6ekk
From Proteopedia
Crystal structure of GEF domain of DENND 1A in complex with Rab GTPase Rab35-GDP bound state.
Structural highlights
Disease[DEN1A_HUMAN] Genetic variants in DENND1A may play a role in susceptibility to polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women. PCOS is a complex disorder characterized by infertility, hirsutism, obesity, various menstrual disturbances, and enlarged ovaries studded with atretic follicles.[1] [2] [3] [4] Function[DEN1A_HUMAN] Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes (PubMed:20154091, PubMed:20937701). Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P (By similarity).[UniProtKB:Q8K382][5] [6] [RAB35_HUMAN] The small GTPases Rab 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. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth.[7] [8] References
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Categories: Arrowsmith, C H | Bountra, C | Burgess-Brown, N A | Chalk, R | Delft, F von | Edwards, A | Gavin, M | Huber, K | Kopec, J | Kupinska, K | Mukhopadhyay, S | Srikannathasan, V | Strain-Damerell, C | Szykowska, A | Tallant, C | Wang, D | Dennd1a- denn domain-containing protein 1a rab35- ras-related protein rab-35 | Transcription
