DIAP3_MOUSE
ID DIAP3_MOUSE Reviewed; 1171 AA.
AC Q9Z207;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein diaphanous homolog 3;
DE AltName: Full=Diaphanous-related formin-3;
DE Short=DRF3;
DE AltName: Full=p134mDIA2;
DE Short=mDIA2 {ECO:0000303|PubMed:23558171};
GN Name=Diaph3; Synonyms=Diap3;
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 [MRNA].
RX PubMed=9535835; DOI=10.1074/jbc.273.15.8616;
RA Alberts A.S., Bouquin N., Johnston L.H., Treisman R.;
RT "Analysis of RhoA-binding proteins reveals an interaction domain conserved
RT in heterotrimeric G protein beta subunits and the yeast response regulator
RT protein Skn7.";
RL J. Biol. Chem. 273:8616-8622(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tominaga T., Sahai E., Treisman R.H., Alberts A.S.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=10678165; DOI=10.1016/s1097-2765(00)80399-8;
RA Tominaga T., Sahai E., Chardin P., McCormick F., Courtneidge S.A.,
RA Alberts A.S.;
RT "Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase
RT signaling.";
RL Mol. Cell 5:13-25(2000).
RN [4]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 18-ARG-LYS-19; 35-LYS-ARG-36;
RP 268-VAL-LYS-269; 274-VAL--VAL-277 AND LEU-1168.
RX PubMed=19117945; DOI=10.1074/jbc.m806191200;
RA Miki T., Okawa K., Sekimoto T., Yoneda Y., Watanabe S., Ishizaki T.,
RA Narumiya S.;
RT "mDia2 shuttles between the nucleus and the cytoplasm through the
RT importin-{alpha}/{beta}- and CRM1-mediated nuclear transport mechanism.";
RL J. Biol. Chem. 284:5753-5762(2009).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF MET-1041 AND
RP LEU-1168.
RX PubMed=23558171; DOI=10.1126/science.1235038;
RA Baarlink C., Wang H., Grosse R.;
RT "Nuclear actin network assembly by formins regulates the SRF coactivator
RT MAL.";
RL Science 340:864-867(2013).
RN [6]
RP UBIQUITINATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF LYS-118; LYS-119;
RP LYS-493 AND LYS-494.
RX PubMed=19457867; DOI=10.1074/jbc.m109.000885;
RA DeWard A.D., Alberts A.S.;
RT "Ubiquitin-mediated degradation of the formin mDia2 upon completion of cell
RT division.";
RL J. Biol. Chem. 284:20061-20069(2009).
CC -!- FUNCTION: Actin nucleation and elongation factor required for the
CC assembly of F-actin structures, such as actin cables and stress fibers
CC (PubMed:10678165, PubMed:23558171). Required for cytokinesis, stress
CC fiber formation and transcriptional activation of the serum response
CC factor (PubMed:10678165, PubMed:23558171). Binds to GTP-bound form of
CC Rho and to profilin: acts in a Rho-dependent manner to recruit profilin
CC to the membrane, where it promotes actin polymerization
CC (PubMed:10678165). DFR proteins couple Rho and Src tyrosine kinase
CC during signaling and the regulation of actin dynamics
CC (PubMed:10678165). Also acts as an actin nucleation and elongation
CC factor in the nucleus by promoting nuclear actin polymerization inside
CC the nucleus to drive serum-dependent SRF-MRTFA activity
CC (PubMed:23558171). {ECO:0000269|PubMed:10678165,
CC ECO:0000269|PubMed:23558171}.
CC -!- INTERACTION:
CC Q9Z207; Q8CBW3: Abi1; NbExp=2; IntAct=EBI-6550123, EBI-375511;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19117945,
CC ECO:0000269|PubMed:23558171}. Nucleus {ECO:0000269|PubMed:19117945,
CC ECO:0000269|PubMed:23558171}. Note=During mitosis, co-localizes with
CC the actin-rich cleavage furrow and with the microtubule-rich central
CC spindle during cytokinesis (By similarity). Shuttles between the
CC cytoplasm and the nucleus (PubMed:19117945).
CC {ECO:0000250|UniProtKB:Q9NSV4, ECO:0000269|PubMed:19117945}.
CC -!- DEVELOPMENTAL STAGE: Increased expression in S phase and mitotic cells;
CC levels decrease as cells enter in G0/G1 phase due to proteasomal
CC degradation (at protein level). {ECO:0000269|PubMed:19457867}.
CC -!- DOMAIN: The DAD domain regulates activation via by an autoinhibitory
CC interaction with the GBD/FH3 domain (PubMed:23558171). This
CC autoinhibition is released upon competitive binding of an activated
CC GTPase (PubMed:23558171). The release of DAD allows the FH2 domain to
CC then nucleate and elongate nonbranched actin filaments
CC (PubMed:23558171). {ECO:0000269|PubMed:23558171}.
CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:19457867}.
CC -!- SIMILARITY: Belongs to the formin homology family. Diaphanous
CC subfamily. {ECO:0000305}.
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DR EMBL; AF094519; AAC71771.1; -; mRNA.
DR CCDS; CCDS36990.1; -.
DR PIR; T17454; T17454.
DR RefSeq; NP_062644.1; NM_019670.1.
DR AlphaFoldDB; Q9Z207; -.
DR SMR; Q9Z207; -.
DR BioGRID; 207965; 16.
DR CORUM; Q9Z207; -.
DR DIP; DIP-29533N; -.
DR IntAct; Q9Z207; 5.
DR MINT; Q9Z207; -.
DR STRING; 10090.ENSMUSP00000022599; -.
DR iPTMnet; Q9Z207; -.
DR PhosphoSitePlus; Q9Z207; -.
DR EPD; Q9Z207; -.
DR MaxQB; Q9Z207; -.
DR PaxDb; Q9Z207; -.
DR PRIDE; Q9Z207; -.
DR ProteomicsDB; 279659; -.
DR Antibodypedia; 24286; 270 antibodies from 30 providers.
DR DNASU; 56419; -.
DR Ensembl; ENSMUST00000168889; ENSMUSP00000129420; ENSMUSG00000022021.
DR GeneID; 56419; -.
DR KEGG; mmu:56419; -.
DR UCSC; uc007uub.1; mouse.
DR CTD; 81624; -.
DR MGI; MGI:1927222; Diaph3.
DR VEuPathDB; HostDB:ENSMUSG00000022021; -.
DR eggNOG; KOG1924; Eukaryota.
DR GeneTree; ENSGT00940000157767; -.
DR InParanoid; Q9Z207; -.
DR OMA; WEVKNPM; -.
DR OrthoDB; 1204639at2759; -.
DR PhylomeDB; Q9Z207; -.
DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9035034; RHOF GTPase cycle.
DR BioGRID-ORCS; 56419; 2 hits in 41 CRISPR screens.
DR ChiTaRS; Diaph3; mouse.
DR PRO; PR:Q9Z207; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z207; protein.
DR Bgee; ENSMUSG00000022021; Expressed in blood and 161 other tissues.
DR ExpressionAtlas; Q9Z207; baseline and differential.
DR Genevisible; Q9Z207; MM.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0030041; P:actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR Gene3D; 1.10.20.40; -; 1.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014767; DAD_dom.
DR InterPro; IPR044933; DIA_GBD_sf.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR010472; FH3_dom.
DR InterPro; IPR027654; Formin_DIAPH3.
DR InterPro; IPR014768; GBD/FH3_dom.
DR InterPro; IPR010473; GTPase-bd.
DR PANTHER; PTHR45691:SF9; PTHR45691:SF9; 1.
DR Pfam; PF06367; Drf_FH3; 1.
DR Pfam; PF06371; Drf_GBD; 1.
DR Pfam; PF02181; FH2; 1.
DR SMART; SM01139; Drf_FH3; 1.
DR SMART; SM01140; Drf_GBD; 1.
DR SMART; SM00498; FH2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51231; DAD; 1.
DR PROSITE; PS51444; FH2; 1.
DR PROSITE; PS51232; GBD_FH3; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..1171
FT /note="Protein diaphanous homolog 3"
FT /id="PRO_0000194898"
FT DOMAIN 93..455
FT /note="GBD/FH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT DOMAIN 540..610
FT /note="FH1"
FT DOMAIN 615..1013
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT DOMAIN 1036..1066
FT /note="DAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 60..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 532..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 373..403
FT /evidence="ECO:0000255"
FT COILED 478..533
FT /evidence="ECO:0000255"
FT COILED 887..918
FT /evidence="ECO:0000255"
FT COILED 988..1038
FT /evidence="ECO:0000255"
FT MOTIF 16..39
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:19117945"
FT MOTIF 1162..1171
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:19117945"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..599
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 47
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MOD_RES 1072
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MOD_RES 1157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSV4"
FT MUTAGEN 18..19
FT /note="RK->AA: Decreased accumulation in the nucleus."
FT /evidence="ECO:0000269|PubMed:19117945"
FT MUTAGEN 35..36
FT /note="KR->AA: Abolished accumulation in the nucleus."
FT /evidence="ECO:0000269|PubMed:19117945"
FT MUTAGEN 118
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-119, R-493 and R-494."
FT /evidence="ECO:0000269|PubMed:19457867"
FT MUTAGEN 119
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-118, R-493 and R-494."
FT /evidence="ECO:0000269|PubMed:19457867"
FT MUTAGEN 268..269
FT /note="VK->AA: Does not affect subcellular location."
FT /evidence="ECO:0000269|PubMed:19117945"
FT MUTAGEN 274..277
FT /note="VCIV->ACIA: Does not affect subcellular location."
FT /evidence="ECO:0000269|PubMed:19117945"
FT MUTAGEN 493
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-118, R-119 and R-494."
FT /evidence="ECO:0000269|PubMed:19457867"
FT MUTAGEN 494
FT /note="K->R: No loss of ubiquitination; when associated
FT with R-118, R-119 and R-493."
FT /evidence="ECO:0000269|PubMed:19457867"
FT MUTAGEN 1041
FT /note="M->A: Impaired ability to release autoinhibition,
FT leading to defects in actin nucleation and elongation
FT factor activity in the nucleus."
FT /evidence="ECO:0000269|PubMed:23558171"
FT MUTAGEN 1168
FT /note="L->G: Accumulation in the nucleus due to defects in
FT nuclear export."
FT /evidence="ECO:0000269|PubMed:19117945,
FT ECO:0000269|PubMed:23558171"
SQ SEQUENCE 1171 AA; 133686 MW; 95347A854CABC7CF CRC64;
MERHRARALG RDSKSSRRKG LQSAPPAGPY EPGEKRPKLH LNIRTLTDDM LDKFASIRIP
GSKKERPPLP HLKTVSGISD SSSLSSETME NNPKALPESE VLKLFEKMME DMNLNEDKKA
PLREKDFGIK KEMVMQYINT ASKTGSLRSS RQISPQEFLH ELKMGYTDER LFTYLESLRV
SLTSHPVSWV QSFGHEGLGL LLDILEKLIN GQIQEKVVKK TQHKVIQCLR ALMNTQYGLE
RIMSDKRSLS LLAKAMDPRQ PAMMADVVKL LSAVCIVGEE SILEEVLEAL TSAGEERKID
RFFSIVEGLR HNSVNLQVAC MQLINALVTS PDDLDFRLHL RNEFMRCGLK EILPNLKGIK
NDGLDIQLKV FDEHKEEDLS EFFHRLEDIR AELDEASDVY SMLWDTVKET RAEGHFLSIL
QHLLLIRNDR FIREQYFKLI DECVSQIVLH RDGTDPDFTY RKRLDLDLSQ FVDVCIDQAK
LDEWEEKASE HCKKFEKECT DHQETQAQLQ KREAKINELQ AELQAFKSQF GALPPGTKIP
LQPSVEGEAG PSALPPAPPA LSGGVPPPPP PPPPPPPPLP GMPMPFGGPV PPPPPLGFLG
GQSSIPLNLP FGLKPKKEFK PEISMRRLNW LKIGPNEMSE NCFWIKVNEN KYENRDLLCK
LENTFCCQEK EKRNTNDFDE KKVIKKRMKE LKFLDPKIAQ NLSIFLSSFR VPYEKIRTMI
LEVDETQLSE SMIQNLIKHL PDEEQLKSLS QFRSDYNSLC EPEQFAVVMS NVKRLRPRLS
AILFKLQFEE QVNNIKPDIM AVSTACEEIK KSKGFSKLLE LVLLMGNYMN AGSRNAQTFG
FDLSSLCKLK DTKSADQKTT LLHFLVDVCE EKHADILHFV DDLAHLDKAS RVSVEMLEKN
VKQMGRQLQQ LEKNLETFPP PEDLHDKFVI KMSSFVISAN EQYEKLSTLL GSMTQLYQSI
MGYYAVDMKK VSVEEFFNDL NNFRTSFMLA LKENIKKREA AEKEKRARIA KERAEKERLE
RQQEKKRLLE MKTEGDETGV MDSLLEALQS GAAFRDRRKR TPKLKDIRQS LSPMSQRPVL
KVCNHENQKM QLTEGSRPHH SINCNSTRTP VAKELNYNLD THASTGRIKA VEKEACNAES
NKKKEMELLG SVAKSESVPE VEALLARLRA L
