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Q2V2M9 (FHOD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
FH1/FH2 domain-containing protein 3
Alternative name(s):
Formactin-2
Formin homolog overexpressed in spleen 2
Short name=hFHOS2
Gene names
Name:FHOD3
Synonyms:FHOS2, KIAA1695
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1422 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Actin-organizing protein that may cause stress fiber formation together with cell elongation By similarity. Isoform 4 may play a role in actin filament polymerization in cardiomyocytes. Ref.2

Subunit structure

Interacts with nestin/NES-based interfilament (IF) By similarity. Interacts with SQSTM1; isoform 4 threonine phosphorylation disrupts SQSTM1-binding. Ref.2

Subcellular location

Cytoplasmcytoskeleton. Note: Main part of the protein localizes to actin fibers and the remaining part displays filamentous staining By similarity. Ref.2

Isoform 4: CytoplasmmyofibrilsarcomereZ line. Note: Threonine phosphorylation in isoform 4-specific sequence TDTDEEEEVE is required for targeting to myofibrils in cardiomyocytes. Ref.2

Tissue specificity

Expressed in the heart, kidney and brain. May be down-regulated in various types of heart diseases, including idiopathic dilated, ventricular dilated, familial dilated and perinatal dilated cardiomyopathies, as well as ischemic heart disease (at protein level). Ref.1 Ref.2

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 By similarity.

Sequence similarities

Belongs to the formin homology family.

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.

Sequence caution

The sequence BAB15292.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAB15463.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SQSTM1Q135016EBI-6395541,EBI-307104

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q2V2M9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q2V2M9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     400-437: Missing.
     481-481: F → FSRDYLDKREEQRQAREE
Isoform 3 (identifier: Q2V2M9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     481-481: F → FSRDYLDKREEQRQAREE
Note: Prediction based on ESTs. No experimental confirmation available.
Isoform 4 (identifier: Q2V2M9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     399-399: K → KEEEEEEEQP...YHFRSFSSNR
     481-481: F → FSRDYLDKREEQRQAREE
     1282-1283: TD → TDTDEEEEVE
Note: Phosphorylated at Thr-1474 and Thr-1476 by CK2.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14221422FH1/FH2 domain-containing protein 3
PRO_0000283791

Regions

Domain18 – 411394GBD/FH3
Domain827 – 85832FH1
Domain883 – 1279397FH2
Domain1359 – 139133DAD
Coiled coil448 – 48033 Potential
Compositional bias626 – 63510Poly-Ser
Compositional bias827 – 87246Pro-rich
Compositional bias889 – 8924Poly-Lys

Natural variations

Alternative sequence3991K → KEEEEEEEQPITEPSSEEER EDDASCQGKDSKVGAASGQS PTGRDAAPKSSALPAVSNAS SQGKPLLVGTAGGTTWHSGS SGSEATPSALLSPPASAARP SSATPGSLKVSPTIDKLPYV PHSPFHLFSYDFEDSSLSTK EKEAESQKENSSSDSFSLST YSASEPYHFRSFSSNR in isoform 4.
VSP_044682
Alternative sequence400 – 43738Missing in isoform 2.
VSP_024397
Alternative sequence4811F → FSRDYLDKREEQRQAREE in isoform 2, isoform 3 and isoform 4.
VSP_024398
Alternative sequence1282 – 12832TD → TDTDEEEEVE in isoform 4.
VSP_044683
Natural variant4751R → W.
Corresponds to variant rs9964535 [ dbSNP | Ensembl ].
VAR_055804

Experimental info

Sequence conflict711D → G in BAC67014. Ref.1
Sequence conflict2021K → E in ADL62709. Ref.2
Sequence conflict4321E → G in ADL62709. Ref.2
Sequence conflict4351L → W in BAC67014. Ref.1
Sequence conflict5271S → G in ADL62709. Ref.2
Sequence conflict5811G → A in ADL62709. Ref.2
Sequence conflict6471S → P in ADL62709. Ref.2
Sequence conflict6541L → K in BAC87252. Ref.4
Sequence conflict11341V → I in AAH81563. Ref.6
Sequence conflict14171T → A in BAB15463. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 13, 2010. Version 2.
Checksum: 7CE7A8C0054856BE

FASTA1,422158,613
        10         20         30         40         50         60 
MATLACRVQF LDDTDPFNST NFPEPSRPPL FTFREDLALG TQLAGVHRLL QAPHKLDDCT 

        70         80         90        100        110        120 
LQLSHNGAYL DLEATLAEQR DELEGFQDDA GRGKKHSIIL RTQLSVRVHA CIEKLYNSSG 

       130        140        150        160        170        180 
RDLRRALFSL KQIFQDDKDL VHEFVVAEGL TCLIKVGAEA DQNYQNYILR ALGQIMLYVD 

       190        200        210        220        230        240 
GMNGVINRNE TIQWLYTLIG SKFRLVVKTA LKLLLVFVEY SESNAPLLIQ AVTAVDTKRG 

       250        260        270        280        290        300 
VKPWSNIMEI LEEKDGVDTE LLVYAMTLVN KTLSGLPDQD TFYDVVDCLE ELGIAAVSQR 

       310        320        330        340        350        360 
HLNKKGTDLD LVEQLNIYEV ALRHEDGDET TEPPPSGCRD RRRASVCSSG GGEHRGLDRR 

       370        380        390        400        410        420 
RSRRHSVQSI KSTLSAPTSP CSQSAPSFKP NQVRDLREKY SNFGNNSYHS SRPSSGSSVP 

       430        440        450        460        470        480 
TTPTSSVSPP QEARLERSSP SGLLTSSFRQ HQESLAAERE RRRQEREERL QRIEREERNK 

       490        500        510        520        530        540 
FRYKYLEQLA AEEHEKELRS RSVSRGRADL SLDLTSPAAP ACLAPLSHSP SSSDSQEALT 

       550        560        570        580        590        600 
VSASSPGTPH HPQASAGDPE PESEAEPEAE AGAGQVADEA GQDIASAHEG AETEVEQALE 

       610        620        630        640        650        660 
QEPEERASLS EKERQNEGVN ERDNCSASSV SSSSSTLERE EKEDKLSRDR TTGLWPAGVQ 

       670        680        690        700        710        720 
DAGVNGQCGD ILTNKRFMLD MLYAHNRKSP DDEEKGDGEA GRTQQEAEAV ASLATRISTL 

       730        740        750        760        770        780 
QANSQTQDES VRRVDVGCLD NRGSVKAFAE KFNSGDLGRG SISPDAEPND KVPETAPVQP 

       790        800        810        820        830        840 
KTESDYIWDQ LMANPRELRI QDMDFTDLGE EDDIDVLDVD LGHREAPGPP PPPPPTFLGL 

       850        860        870        880        890        900 
PPPPPPPLLD SIPPPPVPGN LLVPPPPVFN APQGLGWSQV PRGQPTFTKK KKTIRLFWNE 

       910        920        930        940        950        960 
VRPFDWPCKN NRRCREFLWS KLEPIKVDTS RLEHLFESKS KELSVSKKTA ADGKRQEIIV 

       970        980        990       1000       1010       1020 
LDSKRSNAIN IGLTVLPPPR TIKIAILNFD EYALNKEGIE KILTMIPTDE EKQKIQEAQL 

      1030       1040       1050       1060       1070       1080 
ANPEIPLGSA EQFLLTLSSI SELSARLHLW AFKMDYETTE KEVAEPLLDL KEGIDQLENN 

      1090       1100       1110       1120       1130       1140 
KTLGFILSTL LAIGNFLNGT NAKAFELSYL EKVPEVKDTV HKQSLLHHVC TMVVENFPDS 

      1150       1160       1170       1180       1190       1200 
SDLYSEIGAI TRSAKVDFDQ LQDNLCQMER RCKASWDHLK AIAKHEMKPV LKQRMSEFLK 

      1210       1220       1230       1240       1250       1260 
DCAERIIILK IVHRRIINRF HSFLLFMGHP PYAIREVNIN KFCRIISEFA LEYRTTRERV 

      1270       1280       1290       1300       1310       1320 
LQQKQKRANH RERNKTRGKM ITDSGKFSGS SPAPPSQPQG LSYAEDAAEH ENMKAVLKTS 

      1330       1340       1350       1360       1370       1380 
SPSVEDATPA LGVRTRSRAS RGSTSSWTMG TDDSPNVTDD AADEIMDRIV KSATQVPSQR 

      1390       1400       1410       1420 
VVPRERKRSR ANRKSLRRTL KSGLTPEEAR ALGLVGTSEL QL 

« Hide

Isoform 2 [UniParc].

Checksum: F2B9F0473D7D3BC6
Show »

FASTA1,401156,752
Isoform 3 [UniParc].

Checksum: 72C7122A8348E1A9
Show »

FASTA1,439160,804
Isoform 4 [UniParc].

Checksum: EFCFEA5D7FF75299
Show »

FASTA1,622180,080

References

« Hide 'large scale' references
[1]"Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament."
Kanaya H., Takeya R., Takeuchi K., Watanabe N., Jing N., Sumimoto H.
Genes Cells 10:665-678(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Fetal brain.
[2]"Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance."
Iskratsch T., Lange S., Dwyer J., Kho A.L., dos Remedios C., Ehler E.
J. Cell Biol. 191:1159-1172(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-654 AND 906-1422 (ISOFORM 1).
Tissue: Small intestine and Testis.
[5]"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.
DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 203-1422 (ISOFORM 2).
Tissue: Brain.
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 895-1422.
Tissue: Brain and PNS.
[7]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1009-1422.
Tissue: Melanoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB084087 mRNA. Translation: BAC67014.1.
HM191478 mRNA. Translation: ADL62709.1.
AC023043 Genomic DNA. No translation available.
AC055840 Genomic DNA. No translation available.
AC090333 Genomic DNA. No translation available.
AC131053 Genomic DNA. No translation available.
AK025950 mRNA. Translation: BAB15292.1. Different initiation.
AK026370 mRNA. Translation: BAB15463.1. Different initiation.
AK128053 mRNA. Translation: BAC87252.1.
AB051482 mRNA. Translation: BAB21786.1.
BC050670 mRNA. Translation: AAH50670.1.
BC081563 mRNA. Translation: AAH81563.1.
AL834480 mRNA. Translation: CAD39139.1.
IPIIPI00397675.
IPI00843844.
IPI00939843.
RefSeqNP_079411.2. NM_025135.2.
UniGeneHs.630884.

3D structure databases

ProteinModelPortalQ2V2M9.
SMRQ2V2M9. Positions 2-327, 890-1272.
ModBaseSearch...

Protein-protein interaction databases

IntActQ2V2M9. 3 interactions.
STRING9606.ENSP00000257209.

PTM databases

PhosphoSiteQ2V2M9.

Polymorphism databases

DMDM300669639.

Proteomic databases

PaxDbQ2V2M9.
PRIDEQ2V2M9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257209; ENSP00000257209; ENSG00000134775.
ENST00000359247; ENSP00000352186; ENSG00000134775.
ENST00000445677; ENSP00000411430; ENSG00000134775.
ENST00000590592; ENSP00000466937; ENSG00000134775.
ENST00000592128; ENSP00000467462; ENSG00000134775.
GeneID80206.
KEGGhsa:80206.
UCSCuc002kzs.1. human.
uc002kzt.1. human.
uc010dmz.1. human.

Organism-specific databases

CTD80206.
GeneCardsGC18P033877.
H-InvDBHIX0014410.
HIX0174208.
HGNCHGNC:26178. FHOD3.
HPAHPA021827.
HPA024696.
MIM609691. gene.
neXtProtNX_Q2V2M9.
PharmGKBPA134929910.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG246341.
HOVERGENHBG051615.
OMAPNDKVPE.

Gene expression databases

BgeeQ2V2M9.
CleanExHS_FHOD3.
GenevestigatorQ2V2M9.

Family and domain databases

InterProIPR003104. Actin-bd_FH2/DRF_autoreg.
IPR016024. ARM-type_fold.
IPR014767. Diaphanous_autoregulatory.
IPR015425. FH2_actin-bd.
IPR014768. GTPase-bd/formin_homology_3.
[Graphical view]
PfamPF02181. FH2. 1 hit.
[Graphical view]
SMARTSM00498. FH2. 1 hit.
[Graphical view]
SUPFAMSSF48371. ARM-type_fold. 1 hit.
SSF101447. FH2_actin_bd. 1 hit.
PROSITEPS51231. DAD. 1 hit.
PS51444. FH2. 1 hit.
PS51232. GBD_FH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFHOD3. human.
GenomeRNAi80206.
NextBio35497575.
SOURCESearch...

Entry information

Entry nameFHOD3_HUMAN
AccessionPrimary (citable) accession number: Q2V2M9
Secondary accession number(s): A8MQT4 expand/collapse secondary AC list , E5F5Q0, Q642I2, Q6ZRQ7, Q86TF9, Q8N3A5, Q9C0G8, Q9H604, Q9H6G7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: July 13, 2010
Last modified: May 1, 2013
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families