DEN1B_HUMAN
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 03-AUG-2022, entry version 147.
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};
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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 AlphaFoldDB; Q6P3S1; -.
DR SMR; Q6P3S1; -.
DR BioGRID; 127867; 15.
DR IntAct; Q6P3S1; 3.
DR STRING; 9606.ENSP00000479816; -.
DR iPTMnet; Q6P3S1; -.
DR PhosphoSitePlus; Q6P3S1; -.
DR BioMuta; DENND1B; -.
DR DMDM; 74749089; -.
DR EPD; Q6P3S1; -.
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; 152 antibodies from 19 providers.
DR DNASU; 163486; -.
DR Ensembl; ENST00000235453.8; ENSP00000235453.4; ENSG00000213047.13. [Q6P3S1-4]
DR Ensembl; ENST00000367396.7; ENSP00000356366.3; ENSG00000213047.13. [Q6P3S1-5]
DR Ensembl; ENST00000620048.6; ENSP00000479816.1; ENSG00000213047.13. [Q6P3S1-1]
DR GeneID; 163486; -.
DR KEGG; hsa:163486; -.
DR MANE-Select; ENST00000620048.6; ENSP00000479816.1; NM_001195215.2; NP_001182144.1.
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; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00940000155446; -.
DR HOGENOM; CLU_008196_4_0_1; -.
DR InParanoid; Q6P3S1; -.
DR OMA; HRSNTMK; -.
DR OrthoDB; 1596135at2759; -.
DR TreeFam; TF320336; -.
DR PathwayCommons; Q6P3S1; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q6P3S1; -.
DR BioGRID-ORCS; 163486; 6 hits in 1078 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 jejunal mucosa and 200 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:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
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:2000553; P:positive regulation of T-helper 2 cell cytokine production; IMP:UniProtKB.
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 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 REGION 635..654
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 COMPBIAS 673..695
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007744|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:0007829|PDB:3TW8"
FT STRAND 14..20
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 30..36
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 42..52
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 66..74
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 104..119
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 188..196
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 199..209
FT /evidence="ECO:0007829|PDB:3TW8"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 222..234
FT /evidence="ECO:0007829|PDB:3TW8"
FT TURN 235..238
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 251..258
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:3TW8"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 272..276
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:3TW8"
FT TURN 288..291
FT /evidence="ECO:0007829|PDB:3TW8"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 305..315
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 325..338
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 366..375
FT /evidence="ECO:0007829|PDB:3TW8"
FT HELIX 379..391
FT /evidence="ECO:0007829|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
