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 1034608096 220 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVTGDKLTDRDIIVLQRGGTGFAGSG 287
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 1034608096 220 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVTGDKLTDRDIIVLQRGGTGFAGSG 287
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 1034608096   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 1034608096 194 MSDLTPVHFTP-LDSSVDRVGLITRSERYVCAVTRDSLSNATPCAVLRPSGAVVTlecvEKLIR--KDMVDPVTGDKLTD 270
Cdd:pfam04641  83 LKDVVELKLTPnPAFEGSKVYDDTSEAPFICPVTGLEMNGKYKFVALWPCGCVFS----EKALKevKSKNCPVCGKPYSE 158

                  ....*.
gi 1034608096 271 RDIIVL 276
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 1034608096 220 RYVCAVTRDSLSNATPCAVLRPSGAVVTLECVEKLIRKDMVDPVTGDKLTDRDIIVLQRGGTGFAGSG 287
Cdd:cd16662     1 RYMCAVTKDVLTNSVPCAVLRPSGDVVTMECVEKLIKKDMIDPVTGKKLKEKDIIPLQRGGTGFAASN 68

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
                  ....*....|....*....|....*....|....*..
gi 1034608096  43 FDCCCLSLQPCHDPVVTPDGYLYEREAILEYILHQKK 79
Cdd:cd16663     2 FDCCALSLQPFENPVCTPDGIVFDLLNIVPYLKKYGK 38

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 1034608096 221 YVCAVTRDSlsnaTPCAVLRPSGAVVTLECVEKLIRKDMVDPVTGDKL 268
Cdd:cd16453     1 FLCPISGEL----MKDPVITPSGITYDRSAIERWLLSDNTDPFTREPL 44

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 1034608096   45 CCCLSLQPCHDPVVTPDGYLYEREAILEYIL 75
Cdd:smart00504   3 LCPISLEVMKDPVILPSGQTYERSAIEKWLL 33

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 1034608096  227 RDSLSNATP-CAVLRPSGAVVTLECVEKLIRKDMVDPVTGDKLTDRDII 274
Cdd:smart00504   3 LCPISLEVMkDPVILPSGQTYERSAIEKWLLSHGTDPVTGQPLTHEDLI 51

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 1034608096 194 MSDLTPVHFTP-LDSSVDRVGLITRSERYVCAVTRDSLSNATPCAVLRPSGAVVTlecvEKLIR--KDMVDPVTGDKLTD 270
Cdd:pfam04641  83 LKDVVELKLTPnPAFEGSKVYDDTSEAPFICPVTGLEMNGKYKFVALWPCGCVFS----EKALKevKSKNCPVCGKPYSE 158

                  ....*.
gi 1034608096 271 RDIIVL 276
Cdd:pfam04641 159 EDVIPL 164

first U-box domain, a modified RING finger, found in Legionella pneumophila U-box protein LubX and similar proteins; LubX, also called RING-type E3 ubiquitin transferase LubX, is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. LubX acts as an E3 ubiquitin-protein ligase (EC 2.3.2.27) that interferes with the host's ubiquitination pathway. LubX contains two RING-like U-box domains. U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host target. This model corresponds to the first one.

                          10        20
                  ....*....|....*....|....*.
gi 1034608096  55 DPVVTPDGYLYEREAILEYiLHQKKE 80
Cdd:cd23149    12 DPVITPSGFSYERSAIERW-LETKPE 36