its mammalian homolog, UBE4A. Yeast UFD2p, also known as ubiquitin conjugation factor E4 or UB fusion protein 2, is a polyubiquitin chain conjugation factor (E4) in the ubiquitin fusion degradation (UFD) pathway which catalyzes elongation of the ubiquitin chain through Lys48 linkage. It binds to substrates conjugated with one to three ubiquitin molecules and catalyzes the addition of further ubiquitin moieties in the presence of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3), yielding multiubiquitylated substrates that are targets for the 26S proteasome. UFD2p is implicated in cell survival under stress conditions and is essential for homoeostasis of unsaturated fatty acids. It interacts with UBL-UBA proteins Rad23 and Dsk2, which are involved in the endoplasmic reticulum-associated degradation, ubiquitin fusion degradation, and OLE-1 gene induction pathways. UBE4A is a U-box-type ubiquitin-protein ligase that is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. It may have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation. Members of this family contain an N-terminal ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 149062427  15 PCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLID 54
Cdd:cd16657   15 PVILPSSKVTVDRSTIKRHLLSDQTDPFNRSPLTLDMVIP 54

Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex. This family is the zinc-finger domain similar to the MIZ type of zinc-finger.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 149062427    2 SLICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGT 39
Cdd:pfam11789  11 SLTCPLTLQPFVEPVTSKKCNHVFEKDAILEMLKRNPT 48