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   24-JAN-2024, entry version 137.
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   GlyGen; Q924W7; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q924W7; -.
DR   PhosphoSitePlus; Q924W7; -.
DR   jPOST; Q924W7; -.
DR   MaxQB; Q924W7; -.
DR   PaxDb; 10090-ENSMUSP00000077067; -.
DR   ProteomicsDB; 254573; -. [Q924W7-1]
DR   ProteomicsDB; 254574; -. [Q924W7-2]
DR   ProteomicsDB; 254575; -. [Q924W7-3]
DR   Pumba; Q924W7; -.
DR   Antibodypedia; 24131; 251 antibodies from 30 providers.
DR   DNASU; 76954; -.
DR   Ensembl; ENSMUST00000077909.9; ENSMUSP00000077067.2; ENSMUSG00000031024.14. [Q924W7-1]
DR   Ensembl; ENSMUST00000079282.8; ENSMUSP00000078264.2; ENSMUSG00000031024.14. [Q924W7-1]
DR   Ensembl; ENSMUST00000084738.5; ENSMUSP00000081789.4; ENSMUSG00000031024.14. [Q924W7-2]
DR   Ensembl; ENSMUST00000168005.8; ENSMUSP00000130119.2; ENSMUSG00000031024.14. [Q924W7-2]
DR   GeneID; 76954; -.
DR   KEGG; mmu:76954; -.
DR   UCSC; uc009jds.1; mouse. [Q924W7-1]
DR   UCSC; uc009jdv.1; mouse. [Q924W7-2]
DR   AGR; MGI:108517; -.
DR   CTD; 6764; -.
DR   MGI; MGI:108517; Dennd2b.
DR   VEuPathDB; HostDB:ENSMUSG00000031024; -.
DR   eggNOG; KOG3569; Eukaryota.
DR   GeneTree; ENSGT00950000182931; -.
DR   HOGENOM; CLU_008960_0_0_1; -.
DR   InParanoid; Q924W7; -.
DR   OMA; MDKRDAG; -.
DR   OrthoDB; 5398783at2759; -.
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 78 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 232 other cell types or tissues.
DR   ExpressionAtlas; Q924W7; baseline and differential.
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; 3.30.450.200; -; 1.
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   PANTHER; PTHR15288; DENN DOMAIN-CONTAINING PROTEIN 2; 1.
DR   PANTHER; PTHR15288:SF5; DENN DOMAIN-CONTAINING PROTEIN 2B; 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.
DR   Genevisible; Q924W7; MM.
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
//