Q9Y613 (FHOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
FH1/FH2 domain-containing protein 1

Alternative name(s):
Formin homolog overexpressed in spleen 1
Short name=FHOS
Formin homology 2 domain-containing protein 1

Gene names

Name:	FHOD1
Synonyms:	FHOS, FHOS1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1164 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing. Ref.2 Ref.8 Ref.9
Subunit structure	Self-associates via the FH2 domain. Binds to F-actin via its N-terminus. Binds to the cytoplasmic domain of CD21 via its C-terminus. Interacts with ROCK1 in a Src-dependent manner. Ref.2 Ref.3 Ref.9
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Cell projection › bleb. Note: Predominantly cytoplasmic. Ref.8 Ref.9
Tissue specificity	Ubiquitous. Highly expressed in spleen.
Domain	Regulated by intramolecular binding to a C-terminal auto-inhibitory domain. Effector binding abolishes this interaction and activates the protein.
Post-translational modification	Phosphorylated by ROCK1. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the formin homology family. 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
Cellular component	Cell projection Cytoplasm Cytoskeleton
Domain	Coiled coil
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	actin cytoskeleton organization Inferred from electronic annotation. Source: InterPro positive regulation of stress fiber assembly Inferred from direct assay. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL
Cellular component	bleb Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: HPA cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: BHF-UCL
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 1164

1163

FH1/FH2 domain-containing protein 1

PRO_0000194905

Regions

Domain

53 – 458

406

GBD/FH3

Domain

487 – 615

129

FH1

Domain

616 – 1013

398

FH2

Region

612 – 807

196

Interaction with ROCK1

Coiled coil

884 – 921

38

Potential

Compositional bias

583 – 593

11

Poly-Pro

Compositional bias

597 – 605

9

Poly-Pro

Compositional bias

996 – 1001

6

Poly-Gln

Amino acid modifications

Modified residue

367

1

Phosphoserine Ref.7 Ref.12 Ref.13

Modified residue

486

1

Phosphoserine Ref.12

Modified residue

495

1

Phosphothreonine Ref.10 Ref.12 Ref.13

Modified residue

498

1

Phosphoserine Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Modified residue

523

1

Phosphoserine Ref.10 Ref.12 Ref.13 Ref.14

Modified residue

573

1

Phosphoserine Ref.12

Modified residue

690

1

Phosphothreonine Ref.13

Experimental info

Sequence conflict

249

1

S → T in AAD39906. Ref.1

Sequence conflict

249

1

S → T in AAO38757. Ref.3

Sequence conflict

264

1

E → D in AAO38757. Ref.3

Sequence conflict

277

1

T → M in BAD06250. Ref.2

Sequence conflict

307 – 308

2

EA → DT in AAD39906. Ref.1

Sequence conflict

307 – 308

2

EA → DT in AAO38757. Ref.3

Sequence conflict

359

1

E → D in AAO38757. Ref.3

Sequence conflict

387

1

S → T in AAO38757. Ref.3

Sequence conflict

533

1

P → L in BAD92821. Ref.6

Sequence conflict

633 – 634

2

EL → DV in AAD39906. Ref.1

Sequence conflict

689

1

R → Q in AAO38757. Ref.3

Sequence conflict

700

1

S → T in AAD39906. Ref.1

Sequence conflict

745

1

E → G in AAO38757. Ref.3

Sequence conflict

751

1

E → G in AAD39906. Ref.1

Sequence conflict

849

1

E → D in AAD39906. Ref.1

Sequence conflict

1061

1

P → L in AAD39906. Ref.1

Sequence conflict

1061

1

P → L in AAO38757. Ref.3

Secondary structure

1

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1164

Helix Strand Turn

Details...

Beta strand

16 – 22

7

Beta strand

36 – 39

4

Beta strand

42 – 45

4

Helix

55 – 61

7

Beta strand

68 – 76

9

Turn

88 – 93

6

Turn

99 – 103

5

Beta strand

109 – 114

6

Helix

116 – 129

14

Helix

134 – 147

14

Helix

152 – 158

7

Helix

163 – 167

5

Helix

174 – 183

10

Helix

187 – 189

3

Helix

201 – 209

9

Helix

210 – 212

3

Helix

216 – 232

17

Helix

234 – 236

3

Helix

237 – 250

14

Helix

257 – 263

7

Helix

271 – 287

17

Helix

291 – 303

13

Helix

307 – 313

7

Helix

321 – 337

17

Sequences

	Sequence		Length	Mass (Da)
	Q9Y613 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E6C7AE1FB8DC3FC7	FASTA	1,164	126,551
	10 20 30 40 50 60 MAGGEDRGDG EPVSVVTVRV QYLEDTDPFA CANFPEPRRA PTCSLDGALP LGAQIPAVHR 70 80 90 100 110 120 LLGAPLKLED CALQVSPSGY YLDTELSLEE QREMLEGFYE EISKGRKPTL ILRTQLSVRV 130 140 150 160 170 180 NAILEKLYSS SGPELRRSLF SLKQIFQEDK DLVPEFVHSE GLSCLIRVGA AADHNYQSYI 190 200 210 220 230 240 LRALGQLMLF VDGMLGVVAH SDTIQWLYTL CASLSRLVVK TALKLLLVFV EYSENNAPLF 250 260 270 280 290 300 IRAVNSVAST TGAPPWANLV SILEEKNGAD PELLVYTVTL INKTLAALPD QDSFYDVTDA 310 320 330 340 350 360 LEQQGMEALV QRHLGTAGTD VDLRTQLVLY ENALKLEDGD IEEAPGAGGR RERRKPSSEE 370 380 390 400 410 420 GKRSRRSLEG GGCPARAPEP GPTGPASPVG PTSSTGPALL TGPASSPVGP PSGLQASVNL 430 440 450 460 470 480 FPTISVAPSA DTSSERSIYK ARFLENVAAA ETEKQVALAQ GRAETLAGAM PNEAGGHPDA 490 500 510 520 530 540 RQLWDSPETA PAARTPQSPA PCVLLRAQRS LAPEPKEPLI PASPKAEPIW ELPTRAPRLS 550 560 570 580 590 600 IGDLDFSDLG EDEDQDMLNV ESVEAGKDIP APSPPLPLLS GVPPPPPLPP PPPIKGPFPP 610 620 630 640 650 660 PPPLPLAAPL PHSVPDSSAL PTKRKTVKLF WRELKLAGGH GVSASRFGPC ATLWASLDPV 670 680 690 700 710 720 SVDTARLEHL FESRAKEVLP SKKAGEGRRT MTTVLDPKRS NAINIGLTTL PPVHVIKAAL 730 740 750 760 770 780 LNFDEFAVSK DGIEKLLTMM PTEEERQKIE EAQLANPDIP LGPAENFLMT LASIGGLAAR 790 800 810 820 830 840 LQLWAFKLDY DSMEREIAEP LFDLKVGMEQ LVQNATFRCI LATLLAVGNF LNGSQSSGFE 850 860 870 880 890 900 LSYLEKVSEV KDTVRRQSLL HHLCSLVLQT RPESSDLYSE IPALTRCAKV DFEQLTENLG 910 920 930 940 950 960 QLERRSRAAE ESLRSLAKHE LAPALRARLT HFLDQCARRV AMLRIVHRRV CNRFHAFLLY 970 980 990 1000 1010 1020 LGYTPQAARE VRIMQFCHTL REFALEYRTC RERVLQQQQK QATYRERNKT RGRMITETEK 1030 1040 1050 1060 1070 1080 FSGVAGEAPS NPSVPVAVSS GPGRGDADSH ASMKSLLTSR PEDTTHNRRS RGMVQSSSPI 1090 1100 1110 1120 1130 1140 MPTVGPSTAS PEEPPGSSLP SDTSDEIMDL LVQSVTKSSP RALAARERKR SRGNRKSLRR 1150 1160 TLKSGLGDDL VQALGLSKGP GLEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a protein containing formin homology (FH1/FH2) domains." Westendorf J.J., Mernaugh R., Hiebert S.W. Gene 232:173-182(1999) [PubMed: 10352228] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation." Takeya R., Sumimoto H. J. Cell Sci. 116:4567-4575(2003) [PubMed: 14576350] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT.
[3]	"EBV attachment stimulates FHOS/FHOD1 redistribution and co-aggregation with CD21: formin interactions with the cytoplasmic domain of human CD21." Gill M.B., Roecklein-Canfield J., Sage D.R., Zambela-Soediono M., Longtine N., Uknis M., Fingeroth J.D. J. Cell Sci. 117:2709-2720(2004) [PubMed: 15138285] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[5]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-19. Tissue: Platelet.
[6]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 148-1164. Tissue: Spleen.
[7]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"FHOD1 coordinates actin filament and microtubule alignment to mediate cell elongation." Gasteier J.E., Schroeder S., Muranyi W., Madrid R., Benichou S., Fackler O.T. Exp. Cell Res. 306:192-202(2005) [PubMed: 15878344] [Abstract] Cited for: FUNCTION, AUTOINHIBITION, SUBCELLULAR LOCATION.
[9]	"The diaphanous-related formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing." Hannemann S., Madrid R., Stastna J., Kitzing T., Gasteier J., Schoenichen A., Bouchet J., Jimenez A., Geyer M., Grosse R., Benichou S., Fackler O.T. J. Biol. Chem. 283:27891-27903(2008) [PubMed: 18694941] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ROCK1, PHOSPHORYLATION.
[10]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-495; SER-498 AND SER-523, MASS SPECTROMETRY. Tissue: Platelet.
[11]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-486; THR-495; SER-498; SER-523 AND SER-573, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; THR-495; SER-498; SER-523 AND THR-690, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498 AND SER-523, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF113615 mRNA. Translation: AAD39906.1.
AB041046 mRNA. Translation: BAD06250.1.
AY192154 mRNA. Translation: AAO38757.1.
BC033084 mRNA. Translation: AAH33084.1.
AB209584 mRNA. Translation: BAD92821.1.

IPI

IPI00001730.

RefSeq

NP_037373.2. NM_013241.2.

UniGene

Hs.95231.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DAD	X-ray	2.30	A/B	1-339	[»]

ProteinModelPortal

Q9Y613.

SMR

Q9Y613. Positions 14-339.

DisProt

DP00448.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31134N.

IntAct

Q9Y613. 11 interactions.

MINT

MINT-1033686.

STRING

Q9Y613.

PTM databases

PhosphoSite

Q9Y613.

Polymorphism databases

DMDM

62512187.

Proteomic databases

PeptideAtlas

Q9Y613.

PRIDE

Q9Y613.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258201; ENSP00000258201; ENSG00000135723.

GeneID

29109.

KEGG

hsa:29109.

UCSC

uc002esl.1. human.

Organism-specific databases

CTD

29109.

GeneCards

GC16M067263.

H-InvDB

HIX0013142.

HGNC

HGNC:17905. FHOD1.

HPA

HPA024468.

MIM

606881. gene.

neXtProt

NX_Q9Y613.

PharmGKB

PA28143.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10799.

GeneTree

ENSGT00560000076948.

HOGENOM

HBG446794.

HOVERGEN

HBG051615.

InParanoid

Q9Y613.

OMA

QLMLFVD.

OrthoDB

EOG4Q58NW.

PhylomeDB

Q9Y613.

Gene expression databases

ArrayExpress

Q9Y613.

Bgee

Q9Y613.

CleanEx

HS_FHOD1.

Genevestigator

Q9Y613.

GermOnline

ENSG00000135723. Homo sapiens.

Family and domain databases

InterPro

IPR003104. Actin-bd_FH2/DRF_autoreg.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR015425. FH2_actin-bd.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]

Gene3D

G3DSA:1.25.10.10. ARM-like. 1 hit.

Pfam

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

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

ProtoNet

Search...

Other

NextBio

52175.

SOURCE

Search...

Entry information

Entry name

FHOD1_HUMAN

Accession

Primary (citable) accession number: Q9Y613
Secondary accession number(s): Q59F76 , Q6Y1F2, Q76MS8, Q8N521

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.