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Protein

DENN domain-containing protein 3

Gene

Dennd3

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

Functioni

Guanine nucleotide exchange factor (GEF) activating Rab12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab12 into its active GTP-bound form. Regulates autophagy in response to starvation through Rab12 activation (PubMed:24719330, PubMed:25925668, PubMed:28249939). Starvation leads to ULK1/2-dependent phosphorylation of Ser-554 and Ser-572, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards Rab12 (PubMed:25925668). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:21718402, PubMed:24719330). Starvation also induces phosphorylation at Tyr-940, which leads to up-regulated GEF activity and initiates autophagy (PubMed:28249939).4 Publications

GO - Molecular functioni

  • Rab guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

  • cellular protein catabolic process Source: UniProtKB
  • endosome to lysosome transport Source: UniProtKB

Keywordsi

Molecular functionGuanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-MMU-8876198 RAB GEFs exchange GTP for GDP on RABs

Names & Taxonomyi

Protein namesi
Recommended name:
DENN domain-containing protein 3
Gene namesi
Name:Dennd3
Synonyms:Kiaa0870
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2146009 Dennd3

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi554S → A: Abolishes intreaction with 14-3-3 proteins. 1 Publication1
Mutagenesisi572S → A: Greatly reduces interaction with 14-3-3 proteins. 1 Publication1
Mutagenesisi940Y → D: Abrogates the intramolecular linker-DENN domain interaction and enhances GEF activity towards Rab12. 1 Publication1
Mutagenesisi940Y → F: Retains the intramolecular linker-DENN domain interaction and impairs GEF activity towards Rab12. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003046731 – 1274DENN domain-containing protein 3Add BLAST1274

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei554Phosphoserine; by ULK11 Publication1
Modified residuei572Phosphoserine; by ULK11 Publication1
Modified residuei940Phosphotyrosine1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiA2RT67
MaxQBiA2RT67
PaxDbiA2RT67
PeptideAtlasiA2RT67
PRIDEiA2RT67

PTM databases

iPTMnetiA2RT67
PhosphoSitePlusiA2RT67

Expressioni

Gene expression databases

BgeeiENSMUSG00000036661
CleanExiMM_DENND3
ExpressionAtlasiA2RT67 baseline and differential
GenevisibleiA2RT67 MM

Interactioni

Subunit structurei

Forms oligomers (PubMed:28249939). Interacts with 6 of the 7 known isoforms of 14-3-3 proteins (PubMed:25925668).2 Publications

GO - Molecular functioni

  • Rab guanyl-nucleotide exchange factor activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000046774

Structurei

Secondary structure

11274
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi732 – 742Combined sources11
Helixi748 – 758Combined sources11
Turni759 – 761Combined sources3
Helixi768 – 786Combined sources19
Helixi792 – 796Combined sources5
Beta strandi804 – 813Combined sources10
Beta strandi816 – 835Combined sources20
Beta strandi837 – 842Combined sources6
Helixi843 – 845Combined sources3
Beta strandi846 – 856Combined sources11
Beta strandi859 – 868Combined sources10
Beta strandi875 – 877Combined sources3
Helixi880 – 882Combined sources3
Helixi883 – 903Combined sources21
Helixi907 – 926Combined sources20
Helixi931 – 935Combined sources5
Helixi936 – 938Combined sources3
Helixi940 – 945Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6B3YX-ray1.85A/B720-973[»]
ProteinModelPortaliA2RT67
SMRiA2RT67
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 245uDENNPROSITE-ProRule annotationAdd BLAST171
Domaini268 – 400cDENNPROSITE-ProRule annotationAdd BLAST133
Domaini402 – 506dDENNPROSITE-ProRule annotationAdd BLAST105
Repeati975 – 1013WD 1Sequence analysisAdd BLAST39
Repeati1019 – 1055WD 2Sequence analysisAdd BLAST37
Repeati1059 – 1099WD 3Sequence analysisAdd BLAST41
Repeati1103 – 1140WD 4Sequence analysisAdd BLAST38
Repeati1146 – 1181WD 5Sequence analysisAdd BLAST36
Repeati1186 – 1228WD 6Sequence analysisAdd BLAST43
Repeati1234 – 1273WD 7Sequence analysisAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni520 – 970LinkerCuratedAdd BLAST451

Domaini

Inactive Dennd3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-940 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards Rab12.1 Publication

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IQM8 Eukaryota
ENOG410XTT7 LUCA
GeneTreeiENSGT00760000118819
HOGENOMiHOG000060114
HOVERGENiHBG095574
InParanoidiA2RT67
KOiK20162
OMAiRMVVSMP
OrthoDBiEOG091G0EQ9
PhylomeDBiA2RT67
TreeFamiTF331814

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR001194 cDENN_dom
IPR005112 dDENN_dom
IPR037516 Tripartite_DENN
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF02141 DENN, 1 hit
SMARTiView protein in SMART
SM00801 dDENN, 1 hit
SM00799 DENN, 1 hit
SM00320 WD40, 3 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS50211 DENN, 1 hit
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 1 hit
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

A2RT67-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEPAARHLS LPSGLLELCA LLGASQDSLR GLEQIAQKRG VKSASSLVPE
60 70 80 90 100
VLSVFVPPFT TKEDGQVPGA SCALGKGRRR SFRKKREKPR MEPWKSHPGD
110 120 130 140 150
SKGPDSEDVT IPGGVDLLAL PQLCFPGCVC VASEPKEDYI HFLVLTDVCG
160 170 180 190 200
NRTYGVVAQY YRPLHDEYCF YNGKSHWEPS VISARCFVPF AVCVVSRFPY
210 220 230 240 250
YNSLKDCLSC LLTHLKLCKD FEVDNHIKDF AARLSLIPSP PPGPLHLIFN
260 270 280 290 300
MKPLQVVFPS RADPESPIVD LDLHLPLLCF RPEKVLQILT CILTEQRIVF
310 320 330 340 350
FSSDWALLTL MAECFVAYLH PLQWQHTFVP ILSGQMLDFV MAPTSFLMGC
360 370 380 390 400
HLDHFEEVRK EADGLVLIDI DHGSVTCSKS SDDNIDIPDV PLLLAQTFIQ
410 420 430 440 450
RVQSLQLHPD LHLAHLSAST DLNEGRARRR AWQQTLNCKI QHITLQLLVG
460 470 480 490 500
IFREVKNHLN YEHRVFNSEE FLKTRAAGDQ QFYKQVLDTY MFHSFLKARL
510 520 530 540 550
NGRMDAFARM DLDTQSEEDR IDRMLISPRR PTVEKMASRK ASPLHITHRR
560 570 580 590 600
MVVSMPNLQD ISLPELPPRN SSLRIMDTSN CRSSSPVLKV TPKSTYMFKI
610 620 630 640 650
PDIHFPLESQ CVQAYYTDFV TLLSKAMALL GPGDSLLLAR YFYLRGLLHL
660 670 680 690 700
MQGQLLSALL DFQNLYKTDI GIFPADLVKR TVESMSASER AQAERTPELR
710 720 730 740 750
RLITEVFDKH GEAPKADDAV KNFELPKKHM QLNDFVKRVQ ESGIVKDAVI
760 770 780 790 800
IHRLFDALTF GHEKQIDPET FRDFYTCWKE TEAEAQEVSL PALLMEHLDK
810 820 830 840 850
NECVYKLSSS VKTNRGVGKI AMTQKRLFLL TEGRPGYVEI ATFRNIEEVK
860 870 880 890 900
NSTVAFLLLR IPTLKIKTVA KKEVFEANLK SECDLWHLMV KEMWAGKQLA
910 920 930 940 950
DDHKDPQYVQ QALTNVLLMD AVVGTLQSPS AIHAASKLAY FDNMKKKSPM
960 970 980 990 1000
AVPKTTSETL KHKINPSAGE TAPQAIEVLL YTPGRLDPAE KVEDAHPKLW
1010 1020 1030 1040 1050
CALNEGKVVV FDASSWTVHQ HCFKVGSSKV NCMVMAEHNQ VWVGSEDSVI
1060 1070 1080 1090 1100
YIINVHSMSC NKQLTDHRSP VTGLAVHNGK KPSEIYSCSL DGTVIAWNVS
1110 1120 1130 1140 1150
TLRVISRFQL SYGDLLSISL HNDRIWCCTV HKILVVTPQG FVRQELKHPK
1160 1170 1180 1190 1200
DASFLAFQLL PEEQQLWAAS TGVSELYMWS LKDLDQPPQK TYLQDCSEVT
1210 1220 1230 1240 1250
CMIRVKRQIW VGGRGLSQGK TRGKIYVMDV EKVTVEKELV AHLDTVRTLC
1260 1270
SAEDRYVLSG AGQEEGKIAI WKVE
Length:1,274
Mass (Da):143,888
Last modified:March 20, 2007 - v2
Checksum:i4C465CE967D72DB5
GO

Sequence cautioni

The sequence BAC35269 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD32324 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti126P → S in BAD32324 (PubMed:15368895).Curated1
Sequence conflicti1003L → Q in BAC35269 (PubMed:16141072).Curated1
Sequence conflicti1200T → N in BAC35269 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK173046 mRNA Translation: BAD32324.1 Different initiation.
BC132389 mRNA Translation: AAI32390.2
BC137791 mRNA Translation: AAI37792.1
AK053114 mRNA Translation: BAC35269.1 Different initiation.
CCDSiCCDS37100.1
RefSeqiNP_001074535.1, NM_001081066.1
UniGeneiMm.322557

Genome annotation databases

EnsembliENSMUST00000043414; ENSMUSP00000046774; ENSMUSG00000036661
GeneIDi105841
KEGGimmu:105841
UCSCiuc007wce.1 mouse

Similar proteinsi

Entry informationi

Entry nameiDEND3_MOUSE
AccessioniPrimary (citable) accession number: A2RT67
Secondary accession number(s): B2RQ75, Q69ZX2, Q8C6V5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 20, 2007
Last modified: April 25, 2018
This is version 99 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health