DEN2B_MOUSE
ID DEN2B_MOUSE Reviewed; 1134 AA.
AC Q924W7; Q05BD9; Q78H54; Q8K2P3; Q924W8;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=DENN domain-containing protein 2B;
DE AltName: Full=HeLa tumor suppression 1;
DE AltName: Full=Suppression of tumorigenicity 5 protein;
GN Name=Dennd2b; Synonyms=Denn2b {ECO:0000312|MGI:MGI:108517}, St5;
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 [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=11528127; DOI=10.1159/000056999;
RA Amid C., Bahr A., Mujica A., Sampson N., Bikar S.E., Winterpacht A.,
RA Zabel B., Hankeln T., Schmidt E.R.;
RT "Comparative genomic sequencing reveals a strikingly similar architecture
RT of a conserved syntenic region on human chromosome 11p15.3 (including gene
RT ST5) and mouse chromosome 7.";
RL Cytogenet. Cell Genet. 93:284-290(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=FVB/N; TISSUE=Colon, and 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; THR-228; SER-230;
RP THR-479; SER-542 AND SER-571, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, and Spleen;
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).
CC -!- FUNCTION: [Isoform 1]: May be involved in cytoskeletal organization and
CC tumorogenicity. Seems to be involved in a signaling transduction
CC pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR
CC trafficking from recycling endosomes back to the cell membrane.
CC {ECO:0000250|UniProtKB:P78524}.
CC -!- FUNCTION: [Isoform 2]: Guanine nucleotide exchange factor (GEF) which
CC may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP,
CC converting inactive GDP-bound Rab proteins into their active GTP-bound
CC form. {ECO:0000250|UniProtKB:P78524}.
CC -!- FUNCTION: [Isoform 3]: May block ERK2 activation stimulated by ABL1.
CC May alter cell morphology and cell growth.
CC {ECO:0000250|UniProtKB:P78524}.
CC -!- SUBUNIT: Interacts with ITSN1 and GRB2. Isoform 1 interacts with the
CC SH3 domain of ABL1. {ECO:0000250|UniProtKB:P78524}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:P78524}. Cell membrane
CC {ECO:0000250|UniProtKB:P78524}. Recycling endosome
CC {ECO:0000250|UniProtKB:P78524}. Note=Colocalizes with RAB13 and ITSN1
CC at cytoplasmic vesicles that are most likely recycling endosomes.
CC Colocalizes with the cortical actin cytoskeleton.
CC {ECO:0000250|UniProtKB:P78524}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q924W7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q924W7-2; Sequence=VSP_019990;
CC Name=3;
CC IsoId=Q924W7-3; Sequence=VSP_019989;
CC -!- PTM: Phosphorylated. Phosphorylation decreases ITSN1 binding.
CC {ECO:0000250|UniProtKB:P78524}.
CC -!- MISCELLANEOUS: [Isoform 1]: May be produced by alternative promoter
CC usage. Alternative promoter usage has been proven in human.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced by alternative promoter
CC usage. Alternative promoter usage has been proven in human.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32266.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ307670; CAC38111.1; -; Genomic_DNA.
DR EMBL; AJ307670; CAC38112.1; -; Genomic_DNA.
DR EMBL; BC030391; AAH30391.1; -; mRNA.
DR EMBL; BC032266; AAH32266.1; ALT_INIT; mRNA.
DR EMBL; BC051034; AAH51034.1; -; mRNA.
DR CCDS; CCDS21734.1; -. [Q924W7-1]
DR CCDS; CCDS21735.1; -. [Q924W7-2]
DR RefSeq; NP_001001326.1; NM_001001326.1. [Q924W7-1]
DR RefSeq; NP_084087.2; NM_029811.2. [Q924W7-2]
DR RefSeq; XP_006508383.1; XM_006508320.3. [Q924W7-1]
DR AlphaFoldDB; Q924W7; -.
DR SMR; Q924W7; -.
DR BioGRID; 218424; 6.
DR IntAct; Q924W7; 1.
DR MINT; Q924W7; -.
DR STRING; 10090.ENSMUSP00000077067; -.
DR iPTMnet; Q924W7; -.
DR PhosphoSitePlus; Q924W7; -.
DR jPOST; Q924W7; -.
DR MaxQB; Q924W7; -.
DR PaxDb; Q924W7; -.
DR PRIDE; Q924W7; -.
DR ProteomicsDB; 254573; -. [Q924W7-1]
DR ProteomicsDB; 254574; -. [Q924W7-2]
DR ProteomicsDB; 254575; -. [Q924W7-3]
DR Antibodypedia; 24131; 217 antibodies from 30 providers.
DR DNASU; 76954; -.
DR Ensembl; ENSMUST00000077909; ENSMUSP00000077067; ENSMUSG00000031024. [Q924W7-1]
DR Ensembl; ENSMUST00000079282; ENSMUSP00000078264; ENSMUSG00000031024. [Q924W7-1]
DR Ensembl; ENSMUST00000084738; ENSMUSP00000081789; ENSMUSG00000031024. [Q924W7-2]
DR Ensembl; ENSMUST00000168005; ENSMUSP00000130119; ENSMUSG00000031024. [Q924W7-2]
DR GeneID; 76954; -.
DR KEGG; mmu:76954; -.
DR UCSC; uc009jds.1; mouse. [Q924W7-1]
DR UCSC; uc009jdv.1; mouse. [Q924W7-2]
DR CTD; 76954; -.
DR MGI; MGI:108517; Denn2b.
DR VEuPathDB; HostDB:ENSMUSG00000031024; -.
DR eggNOG; KOG3569; Eukaryota.
DR GeneTree; ENSGT00950000182931; -.
DR HOGENOM; CLU_008960_0_0_1; -.
DR InParanoid; Q924W7; -.
DR OMA; SHVRKES; -.
DR OrthoDB; 138384at2759; -.
DR PhylomeDB; Q924W7; -.
DR TreeFam; TF320336; -.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 76954; 1 hit in 73 CRISPR screens.
DR ChiTaRS; St5; mouse.
DR PRO; PR:Q924W7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q924W7; protein.
DR Bgee; ENSMUSG00000031024; Expressed in ascending aorta and 229 other tissues.
DR ExpressionAtlas; Q924W7; baseline and differential.
DR Genevisible; Q924W7; MM.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO: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; IPR037516; Tripartite_DENN.
DR InterPro; IPR005113; uDENN_dom.
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 Alternative promoter usage; Alternative splicing; Cell membrane; Cytoplasm;
KW Endosome; Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1134
FT /note="DENN domain-containing protein 2B"
FT /id="PRO_0000247449"
FT DOMAIN 695..843
FT /note="uDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 865..998
FT /note="cDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT DOMAIN 1000..1093
FT /note="dDENN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304"
FT REGION 1..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 633..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..268
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..427
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..478
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 497..511
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..554
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 555..571
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 644..658
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78524"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 228
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 361
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P78524"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78524"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P78524"
FT VAR_SEQ 1..525
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019989"
FT VAR_SEQ 28..444
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_019990"
SQ SEQUENCE 1134 AA; 126861 MW; 36F8404D63818579 CRC64;
MTMTANKNSS ITHGTGGTKA PRETLSRSQS VSPPPVLYPP RSPIYPLSDS ETSACRYPSH
SKSQVLLKDR HSRNPSLLGQ DPSPETSPPI CTLKATSFSY LDRTPSLRKR EDQKETVQGA
VQDVEGVAAC LPLAQSTPFL GAGSRSVLLS CTGTRAHSLG IREKISAWEG RREASPRMSL
CGEKREGPGS EWSVSEGCPS VGCPSVVPSP CSSEKTFDFK GLRRMSRTFS ECSYPETEEE
AEALPGRDSL YRLEKRPGRT EPSALLRGHG IRKESSAVLS RIQKIEQALK EQPGRGLPQL
PSSCYSVDQG RRKTGTLGTL EEPTGTASVS PSSRAGGVAG VAGEAGPPLD REGSASMKSE
TPGNSSSPQL LPPKSSPDPA VNPVPKPKRT FEYEADKNPK TKPSNGLPPS PTPAAPPPLP
STPAPPVTRR PKKDMRGHRK SQNRKSFEFE DASSLQSLYP SSPTENGTES QPKFGSKSTL
EENAYEDIVG GLPKENPYED VDLKNRRAGR KSQQLSENSL DSLHRMWSPQ DRKYNHPPMQ
LSLKSNSQSL RSGNWSERKS HRLPRLPKRH SHDDMMLLAQ LSLPSSPSSL NEDSLSTTSE
LLSSRRSRRI PKLVQRINSI YNAKRGKKRL KKLSMSSLET ASLRDENSES ESDSDDRFKA
HTQRLVHIQS MLKRAPSYRT LELELLEWQE RELFEYFVVV SLKKKPSRNT YLPEVSYQFP
KLDRPTKQMR EAEERLKAIP QFCFPDAKDW LPVSEYSSET FSFMLTGEDG SRRFGYCRRL
LPSGKGPRLP EVYCVISRLG CFGLFSKVLD EVERRRGISA ALVYPFMRSL MESPFPAPGK
TIKVKTFLPG AGNEVLELRR PMDSRLEHVD FECLFTCLSV RQLIRIFASL LLERRVIFVA
DKLSTLSSCS HAVVALLYPF SWQHTFIPVL PASMIDIVCC PTPFLVGLLS SSLPKLKELP
VEEALMVNLG SDRFIRQMDD EDTLLPRKLQ AALEQALERK SELISQDSDS DSDDECNTLN
GLVSEVFIRF FVETVGHYSL FLTHSEKGER AFQREAFRKS VASKSIRRFL EVFMESQMFA
GFIQDRELRK CRAKGLFEQR VEQYLEELPD TEQSGMNKFL RGLGNKMKFL HKKN
