O08808 (DIAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1255 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7
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.7 Ref.8 Ref.9 Ref.11
Subcellular location	Cell membrane. Cell projection › ruffle membrane. Cytoplasm › cytoskeleton. 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.10
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 process	Hearing
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Domain	Coiled coil Repeat
Ligand	Actin-binding
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin filament polymerization Inferred from direct assay Ref.9. Source: MGI cellular response to histamine Inferred from electronic annotation. Source: Compara neuron projection development Inferred from direct assay Ref.7. Source: UniProtKB protein localization to microtubule Inferred from electronic annotation. Source: Compara 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: Compara sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle Inferred from electronic annotation. Source: Compara neuron projection Inferred from direct assay Ref.7. Source: UniProtKB ruffle membrane Inferred from direct assay Ref.1. Source: MGI
Molecular_function	Rho GTPase binding Inferred from direct assay Ref.1. Source: MGI actin binding Inferred from direct assay Ref.9. Source: MGI profilin binding Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-1026445,EBI-1026445
Baiap2	Q8BKX1	3	EBI-1026445,EBI-771498
IQGAP1	P46940	8	EBI-1026445,EBI-297509	From a different organism.
RHOA	P61586	3	EBI-1026445,EBI-446668	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1255

1255

Protein diaphanous homolog 1

PRO_0000194894

Regions

Domain

75 – 440

366

GBD/FH3

Domain

586 – 747

162

FH1

Domain

752 – 1154

403

FH2

Domain

1177 – 1205

29

DAD

Coiled coil

460 – 562

103

Potential

Coiled coil

1027 – 1179

153

Potential

Compositional bias

1196 – 1199

4

Arg/Lys-rich (basic)

Amino acid modifications

Modified residue

22

1

Phosphoserine By similarity

Modified residue

1040

1

N6-acetyllysine By similarity

Modified residue

1086

1

N6-acetyllysine By similarity

Modified residue

1104

1

Phosphotyrosine Ref.6

Cross-link

477

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Secondary structure

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1255

Helix Strand Turn

Details...

Helix

85 – 93

9

Helix

98 – 105

8

Helix

109 – 122

14

Helix

136 – 143

8

Turn

144 – 146

3

Helix

149 – 165

17

Helix

168 – 190

23

Turn

194 – 196

3

Helix

201 – 215

15

Helix

219 – 227

9

Beta strand

228 – 230

3

Helix

231 – 237

7

Helix

244 – 258

15

Helix

266 – 281

16

Helix

287 – 292

6

Helix

299 – 313

15

Helix

319 – 331

13

Helix

334 – 341

8

Helix

347 – 377

31

Helix

381 – 392

12

Helix

397 – 408

12

Turn

415 – 417

3

Helix

418 – 433

16

Helix

436 – 438

3

Turn

453 – 455

3

Helix

464 – 469

6

Turn

470 – 472

3

Beta strand

833 – 835

3

Helix

837 – 850

14

Helix

854 – 863

10

Turn

866 – 868

3

Helix

871 – 880

10

Helix

884 – 891

8

Helix

894 – 899

6

Helix

902 – 911

10

Helix

916 – 934

19

Helix

937 – 951

15

Helix

954 – 958

5

Helix

987 – 992

6

Helix

1002 – 1012

11

Helix

1020 – 1023

4

Helix

1027 – 1032

6

Helix

1035 – 1057

23

Beta strand

1063 – 1066

4

Helix

1069 – 1104

36

Turn

1109 – 1111

3

Helix

1114 – 1159

46

Sequences

	Sequence		Length	Mass (Da)
	O08808 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 09404164873CA7C1	FASTA	1,255	139,343
	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

References

	« Hide 'large scale' referencesShow '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]	"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, MASS SPECTROMETRY. Tissue: Mast cell.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.

IPI

IPI00808370.

PIR

T31065.

RefSeq

NP_031884.1. NM_007858.2.

UniGene

Mm.195916.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1V9D	X-ray	2.60	A/B/C/D	826-1163	[»]
1Z2C	X-ray	3.00	B/D	69-451	[»]
2BAP	X-ray	3.30	A/B	135-451	[»]
			C/D	1145-1200	[»]
2BNX	X-ray	2.40	A/B	131-516	[»]
2F31	X-ray	2.10	A	135-367	[»]
			B	1177-1196	[»]
2V8F	X-ray	1.10	C	635-655	[»]
3EG5	X-ray	2.70	B/D	69-451	[»]
3O4X	X-ray	3.20	A/B/C/D	131-458	[»]
			E/F/G/H	736-1200	[»]
3OBV	X-ray	2.75	A/B/C/D	131-457	[»]
			E/F/G/H	753-1209	[»]

ProteinModelPortal

O08808.

SMR

O08808. Positions 83-457, 745-1198.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29028N.

IntAct

O08808. 9 interactions.

PTM databases

PhosphoSite

O08808.

Proteomic databases

PaxDb

O08808.

PRIDE

O08808.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000115634; ENSMUSP00000111297; ENSMUSG00000024456.

GeneID

13367.

KEGG

mmu:13367.

UCSC

uc008erj.1. mouse.

Organism-specific databases

CTD

13367.

MGI

MGI:1194490. Diap1.

Phylogenomic databases

eggNOG

NOG149898.

GeneTree

ENSGT00700000104080.

HOGENOM

HOG000293231.

HOVERGEN

HBG051357.

KO

K05740.

OrthoDB

EOG4VQ9NP.

Gene expression databases

ArrayExpress

O08808.

Bgee

O08808.

CleanEx

MM_DIAP1.

Genevestigator

O08808.

GermOnline

ENSMUSG00000024456. Mus musculus.

Family and domain databases

InterPro

IPR003104. Actin-bd_FH2/DRF_autoreg.
IPR016024. ARM-type_fold.
IPR014767. Diaphanous_autoregulatory.
IPR010465. Drf_DAD.
IPR010472. Drf_FH3.
IPR010473. Drf_GTPase-bd.
IPR015425. FH2_actin-bd.
IPR009408. Formin_homology_1.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]

Pfam

PF06345. 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]

SMART

SM00498. FH2. 1 hit.
[Graphical view]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF101447. FH2_actin_bd. 1 hit.

PROSITE

PS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O08808.

NextBio

283706.

SOURCE

Search...

Entry information

Entry name

DIAP1_MOUSE

Accession

Primary (citable) accession number: O08808

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program