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Protein

DENN domain-containing protein 1B

Gene

Dennd1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells. Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Plays a role in clathrin-mediated endocytosis. Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity. Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells.1 Publication

GO - Molecular functioni

  • Rab GTPase binding Source: UniProtKB
  • Rab guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

  • endocytic recycling Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of immune response Source: UniProtKB
  • T cell receptor signaling pathway Source: UniProtKB
  • T-helper 2 cell cytokine production Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
DENN domain-containing protein 1BImported
Alternative name(s):
Connecdenn 2By similarity
Gene namesi
Name:Dennd1bImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2447812. Dennd1b.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Cytoplasmic vesicleclathrin-coated vesicle By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle

Pathology & Biotechi

Disruption phenotypei

Mice are developmentally normal and fertile but accumulate more splenic and lymph node CD4+ and CD8+ effector/memory T-cells with age. TH2 cells display increased TCR-mediated responses, due to delayed surface TCR down-modulation and recycling, and increased production of cytokines. Mice have increased antigen-induced allergic responses.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi246 – 2461G → D: Abolishes guanine nucleotide exchange factor (GEF) activity and impaired TCR down-modulation and recycling in TH2 cells. 1 Publication
Mutagenesisi482 – 4821K → A: Impaired interaction with the AP-2 complex and impaired TCR down-modulation and recycling in TH2 cells; when associated with 547-A--A-549. 1 Publication
Mutagenesisi547 – 5493DLL → AAA: Impaired interaction with the AP-2 complex and impaired TCR down-modulation and recycling in TH2 cells; when associated with A-482. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 766766DENN domain-containing protein 1BPRO_0000304675Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei500 – 5001PhosphotyrosineCombined sources
Modified residuei516 – 5161PhosphoserineCombined sources
Modified residuei517 – 5171PhosphoserineCombined sources
Modified residuei530 – 5301PhosphoserineCombined sources
Modified residuei533 – 5331PhosphoserineCombined sources
Modified residuei632 – 6321PhosphoserineCombined sources
Modified residuei633 – 6331PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ3U1T9.
MaxQBiQ3U1T9.
PaxDbiQ3U1T9.
PRIDEiQ3U1T9.

PTM databases

PhosphoSiteiQ3U1T9.

Expressioni

Tissue specificityi

Expressed in a subset of dendritic cells (DCs).1 Publication

Gene expression databases

BgeeiQ3U1T9.
CleanExiMM_DENND1B.
ExpressionAtlasiQ3U1T9. baseline and differential.
GenevisibleiQ3U1T9. MM.

Interactioni

Subunit structurei

Interacts with RAB35 (PubMed:26774822). Interacts with clathrin heavy chain/CLTC (By similarity). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (By similarity). Interacts with CD3E (PubMed:26774822).By similarity1 Publication

GO - Molecular functioni

  • Rab GTPase binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000127580.

Structurei

3D structure databases

ProteinModelPortaliQ3U1T9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 8968UDENNAdd
BLAST
Domaini90 – 271182DENNPROSITE-ProRule annotationAdd
BLAST
Domaini302 – 36867dDENNPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi378 – 3825FXDXF motif1 Publication
Motifi547 – 55610Clathrin box1 Publication

Domaini

The FXDXF motif mediates interaction the AP-2 complex.1 Publication
The clathrin box motif mediates interaction with clathrin.1 Publication

Sequence similaritiesi

Contains 1 dDENN domain.PROSITE-ProRule annotation
Contains 1 DENN domain.PROSITE-ProRule annotation
Contains 1 uDENN domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3569. Eukaryota.
ENOG410XT3N. LUCA.
GeneTreeiENSGT00760000118819.
HOGENOMiHOG000060237.
HOVERGENiHBG059209.
InParanoidiQ3U1T9.
OrthoDBiEOG73Z2SH.
TreeFamiTF343037.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF03455. dDENN. 1 hit.
PF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 5 (identifier: Q3U1T9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDRRTRENPE RTFDLVLKVK CHASENEDPE VLWKFPEDFG DQEVLQSVPK
60 70 80 90 100
FCFPFDVERV SQNQVGQHFT FVLTDMESKQ RFGFCRLTSG GRICLCILSY
110 120 130 140 150
LPWFEVYYKL LNTLADYLAK ELEEDLNETL KSLYNHPVPK ANTPVNLSVH
160 170 180 190 200
SCFITPDITG LPTIPESRNL TEYFVAVDVN NMLRLYASML HERRIIITSS
210 220 230 240 250
KLSTLTACLH GSAALLYPMY WQHIYIPVLP PHLLDYCCAP MPYLIGIHSS
260 270 280 290 300
LIERVKNKSL EDVVVLNVDT NTLESPFNDL SSLPSDVVSA LKNKLKKQST
310 320 330 340 350
ATGDGVARAF LRAQAALFGS YRDALRYKPG EPITFCEESF VKHRSSVMKQ
360 370 380 390 400
FLETAVNLQL FKQFIDGRLA KLNAGRGFSD IFEEEITSGG FCGGSPRSYQ
410 420 430 440 450
QWVYTVKKGG ALFNTAVTKA TPAVRTAYKF AKSHARLGLK EVKSRLKHKD
460 470 480 490 500
NEEEYGTCSG LVQYTPVYTL HNEKGENREK HKLSQTHLKR PHKSLDGTLY
510 520 530 540 550
DDDDDDDDIE RASKISSEDG EETRAYFYES DDSVEAQVKA PYSGEMDLLG
560 570 580 590 600
EILDTLSTHS SDQGKLAPAK SLDFFRSMDD IDYKPTNKSN APSENNLALL
610 620 630 640 650
CASGDQGEWN LGQDDSALHG RQLPPSPRKR VSSGGLTESL FILKEESREK
660 670 680 690 700
PLCADSVSGP TVVGKPAPTS GLRSQPAAPE ASQTERGRAE VKQTPGQAPL
710 720 730 740 750
QSEDLSVPGP GSRQSTFVPW EKAGKEDTKP SKDVGLLQEV VSLCHMSCDF
760
QQDLNISEES RSGNQT
Length:766
Mass (Da):85,526
Last modified:March 16, 2016 - v3
Checksum:i1CF3B3EEC8E5FB7F
GO
Isoform 2 (identifier: Q3U1T9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Show »
Length:691
Mass (Da):76,641
Checksum:iFABD204CCFDEC4D0
GO
Isoform 3 (identifier: Q3U1T9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     149-149: V → VNQELFIASEQVLKDDPSLIP
     205-766: LTACLHGSAA...SEESRSGNQT → VSPSHLRL

Note: No experimental confirmation available.
Show »
Length:232
Mass (Da):26,821
Checksum:iE723C1A3DAC915E4
GO
Isoform 4 (identifier: Q3U1T9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-363: MDRRTRENPE...TAVNLQLFKQ → MVLFISITCL...WSFLHRILPM

Note: No experimental confirmation available.
Show »
Length:499
Mass (Da):55,113
Checksum:i5664E9D281CCD5D4
GO
Isoform 1 (identifier: Q3U1T9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     149-149: V → VNQELFIASEQVLKDDPSLIP
     394-766: GSPRSYQQWV...SEESRSGNQT → GKDSLESNYLDI

Show »
Length:425
Mass (Da):48,210
Checksum:iC68D50F63F752F6A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 363363MDRRT…QLFKQ → MVLFISITCLYVFSSFSVRT STCLIMFSCFSLRTCNSLAV FSCISLSDLLKSFLMSSTII MRYAFKSRSRFSASLKLRAH LITMFAWSFLHRILPM in isoform 4. 1 PublicationVSP_058172Add
BLAST
Alternative sequencei1 – 7575Missing in isoform 2. 2 PublicationsVSP_058173Add
BLAST
Alternative sequencei149 – 1491V → VNQELFIASEQVLKDDPSLI P in isoform 1 and isoform 3. VSP_058174
Alternative sequencei205 – 766562LTACL…SGNQT → VSPSHLRL in isoform 3. 1 PublicationVSP_058175Add
BLAST
Alternative sequencei394 – 766373GSPRS…SGNQT → GKDSLESNYLDI in isoform 1. 2 PublicationsVSP_058176Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK015524 mRNA. Translation: BAB29881.1.
AK155727 mRNA. Translation: BAE33404.1.
AC138741 Genomic DNA. No translation available.
AC117623 Genomic DNA. No translation available.
BC042698 mRNA. Translation: AAH42698.1.
BC141388 mRNA. Translation: AAI41389.1.
BC141389 mRNA. Translation: AAI41390.1.
CCDSiCCDS35728.1. [Q3U1T9-2]
CCDS48384.1. [Q3U1T9-1]
RefSeqiNP_001159973.1. NM_001166501.1. [Q3U1T9-1]
NP_851992.1. NM_181347.3. [Q3U1T9-2]
UniGeneiMm.337604.
Mm.474921.
Mm.475093.

Genome annotation databases

EnsembliENSMUST00000094505; ENSMUSP00000092082; ENSMUSG00000056268. [Q3U1T9-2]
ENSMUST00000168527; ENSMUSP00000127580; ENSMUSG00000056268. [Q3U1T9-1]
ENSMUST00000200533; ENSMUSP00000142738; ENSMUSG00000056268. [Q3U1T9-3]
GeneIDi329260.
KEGGimmu:329260.
UCSCiuc007cvy.2. mouse. [Q3U1T9-3]
uc007cvz.2. mouse. [Q3U1T9-2]
uc011wtc.1. mouse. [Q3U1T9-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK015524 mRNA. Translation: BAB29881.1.
AK155727 mRNA. Translation: BAE33404.1.
AC138741 Genomic DNA. No translation available.
AC117623 Genomic DNA. No translation available.
BC042698 mRNA. Translation: AAH42698.1.
BC141388 mRNA. Translation: AAI41389.1.
BC141389 mRNA. Translation: AAI41390.1.
CCDSiCCDS35728.1. [Q3U1T9-2]
CCDS48384.1. [Q3U1T9-1]
RefSeqiNP_001159973.1. NM_001166501.1. [Q3U1T9-1]
NP_851992.1. NM_181347.3. [Q3U1T9-2]
UniGeneiMm.337604.
Mm.474921.
Mm.475093.

3D structure databases

ProteinModelPortaliQ3U1T9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000127580.

PTM databases

PhosphoSiteiQ3U1T9.

Proteomic databases

EPDiQ3U1T9.
MaxQBiQ3U1T9.
PaxDbiQ3U1T9.
PRIDEiQ3U1T9.

Protocols and materials databases

DNASUi329260.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000094505; ENSMUSP00000092082; ENSMUSG00000056268. [Q3U1T9-2]
ENSMUST00000168527; ENSMUSP00000127580; ENSMUSG00000056268. [Q3U1T9-1]
ENSMUST00000200533; ENSMUSP00000142738; ENSMUSG00000056268. [Q3U1T9-3]
GeneIDi329260.
KEGGimmu:329260.
UCSCiuc007cvy.2. mouse. [Q3U1T9-3]
uc007cvz.2. mouse. [Q3U1T9-2]
uc011wtc.1. mouse. [Q3U1T9-4]

Organism-specific databases

CTDi163486.
MGIiMGI:2447812. Dennd1b.

Phylogenomic databases

eggNOGiKOG3569. Eukaryota.
ENOG410XT3N. LUCA.
GeneTreeiENSGT00760000118819.
HOGENOMiHOG000060237.
HOVERGENiHBG059209.
InParanoidiQ3U1T9.
OrthoDBiEOG73Z2SH.
TreeFamiTF343037.

Miscellaneous databases

ChiTaRSiDennd1b. mouse.
NextBioi398655.
PROiQ3U1T9.
SOURCEiSearch...

Gene expression databases

BgeeiQ3U1T9.
CleanExiMM_DENND1B.
ExpressionAtlasiQ3U1T9. baseline and differential.
GenevisibleiQ3U1T9. MM.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF03455. dDENN. 1 hit.
PF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
    Strain: C57BL/6J.
    Tissue: Testis.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Strain: Czech II.
    Tissue: Brain and Mammary tumor.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-500; SER-516; SER-517; SER-530; SER-533; SER-632 AND SER-633, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  5. "Regulation of T cell receptor signaling by DENND1B in TH2 cells and allergic disease."
    Yang C.W., Hojer C.D., Zhou M., Wu X., Wuster A., Lee W.P., Yaspan B.L., Chan A.C.
    Cell 164:141-155(2016) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, INTERACTION WITH CD3E AND RAB35, MUTAGENESIS OF GLY-246; LYS-482 AND 547-ASP--LEU-549.

Entry informationi

Entry nameiDEN1B_MOUSE
AccessioniPrimary (citable) accession number: Q3U1T9
Secondary accession number(s): B2RUR7
, E9Q246, Q8CG96, Q9D5B9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 16, 2016
Last modified: May 11, 2016
This is version 84 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.