U-box domain 2, a modified RING finger, found in nitric oxide synthase-interacting protein (NOSIP) and similar proteins; NOSIP, also known as endothelial NO synthase (eNOS)-interacting protein, p33RUL, is an E3 ubiquitin-protein ligase implicated in the control of airway and vascular diameter, mucosal secretion, NO synthesis in ciliated epithelium, and, therefore, of mucociliary and bronchial function. The loss of NOSIP may cause holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. NOSIP interacts with neuronal nitric oxide synthase (nNOS) and eNOS by inhibiting nitric oxide (NO) production. It acts as a novel type of modulator that promotes translocation of eNOS from the plasma membrane to intracellular sites, thereby uncoupling eNOS from plasma membrane caveolae and inhibiting NO synthesis. NOSIP also interacts with protein phosphatase PP2A and mediates the monoubiquitination of the PP2A catalytic subunit. Thus, it is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. Moreover, NOSIP associates with the erythropoietin (Epo) receptor (EpoR), mediates ubiquitination of EpoR, and plays an essential role in erythropoietin-induced proliferation. NOSIP contains an atypical N-terminal RING-like U-box domain that is split into two parts by an interjacent stretch of 104 amino acid residues, as well as a C-terminal RING-like U-box domain. This model corresponds to the second U-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907183449 218 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVNGDTLTERDIIVLQRGGTGFAGSG 285
Cdd:cd16662     1 RYMCAVTKDVLTNSVPCAVLRPSGDVVTMECVEKLIKKDMIDPVTGKKLKEKDIIPLQRGGTGFAASN 68

U-box domain 2, a modified RING finger, found in nitric oxide synthase-interacting protein (NOSIP) and similar proteins; NOSIP, also known as endothelial NO synthase (eNOS)-interacting protein, p33RUL, is an E3 ubiquitin-protein ligase implicated in the control of airway and vascular diameter, mucosal secretion, NO synthesis in ciliated epithelium, and, therefore, of mucociliary and bronchial function. The loss of NOSIP may cause holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. NOSIP interacts with neuronal nitric oxide synthase (nNOS) and eNOS by inhibiting nitric oxide (NO) production. It acts as a novel type of modulator that promotes translocation of eNOS from the plasma membrane to intracellular sites, thereby uncoupling eNOS from plasma membrane caveolae and inhibiting NO synthesis. NOSIP also interacts with protein phosphatase PP2A and mediates the monoubiquitination of the PP2A catalytic subunit. Thus, it is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. Moreover, NOSIP associates with the erythropoietin (Epo) receptor (EpoR), mediates ubiquitination of EpoR, and plays an essential role in erythropoietin-induced proliferation. NOSIP contains an atypical N-terminal RING-like U-box domain that is split into two parts by an interjacent stretch of 104 amino acid residues, as well as a C-terminal RING-like U-box domain. This model corresponds to the second U-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907183449 218 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVNGDTLTERDIIVLQRGGTGFAGSG 285
Cdd:cd16662     1 RYMCAVTKDVLTNSVPCAVLRPSGDVVTMECVEKLIKKDMIDPVTGKKLKEKDIIPLQRGGTGFAASN 68

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1907183449   45 CCCLSLQPCHDPVVTPDGYLYEREAILEYIL 75
Cdd:smart00504   3 LCPISLEVMKDPVILPSGQTYERSAIEKWLL 33

Rtf2 RING-finger; It is vital for effective cell-replication that replication is not stalled at any point by, for instance, damaged bases. Replication termination factor 2 (Rtf2) stabilizes the replication fork stalled at the site-specific replication barrier RTS1 by preventing replication restart until completion of DNA synthesis by a converging replication fork initiated at a flanking origin. The RTS1 element terminates replication forks that are moving in the cen2-distal direction while allowing forks moving in the cen2-proximal direction to pass through the region. Rtf2 contains a C2HC2 motif related to the C3HC4 RING-finger motif, and would appear to fold up, creating a RING finger-like structure but forming only one functional Zn2+ ion-binding site. This domain is also found at the N-terminus of peptidyl-prolyl cis-trans isomerase 4, a divergent cyclophilin family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907183449 192 MSDLTSVRFT-QLDDSVDRVGLITRSERYVCAVTRDSLSNATPCAVLRPSGAVVTlecvEKLIR--KDMVDPVNGDTLTE 268
Cdd:pfam04641  83 LKDVVELKLTpNPAFEGSKVYDDTSEAPFICPVTGLEMNGKYKFVALWPCGCVFS----EKALKevKSKNCPVCGKPYSE 158

                  ....*.
gi 1907183449 269 RDIIVL 274
Cdd:pfam04641 159 EDVIPL 164

U-box domain 2, a modified RING finger, found in nitric oxide synthase-interacting protein (NOSIP) and similar proteins; NOSIP, also known as endothelial NO synthase (eNOS)-interacting protein, p33RUL, is an E3 ubiquitin-protein ligase implicated in the control of airway and vascular diameter, mucosal secretion, NO synthesis in ciliated epithelium, and, therefore, of mucociliary and bronchial function. The loss of NOSIP may cause holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. NOSIP interacts with neuronal nitric oxide synthase (nNOS) and eNOS by inhibiting nitric oxide (NO) production. It acts as a novel type of modulator that promotes translocation of eNOS from the plasma membrane to intracellular sites, thereby uncoupling eNOS from plasma membrane caveolae and inhibiting NO synthesis. NOSIP also interacts with protein phosphatase PP2A and mediates the monoubiquitination of the PP2A catalytic subunit. Thus, it is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. Moreover, NOSIP associates with the erythropoietin (Epo) receptor (EpoR), mediates ubiquitination of EpoR, and plays an essential role in erythropoietin-induced proliferation. NOSIP contains an atypical N-terminal RING-like U-box domain that is split into two parts by an interjacent stretch of 104 amino acid residues, as well as a C-terminal RING-like U-box domain. This model corresponds to the second U-box domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907183449 218 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVNGDTLTERDIIVLQRGGTGFAGSG 285
Cdd:cd16662     1 RYMCAVTKDVLTNSVPCAVLRPSGDVVTMECVEKLIKKDMIDPVTGKKLKEKDIIPLQRGGTGFAASN 68

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
                  ....*....|....*....|....*....|....*
gi 1907183449  45 CCCLSLQPCHDPVVTPDGYLYEREAILEYILHQKR 79
Cdd:cd16453     2 LCPISGELMKDPVITPSGITYDRSAIERWLLSDNT 36

U-box domain, a modified RING finger, found in WD repeat, SAM and U-box domain-containing protein 1 (WDSUB1) and similar proteins; WDSUB1 is an uncharacterized protein containing seven WD40 repeats and a SAM domain in addition to the U-box. Its biological role remains unclear. This subfamily also includes many uncharacterized kinase domain-containing U-box (AtPUB) proteins and several MIF4G motif-containing AtPUB proteins from Arabidopsis.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1907183449  45 CCCLSLQPCHDPVVTPDGYLYEREAILEYI 74
Cdd:cd16655     5 LCPITQELMRDPVVAADGHTYERSAIEEWL 34

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 1907183449 219 YVCAVTRDSlsnaTPCAVLRPSGAVVTLECVEKLIRKDMVDPVNGDTL 266
Cdd:cd16453     1 FLCPISGEL----MKDPVITPSGITYDRSAIERWLLSDNTDPFTREPL 44

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1907183449  41 KDFdCCCLSLQPCHDPVVTPDGYLYEREAILEYI 74
Cdd:cd16664     2 EEF-ICPISLELMKDPVILATGQTYERAAIEKWL 34

Modified RING finger domain; Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1907183449  225 RDSLSNATP-CAVLRPSGAVVTLECVEKLIRKDMVDPVNGDTLTERDII 272
Cdd:smart00504   3 LCPISLEVMkDPVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLI 51

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 1907183449 220 VCAvtrdsLSNATPC-AVLRP-SGAVVTLECVEKLIRKDMVDPVNGDTLTERDII 272
Cdd:cd16656     2 VCA-----ISGEVPEePVVSPkSGHVFEKRLIEKYIAENGTDPVTGEPLTEEDLI 51