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DENND3

Gene
Dennd3
Protein
DENN domain-containing protein 3
Organism
Mus musculus
Length
1274 amino acids
Function
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. Regulates autophagy in response to starvation through Rab12 activation (PubMed:24719330, PubMed:25925668, PubMed:28249939). Starvation leads to ULK1/2-dependent phosphorylation of Ser-554 and Ser-572, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards Rab12 (PubMed:25925668). 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:21718402, PubMed:24719330). Starvation also induces phosphorylation at Tyr-940, which leads to up-regulated GEF activity and initiates autophagy (PubMed:28249939).
Mass
143.888 kDa
Sequence
MAEPAARHLSLPSGLLELCALLGASQDSLRGLEQIAQKRGVKSASSLVPEVLSVFVPPFTTKEDGQVPGASCALGKGRRRSFRKKREKPRMEPWKSHPGDSKGPDSEDVTIPGGVDLLALPQLCFPGCVCVASEPKEDYIHFLVLTDVCGNRTYGVVAQYYRPLHDEYCFYNGKSHWEPSVISARCFVPFAVCVVSRFPYYNSLKDCLSCLLTHLKLCKDFEVDNHIKDFAARLSLIPSPPPGPLHLIFNMKPLQVVFPSRADPESPIVDLDLHLPLLCFRPEKVLQILTCILTEQRIVFFSSDWALLTLMAECFVAYLHPLQWQHTFVPILSGQMLDFVMAPTSFLMGCHLDHFEEVRKEADGLVLIDIDHGSVTCSKSSDDNIDIPDVPLLLAQTFIQRVQSLQLHPDLHLAHLSASTDLNEGRARRRAWQQTLNCKIQHITLQLLVGIFREVKNHLNYEHRVFNSEEFLKTRAAGDQQFYKQVLDTYMFHSFLKARLNGRMDAFARMDLDTQSEEDRIDRMLISPRRPTVEKMASRKASPLHITHRRMVVSMPNLQDISLPELPPRNSSLRIMDTSNCRSSSPVLKVTPKSTYMFKIPDIHFPLESQCVQAYYTDFVTLLSKAMALLGPGDSLLLARYFYLRGLLHLMQGQLLSALLDFQNLYKTDIGIFPADLVKRTVESMSASERAQAERTPELRRLITEVFDKHGEAPKADDAVKNFELPKKHMQLNDFVKRVQESGIVKDAVIIHRLFDALTFGHEKQIDPETFRDFYTCWKETEAEAQEVSLPALLMEHLDKNECVYKLSSSVKTNRGVGKIAMTQKRLFLLTEGRPGYVEIATFRNIEEVKNSTVAFLLLRIPTLKIKTVAKKEVFEANLKSECDLWHLMVKEMWAGKQLADDHKDPQYVQQALTNVLLMDAVVGTLQSPSAIHAASKLAYFDNMKKKSPMAVPKTTSETLKHKINPSAGETAPQAIEVLLYTPGRLDPAEKVEDAHPKLWCALNEGKVVVFDASSWTVHQHCFKVGSSKVNCMVMAEHNQVWVGSEDSVIYIINVHSMSCNKQLTDHRSPVTGLAVHNGKKPSEIYSCSLDGTVIAWNVSTLRVISRFQLSYGDLLSISLHNDRIWCCTVHKILVVTPQGFVRQELKHPKDASFLAFQLLPEEQQLWAASTGVSELYMWSLKDLDQPPQKTYLQDCSEVTCMIRVKRQIWVGGRGLSQGKTRGKIYVMDVEKVTVEKELVAHLDTVRTLCSAEDRYVLSGAGQEEGKIAIWKVE

Gene
DENND3
Protein
DENN domain-containing protein 3
Organism
Homo sapiens
Length
1198 amino acids
Function
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).
Mass
135.89 kDa
Sequence
MRSLRKKREKPRPEQWKGLPGPPRAPEPEDVAVPGGVDLLTLPQLCFPGGVCVATEPKEDCVHFLVLTDVCGNRTYGVVAQYYRPLHDEYCFYNGKTHRECPGCFVPFAVCVVSRFPYYNSLKDCLSCLLALLKPCKDFEVDSHIKDFAAKLSLIPSPPPGPLHLVFNMKSLQIVLPARADPESPILDLDLHLPLLCFRPEKVLQILTCILTEQRIVFFSSDWALLTLVTECFMAYLYPLQWQHPFVPILSDQMLDFVMAPTSFLMGCHLDHFEEVSKEADGLVLINIDHGSITYSKSTDDNVDIPDVPLLAAQTFIQRVQSLQLHHELHAAHLLSSTDLKEGRAHRRSWQQKLNCQIQQTTLQLLVSIFRDVKNHLNYEHRVFNSEEFLKTRAPGDHQFYKQVLDTYMFHSFLKARLNRRMDAFAQMDLDTQSEEDRINGMLLSPRRPTVEKRASRKSSHLHVTHRRMVVSMPNLQDIAMPELAPRNSSLRLTDTAGCRGSSAVLNVTPKSPYTFKIPEIHFPLESKCVQAYHAHFVSMLSEAMCFLAPDNSLLLARYLYLRGLVYLMQGQLLNALLDFQNLYKTDIRIFPTDLVKRTVESMSAPEWEGAEQAPELMRLISEILDKPHEASKLDDHVKKFKLPKKHMQLGDFMKRVQESGIVKDASIIHRLFEALTVGQEKQIDPETFKDFYNCWKETEAEAQEVSLPWLVMEHLDKNECVCKLSSSVKTNLGVGKIAMTQKRLFLLTEGRPGYLEISTFRNIEEVRRTTTTFLLRRIPTLKIRVASKKEVFEANLKTECDLWHLMVKEMWAGKKLADDHKDPHYVQQALTNVLLMDAVVGTLQSPGAIYAASKLSYFDKMSNEMPMTLPETTLETLKHKINPSAGEAFPQAVDVLLYTPGHLDPAEKVEDAHPKLWCALSEGKVTVFNASSWTIHQHSFKVGTAKVNCMVMADQNQVWVGSEDSVIYIINVHSMSCNKQLTAHCSSVTDLIVQDGQEAPSNVYSCSMDGMVLVWNVSTLQVTSRFQLPRGGLTSIRLHGGRLWCCTGNSIMVMKMNGSLHQELKIEENFKDTSTSFLAFQLLPEEEQLWAACAGRSEVYIWSLKDLAQPPQRVPLEDCSEINCMIRVKKQVWVGSRGLGQGTPKGKIYVIDAERKTVEKELVAHMDTVRTLCSAEDRYVLSGSGREEGKVAIWKGE