UniProt:Q12829 RAB40B

chain
  • chain:1-278
checksum 8AC3CD180C0CCA2C
comment
  • FUNCTION RAB40B small GTPase acts as substrate-recognition components of the ECS(RAB40B) E3 ubiquitin ligase complex which mediates the ubiquitination of target proteins (PubMed:33999101, PubMed:35293963). The Rab40 subfamily belongs to the Rab family that are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:27789576). As part of the ECS(RAB40B) complex, GTP-bound RAB40B promotes LIMA1/EPLIN ubiquitination and degradation, thereby regulating leading-edge actin dynamics during cell migration (PubMed:33999101). As part of the ECS(RAB40B) complex, GTP-bound RAB40B also ubiquitinates RAP2A GTPase which promotes its localization to lamellipodia and activation to drive cell migration. The ECS(RAB40B) complex does not mediate canonical ubiquitin-dependent degradation of RAP2 (PubMed:35293963). RAB40B also binds TKS5/SH3PXD2A effector independently from ECS complex to promote invadopodia-mediated extracellular matrix degradation (PubMed:27789576).CATALYTIC ACTIVITY GTP + H2O = GDP + phosphate + H(+)COFACTOR Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of the cullin-5-RING E3 ubiquitin-protein ligase complex (ECS(RAB40B) complex) composed of CUL5, Elongin BC (ELOB and ELOC), RNF7/RBX2 and RAB40B; RAB40B interaction with ECS complex is GTP-independent (PubMed:33999101, PubMed:35293963). Binds (GTP-bound) LIMA1; interaction promotes LIMA1 subcellular localization in lamellipodia during cell migration (PubMed:33999101). Interacts (GTP-bound) with TKS5/SH3PXD2A (via PX domain); interaction promotes invadopodia-mediated extracellular matrix degradation (PubMed:27789576).INTERACTION Mainly localized in the cytosol (PubMed:33999101). A subpopulation is present at the lamellipodia, where it colocalizes with actin ruffles (PubMed:33999101). Colocalized with RAP2A at the lamellipodia plasma membrane (PubMed:35293963).DOMAIN The SOCS box contains two defined motifs including the BC box that recruits and binds Elongin BC complex, and the Cul box which interacts with the Cullin family of proteins to form a ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex.DOMAIN Switch I, switch II and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drive interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.SIMILARITY Belongs to the small GTPase superfamily. Rab family.
crossReference
databaseName UniProt
dbId 62622
description
  • recommendedName: Ras-related protein Rab-40B ecNumber evidence="2"3.6.5.2 alternativeName: SOCS box-containing protein RAR shortName: Protein Rar
displayName UniProt:Q12829 RAB40B
geneName
  • RAB40B
  • SEC4L
identifier Q12829
isSequenceChanged false
keyword
  • Cell membrane
  • Cell projection
  • Cytoplasm
  • GTP-binding
  • Hydrolase
  • Lipoprotein
  • Magnesium
  • Membrane
  • Metal-binding
  • Nucleotide-binding
  • Palmitate
  • Prenylation
  • Proteomics identification
  • Reference proteome
  • Ubl conjugation pathway
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • RAB40B
otherIdentifier
  • 108_g_at
  • 10966
  • 11751063_a_at
  • 16850278
  • 204547_PM_at
  • 204547_at
  • 217597_3p_x_at
  • 217597_PM_x_at
  • 217597_x_at
  • 236211_PM_at
  • 236211_at
  • 2679190
  • 3775204
  • 3775206
  • 3775207
  • 3775208
  • 3775209
  • 3775210
  • 3775212
  • 3775213
  • 3775214
  • 3775215
  • 3775216
  • 3775217
  • 3775218
  • 3775219
  • 3775220
  • 3775221
  • 3775222
  • 3775223
  • 3775224
  • 3775225
  • 3775226
  • 3775227
  • 3775233
  • 3775234
  • 3775244
  • 3775245
  • 3775246
  • 3775247
  • 3775248
  • 3775249
  • 3775250
  • 3775252
  • 3775253
  • 3985429
  • 3985430
  • 4016492
  • 47041_at
  • 47236_at
  • 555_at
  • 8019532
  • A_23_P129801
  • GE539090
  • GE58878
  • GE84296
  • GO:0000166
  • GO:0001726
  • GO:0003924
  • GO:0005515
  • GO:0005525
  • GO:0005635
  • GO:0005737
  • GO:0005768
  • GO:0005829
  • GO:0005886
  • GO:0006887
  • GO:0008021
  • GO:0016020
  • GO:0016192
  • GO:0016567
  • GO:0016787
  • GO:0030027
  • GO:0030163
  • GO:0030335
  • GO:0031258
  • GO:0031410
  • GO:0032232
  • GO:0035556
  • GO:0042995
  • GO:0043161
  • GO:0046872
  • GO:0048471
  • GO:0060090
  • GO:0098754
  • GO:1902743
  • GO:1990748
  • GO:1990756
  • HMNXSV003010890
  • HMNXSV003026638
  • Hs.229850.0.A1_3p_at
  • Hs.229850.0.A1_3p_x_at
  • Hs.50925.0.A1_3p_at
  • ILMN_1876221
  • PH_hs_0003519
  • PH_hs_0015625
  • TC17001985.hg
  • U05227_at
  • g5803162_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • RB40B_HUMAN
  • Q8WVG3
sequenceLength 278
species [Species:48887] Homo sapiens
stId uniprot:Q12829
url http://purl.uniprot.org/uniprot/Q12829
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