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Details on Person UniProt:A2RUS2 DENND3

Class:IdReferenceGeneProduct:226825
_chainChangeLogchain:1-1198 added on Fri February 6 2015
_displayNameUniProt:A2RUS2 DENND3
_timestamp2024-11-03 20:14:00
chainchain:1-1198
checksum52D51635DDD88A4E
commentFUNCTION Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity).SUBUNIT Forms oligomers. Interacts with 6 of the 7 known isoforms of 14-3-3 proteins.SUBCELLULAR LOCATION Transiently recruited to membranes to activate RAB12.ALTERNATIVE PRODUCTS Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.
created[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
descriptionrecommendedName: DENN domain-containing protein 3
geneNameDENND3
KIAA0870
identifierA2RUS2
isSequenceChangedFALSE
keywordAlternative splicing
Cytoplasm
Guanine-nucleotide releasing factor
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
WD repeat
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
nameDENND3
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8961064] ENSEMBL:ENSG00000105339 DENND3 [Homo sapiens]
secondaryIdentifierDEND3_HUMAN
B7ZM28
O94947
Q2TAM7
Q6ZMS6
Q96DK3
sequenceLength1198
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:226826] UniProt:A2RUS2-2 DENND3 [Homo sapiens]
[ReferenceIsoform:226827] UniProt:A2RUS2-3 DENND3 [Homo sapiens]
[ReferenceIsoform:226828] UniProt:A2RUS2-4 DENND3 [Homo sapiens]
[ReferenceIsoform:400869] UniProt:A2RUS2-1 DENND3 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:8876434] p-S472,S490-DENND3 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8876435] DENND3 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8961275] DENND3 [extracellular region] [Homo sapiens]
(referenceSequence)[ModifiedResidue:8876436] O-phospho-L-serine at 490
[ModifiedResidue:8876438] O-phospho-L-serine at 472
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