ID DEN1B_HUMAN Reviewed; 775 AA. AC Q6P3S1; B5MD89; D3PFD5; Q5T3B8; Q5T3B9; Q5T3C1; Q5TAI8; Q6B0I8; Q8NDT1; AC Q8TBE6; Q9H774; Q9NXU2; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 16-MAR-2016, sequence version 2. DT 10-FEB-2021, entry version 141. DE RecName: Full=DENN domain-containing protein 1B {ECO:0000312|HGNC:HGNC:28404}; DE AltName: Full=Connecdenn 2 {ECO:0000303|PubMed:20154091}; DE AltName: Full=Protein FAM31B {ECO:0000312|HGNC:HGNC:28404}; GN Name=DENND1B {ECO:0000312|HGNC:HGNC:28404}; GN Synonyms=C1orf218 {ECO:0000312|HGNC:HGNC:28404}, GN FAM31B {ECO:0000312|HGNC:HGNC:28404}; 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 GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 427-775 (ISOFORM 5). RC TISSUE=Brain, and Testis; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-775 (ISOFORM 3). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 376-775 (ISOFORM 5). 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652, AND IDENTIFICATION BY RP 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 [9] RP IDENTIFICATION (ISOFORM 5), SUBCELLULAR LOCATION, FUNCTION, INTERACTION RP WITH AP2A2; AP2B1; CLTC AND RAB35, AND MUTAGENESIS OF LYS-489; LYS-500; RP ARG-501; LYS-502; ARG-507 AND LYS-509. 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 [10] RP FUNCTION. 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 [11] RP INVOLVEMENT IN ASTHMA, AND TISSUE SPECIFICITY. RX PubMed=20032318; DOI=10.1056/nejmoa0901867; RA Sleiman P.M., Flory J., Imielinski M., Bradfield J.P., Annaiah K., RA Willis-Owen S.A., Wang K., Rafaels N.M., Michel S., Bonnelykke K., RA Zhang H., Kim C.E., Frackelton E.C., Glessner J.T., Hou C., Otieno F.G., RA Santa E., Thomas K., Smith R.M., Glaberson W.R., Garris M., Chiavacci R.M., RA Beaty T.H., Ruczinski I., Orange J.M., Allen J., Spergel J.M., RA Grundmeier R., Mathias R.A., Christie J.D., von Mutius E., Cookson W.O., RA Kabesch M., Moffatt M.F., Grunstein M.M., Barnes K.C., Devoto M., RA Magnusson M., Li H., Grant S.F., Bisgaard H., Hakonarson H.; RT "Variants of DENND1B associated with asthma in children."; RL N. Engl. J. Med. 362:36-44(2010). RN [12] RP FUNCTION, AND INTERACTION WITH RAB35. RX PubMed=24520163; DOI=10.7554/elife.01623; RA Langemeyer L., Nunes Bastos R., Cai Y., Itzen A., Reinisch K.M., Barr F.A.; RT "Diversity and plasticity in Rab GTPase nucleotide release mechanism has RT consequences for Rab activation and inactivation."; RL Elife 3:E01623-E01623(2014). RN [13] RP PHOSPHORYLATION. 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). RN [14] RP FUNCTION, AND INVOLVEMENT IN ASTHMA. RX PubMed=26774822; DOI=10.1016/j.cell.2015.11.052; RA Yang C.W., Hojer C.D., Zhou M., Wu X., Wuster A., Lee W.P., Yaspan B.L., RA Chan A.C.; RT "Regulation of T cell receptor signaling by DENND1B in TH2 cells and RT allergic disease."; RL Cell 164:141-155(2016). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-410 IN COMPLEX WITH RAB35. RX PubMed=22065758; DOI=10.1073/pnas.1110415108; RA Wu X., Bradley M.J., Cai Y., Kummel D., De La Cruz E.M., Barr F.A., RA Reinisch K.M.; RT "Insights regarding guanine nucleotide exchange from the structure of a RT DENN-domain protein complexed with its Rab GTPase substrate."; RL Proc. Natl. Acad. Sci. U.S.A. 108:18672-18677(2011). CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAB35 that acts CC as a regulator of T-cell receptor (TCR) internalization in TH2 cells CC (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). CC Acts by promoting the exchange of GDP to GTP, converting inactive GDP- CC bound RAB35 into its active GTP-bound form (PubMed:20154091, CC PubMed:20937701). Plays a role in clathrin-mediated endocytosis CC (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by CC controlling the rate of TCR internalization and routing to endosomes: CC acts by mediating clathrin-mediated endocytosis of TCR via its CC interaction with the adapter protein complex 2 (AP-2) and GEF activity CC (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation CC and recycling, affecting cytokine production in TH2 cells CC (PubMed:26774822). {ECO:0000269|PubMed:20154091, CC ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, CC ECO:0000269|PubMed:26774822}. CC -!- SUBUNIT: Interacts with RAB35 (PubMed:24520163, PubMed:22065758). CC Interacts with clathrin heavy chain/CLTC (PubMed:20154091). Interacts CC with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 CC (PubMed:20154091). Interacts with CD3E (By similarity). CC {ECO:0000250|UniProtKB:Q3U1T9, ECO:0000269|PubMed:20154091, CC ECO:0000269|PubMed:22065758, ECO:0000269|PubMed:24520163}. CC -!- INTERACTION: CC Q6P3S1-5; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-12105346, EBI-739832; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20154091}. CC Cytoplasmic vesicle, clathrin-coated vesicle CC {ECO:0000269|PubMed:20154091}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=5; CC IsoId=Q6P3S1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6P3S1-2; Sequence=VSP_028083, VSP_034515; CC Name=3; CC IsoId=Q6P3S1-3; Sequence=VSP_028083, VSP_028084, VSP_028085; CC Name=4; CC IsoId=Q6P3S1-4; Sequence=VSP_028082, VSP_028083, VSP_034515; CC Name=1; Synonyms=DENND1B-S; CC IsoId=Q6P3S1-5; Sequence=VSP_034515; CC -!- TISSUE SPECIFICITY: Highly expressed in dendritic and natural killer CC cells and at lower levels in other myeloid lineage cells and in CC pituitary. Significantly up-regulated in effector memory T-cells as CC compared with naive T-cells. {ECO:0000269|PubMed:20032318}. CC -!- DOMAIN: The FXDXF motif mediates interaction the AP-2 complex. CC {ECO:0000250|UniProtKB:Q3U1T9}. CC -!- DOMAIN: The clathrin box motif mediates interaction with clathrin. CC {ECO:0000250|UniProtKB:Q3U1T9}. CC -!- PTM: Phosphorylated on serine and/or threonine, possibly regulating the CC guanine nucleotide exchange factor (GEF) activity. CC {ECO:0000269|PubMed:26055712}. CC -!- DISEASE: Asthma (ASTHMA) [MIM:600807]: The most common chronic disease CC affecting children and young adults. It is a complex genetic disorder CC with a heterogeneous phenotype, largely attributed to the interactions CC among many genes and between these genes and the environment. It is CC characterized by recurrent attacks of paroxysmal dyspnea, with wheezing CC due to spasmodic contraction of the bronchi. CC {ECO:0000269|PubMed:20032318, ECO:0000269|PubMed:26774822}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. Asthma susceptibility is probably CC caused by decreased TCR down-modulation and recycling in TH2 cells, CC causing prolonged TCR signaling and increased cytokine production in CC TH2 lymphocytes (PubMed:26774822). {ECO:0000269|PubMed:26774822}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH74735.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA90918.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15024.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=EAW91280.1; Type=Erroneous gene model prediction; 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; AL139136; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL365258; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91280.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471067; EAW91281.1; -; Genomic_DNA. DR EMBL; CH471067; EAW91285.1; -; Genomic_DNA. DR EMBL; BC022561; AAH22561.1; -; mRNA. DR EMBL; BC063877; AAH63877.1; -; mRNA. DR EMBL; BC074735; AAH74735.2; ALT_INIT; mRNA. DR EMBL; AL831839; CAD38548.1; -; mRNA. DR EMBL; AK000061; BAA90918.1; ALT_INIT; mRNA. DR EMBL; AK024832; BAB15024.1; ALT_INIT; mRNA. DR EMBL; BK006960; DAA12502.1; -; mRNA. DR CCDS; CCDS41452.2; -. [Q6P3S1-5] DR CCDS; CCDS72996.1; -. [Q6P3S1-4] DR CCDS; CCDS72997.1; -. [Q6P3S1-1] DR RefSeq; NP_001182144.1; NM_001195215.1. [Q6P3S1-1] DR RefSeq; NP_001182145.1; NM_001195216.1. DR RefSeq; NP_001287787.1; NM_001300858.1. [Q6P3S1-4] DR RefSeq; NP_659414.2; NM_144977.4. [Q6P3S1-5] DR PDB; 3TW8; X-ray; 2.10 A; A/C=1-410. DR PDBsum; 3TW8; -. DR SMR; Q6P3S1; -. DR BioGRID; 127867; 5. DR IntAct; Q6P3S1; 3. DR STRING; 9606.ENSP00000479816; -. DR iPTMnet; Q6P3S1; -. DR PhosphoSitePlus; Q6P3S1; -. DR BioMuta; DENND1B; -. DR DMDM; 74749089; -. DR jPOST; Q6P3S1; -. DR MassIVE; Q6P3S1; -. DR MaxQB; Q6P3S1; -. DR PaxDb; Q6P3S1; -. DR PeptideAtlas; Q6P3S1; -. DR PRIDE; Q6P3S1; -. DR ProteomicsDB; 66926; -. [Q6P3S1-1] DR ProteomicsDB; 66927; -. [Q6P3S1-2] DR ProteomicsDB; 66928; -. [Q6P3S1-3] DR ProteomicsDB; 66929; -. [Q6P3S1-4] DR ProteomicsDB; 66930; -. [Q6P3S1-5] DR Antibodypedia; 34481; 150 antibodies. DR DNASU; 163486; -. DR Ensembl; ENST00000235453; ENSP00000235453; ENSG00000213047. [Q6P3S1-4] DR Ensembl; ENST00000367396; ENSP00000356366; ENSG00000213047. [Q6P3S1-5] DR Ensembl; ENST00000620048; ENSP00000479816; ENSG00000213047. [Q6P3S1-1] DR GeneID; 163486; -. DR KEGG; hsa:163486; -. DR UCSC; uc001gue.4; human. [Q6P3S1-1] DR CTD; 163486; -. DR DisGeNET; 163486; -. DR GeneCards; DENND1B; -. DR HGNC; HGNC:28404; DENND1B. DR HPA; ENSG00000213047; Low tissue specificity. DR MIM; 600807; phenotype. DR MIM; 613292; gene. DR neXtProt; NX_Q6P3S1; -. DR OpenTargets; ENSG00000213047; -. DR PharmGKB; PA134951951; -. DR VEuPathDB; HostDB:ENSG00000213047.11; -. DR eggNOG; KOG3569; Eukaryota. DR GeneTree; ENSGT00940000155446; -. DR HOGENOM; CLU_008196_4_0_1; -. DR InParanoid; Q6P3S1; -. DR OMA; MHSYFIA; -. DR OrthoDB; 1596135at2759; -. DR TreeFam; TF320336; -. DR PathwayCommons; Q6P3S1; -. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR BioGRID-ORCS; 163486; 2 hits in 876 CRISPR screens. DR ChiTaRS; DENND1B; human. DR GenomeRNAi; 163486; -. DR Pharos; Q6P3S1; Tbio. DR PRO; PR:Q6P3S1; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q6P3S1; protein. DR Bgee; ENSG00000213047; Expressed in blood and 234 other tissues. DR ExpressionAtlas; Q6P3S1; baseline and differential. DR Genevisible; Q6P3S1; HS. DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central. DR GO; GO:0017137; F:Rab GTPase binding; IBA:GO_Central. DR GO; GO:0017112; F:Rab guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0032456; P:endocytic recycling; ISS:UniProtKB. DR GO; GO:0006897; P:endocytosis; IBA:GO_Central. DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0050776; P:regulation of immune response; ISS:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0035745; P:T-helper 2 cell cytokine production; IMP:UniProtKB. 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; 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; Asthma; Cytoplasm; Cytoplasmic vesicle; KW Guanine-nucleotide releasing factor; Phosphoprotein; Protein transport; KW Reference proteome; Transport. FT CHAIN 1..775 FT /note="DENN domain-containing protein 1B" FT /id="PRO_0000304674" FT DOMAIN 14..143 FT /note="uDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 180..316 FT /note="cDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 318..395 FT /note="dDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT MOTIF 398..402 FT /note="FXDXF motif" FT /evidence="ECO:0000305|PubMed:20154091" FT MOTIF 566..575 FT /note="Clathrin box" FT /evidence="ECO:0000305|PubMed:20154091" FT MOD_RES 520 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT MOD_RES 535 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT MOD_RES 536 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT MOD_RES 549 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT MOD_RES 552 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT MOD_RES 652 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:19690332" FT MOD_RES 653 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3U1T9" FT VAR_SEQ 1..28 FT /note="MDCRTKANPDRTFDLVLKVKCHASENED -> MAAAPREEKRWPQPVFSN FT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028082" FT VAR_SEQ 150..169 FT /note="Missing (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_028083" FT VAR_SEQ 310..315 FT /note="ALKNKL -> MKAIQW (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_028084" FT VAR_SEQ 316..775 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_028085" FT VAR_SEQ 415..775 FT /note="NPRSYQQWVHTVKKGGALFNTAMTKATPAVRTAYKFAKNHAKLGLKEVKSKL FT KHKENEEDYGTCSSSVQYTPVYKLHNEKGGNSEKRKLAQARLKRPLKSLDGALYDDEDD FT DDIERASKLSSEDGEEASAYLYESDDSVETRVKTPYSGEMDLLGEILDTLSTHSSDQGK FT LAAAKSLDFFRSMDDIDYKPTNKSNAPSENNLAFLCGGSGDQAEWNLGQDDSALHGKHL FT PPSPRKRVSSSGLTDSLFILKEENSNKHLGADNVSDPTSGLDFQLTSPEVSQTDKGKTE FT KRETLSQISDDLLIPGLGRHSSTFVPWEKEGKEAKETSEDIGLLHEVVSLCHMTSDFQQ FT SLNISDKNTNGNQT -> KDKLQYDYPFSQ (in isoform 4, isoform 2 and FT isoform 1)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_034515" FT VARIANT 216 FT /note="V -> M (in dbSNP:rs7546381)" FT /id="VAR_035055" FT MUTAGEN 489 FT /note="K->A: Causes only a slight reduction in AP2B1- FT binding." FT /evidence="ECO:0000269|PubMed:20154091" FT MUTAGEN 500 FT /note="K->A: Greatly reduce AP2B1-binding." FT /evidence="ECO:0000269|PubMed:20154091" FT MUTAGEN 501 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:20154091" FT MUTAGEN 502 FT /note="K->A: Almost completely abolishes AP2B1-binding." FT /evidence="ECO:0000269|PubMed:20154091" FT MUTAGEN 507 FT /note="R->A: No effect." FT /evidence="ECO:0000269|PubMed:20154091" FT MUTAGEN 509 FT /note="K->A: Greatly reduce AP2B1-binding." FT /evidence="ECO:0000269|PubMed:20154091" FT CONFLICT 340 FT /note="S -> Y (in Ref. 3; AAH22561)" FT /evidence="ECO:0000305" FT STRAND 10..12 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 14..20 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 30..36 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 42..52 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 57..60 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 61..63 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 66..74 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 80..87 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 91..101 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 104..119 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 123..135 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 188..196 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 199..209 FT /evidence="ECO:0000244|PDB:3TW8" FT TURN 210..212 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 214..220 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 222..234 FT /evidence="ECO:0000244|PDB:3TW8" FT TURN 235..238 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 243..248 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 251..258 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 263..268 FT /evidence="ECO:0000244|PDB:3TW8" FT TURN 269..271 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 272..276 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 284..287 FT /evidence="ECO:0000244|PDB:3TW8" FT TURN 288..291 FT /evidence="ECO:0000244|PDB:3TW8" FT STRAND 292..294 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 300..302 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 305..315 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 318..321 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 325..338 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 339..341 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 357..360 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 366..375 FT /evidence="ECO:0000244|PDB:3TW8" FT HELIX 379..391 FT /evidence="ECO:0000244|PDB:3TW8" SQ SEQUENCE 775 AA; 86552 MW; ED44D8F693DF3983 CRC64; MDCRTKANPD RTFDLVLKVK CHASENEDPV VLWKFPEDFG DQEILQSVPK FCFPFDVERV SQNQVGQHFT FVLTDIESKQ RFGFCRLTSG GTICLCILSY LPWFEVYYKL LNTLADYLAK ELENDLNETL RSLYNHPVPK ANTPVNLSVN QEIFIACEQV LKDQPALVPH SYFIAPDVTG LPTIPESRNL TEYFVAVDVN NMLQLYASML HERRIVIISS KLSTLTACIH GSAALLYPMY WQHIYIPVLP PHLLDYCCAP MPYLIGIHSS LIERVKNKSL EDVVMLNVDT NTLESPFSDL NNLPSDVVSA LKNKLKKQST ATGDGVARAF LRAQAALFGS YRDALRYKPG EPITFCEESF VKHRSSVMKQ FLETAINLQL FKQFIDGRLA KLNAGRGFSD VFEEEITSGG FCGGNPRSYQ QWVHTVKKGG ALFNTAMTKA TPAVRTAYKF AKNHAKLGLK EVKSKLKHKE NEEDYGTCSS SVQYTPVYKL HNEKGGNSEK RKLAQARLKR PLKSLDGALY DDEDDDDIER ASKLSSEDGE EASAYLYESD DSVETRVKTP YSGEMDLLGE ILDTLSTHSS DQGKLAAAKS LDFFRSMDDI DYKPTNKSNA PSENNLAFLC GGSGDQAEWN LGQDDSALHG KHLPPSPRKR VSSSGLTDSL FILKEENSNK HLGADNVSDP TSGLDFQLTS PEVSQTDKGK TEKRETLSQI SDDLLIPGLG RHSSTFVPWE KEGKEAKETS EDIGLLHEVV SLCHMTSDFQ QSLNISDKNT NGNQT //