FHOD3

Protein identityUniProt · HPA

UniProt accession

Q2V2M9

Gene

FHOD3

Ensembl

ENSG00000134775

Chromosome

18

Canonical length

1422 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene is a member of the diaphanous-related formins (DRF), and contains multiple domains, including GBD (GTPase-binding domain), DID (diaphanous inhibitory domain), FH1 (formin homology 1), FH2 (formin homology 2), and DAD (diaphanous auto-regulatory domain) domains. This protein is thought to play a role in actin filament polymerization in cardiomyocytes. Mutations in this gene have been associated with dilated cardiomyopathy (DCM), characterized by dilation of the ventricular chamber, leading to impairment of systolic pump function and subsequent heart failure. Increased levels of the protein encoded by this gene have been observed in individuals with hypertrophic cardiomyopathy (HCM). Alternative splicing results in multiple transcript variants encoding different isoforms. A muscle-specific isoform has been shown to possess a casein kinase 2 (CK2) phosphorylation site at the C-terminal end of the FH2 domain. Phosphorylation of this site alters its interaction with sequestosome 1 (SQSTM1), and targets this isoform to myofibrils, while other isoforms form cytoplasmic aggregates. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

1422 residues, UniProt reviewed canonical sequence.

>Q2V2M9|FHOD3
     1  MATLACRVQF LDDTDPFNST NFPEPSRPPL FTFREDLALG TQLAGVHRLL QAPHKLDDCT
    61  LQLSHNGAYL DLEATLAEQR DELEGFQDDA GRGKKHSIIL RTQLSVRVHA CIEKLYNSSG
   121  RDLRRALFSL KQIFQDDKDL VHEFVVAEGL TCLIKVGAEA DQNYQNYILR ALGQIMLYVD
   181  GMNGVINRNE TIQWLYTLIG SKFRLVVKTA LKLLLVFVEY SESNAPLLIQ AVTAVDTKRG
   241  VKPWSNIMEI LEEKDGVDTE LLVYAMTLVN KTLSGLPDQD TFYDVVDCLE ELGIAAVSQR
   301  HLNKKGTDLD LVEQLNIYEV ALRHEDGDET TEPPPSGCRD RRRASVCSSG GGEHRGLDRR
   361  RSRRHSVQSI KSTLSAPTSP CSQSAPSFKP NQVRDLREKY SNFGNNSYHS SRPSSGSSVP
   421  TTPTSSVSPP QEARLERSSP SGLLTSSFRQ HQESLAAERE RRRQEREERL QRIEREERNK
   481  FRYKYLEQLA AEEHEKELRS RSVSRGRADL SLDLTSPAAP ACLAPLSHSP SSSDSQEALT
   541  VSASSPGTPH HPQASAGDPE PESEAEPEAE AGAGQVADEA GQDIASAHEG AETEVEQALE
   601  QEPEERASLS EKERQNEGVN ERDNCSASSV SSSSSTLERE EKEDKLSRDR TTGLWPAGVQ
   661  DAGVNGQCGD ILTNKRFMLD MLYAHNRKSP DDEEKGDGEA GRTQQEAEAV ASLATRISTL
   721  QANSQTQDES VRRVDVGCLD NRGSVKAFAE KFNSGDLGRG SISPDAEPND KVPETAPVQP
   781  KTESDYIWDQ LMANPRELRI QDMDFTDLGE EDDIDVLDVD LGHREAPGPP PPPPPTFLGL
   841  PPPPPPPLLD SIPPPPVPGN LLVPPPPVFN APQGLGWSQV PRGQPTFTKK KKTIRLFWNE
   901  VRPFDWPCKN NRRCREFLWS KLEPIKVDTS RLEHLFESKS KELSVSKKTA ADGKRQEIIV
   961  LDSKRSNAIN IGLTVLPPPR TIKIAILNFD EYALNKEGIE KILTMIPTDE EKQKIQEAQL
  1021  ANPEIPLGSA EQFLLTLSSI SELSARLHLW AFKMDYETTE KEVAEPLLDL KEGIDQLENN
  1081  KTLGFILSTL LAIGNFLNGT NAKAFELSYL EKVPEVKDTV HKQSLLHHVC TMVVENFPDS
  1141  SDLYSEIGAI TRSAKVDFDQ LQDNLCQMER RCKASWDHLK AIAKHEMKPV LKQRMSEFLK
  1201  DCAERIIILK IVHRRIINRF HSFLLFMGHP PYAIREVNIN KFCRIISEFA LEYRTTRERV
  1261  LQQKQKRANH RERNKTRGKM ITDSGKFSGS SPAPPSQPQG LSYAEDAAEH ENMKAVLKTS
  1321  SPSVEDATPA LGVRTRSRAS RGSTSSWTMG TDDSPNVTDD AADEIMDRIV KSATQVPSQR
  1381  VVPRERKRSR ANRKSLRRTL KSGLTPEEAR ALGLVGTSEL QL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FHOD3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

143 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FHOD3.

Disease | AllUniProt

Conditions FHOD3 is implicated in, by any mechanism.

• Cardiomyopathy, familial hypertrophic, 28 (CMH28) MIM:619402

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 500 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cardiomyopathy, familial hypertrophic, 28
• Cardiovascular phenotype
• Inborn genetic diseases
• Primary dilated cardiomyopathy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.37

gnomAD pLI

0.07

gnomAD missense Z

0.88

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• actin filament organization
• cardiac myofibril assembly
• positive regulation of stress fiber assembly
• sarcomere organization

Molecular functions

• actin filament binding

Cellular components

• cytoplasm
• cytoskeleton
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Armadillo-like helical
• Diaphanous autoregulatory domain
• Rho GTPase-binding/formin homology 3 (GBD/FH3) domain
• Formin, FH2 domain
• Armadillo-type fold
• FHOD1, N-terminal GTPase-binding domain
• Formin, FH2 domain superfamily
• FHOD1/3-like, FH3 domain
• Formin Homology 2 Domain
• Formin N-terminal GBD
• FHOD1/3 FH3 domain

KeywordsUniProt

• Actin-binding
• Cardiomyopathy
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of FHOD3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SQSTM1
• NES