3RAB,1ZBD,2GF9


Conserved Protein Domain Family
Rab3

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cd01865: Rab3 
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Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D
The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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: 206657
Aligned: 12 rows
Threshold Bit Score: 329.566
Created: 6-Jan-2012
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 20 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:3RAB: Rattus norvegicus Rab3a binds GppNHp, a GTP analog and Mg2+, defined at 3.5 A contacts
  • Structure:1ZBD: Rattus norvegicus Rab3a binds GTP and Mg2+, defined using 3.5 A contacts
  • Comment:the Thr residues coordinate Mg2+

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 #######         ##  # ##                         #                     
3RAB_A         5 MFKILIIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTIYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 84  Norway rat
1ZBD_A         8 XFKILIIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTIYRNDKRIKLQIWDTAGLERYRTITTAYYRGAXGFILX 87  Norway rat
P25228        21 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVFRHDKRVKLQIWDTAGQERYRTITTAYYRGAMGFILM 100 fruit fly
AAA03315      21 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVFRQDKRVKLQIWDTAGQERYPTITTAYYRGAMGFLLM 100 California sea ...
G42148         1 MFKLLLIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTVYRHDKRIKLQIWDTAGQERYRTITTAYYRGAMGFLLM 80  Norway rat
AAK68195      36 MFKLLIIGNSSVGKTSFLFRYCDDSFTSAFVSTVGIDFKVKTVFRGDKRVKLQIWDTAGQERYRTITTAYYRGAMGFILM 115 nematode
AAK08968      30 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVFKNEKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 109 human
AAH43857      51 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVYRNEKRVKLQIWDTAGQERYRTITTAYYRGAMGFLLM 130 African clawed ...
AAP06159      15 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTIFRQDKRVKLQIWDTAGQERYRTITTAYYRGAMGFILM 94  Schistosoma jap...
AAB67800      22 MFKLLIIGNSSVGKTSFLFRYADDSFTSAFVSTVGIDFKVKTVFRQDKRVKLQIWDTAGQERYRTITTAYYRGAMGFILM 101 Strongylocentro...
NP_001017761  22 MFKILIIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTIYRNDKRIKLQIWDTAGQERYRTITTAYYRGAMGFILM 101 zebrafish
2GF9_A        22 MFKLLLIGNSSVGKTSFLFRYADDSFTPAFVSTVGIDFKVKTVYRHDKRIKLQIWDTAGQERYRTITTAYYRGAMGFLLM 101 human
Feature 1                                         ## ##                         ###              
3RAB_A        85 YDITNEESFNAVQDWSTQIKTYSWDNAQVLLVGNKCDMEDERVVSSERGRQLADHLGFEFFEASAKDNINVKQTFERLVD 164 Norway rat
1ZBD_A        88 YDITNEESFNAVQDWSTQIKTYSWDNAQVLLVGNKCDXEDERVVSSERGRQLADHLGFEFFEASAKDNINVKQTFERLVD 167 Norway rat
P25228       101 YDVTNEDSFNSVQDWVTQIKTYSWDNAQVILVGNKCDMEDQRVISFERGRQLADQLGVEFFETSAKENVNVKAVFERLVD 180 fruit fly
AAA03315     101 YDITNEESFNAVQDWCTQIKTYSWDNAQVVLVGNKCDLEDERVVSTERGKQLADQLGLEFFETSAKENINVKAVFERLVD 180 California sea ...
G42148        81 YDIANQESFTAVQDWLRRLKPIPGTTPQVILVGNKCDLEDERVVSAEDGQRLAGDLGFEFFEASAKENINVKQVFERLVD 160 Norway rat
AAK68195     116 YDITNEESFNSVQDWCTQIKTYSWENAQVVLVGNKCDMDSERVVSMDRGRQLADQLGLEFFETSAKENINVKAVFEKLVE 195 nematode
AAK08968     110 YDITNEESFNAVQDWSTQIKTYSWDNAQVILVGNKCDMEDERVISTERGQHLGEQLGFEFFETSAKDNINVKQTFERLVD 189 human
AAH43857     131 YDISNLESFNAVQDWATQIKTYSWDNAQVLLVGNKCDLEDDRVIAAEDGRKLAEELGFEFFEASAKDNINVKQVFERLVD 210 African clawed ...
AAP06159      95 YDITNEESFNAVQDWVTQIKTYSWDNAQVVLVGNKCDLVDDRVVSVDRGRHLAHQLGLEFFEASAKENINVKNVFERLVD 174 Schistosoma jap...
AAB67800     102 YDVTNEESFNSVQDWCTQIKTYSWDNAQVILVGNKCDMEDERVISTDKGKQLADQLGLEFFETSAKENINVKQTFERLVD 181 Strongylocentro...
NP_001017761 102 YDITNEESFAAVQDWSTQIKTYSWDNAQVLLVGNKCDMEDERVVASERGRQLSEHLGFEYFEASAKDNINVKQTFERLVD 181 zebrafish
2GF9_A       102 YDIANQESFAAVQDWATQIKTYSWDNAQVILVGNKCDLEDERVVPAEDGRRLADDLGFEFFEASAKENINVKQVFERLVD 181 human
Feature 1             
3RAB_A       165 VICEK 169 Norway rat
1ZBD_A       168 VICEK 172 Norway rat
P25228       181 IICDK 185 fruit fly
AAA03315     181 IICDK 185 California sea hare
G42148       161 IICDK 165 Norway rat
AAK68195     196 IICDK 200 nematode
AAK08968     190 IICDK 194 human
AAH43857     211 IICEK 215 African clawed frog
AAP06159     175 IICDK 179 Schistosoma japonicum
AAB67800     182 IICDK 186 Strongylocentrotus purpuratus
NP_001017761 182 IICEK 186 zebrafish
2GF9_A       182 VICEK 186 human

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