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Protein

FH1/FH2 domain-containing protein 3

Gene

FHOD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding

Enzyme and pathway databases

SIGNORiQ2V2M9

Names & Taxonomyi

Protein namesi
Recommended name:
FH1/FH2 domain-containing protein 3
Alternative name(s):
Formactin-2
Formin homolog overexpressed in spleen 2
Short name:
hFHOS2
Gene namesi
Name:FHOD3
Synonyms:FHOS2, KIAA1695
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000134775.15
HGNCiHGNC:26178 FHOD3
MIMi609691 gene
neXtProtiNX_Q2V2M9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Organism-specific databases

DisGeNETi80206
OpenTargetsiENSG00000134775
PharmGKBiPA134929910

Polymorphism and mutation databases

DMDMi300669639

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002837911 – 1422FH1/FH2 domain-containing protein 3Add BLAST1422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei345PhosphoserineBy similarity1
Modified residuei375PhosphoserineBy similarity1
Modified residuei763PhosphoserineBy similarity1
Modified residuei775PhosphothreonineBy similarity1
Isoform 4 (identifier: Q2V2M9-4)
Modified residuei1474Phosphothreonine1 Publication1
Modified residuei1476Phosphothreonine1 Publication1

Post-translational modificationi

Isoform 4: Phosphorylated on Thr-1474 and Thr-1476 by CK2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ2V2M9
PaxDbiQ2V2M9
PeptideAtlasiQ2V2M9
PRIDEiQ2V2M9
ProteomicsDBi61508
61509 [Q2V2M9-2]
61510 [Q2V2M9-3]

PTM databases

iPTMnetiQ2V2M9
PhosphoSitePlusiQ2V2M9

Expressioni

Tissue specificityi

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).2 Publications

Gene expression databases

BgeeiENSG00000134775 Expressed in 182 organ(s), highest expression level in apex of heart
CleanExiHS_FHOD3
ExpressionAtlasiQ2V2M9 baseline and differential
GenevisibleiQ2V2M9 HS

Organism-specific databases

HPAiHPA021827
HPA024696

Interactioni

Subunit structurei

Interacts with nestin/NES-based interfilament (IF) (By similarity). Interacts with SQSTM1; isoform 4 threonine phosphorylation disrupts SQSTM1-binding.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
SQSTM1Q135016EBI-6395541,EBI-307104

GO - Molecular functioni

Protein-protein interaction databases

BioGridi123175, 2 interactors
ELMiQ2V2M9
IntActiQ2V2M9, 3 interactors
STRINGi9606.ENSP00000257209

Structurei

3D structure databases

ProteinModelPortaliQ2V2M9
SMRiQ2V2M9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 411GBD/FH3PROSITE-ProRule annotationAdd BLAST394
Domaini827 – 858FH1Add BLAST32
Domaini883 – 1279FH2PROSITE-ProRule annotationAdd BLAST397
Domaini1359 – 1391DADPROSITE-ProRule annotationAdd BLAST33

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili448 – 480Sequence analysisAdd BLAST33

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi626 – 635Poly-Ser10
Compositional biasi827 – 872Pro-richAdd BLAST46
Compositional biasi889 – 892Poly-Lys4

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the formin homology family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1925 Eukaryota
ENOG410XRBZ LUCA
GeneTreeiENSGT00870000136417
HOVERGENiHBG051615
InParanoidiQ2V2M9
OMAiRIQDMDF
OrthoDBiEOG091G00OX
PhylomeDBiQ2V2M9
TreeFamiTF316268

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR014767 DAD_dom
IPR015425 FH2_Formin
IPR027651 FHOD3
IPR014768 GBD/FH3_dom
PANTHERiPTHR23213:SF213 PTHR23213:SF213, 2 hits
PfamiView protein in Pfam
PF02181 FH2, 1 hit
SMARTiView protein in SMART
SM00498 FH2, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS51231 DAD, 1 hit
PS51444 FH2, 1 hit
PS51232 GBD_FH3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q2V2M9-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MATLACRVQF LDDTDPFNST NFPEPSRPPL FTFREDLALG TQLAGVHRLL
60 70 80 90 100
QAPHKLDDCT LQLSHNGAYL DLEATLAEQR DELEGFQDDA GRGKKHSIIL
110 120 130 140 150
RTQLSVRVHA CIEKLYNSSG RDLRRALFSL KQIFQDDKDL VHEFVVAEGL
160 170 180 190 200
TCLIKVGAEA DQNYQNYILR ALGQIMLYVD GMNGVINRNE TIQWLYTLIG
210 220 230 240 250
SKFRLVVKTA LKLLLVFVEY SESNAPLLIQ AVTAVDTKRG VKPWSNIMEI
260 270 280 290 300
LEEKDGVDTE LLVYAMTLVN KTLSGLPDQD TFYDVVDCLE ELGIAAVSQR
310 320 330 340 350
HLNKKGTDLD LVEQLNIYEV ALRHEDGDET TEPPPSGCRD RRRASVCSSG
360 370 380 390 400
GGEHRGLDRR RSRRHSVQSI KSTLSAPTSP CSQSAPSFKP NQVRDLREKY
410 420 430 440 450
SNFGNNSYHS SRPSSGSSVP TTPTSSVSPP QEARLERSSP SGLLTSSFRQ
460 470 480 490 500
HQESLAAERE RRRQEREERL QRIEREERNK FRYKYLEQLA AEEHEKELRS
510 520 530 540 550
RSVSRGRADL SLDLTSPAAP ACLAPLSHSP SSSDSQEALT VSASSPGTPH
560 570 580 590 600
HPQASAGDPE PESEAEPEAE AGAGQVADEA GQDIASAHEG AETEVEQALE
610 620 630 640 650
QEPEERASLS EKERQNEGVN ERDNCSASSV SSSSSTLERE EKEDKLSRDR
660 670 680 690 700
TTGLWPAGVQ DAGVNGQCGD ILTNKRFMLD MLYAHNRKSP DDEEKGDGEA
710 720 730 740 750
GRTQQEAEAV ASLATRISTL QANSQTQDES VRRVDVGCLD NRGSVKAFAE
760 770 780 790 800
KFNSGDLGRG SISPDAEPND KVPETAPVQP KTESDYIWDQ LMANPRELRI
810 820 830 840 850
QDMDFTDLGE EDDIDVLDVD LGHREAPGPP PPPPPTFLGL PPPPPPPLLD
860 870 880 890 900
SIPPPPVPGN LLVPPPPVFN APQGLGWSQV PRGQPTFTKK KKTIRLFWNE
910 920 930 940 950
VRPFDWPCKN NRRCREFLWS KLEPIKVDTS RLEHLFESKS KELSVSKKTA
960 970 980 990 1000
ADGKRQEIIV LDSKRSNAIN IGLTVLPPPR TIKIAILNFD EYALNKEGIE
1010 1020 1030 1040 1050
KILTMIPTDE EKQKIQEAQL ANPEIPLGSA EQFLLTLSSI SELSARLHLW
1060 1070 1080 1090 1100
AFKMDYETTE KEVAEPLLDL KEGIDQLENN KTLGFILSTL LAIGNFLNGT
1110 1120 1130 1140 1150
NAKAFELSYL EKVPEVKDTV HKQSLLHHVC TMVVENFPDS SDLYSEIGAI
1160 1170 1180 1190 1200
TRSAKVDFDQ LQDNLCQMER RCKASWDHLK AIAKHEMKPV LKQRMSEFLK
1210 1220 1230 1240 1250
DCAERIIILK IVHRRIINRF HSFLLFMGHP PYAIREVNIN KFCRIISEFA
1260 1270 1280 1290 1300
LEYRTTRERV LQQKQKRANH RERNKTRGKM ITDSGKFSGS SPAPPSQPQG
1310 1320 1330 1340 1350
LSYAEDAAEH ENMKAVLKTS SPSVEDATPA LGVRTRSRAS RGSTSSWTMG
1360 1370 1380 1390 1400
TDDSPNVTDD AADEIMDRIV KSATQVPSQR VVPRERKRSR ANRKSLRRTL
1410 1420
KSGLTPEEAR ALGLVGTSEL QL
Length:1,422
Mass (Da):158,613
Last modified:July 13, 2010 - v2
Checksum:i7CE7A8C0054856BE
GO
Isoform 2 (identifier: Q2V2M9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     400-437: Missing.
     481-481: F → FSRDYLDKREEQRQAREE

Show »
Length:1,401
Mass (Da):156,752
Checksum:iF2B9F0473D7D3BC6
GO
Isoform 3 (identifier: Q2V2M9-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:1,439
Mass (Da):160,804
Checksum:i72C7122A8348E1A9
GO
Isoform 4 (identifier: Q2V2M9-4) [UniParc]FASTAAdd to basket

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

Show »
Length:1,622
Mass (Da):180,080
Checksum:iEFCFEA5D7FF75299
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ER94K7ER94_HUMAN
FH1/FH2 domain-containing protein 3
FHOD3
1,200Annotation score:
K7EP24K7EP24_HUMAN
FH1/FH2 domain-containing protein 3
FHOD3
635Annotation score:
K7EKZ0K7EKZ0_HUMAN
FH1/FH2 domain-containing protein 3
FHOD3
375Annotation score:
A0A0A0MTS9A0A0A0MTS9_HUMAN
FH1/FH2 domain-containing protein 3
FHOD3
528Annotation score:

Sequence cautioni

The sequence BAB15292 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15463 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71D → G in BAC67014 (PubMed:15966898).Curated1
Sequence conflicti202K → E in ADL62709 (PubMed:21149568).Curated1
Sequence conflicti432E → G in ADL62709 (PubMed:21149568).Curated1
Sequence conflicti435L → W in BAC67014 (PubMed:15966898).Curated1
Sequence conflicti527S → G in ADL62709 (PubMed:21149568).Curated1
Sequence conflicti581G → A in ADL62709 (PubMed:21149568).Curated1
Sequence conflicti647S → P in ADL62709 (PubMed:21149568).Curated1
Sequence conflicti654L → K in BAC87252 (PubMed:14702039).Curated1
Sequence conflicti1134V → I in AAH81563 (PubMed:15489334).Curated1
Sequence conflicti1417T → A in BAB15463 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055804475R → W. Corresponds to variant dbSNP:rs9964535Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044682399K → KEEEEEEEQPITEPSSEEER EDDASCQGKDSKVGAASGQS PTGRDAAPKSSALPAVSNAS SQGKPLLVGTAGGTTWHSGS SGSEATPSALLSPPASAARP SSATPGSLKVSPTIDKLPYV PHSPFHLFSYDFEDSSLSTK EKEAESQKENSSSDSFSLST YSASEPYHFRSFSSNR in isoform 4. 1 Publication1
Alternative sequenceiVSP_024397400 – 437Missing in isoform 2. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_024398481F → FSRDYLDKREEQRQAREE in isoform 2, isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_0446831282 – 1283TD → TDTDEEEEVE in isoform 4. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS32816.1 [Q2V2M9-3]
CCDS62418.1 [Q2V2M9-4]
CCDS62419.1 [Q2V2M9-1]
RefSeqiNP_001268668.1, NM_001281739.2 [Q2V2M9-1]
NP_001268669.1, NM_001281740.2 [Q2V2M9-4]
NP_079411.2, NM_025135.4 [Q2V2M9-3]
XP_005258412.1, XM_005258355.1 [Q2V2M9-2]
UniGeneiHs.436636
Hs.630884

Genome annotation databases

EnsembliENST00000257209; ENSP00000257209; ENSG00000134775 [Q2V2M9-3]
ENST00000359247; ENSP00000352186; ENSG00000134775 [Q2V2M9-1]
ENST00000590592; ENSP00000466937; ENSG00000134775 [Q2V2M9-4]
GeneIDi80206
KEGGihsa:80206
UCSCiuc002kzs.3 human [Q2V2M9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFHOD3_HUMAN
AccessioniPrimary (citable) accession number: Q2V2M9
Secondary accession number(s): A8MQT4
, E5F5Q0, Q642I2, Q6ZRQ7, Q86TF9, Q8N3A5, Q9C0G8, Q9H604, Q9H6G7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: July 13, 2010
Last modified: September 12, 2018
This is version 110 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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