This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript vari... See more...

Aliases for ZFYVE9 Gene

Aliases for ZFYVE9 Gene

  • Zinc Finger FYVE-Type Containing 9 2 3 5
  • SMADIP 2 3 4
  • SARA 2 3 4
  • Protein Phosphatase 1, Regulatory Subunit 173 2 3
  • Zinc Finger FYVE Domain-Containing Protein 9 3 4
  • Zinc Finger, FYVE Domain Containing 9 2 3
  • Smad Anchor For Receptor Activation 3 4
  • Novel Serine Protease 3 4
  • PPP1R173 2 3
  • MADHIP 3 4
  • NSP 3 4
  • MAD, Mothers Against Decapentaplegic Homolog (Drosophila) Interacting Protein, Receptor Activation Anchor 2
  • MAD, Mothers Against Decapentaplegic Homolog Interacting Protein, Receptor Activation Anchor 3
  • Mothers Against Decapentaplegic Homolog-Interacting Protein 4
  • Receptor Activation Anchor 4
  • MADH-Interacting Protein 3
  • Madh-Interacting Protein 4
  • ZFYVE9 5
  • HSARA 4

External Ids for ZFYVE9 Gene

Previous HGNC Symbols for ZFYVE9 Gene

  • MADHIP

Previous GeneCards Identifiers for ZFYVE9 Gene

  • GC01P051978
  • GC01P052320
  • GC01P052394
  • GC01P052380
  • GC01P052608
  • GC01P050725

Summaries for ZFYVE9 Gene

Entrez Gene Summary for ZFYVE9 Gene

  • This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

GeneCards Summary for ZFYVE9 Gene

ZFYVE9 (Zinc Finger FYVE-Type Containing 9) is a Protein Coding gene. Diseases associated with ZFYVE9 include Spinal Cord Neuroblastoma and Spinal Cord Primitive Neuroectodermal Neoplasm. Among its related pathways are Signaling by GPCR and SMAD2/3 MH2 Domain Mutants in Cancer. Gene Ontology (GO) annotations related to this gene include serine-type peptidase activity and 1-phosphatidylinositol binding.

UniProtKB/Swiss-Prot Summary for ZFYVE9 Gene

  • Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization.

Gene Wiki entry for ZFYVE9 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ZFYVE9 Gene

Genomics for ZFYVE9 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ZFYVE9 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ZFYVE9 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ZFYVE9

Top Transcription factor binding sites by QIAGEN in the ZFYVE9 gene promoter:
  • c-Myc
  • C/EBPbeta
  • CUTL1
  • Evi-1
  • FOXL1
  • GATA-2
  • Max
  • N-Myc
  • RORalpha1
  • ZIC2

Genomic Locations for ZFYVE9 Gene

Latest Assembly
chr1:52,142,001-52,348,671
(GRCh38/hg38)
Size:
206,671 bases
Orientation:
Plus strand

Previous Assembly
chr1:52,607,761-52,812,306
(GRCh37/hg19 by Entrez Gene)
Size:
204,546 bases
Orientation:
Plus strand

chr1:52,608,046-52,812,358
(GRCh37/hg19 by Ensembl)
Size:
204,313 bases
Orientation:
Plus strand

Genomic View for ZFYVE9 Gene

Genes around ZFYVE9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ZFYVE9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ZFYVE9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ZFYVE9 Gene

Proteins for ZFYVE9 Gene

  • Protein details for ZFYVE9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95405-ZFYV9_HUMAN
    Recommended name:
    Zinc finger FYVE domain-containing protein 9
    Protein Accession:
    O95405
    Secondary Accessions:
    • Q5T0F6
    • Q5T0F7
    • Q9UNE1
    • Q9Y5R7

    Protein attributes for ZFYVE9 Gene

    Size:
    1425 amino acids
    Molecular mass:
    156403 Da
    Quaternary structure:
    • Interacts (via the SBD region) with SMAD2; the interaction recruits SMAD2 to the TGF-beta receptor and is disrupted by phosphorylation of SMAD2 upon TGF-beta receptor activation. Interacts with SMAD3. Interacts with TGFBR1 and TGFBR2; the interaction recruits SMAD2 to the TGF-beta receptor. Interacts with PML.
    SequenceCaution:
    • Sequence=AAC99462.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD31694.1; Type=Frameshift; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for ZFYVE9 Gene

    Alternative splice isoforms for ZFYVE9 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ZFYVE9 Gene

Post-translational modifications for ZFYVE9 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ZFYVE9 Gene

No data available for DME Specific Peptides for ZFYVE9 Gene

Domains & Families for ZFYVE9 Gene

Gene Families for ZFYVE9 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for ZFYVE9 Gene

Suggested Antigen Peptide Sequences for ZFYVE9 Gene

GenScript: Design optimal peptide antigens:
  • Smad anchor for receptor activation (ZFYV9_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95405

UniProtKB/Swiss-Prot:

ZFYV9_HUMAN :
  • The SMAD binding domain (SBD) interacts with the MH2 domains of SMAD2 or SMAD3.
Domain:
  • The SMAD binding domain (SBD) interacts with the MH2 domains of SMAD2 or SMAD3.
  • The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P.
genes like me logo Genes that share domains with ZFYVE9: view

Function for ZFYVE9 Gene

Molecular function for ZFYVE9 Gene

UniProtKB/Swiss-Prot Function:
Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization.

Phenotypes From GWAS Catalog for ZFYVE9 Gene

Gene Ontology (GO) - Molecular Function for ZFYVE9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 9865696
GO:0005545 1-phosphatidylinositol binding IDA 11877415
GO:0019904 protein domain specific binding IPI 15231848
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with ZFYVE9: view
genes like me logo Genes that share phenotypes with ZFYVE9: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZFYVE9

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ZFYVE9 Gene

Localization for ZFYVE9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ZFYVE9 Gene

Cytoplasm. Early endosome membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ZFYVE9 gene
Compartment Confidence
endosome 5
cytosol 5
nucleus 3
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Vesicles (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ZFYVE9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome NAS 12809483
GO:0005829 cytosol IDA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with ZFYVE9: view

Pathways & Interactions for ZFYVE9 Gene

genes like me logo Genes that share pathways with ZFYVE9: view

Pathways by source for ZFYVE9 Gene

3 GeneGo (Thomson Reuters) pathways for ZFYVE9 Gene
  • Cell cycle Regulation of G1/S transition (part 1)
  • Cytokine production by Th17 cells in CF (Mouse model)
  • Development_TGF-beta receptor signaling
1 Qiagen pathway for ZFYVE9 Gene
  • SMAD Signaling Network
1 Cell Signaling Technology pathway for ZFYVE9 Gene

SIGNOR curated interactions for ZFYVE9 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for ZFYVE9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis NAS 12809483
GO:0007179 transforming growth factor beta receptor signaling pathway TAS --
GO:0016197 endosomal transport IBA 21873635
genes like me logo Genes that share ontologies with ZFYVE9: view

Drugs & Compounds for ZFYVE9 Gene

(5) Drugs for ZFYVE9 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for ZFYVE9 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ZFYVE9: view

Transcripts for ZFYVE9 Gene

mRNA/cDNA for ZFYVE9 Gene

3 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ZFYVE9

Alternative Splicing Database (ASD) splice patterns (SP) for ZFYVE9 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b
SP1: -
SP2: - -
SP3:
SP4:

Relevant External Links for ZFYVE9 Gene

GeneLoc Exon Structure for
ZFYVE9

Expression for ZFYVE9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ZFYVE9 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for ZFYVE9 Gene

This gene is overexpressed in Adrenal (55.2) and Adipocyte (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ZFYVE9 Gene



Protein tissue co-expression partners for ZFYVE9 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ZFYVE9

SOURCE GeneReport for Unigene cluster for ZFYVE9 Gene:

Hs.532345

mRNA Expression by UniProt/SwissProt for ZFYVE9 Gene:

O95405-ZFYV9_HUMAN
Tissue specificity: Ubiquitous. In the brain found primarily in the cerebrovascular smooth muscle cells and reactive astrocytes.

Evidence on tissue expression from TISSUES for ZFYVE9 Gene

  • Nervous system(4.6)
  • Liver(4.4)
  • Kidney(2.4)
  • Muscle(2.3)
  • Heart(2.1)
  • Lung(2)
genes like me logo Genes that share expression patterns with ZFYVE9: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ZFYVE9 Gene

Orthologs for ZFYVE9 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ZFYVE9 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ZFYVE9 29 30
  • 99.49 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ZFYVE9 30
  • 94 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia ZFYVE9 29 30
  • 92.56 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Zfyve9 29 16 30
  • 91.94 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ZFYVE9 29 30
  • 91.82 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Zfyve9 29
  • 87.74 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 13 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves ZFYVE9 29 30
  • 77.38 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ZFYVE9 30
  • 73 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia zfyve9 29
  • 70.7 (n)
Str.7299 29
African clawed frog
(Xenopus laevis)
Amphibia madhip-A 29
Zebrafish
(Danio rerio)
Actinopterygii zfyve9a 29 30
  • 70.73 (n)
ManyToMany
BX511174.1 30
  • 55 (a)
ManyToMany
CR762408.1 30
  • 55 (a)
ManyToMany
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.13130 29
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes FAB1 30
  • 6 (a)
OneToMany
Species where no ortholog for ZFYVE9 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ZFYVE9 Gene

ENSEMBL:
Gene Tree for ZFYVE9 (if available)
TreeFam:
Gene Tree for ZFYVE9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ZFYVE9: view image
Alliance of Genome Resources:
Additional Orthologs for ZFYVE9

Paralogs for ZFYVE9 Gene

(1) SIMAP similar genes for ZFYVE9 Gene using alignment to 3 proteins:

  • ZFYV9_HUMAN
  • L8E993_HUMAN
  • L8ECB6_HUMAN
genes like me logo Genes that share paralogs with ZFYVE9: view

No data available for Paralogs for ZFYVE9 Gene

Variants for ZFYVE9 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ZFYVE9 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs11809887 -- p.Ile639Val
rs3790525 -- p.Gln414Pro
rs9803965 -- p.Tyr287Cys

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ZFYVE9 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ZFYVE9 Gene

Variant ID Type Subtype PubMed ID
dgv273n54 CNV gain 21841781
dgv274n54 CNV gain 21841781
esv1012300 CNV deletion 17803354
esv25536 CNV loss 19812545
esv2669236 CNV deletion 23128226
esv2748118 CNV deletion 23290073
esv3586047 CNV loss 21293372
esv3586048 CNV loss 21293372
esv3586050 CNV loss 21293372
nsv1137757 CNV deletion 24896259
nsv1137758 CNV deletion 24896259
nsv1141744 CNV insertion 24896259
nsv546232 CNV loss 21841781
nsv546234 CNV gain 21841781
nsv546235 CNV gain+loss 21841781
nsv546237 CNV gain 21841781
nsv546238 CNV loss 21841781
nsv819763 CNV gain 19587683
nsv822553 CNV loss 20364138
nsv855 CNV insertion 18451855
nsv945945 CNV duplication 23825009
nsv945946 CNV duplication 23825009

Variation tolerance for ZFYVE9 Gene

Residual Variation Intolerance Score: 68.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.27; 70.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ZFYVE9 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ZFYVE9
Leiden Open Variation Database (LOVD)
ZFYVE9

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ZFYVE9 Gene

Disorders for ZFYVE9 Gene

MalaCards: The human disease database

(5) MalaCards diseases for ZFYVE9 Gene - From: COP

Disorder Aliases PubMed IDs
spinal cord neuroblastoma
  • neuroblastoma of the spinal cord
spinal cord primitive neuroectodermal neoplasm
  • spinal cord pnet
gallbladder squamous cell carcinoma
  • epidermoid gallbladder carcinoma
iga glomerulonephritis
  • berger's iga or igg nephropathy
spinal muscular atrophy, type ii
  • sma2
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ZFYVE9

genes like me logo Genes that share disorders with ZFYVE9: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ZFYVE9 Gene

Publications for ZFYVE9 Gene

  1. SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor. (PMID: 9865696) Tsukazaki T … Wrana JL (Cell 1998) 2 3 4 22
  2. Cytoplasmic PML function in TGF-beta signalling. (PMID: 15356634) Lin HK … Pandolfi PP (Nature 2004) 3 4 22
  3. Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control. (PMID: 12154125) Qin BY … Lin K (Genes & development 2002) 3 4 22
  4. Early endosomal regulation of Smad-dependent signaling in endothelial cells. (PMID: 11877415) Panopoulou E … Fotsis T (The Journal of biological chemistry 2002) 3 4 22
  5. Identification of a novel serine protease-like molecule in human brain. (PMID: 9582421) Meckelein B … Abraham CR (Brain research. Molecular brain research 1998) 3 4 22

Products for ZFYVE9 Gene

Sources for ZFYVE9 Gene