Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O08808 (DIAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein diaphanous homolog 1
Alternative name(s):
Diaphanous-related formin-1
Short name=DRF1
p140mDIA
Short name=mDIA1
Gene names
Name:Diaph1
Synonyms:Diap1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1255 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts in a Rho-dependent manner to recruit PFY1 to the membrane. Required for the assembly of F-actin structures, such as actin cables and stress fibers. Nucleates actin filaments. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Has neurite outgrowth promoting activity. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape By similarity. Ref.1 Ref.3 Ref.5 Ref.8

Subunit structure

Homodimer. Interacts with the GTP-bound form of RHOA. Interacts with RHOC, PFY1, MAPRE1, BAIAP2 and APC. Interacts with SCAI. Interacts with DCAF7, via FH2 domain By similarity. Interacts with NCDN. Ref.1 Ref.2 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.12

Subcellular location

Cell membrane. Cell projectionruffle membrane. Cytoplasmcytoskeleton. Note: Membrane ruffles, especially at the tip of ruffles, of motile cells. Ref.1

Tissue specificity

Ubiquitous.

Domain

The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments. Ref.11

Sequence similarities

Belongs to the formin homology family. Diaphanous subfamily.

Contains 1 DAD (diaphanous autoregulatory) domain.

Contains 1 FH1 (formin homology 1) domain.

Contains 1 FH2 (formin homology 2) domain.

Contains 1 GBD/FH3 (Rho GTPase-binding/formin homology 3) domain.

Ontologies

Keywords
   Biological processHearing
   Cellular componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
   DomainCoiled coil
Repeat
   LigandActin-binding
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from direct assay Ref.1. Source: MGI

actin filament polymerization

Inferred from direct assay Ref.10. Source: MGI

cellular response to histamine

Inferred from electronic annotation. Source: Ensembl

cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection development

Inferred from direct assay Ref.8. Source: UniProtKB

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

protein localization to microtubule

Inferred from electronic annotation. Source: Ensembl

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of microtubule-based process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of release of sequestered calcium ion into cytosol

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic spindle

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from direct assay Ref.8. Source: UniProtKB

ruffle membrane

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionRho GTPase binding

Inferred from direct assay Ref.1. Source: MGI

actin binding

Inferred from direct assay Ref.10. Source: MGI

identical protein binding

Inferred from physical interaction PubMed 10559899PubMed 12906795. Source: IntAct

ion channel binding

Inferred from physical interaction PubMed 15123714. Source: BHF-UCL

profilin binding

Inferred from direct assay Ref.1. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-1026445,EBI-1026445
Baiap2Q8BKX13EBI-1026445,EBI-771498
IQGAP1P469408EBI-1026445,EBI-297509From a different organism.
RHOAP615863EBI-1026445,EBI-446668From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12551255Protein diaphanous homolog 1
PRO_0000194894

Regions

Domain75 – 440366GBD/FH3
Domain586 – 747162FH1
Domain752 – 1154403FH2
Domain1177 – 120529DAD
Coiled coil460 – 562103 Potential
Coiled coil1027 – 1179153 Potential
Compositional bias1196 – 11994Arg/Lys-rich (basic)

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue221Phosphoserine By similarity
Modified residue10401N6-acetyllysine By similarity
Modified residue10861N6-acetyllysine By similarity
Modified residue11041Phosphotyrosine Ref.7
Cross-link477Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Secondary structure

................................................................................................................... 1255
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O08808 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 09404164873CA7C1

FASTA1,255139,343
        10         20         30         40         50         60 
MEPSGGGLGP GRGTRDKKKG RSPDELPATG GDGGKHKKFL ERFTSMRIKK EKEKPNSAHR 

        70         80         90        100        110        120 
NSSASYGDDP TAQSLQDISD EQVLVLFEQM LVDMNLNEEK QQPLREKDIV IKREMVSQYL 

       130        140        150        160        170        180 
HTSKAGMNQK ESSRSAMMYI QELRSGLRDM HLLSCLESLR VSLNNNPVSW VQTFGAEGLA 

       190        200        210        220        230        240 
SLLDILKRLH DEKEETSGNY DSRNQHEIIR CLKAFMNNKF GIKTMLETEE GILLLVRAMD 

       250        260        270        280        290        300 
PAVPNMMIDA AKLLSALCIL PQPEDMNERV LEAMTERAEM DEVERFQPLL DGLKSGTSIA 

       310        320        330        340        350        360 
LKVGCLQLIN ALITPAEELD FRVHIRSELM RLGLHQVLQE LREIENEDMK VQLCVFDEQG 

       370        380        390        400        410        420 
DEDFFDLKGR LDDIRMEMDD FGEVFQIILN TVKDSKAEPH FLSILQHLLL VRNDYEARPQ 

       430        440        450        460        470        480 
YYKLIEECVS QIVLHKNGTD PDFKCRHLQI DIERLVDQMI DKTKVEKSEA KATELEKKLD 

       490        500        510        520        530        540 
SELTARHELQ VEMKKMENDF EQKLQDLQGE KDALDSEKQQ ITAQKQDLEA EVSKLTGEVA 

       550        560        570        580        590        600 
KLSKELEDAK NEMASLSAVV VAPSVSSSAA VPPAPPLPGD SGTVIPPPPP PPPLPGGVVP 

       610        620        630        640        650        660 
PSPPLPPGTC IPPPPPLPGG ACIPPPPQLP GSAAIPPPPP LPGVASIPPP PPLPGATAIP 

       670        680        690        700        710        720 
PPPPLPGATA IPPPPPLPGG TGIPPPPPPL PGSVGVPPPP PLPGGPGLPP PPPPFPGAPG 

       730        740        750        760        770        780 
IPPPPPGMGV PPPPPFGFGV PAAPVLPFGL TPKKVYKPEV QLRRPNWSKF VAEDLSQDCF 

       790        800        810        820        830        840 
WTKVKEDRFE NNELFAKLTL AFSAQTKTSK AKKDQEGGEE KKSVQKKKVK ELKVLDSKTA 

       850        860        870        880        890        900 
QNLSIFLGSF RMPYQEIKNV ILEVNEAVLT ESMIQNLIKQ MPEPEQLKML SELKEEYDDL 

       910        920        930        940        950        960 
AESEQFGVVM GTVPRLRPRL NAILFKLQFS EQVENIKPEI VSVTAACEEL RKSENFSSLL 

       970        980        990       1000       1010       1020 
ELTLLVGNYM NAGSRNAGAF GFNISFLCKL RDTKSADQKM TLLHFLAELC ENDHPEVLKF 

      1030       1040       1050       1060       1070       1080 
PDELAHVEKA SRVSAENLQK SLDQMKKQIA DVERDVQNFP AATDEKDKFV EKMTSFVKDA 

      1090       1100       1110       1120       1130       1140 
QEQYNKLRMM HSNMETLYKE LGDYFVFDPK KLSVEEFFMD LHNFRNMFLQ AVKENQKRRE 

      1150       1160       1170       1180       1190       1200 
TEEKMRRAKL AKEKAEKERL EKQQKREQLI DMNAEGDETG VMDSLLEALQ SGAAFRRKRG 

      1210       1220       1230       1240       1250 
PRQVNRKAGC AVTSLLASEL TKDDAMAPGP VKVPKKSEGV PTILEEAKEL VGRAS 

« Hide

References

« Hide 'large scale' references
[1]"p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin."
Watanabe N., Madaule P., Reid T., Ishizaki T., Watanabe G., Kakizuka A., Saito Y., Nakao K., Jockusch B.M., Narumiya S.
EMBO J. 16:3044-3056(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH RHOA, SUBCELLULAR LOCATION.
[2]"Rho small G-protein-dependent binding of mDia to an Src homology 3 domain-containing IRSp53/BAIAP2."
Fujiwara T., Mammoto A., Kim Y., Takai Y.
Biochem. Biophys. Res. Commun. 271:626-629(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAIAP2.
[3]"Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling."
Tominaga T., Sahai E., Chardin P., McCormick F., Courtneidge S.A., Alberts A.S.
Mol. Cell 5:13-25(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration."
Wen Y., Eng C.H., Schmoranzer J., Cabrera-Poch N., Morris E.J.S., Chen M., Wallar B.J., Alberts A.S., Gundersen G.G.
Nat. Cell Biol. 6:820-830(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APC AND MAPRE1.
[5]"Actin polymerization-driven molecular movement of mDia1 in living cells."
Higashida C., Miyoshi T., Fujita A., Oceguera-Yanez F., Monypenny J., Andou Y., Narumiya S., Watanabe N.
Science 303:2007-2010(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACTIN.
[6]"Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[7]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1104, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[8]"Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1."
Schwaibold E.M., Brandt D.T.
Biochem. Biophys. Res. Commun. 373:366-372(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCDN.
[9]"SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin."
Brandt D.T., Baarlink C., Kitzing T.M., Kremmer E., Ivaska J., Nollau P., Grosse R.
Nat. Cell Biol. 11:557-568(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCAI.
[10]"The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization."
Shimada A., Nyitrai M., Vetter I.R., Kuehlmann D., Bugyi B., Narumiya S., Geeves M.A., Wittinghofer A.
Mol. Cell 13:511-522(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 826-1163, OLIGOMERIZATION, INTERACTION WITH ACTIN.
[11]"The regulation of mDia1 by autoinhibition and its release by Rho*GTP."
Lammers M., Rose R., Scrima A., Wittinghofer A.
EMBO J. 24:4176-4187(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 135-451 AND 1145-1200, DOMAIN DAD, AUTOINHIBITION.
[12]"Structural and mechanistic insights into the interaction between Rho and mammalian Dia."
Rose R., Weyand M., Lammers M., Ishizaki T., Ahmadian M.R., Wittinghofer A.
Nature 435:513-518(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 69-451 IN COMPLEX WITH RHOC, HOMODIMERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U96963 mRNA. Translation: AAC53280.1.
PIRT31065.
RefSeqNP_031884.1. NM_007858.2.
UniGeneMm.195916.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1V9DX-ray2.60A/B/C/D826-1163[»]
1Z2CX-ray3.00B/D69-451[»]
2BAPX-ray3.30A/B135-451[»]
C/D1145-1200[»]
2BNXX-ray2.40A/B131-516[»]
2F31X-ray2.10A135-367[»]
B1177-1196[»]
2V8FX-ray1.10C635-655[»]
3EG5X-ray2.70B/D69-451[»]
3O4XX-ray3.20A/B/C/D131-458[»]
E/F/G/H736-1200[»]
3OBVX-ray2.75A/B/C/D131-457[»]
E/F/G/H753-1209[»]
ProteinModelPortalO08808.
SMRO08808. Positions 83-457, 745-1198.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199221. 6 interactions.
DIPDIP-29028N.
IntActO08808. 13 interactions.
MINTMINT-4093098.

PTM databases

PhosphoSiteO08808.

Proteomic databases

PaxDbO08808.
PRIDEO08808.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000115634; ENSMUSP00000111297; ENSMUSG00000024456.
GeneID13367.
KEGGmmu:13367.
UCSCuc008erj.1. mouse.

Organism-specific databases

CTD13367.
MGIMGI:1194490. Diap1.

Phylogenomic databases

eggNOGNOG149898.
GeneTreeENSGT00730000110702.
HOGENOMHOG000293231.
HOVERGENHBG051357.
KOK05740.
OrthoDBEOG7G1V5D.
PhylomeDBO08808.

Gene expression databases

ArrayExpressO08808.
BgeeO08808.
CleanExMM_DIAP1.
GenevestigatorO08808.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR014767. Diaphanous_autoregulatory.
IPR010465. Drf_DAD.
IPR015425. FH2_Formin.
IPR010472. FH3_dom.
IPR027653. Formin_Diaph1.
IPR009408. Formin_homology_1.
IPR010473. GTPase-bd.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]
PANTHERPTHR23213:SF17. PTHR23213:SF17. 1 hit.
PfamPF06345. Drf_DAD. 1 hit.
PF06346. Drf_FH1. 1 hit.
PF06367. Drf_FH3. 1 hit.
PF06371. Drf_GBD. 1 hit.
PF02181. FH2. 1 hit.
[Graphical view]
SMARTSM00498. FH2. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
PROSITEPS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO08808.
NextBio283706.
PROO08808.
SOURCESearch...

Entry information

Entry nameDIAP1_MOUSE
AccessionPrimary (citable) accession number: O08808
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot