ID DEN1A_HUMAN Reviewed; 1009 AA. AC Q8TEH3; A8MZA3; B1AM80; B7Z3C8; B7Z669; D3PFD3; Q05C88; Q5VWF0; Q6PJZ5; AC Q8IVD6; Q9H796; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUN-2006, sequence version 2. DT 24-JAN-2024, entry version 152. DE RecName: Full=DENN domain-containing protein 1A {ECO:0000312|HGNC:HGNC:29324}; DE AltName: Full=Connecdenn 1 {ECO:0000303|PubMed:20154091}; DE Short=Connecdenn {ECO:0000303|PubMed:20154091}; DE AltName: Full=Protein FAM31A; GN Name=DENND1A {ECO:0000312|HGNC:HGNC:29324}; GN Synonyms=FAM31A {ECO:0000312|HGNC:HGNC:29324}, KIAA1608; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 6), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 114-1009 (ISOFORM 1), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 217-1009 (ISOFORM 7). RC TISSUE=Artery smooth muscle, Fetal brain, Hippocampus, and Spleen; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-519; SER-520; SER-523; RP SER-536; SER-538 AND SER-546, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-538 AND SER-546, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP IDENTIFICATION (ISOFORM 1), SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION RP WITH AP2A2; CLTC AND RAB35. RX PubMed=20154091; DOI=10.1074/jbc.m109.050930; RA Marat A.L., McPherson P.S.; RT "The connecdenn family, Rab35 guanine nucleotide exchange factors RT interfacing with the clathrin machinery."; RL J. Biol. Chem. 285:10627-10637(2010). RN [11] RP FUNCTION, INTERACTION WITH CLATHRIN AND AP-2, AND SUBCELLULAR LOCATION. RX PubMed=20937701; DOI=10.1083/jcb.201008051; RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.; RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange RT factors."; RL J. Cell Biol. 191:367-381(2010). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-520; SER-523 AND SER-592, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [14] RP POSSIBLE INVOLVEMENT IN PCOS. RX PubMed=22180642; DOI=10.1136/jmedgenet-2011-100427; RA Goodarzi M.O., Jones M.R., Li X., Chua A.K., Garcia O.A., Chen Y.D., RA Krauss R.M., Rotter J.I., Ankener W., Legro R.S., Azziz R., RA Strauss J.F. III, Dunaif A., Urbanek M.; RT "Replication of association of DENND1A and THADA variants with polycystic RT ovary syndrome in European cohorts."; RL J. Med. Genet. 49:90-95(2012). RN [15] RP POSSIBLE INVOLVEMENT IN PCOS. RX PubMed=23208300; DOI=10.1093/humrep/des424; RA Cui L., Zhao H., Zhang B., Qu Z., Liu J., Liang X., Zhao X., Zhao J., RA Sun Y., Wang P., Li T., Shi Y., Chen Z.J.; RT "Genotype-phenotype correlations of PCOS susceptibility SNPs identified by RT GWAS in a large cohort of Han Chinese women."; RL Hum. Reprod. 28:538-544(2013). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-473; SER-520; SER-523; RP SER-546 AND SER-592, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP POSSIBLE INVOLVEMENT IN PCOS. RX PubMed=24086769; DOI=10.1371/journal.pone.0077186; RA Eriksen M.B., Nielsen M.F., Brusgaard K., Tan Q., Andersen M.S., RA Glintborg D., Gaster M.; RT "Genetic alterations within the DENND1A gene in patients with polycystic RT ovary syndrome (PCOS)."; RL PLoS ONE 8:E77186-E77186(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-546 AND SER-749, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP POSSIBLE INVOLVEMENT IN PCOS. RX PubMed=25626177; DOI=10.1016/j.gene.2015.01.034; RA Gammoh E., Arekat M.R., Saldhana F.L., Madan S., Ebrahim B.H., Almawi W.Y.; RT "DENND1A gene variants in Bahraini Arab women with polycystic ovary RT syndrome."; RL Gene 560:30-33(2015). RN [20] RP ACTIVITY REGULATION, INTERACTION WITH YWHAE, PHOSPHORYLATION AT SER-536 AND RP SER-538, AND MUTAGENESIS OF 536-SER--SER-538. RX PubMed=26055712; DOI=10.1074/jbc.m115.636712; RA Kulasekaran G., Nossova N., Marat A.L., Lund I., Cremer C., Ioannou M.S., RA McPherson P.S.; RT "Phosphorylation-dependent regulation of Connecdenn/DENND1 guanine RT nucleotide exchange factors."; RL J. Biol. Chem. 290:17999-18008(2015). CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) regulating clathrin- CC mediated endocytosis through RAB35 activation. Promotes the exchange of CC GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP- CC bound form. Regulates clathrin-mediated endocytosis of synaptic CC vesicles and mediates exit from early endosomes (PubMed:20154091, CC PubMed:20937701). Binds phosphatidylinositol-phosphates (PtdInsPs), CC with some preference for PtdIns(3)P (By similarity). CC {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, CC ECO:0000269|PubMed:20937701}. CC -!- ACTIVITY REGULATION: The guanine nucleotide exchange factor (GEF) CC activity is autoinhibited. Autoinhibition may be the result of CC intramolecular interaction between the DENN domain and the C-terminus, CC which is disrupted upon phosphorylation. Activation is regulated by Akt CC activation. {ECO:0000269|PubMed:26055712}. CC -!- SUBUNIT: Interacts with RAB35 (PubMed:20154091). Interacts with CC clathrin and with the adapter protein complex 2, AP-2 (PubMed:20154091, CC PubMed:20937701). Interacts with ITSN1 and SH3GL2 (By similarity). CC Interacts (when phosphorylated) with YWHAE (PubMed:26055712). CC {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, CC ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:26055712}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle CC membrane {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}; CC Peripheral membrane protein {ECO:0000269|PubMed:20937701}. Presynaptic CC cell membrane {ECO:0000269|PubMed:20937701}. Note=Associates to CC membranes via lipid-binding activity. {ECO:0000250|UniProtKB:Q8K382}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=Q8TEH3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TEH3-2; Sequence=VSP_019464, VSP_019465; CC Name=3; CC IsoId=Q8TEH3-3; Sequence=VSP_034513, VSP_034514; CC Name=4; CC IsoId=Q8TEH3-4; Sequence=VSP_034509, VSP_034512, VSP_034513, CC VSP_034514; CC Name=5; CC IsoId=Q8TEH3-5; Sequence=VSP_034510, VSP_034511, VSP_019464, CC VSP_019465; CC Name=6; CC IsoId=Q8TEH3-6; Sequence=VSP_034509, VSP_040666, VSP_040668; CC Name=7; CC IsoId=Q8TEH3-7; Sequence=VSP_040667, VSP_040668; CC -!- PTM: Phosphorylated on serine and/or threonine in an Akt-dependent CC manner. Phosphorylation probably regulates the guanine nucleotide CC exchange factor (GEF) activity, possibly by disrupting an CC intramolecular interaction between the DENN domain and the C-terminus CC of the protein, thereby relieving the autoinhibition. CC {ECO:0000269|PubMed:26055712}. CC -!- DISEASE: Note=Genetic variants in DENND1A may play a role in CC susceptibility to polycystic ovary syndrome (PCOS), the most common CC endocrine disease among premenopausal women. PCOS is a complex disorder CC characterized by infertility, hirsutism, obesity, various menstrual CC disturbances, and enlarged ovaries studded with atretic follicles. CC {ECO:0000269|PubMed:22180642, ECO:0000269|PubMed:23208300, CC ECO:0000269|PubMed:24086769, ECO:0000269|PubMed:25626177}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH09616.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH28061.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAH13155.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK024782; BAB15002.1; -; mRNA. DR EMBL; AK074151; BAB84977.1; -; mRNA. DR EMBL; AK295710; BAH12164.1; -; mRNA. DR EMBL; AK299867; BAH13155.1; ALT_INIT; mRNA. DR EMBL; AC006450; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161790; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL390774; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445489; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87571.1; -; Genomic_DNA. DR EMBL; CH471090; EAW87575.1; -; Genomic_DNA. DR EMBL; BC009616; AAH09616.1; ALT_INIT; mRNA. DR EMBL; BC028061; AAH28061.1; ALT_INIT; mRNA. DR EMBL; BC039703; AAH39703.1; -; mRNA. DR EMBL; BK006958; DAA12500.1; -; mRNA. DR CCDS; CCDS35133.1; -. [Q8TEH3-1] DR CCDS; CCDS35134.1; -. [Q8TEH3-2] DR CCDS; CCDS87687.1; -. [Q8TEH3-4] DR RefSeq; NP_065997.1; NM_020946.1. [Q8TEH3-1] DR RefSeq; NP_079096.2; NM_024820.2. [Q8TEH3-2] DR PDB; 6EKK; X-ray; 1.82 A; A/B=2-394. DR PDBsum; 6EKK; -. DR AlphaFoldDB; Q8TEH3; -. DR SMR; Q8TEH3; -. DR BioGRID; 121730; 105. DR IntAct; Q8TEH3; 23. DR STRING; 9606.ENSP00000362727; -. DR iPTMnet; Q8TEH3; -. DR PhosphoSitePlus; Q8TEH3; -. DR BioMuta; DENND1A; -. DR DMDM; 109825594; -. DR EPD; Q8TEH3; -. DR jPOST; Q8TEH3; -. DR MassIVE; Q8TEH3; -. DR MaxQB; Q8TEH3; -. DR PaxDb; 9606-ENSP00000362727; -. DR PeptideAtlas; Q8TEH3; -. DR ProteomicsDB; 74459; -. [Q8TEH3-1] DR ProteomicsDB; 74460; -. [Q8TEH3-2] DR ProteomicsDB; 74461; -. [Q8TEH3-3] DR ProteomicsDB; 74462; -. [Q8TEH3-4] DR ProteomicsDB; 74463; -. [Q8TEH3-5] DR ProteomicsDB; 74464; -. [Q8TEH3-6] DR ProteomicsDB; 74465; -. [Q8TEH3-7] DR Pumba; Q8TEH3; -. DR Antibodypedia; 16262; 176 antibodies from 24 providers. DR DNASU; 57706; -. DR Ensembl; ENST00000373618.1; ENSP00000362720.1; ENSG00000119522.18. [Q8TEH3-4] DR Ensembl; ENST00000373620.7; ENSP00000362722.3; ENSG00000119522.18. [Q8TEH3-2] DR Ensembl; ENST00000373624.6; ENSP00000362727.2; ENSG00000119522.18. [Q8TEH3-1] DR GeneID; 57706; -. DR KEGG; hsa:57706; -. DR UCSC; uc004bnz.2; human. [Q8TEH3-1] DR AGR; HGNC:29324; -. DR CTD; 57706; -. DR DisGeNET; 57706; -. DR GeneCards; DENND1A; -. DR HGNC; HGNC:29324; DENND1A. DR HPA; ENSG00000119522; Low tissue specificity. DR MIM; 613633; gene. DR neXtProt; NX_Q8TEH3; -. DR OpenTargets; ENSG00000119522; -. DR PharmGKB; PA134876117; -. DR VEuPathDB; HostDB:ENSG00000119522; -. DR eggNOG; KOG3569; Eukaryota. DR GeneTree; ENSGT00940000156261; -. DR HOGENOM; CLU_008196_1_1_1; -. DR InParanoid; Q8TEH3; -. DR OMA; NTAWSGD; -. DR OrthoDB; 5398783at2759; -. DR PhylomeDB; Q8TEH3; -. DR TreeFam; TF343037; -. DR PathwayCommons; Q8TEH3; -. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SignaLink; Q8TEH3; -. DR BioGRID-ORCS; 57706; 19 hits in 1158 CRISPR screens. DR ChiTaRS; DENND1A; human. DR GeneWiki; DENND1A; -. DR GenomeRNAi; 57706; -. DR Pharos; Q8TEH3; Tbio. DR PRO; PR:Q8TEH3; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q8TEH3; Protein. DR Bgee; ENSG00000119522; Expressed in monocyte and 144 other cell types or tissues. DR ExpressionAtlas; Q8TEH3; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB. DR GO; GO:0030665; C:clathrin-coated vesicle membrane; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; ISS:UniProtKB. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB. DR GO; GO:0032456; P:endocytic recycling; ISS:UniProtKB. DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0032483; P:regulation of Rab protein signal transduction; IDA:FlyBase. DR Gene3D; 3.30.450.200; -; 1. DR Gene3D; 3.40.50.11500; -; 1. DR Gene3D; 6.10.140.1000; -; 1. DR InterPro; IPR001194; cDENN_dom. DR InterPro; IPR005112; dDENN_dom. DR InterPro; IPR043153; DENN_C. DR InterPro; IPR040032; DENND1A/B/C. DR InterPro; IPR037516; Tripartite_DENN. DR InterPro; IPR005113; uDENN_dom. DR PANTHER; PTHR13196; DENN DOMAIN-CONTAINING; 1. DR PANTHER; PTHR13196:SF22; DENN DOMAIN-CONTAINING PROTEIN 1A; 1. DR Pfam; PF03455; dDENN; 1. DR Pfam; PF02141; DENN; 1. DR Pfam; PF03456; uDENN; 1. DR SMART; SM00801; dDENN; 1. DR SMART; SM00799; DENN; 1. DR SMART; SM00800; uDENN; 1. DR PROSITE; PS50211; DENN; 1. DR Genevisible; Q8TEH3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Cytoplasmic vesicle; Guanine-nucleotide releasing factor; Lipid-binding; KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Synapse; KW Transport. FT CHAIN 1..1009 FT /note="DENN domain-containing protein 1A" FT /id="PRO_0000242680" FT DOMAIN 13..145 FT /note="uDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 162..298 FT /note="cDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 300..378 FT /note="dDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT REGION 453..564 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 648..714 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 796..831 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 928..1009 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 381..385 FT /note="FXDXF motif" FT /evidence="ECO:0000305|PubMed:20154091" FT MOTIF 569..578 FT /note="Clathrin box" FT /evidence="ECO:0000305|PubMed:20154091" FT COMPBIAS 478..492 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 535..549 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 796..815 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 816..831 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 945..961 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 519 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 520 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 523 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 536 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26055712, FT ECO:0007744|PubMed:18669648" FT MOD_RES 538 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:26055712, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332" FT MOD_RES 546 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 592 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 749 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..32 FT /note="Missing (in isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_034509" FT VAR_SEQ 1..30 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034510" FT VAR_SEQ 31..43 FT /note="PEVQRQFPEDYSD -> MLKWPIPGQVALF (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034511" FT VAR_SEQ 33..60 FT /note="VQRQFPEDYSDQEVLQTLTKFCFPFYVD -> MLKWPIPGQVALFQILRCRG FT NSRRTTVT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034512" FT VAR_SEQ 33..42 FT /note="VQRQFPEDYS -> MRRPGDHGLQ (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040666" FT VAR_SEQ 290..331 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040667" FT VAR_SEQ 497..498 FT /note="VR -> AL (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034513" FT VAR_SEQ 499..1009 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034514" FT VAR_SEQ 526 FT /note="Q -> HLVKPLRHYAVFLSEDSSDDECQREEGPSSGFTESFFFSAPFEW FT (in isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040668" FT VAR_SEQ 527..559 FT /note="PQPYRTLRESDSAEGDEAESPEQQVRKSTGPVP -> NTIATPATLHILQKS FT ITHFAAKFPTRGWTSSSH (in isoform 2 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_019464" FT VAR_SEQ 560..1009 FT /note="Missing (in isoform 2 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_019465" FT MUTAGEN 536..538 FT /note="SDS->EDE: Phosphomimetic mutant; abolishes the FT intramolecular interaction between the DENN domain and the FT C-terminus of the protein." FT /evidence="ECO:0000269|PubMed:26055712" FT CONFLICT 456 FT /note="E -> G (in Ref. 1; BAB15002)" FT /evidence="ECO:0000305" FT STRAND 10..12 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 14..20 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 32..38 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 44..53 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 69..76 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 82..89 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 93..103 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 106..121 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 125..137 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 146..152 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 170..178 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 181..192 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 196..202 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 204..216 FT /evidence="ECO:0007829|PDB:6EKK" FT TURN 217..220 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 225..230 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 233..240 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 245..250 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 251..253 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 254..259 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:6EKK" FT TURN 270..273 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 281..284 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 287..298 FT /evidence="ECO:0007829|PDB:6EKK" FT TURN 301..303 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 307..320 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 321..326 FT /evidence="ECO:0007829|PDB:6EKK" FT STRAND 331..333 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 339..343 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 349..358 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 362..377 FT /evidence="ECO:0007829|PDB:6EKK" FT HELIX 384..389 FT /evidence="ECO:0007829|PDB:6EKK" FT TURN 391..393 FT /evidence="ECO:0007829|PDB:6EKK" SQ SEQUENCE 1009 AA; 110577 MW; ECEE79CFCD5E2D0C CRC64; MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT TKRQENQWNE LLETLHKLPI PDPGVSVHLS VHSYFTVPDT RELPSIPENR NLTEYFVAVD VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFCEE AFVSHYRSGA MRQFLQNATQ LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDIAENGCA PTPEEQLPKT APSPLVEAKD PKLREDRRPI TVHFGQVRPP RPHVVKRPKS NIAVEGRRTS VPSPEQPQPY RTLRESDSAE GDEAESPEQQ VRKSTGPVPA PPDRAASIDL LEDVFSNLDM EAALQPLGQA KSLEDLRAPK DLREQPGTFD YQRLDLGGSE RSRGVTVALK LTHPYNKLWS LGQDDMAIPS KPPAASPEKP SALLGNSLAL PRRPQNRDSI LNPSDKEEVP TPTLGSITIP RPQGRKTPEL GIVPPPPIPR PAKLQAAGAA LGDVSERLQT DRDRRAALSP GLLPGVVPQG PTELLQPLSP GPGAAGTSSD ALLALLDPLS TAWSGSTLPS RPATPNVATP FTPQFSFPPA GTPTPFPQPP LNPFVPSMPA APPTLPLVST PAGPFGAPPA SLGPAFASGL LLSSAGFCAP HRSQPNLSAL SMPNLFGQMP MGTHTSPLQP LGPPAVAPSR IRTLPLARSS ARAAETKQGL ALRPGDPPLL PPRPPQGLEP TLQPSAPQQA RDPFEDLLQK TKQDVSPSPA LAPAPDSVEQ LRKQWETFE //