Conserved Protein Domain Family
RING-Ubox2_NOSIP

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cd16662: RING-Ubox2_NOSIP 
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 family corresponds to the second U-box domain.
Statistics
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PSSM-Id: 319576
View PSSM: cd16662
Aligned: 20 rows
Threshold Bit Score: 111.682
Threshold Setting Gi: 353232121
Created: 20-Apr-2015
Updated: 18-Aug-2016
Structure
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Aligned Rows:
 
U-box domain, a
Feature 1:U-box domain, a modified RING finger [structural motif]
Evidence:
  • Comment:The U-box is a modified form of the RING finger domain that lacks metal chelating cysteines and histidines. Like the RING finger, the U-box is thought to form a structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
Feature 1           #  #               # #  #  #           #  #                    
gi 74735248  220 RYVCAVTRDSLSNAtPCAVLRPSGAVVTLECVEKLIRk-DMVDPVTGdkLTDRDIIVLQRGGTGFA 284
gi 321475265 209 RYMCPVTRDVLSNSvPCTILKPTGDVVTTECFEKLIKk-DMIHPLTGkkLKEKDIITLQRGGTGFA 273
gi 612149077 222 RYMCPVTHDVLGNSiPCAVLRPSGEVVTMECVEKLIRtsDMMCPLTGkkLKESDIIQLDRGGTGYA 287
gi 459184709 216 RWMCAVTHDTLGNSvPSVVLRPTGDVVTLECVDKIIRknGMRHPVTDevMSENDIIPLTRGGTGFA 281
gi 196002581 209 RYMCPITHDTLSNSvPAAVLRSSGKVVSMESIEKIVKk-DMIDPFTStkITEKDIIVLQRGGTGFS 273
gi 167520936 224 RYMCPVTRTALKGNvEAAVLRPTGRVVTMDCIKRLIKp-DMRDPISGeaLTDADIIPLKLKASGFA 288
gi 115908651 216 RYKCAVTHDVLSNStMCAVLKPSGKVVTLECIKKLIKk-DMTDPFTEvkLKESDIIEFKRGGTGYA 280
gi 353232121 218 KYCCAVSKDPLTNAtVCVVLKTSGAVVTKEVVDTVIKk-EMIDPINGkkMKSSDFIELQRGSLGFA 282
gi 585652102 176 RYMCAVTHDVLSNStPCAILKTSRKVITMECINKLIKk-DMVDPLTEtkITDSDIIQLQRGGTGYA 240
gi 74871417  226 RYMCPITHDVLSNAvPCAVLRPTGDVVTMECVERLIRk-DMIHPLTDrkLKEKDIIPLQRGGTGYA 290

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