DEN1A_MOUSE
ID DEN1A_MOUSE Reviewed; 1016 AA.
AC Q8K382; A0MCI0; A2ALU2;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=DENN domain-containing protein 1A;
DE AltName: Full=Connecdenn 1 {ECO:0000303|PubMed:17182770};
DE Short=Connecdenn {ECO:0000303|PubMed:17182770};
GN Name=Dennd1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH AP2B1; ITSN1 AND
RP SH3GL2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=FVB/N;
RX PubMed=17182770; DOI=10.1523/jneurosci.4608-06.2006;
RA Allaire P.D., Ritter B., Thomas S., Burman J.L., Denisov A.Y.,
RA Legendre-Guillemin V., Harper S.Q., Davidson B.L., Gehring K.,
RA McPherson P.S.;
RT "Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-
RT coated vesicles functioning in synaptic vesicle endocytosis.";
RL J. Neurosci. 26:13202-13212(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-473; SER-520 AND SER-523, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-520; SER-522; SER-523;
RP SER-538 AND SER-546, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB35, AND LIPID-BINDING.
RX PubMed=20159556; DOI=10.1016/j.molcel.2009.12.037;
RA Allaire P.D., Marat A.L., Dall'Armi C., Di Paolo G., McPherson P.S.,
RA Ritter B.;
RT "The Connecdenn DENN domain: a GEF for Rab35 mediating cargo-specific exit
RT from early endosomes.";
RL Mol. Cell 37:370-382(2010).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-760, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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:17182770,
CC PubMed:20159556). Binds phosphatidylinositol-phosphates (PtdInsPs),
CC with some preference for PtdIns(3)P (PubMed:20159556).
CC {ECO:0000269|PubMed:17182770, ECO:0000269|PubMed:20159556}.
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:0000250|UniProtKB:Q8TEH3}.
CC -!- SUBUNIT: Interacts with RAB35 (PubMed:20159556). Interacts with
CC clathrin and with the adapter protein complex 2, AP-2 (By similarity).
CC Interacts with ITSN1 AND SH3GL2 (PubMed:17182770). Interacts (when
CC phosphorylated) with YWHAE (By similarity).
CC {ECO:0000250|UniProtKB:Q8TEH3, ECO:0000269|PubMed:17182770,
CC ECO:0000269|PubMed:20159556}.
CC -!- INTERACTION:
CC Q8K382; Q9Z0R4: Itsn1; NbExp=3; IntAct=EBI-7186684, EBI-645386;
CC Q8K382; Q62420: Sh3gl2; NbExp=2; IntAct=EBI-7186684, EBI-77971;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle
CC membrane {ECO:0000269|PubMed:17182770, ECO:0000269|PubMed:20159556};
CC Peripheral membrane protein {ECO:0000269|PubMed:17182770,
CC ECO:0000269|PubMed:20159556}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:17182770}. Note=Associates to membranes via lipid-
CC binding activity. {ECO:0000269|PubMed:20159556}.
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:0000250|UniProtKB:Q8TEH3}.
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; DQ448594; ABD93329.1; -; mRNA.
DR EMBL; AL805959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928810; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027786; AAH27786.1; -; mRNA.
DR CCDS; CCDS16007.1; -.
DR RefSeq; NP_666234.3; NM_146122.3.
DR AlphaFoldDB; Q8K382; -.
DR SMR; Q8K382; -.
DR IntAct; Q8K382; 2.
DR MINT; Q8K382; -.
DR STRING; 10090.ENSMUSP00000099848; -.
DR iPTMnet; Q8K382; -.
DR PhosphoSitePlus; Q8K382; -.
DR EPD; Q8K382; -.
DR jPOST; Q8K382; -.
DR MaxQB; Q8K382; -.
DR PaxDb; Q8K382; -.
DR PRIDE; Q8K382; -.
DR ProteomicsDB; 279339; -.
DR Antibodypedia; 16262; 157 antibodies from 24 providers.
DR Ensembl; ENSMUST00000102787; ENSMUSP00000099848; ENSMUSG00000035392.
DR GeneID; 227801; -.
DR KEGG; mmu:227801; -.
DR UCSC; uc008jng.2; mouse.
DR CTD; 57706; -.
DR MGI; MGI:2442794; Dennd1a.
DR VEuPathDB; HostDB:ENSMUSG00000035392; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00940000156261; -.
DR HOGENOM; CLU_008196_1_1_1; -.
DR InParanoid; Q8K382; -.
DR OMA; NTAWSGD; -.
DR OrthoDB; 189322at2759; -.
DR PhylomeDB; Q8K382; -.
DR TreeFam; TF343037; -.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 227801; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Dennd1a; mouse.
DR PRO; PR:Q8K382; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K382; protein.
DR Bgee; ENSMUSG00000035392; Expressed in retinal neural layer and 223 other tissues.
DR ExpressionAtlas; Q8K382; baseline and differential.
DR Genevisible; Q8K382; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:MGI.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IDA:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IPI:MGI.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; ISO:MGI.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:MGI.
DR Gene3D; 3.40.50.11500; -; 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; PTHR13196; 2.
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 Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Guanine-nucleotide releasing factor; Lipid-binding; Membrane; Methylation;
KW Phosphoprotein; Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..1016
FT /note="DENN domain-containing protein 1A"
FT /id="PRO_0000242681"
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..565
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 681..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 763..783
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 935..1016
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 381..385
FT /note="FXDXF motif"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOTIF 569..578
FT /note="Clathrin box"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT COMPBIAS 514..533
FT /note="Polar 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 952..967
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 997..1011
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 519
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOD_RES 520
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 546
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOD_RES 750
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TEH3"
FT MOD_RES 760
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CONFLICT 152
FT /note="H -> Y (in Ref. 1; ABD93329 and 3; AAH27786)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1016 AA; 111538 MW; 352A1A6F940D7382 CRC64;
MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD
SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT
TKRQESQWNE LLETLHRLPI PDPGVSVHLS VHSYFTVPDS RELPSIPENR NLTEYFVAVD
VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC
APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV
STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFSEE AFVSHYRSGA MKQFLQNATQ
LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK
TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDITENGCV SSAEDPLPKT MPSPQAETQD
PRLREDRRPI TVHFGQVRPP RPHVVRRPKS NITVEGRRTS VSSPEQPQPY RTLKESDSAE
GDETESPEQL VREPWGPTPA PPDRAASIDL LEDVFSSLDV EAPLQPLGQA KSLEDLRAPK
DLREQPGSFD YQRLDLCRSE RGLSMAAALK LAHPYTKLWS LGQDDMAIPS KPSITSPEKP
SALLGTSPAL PLRPQNQEGI LSPSIKEETP IPTPGSITIP RPQGRKTPEL GIVPPPPTAR
PAKLQAAGGP LGDFSSEPLQ MDRERQAALS PALLSGLLPR AVPQGPTELL QPPSPAPGAA
GTGSDALLAL LDPLNTAWSG STIPSHPATP SAATPFIPQL SFPPTVTPTP FVQTPLNPFV
PSVPVVPPSM PLSSTPARPF GTPPASLGPA YAPSILLSSS GFYAPHRSQP NLSALSMPNL
FGQIPMGAHT SPLQPLGPPA VAPSRIRTLP LARSSARAAE AKQGLALRPG ESPLLPPRPP
QSLQPTPQPS VPTQARDPFE DLLRKTKQDV SPSPAPALAP ASTSVEQLRR QWETFE
