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};
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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 Genevisible; Q8TEH3; HS.
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.
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
//
