1Z2A


Conserved Protein Domain Family
Rab23_like

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cd04106: Rab23_like 
Click on image for an interactive view with Cn3D
Rab GTPase family 23 (Rab23)-like
Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.
Statistics
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PSSM-Id: 133306
View PSSM: cd04106
Aligned: 9 rows
Threshold Bit Score: 265.459
Threshold Setting Gi: 21357169
Created: 9-Aug-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:GTP/Mg2+ binding site [chemical binding site]
Evidence:
  • Comment:The active conformation of Rab is stabilized by interations between the gamma phosphate of GTP and two critically conserved residues, Thr in switch I and Gly in switch II
  • Structure:1Z2A: Mus musculus Rab23 binds GDP and Mg2+, defined using 3.5 A contacts
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 ######            ## #                                                 
1Z2A_A         6 IKMVVVGNGAVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIQvn--deDVRLMLWDTAGQEEFDAITKAYYRGAQACVL 83  house mouse
Q9ULC3        10 IKMVVVGNGAVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIQvn--deDVRLMLWDTAGQEEFDAITKAYYRGAQACVL 87  human
NP_001018579  10 IKVVVVGNGAVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIIvn--geDVRLMLWDTAGQEEFDAITKAYYRGAQACVL 87  zebrafish
AAH75188      10 IKVVVVGNGAVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIQln--deDVRLMLWDTAGQEEFDAITKAYYRGAQACVL 87  African clawed ...
CAJ09600       9 IKVIVVGDGNVGKTCMLRRFVRGDFVEQYRKTIGAEFMEKDVFlrssktMVKLMLWDTAGQEVFNALTQAYYRGAGAAIL 88  Leishmania major
AAT11256       8 MKVIVLGXGRIGKTCLITRFVXNVFLDEYKKTLGVDFLQKKHFikelxeDVEFYIWDTAGQEEYNSLTRKYYKGASACIL 87  Holosticha sp. ...
XP_806815      9 IKVIVVGDGNVGKTSMLRRFVKGEFVNQYKKTIGAEFMEKNVFlrqsntTVKLMLWDTAGQEVFNSLTQAYYRGAGAAIV 88  Trypanosoma cru...
XP_823082     10 VKVIVIGDGNVGKSSLLRRFVTGTFSNQYNRTVGVEYMEKSVClrqrstTVNLFLWDTAGQETVSSVKDIYYLDAAVAIL 89  Trypanosoma brucei
NP_649574     38 IKVVIVGNGGVGKSSMIQRYCKGIFTKDYKKTIGVDFLERQIEid--geDVRIMLWDTAGQEEFDCITKAYYRGAQASVL 115 fruit fly
Feature 1                                         ## #                           ##              
1Z2A_A        84 VFSTTDRESFEAISSWREKVVAEVGDIPTALVQNKIDLLDDSCIKNEEAEGLAKRLKLRFYRTSVKEDLNVSEVFKYLAE 163 house mouse
Q9ULC3        88 VFSTTDRESFEAVSSWREKVVAEVGDIPTVLVQNKIDLLDDSCIKNEEAEALAKRLKLRFYRTSVKEDLNVNEVFKYLAE 167 human
NP_001018579  88 VFSTTDRESFEAISSWKEKVEMEVGDIPTVLVQNKIDLLDDTVIKNEEAEGLAKRLKLRFYRTSVKEDLNVNEVFKYLAD 167 zebrafish
AAH75188      88 VFSTTDRESLESIPSWREKVVAEVGDIPTVLVQNKIDLLDDTVIKNEEAEALAKRLKLRFYRTSVKEDLNVTEVFKYLSD 167 African clawed ...
CAJ09600      89 TFSTVDRDSLMSIAGWKQRVESVCGCITMVLCQTKFDLSHEAVITHAEAEGLASQLEVPLFRVSAKDDFNVRQLFEFTAQ 168 Leishmania major
AAT11256      88 AFSITDRESFNHVEKWRDAAEEECGNIPMVLVQTKIDLIDQATMTTQETEALAKKLQLPLFRICSKDGIMITELFEYLAV 167 Holosticha sp. ...
XP_806815     89 AFSTVDKDSFMNVESWKKNVENVCGSILMVLCQTKFDLAHEAAVTNEEAEQLAIQLQLPFFRVSTKDDFNVTQLFEYTAS 168 Trypanosoma cru...
XP_823082     90 VFSTDSSESFARIEMWKRCVERVCGSIPMVLCQTKFDLARQAAVVAEEVEKLAVKLQLPLFRVSTKDGFNVTQLFEYVAA 169 Trypanosoma brucei
NP_649574    116 VFSTTDRASFDAIKDWKRKVENECNEIPTVIVQNKIDLIEQAVVTADEVETLAKLLNCRLIRTSVKEDINVASVFRYLAT 195 fruit fly
Feature 1          
1Z2A_A       164 KH 165 house mouse
Q9ULC3       168 KY 169 human
NP_001018579 168 KY 169 zebrafish
AAH75188     168 KY 169 African clawed frog
CAJ09600     169 QC 170 Leishmania major
AAT11256     168 KF 169 Holosticha sp. WJC-2003
XP_806815    169 MC 170 Trypanosoma cruzi strain CL Brener
XP_823082    170 MC 171 Trypanosoma brucei
NP_649574    196 KC 197 fruit fly

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