Human Gene ZFYVE9 (ENST00000371591.2) from GENCODE V38
  Description: 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. (from UniProt O95405)
RefSeq Summary (NM_004799): 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].
Gencode Transcript: ENST00000371591.2
Gencode Gene: ENSG00000157077.16
Transcript (Including UTRs)
   Position: hg38 chr1:52,142,212-52,348,671 Size: 206,460 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg38 chr1:52,233,207-52,346,221 Size: 113,015 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsCTDRNA-Seq ExpressionMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated at UCSC: 2021-09-27 09:51:20

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:52,142,212-52,348,671)mRNA (may differ from genome)Protein (1425 aa)
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Wikipedia

-  Comments and Description Text from UniProtKB
  ID: ZFYV9_HUMAN
DESCRIPTION: RecName: Full=Zinc finger FYVE domain-containing protein 9; AltName: Full=Mothers against decapentaplegic homolog-interacting protein; Short=Madh-interacting protein; AltName: Full=Novel serine protease; Short=NSP; AltName: Full=Receptor activation anchor; Short=hSARA; AltName: Full=Smad anchor for receptor activation;
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.
SUBUNIT: 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.
INTERACTION: Q9Y561:LRP12; NbExp=2; IntAct=EBI-296817, EBI-296693; P08100:RHO; NbExp=2; IntAct=EBI-296817, EBI-1394177; Q13277:STX3; NbExp=3; IntAct=EBI-296817, EBI-1394295;
SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane.
TISSUE SPECIFICITY: Ubiquitous. In the brain found primarily in the cerebrovascular smooth muscle cells and reactive astrocytes.
DOMAIN: The SMAD binding domain (SBD) interacts with the MH2 domains of SMAD2 or SMAD3.
DOMAIN: The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P.
SIMILARITY: Contains 1 FYVE-type zinc finger.
SEQUENCE CAUTION: Sequence=AAC99462.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAD31694.1; Type=Frameshift; Positions=1243;

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.42 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 346.89 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -201.10515-0.390 Picture PostScript Text
3' UTR -654.802450-0.267 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR022557 - DUF3480
IPR024608 - SARA_Smad-bd
IPR000306 - Znf_FYVE
IPR017455 - Znf_FYVE-rel
IPR011011 - Znf_FYVE_PHD
IPR017165 - Znf_FYVE_SARA/endofin
IPR013083 - Znf_RING/FYVE/PHD

Pfam Domains:
PF11979 - Domain of unknown function (DUF3480)
PF01363 - FYVE zinc finger
PF11409 - Smad anchor for receptor activation (SARA)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

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ModBase Predicted Comparative 3D Structure on O95405
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0005545 1-phosphatidylinositol binding
GO:0008236 serine-type peptidase activity
GO:0019904 protein domain specific binding
GO:0046872 metal ion binding

Biological Process:
GO:0006508 proteolysis
GO:0006897 endocytosis
GO:0007179 transforming growth factor beta receptor signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005769 early endosome
GO:0005829 cytosol
GO:0016020 membrane
GO:0031901 early endosome membrane
GO:0032991 macromolecular complex
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  AF130420 - Homo sapiens serine protease-like protein isoform (NSP) mRNA, alternatively spliced, complete cds.
AF130419 - Homo sapiens serine protease-like protein isoform (NSP) mRNA, alternatively spliced, complete cds.
AF104304 - Homo sapiens Smad anchor for receptor activation (SARA) mRNA, complete cds.
BC032680 - Homo sapiens zinc finger, FYVE domain containing 9, mRNA (cDNA clone MGC:45259 IMAGE:5585817), complete cds.
EU176568 - Synthetic construct Homo sapiens clone IMAGE:100011385; FLH170642.01L; RZPDo839A12253D zinc finger, FYVE domain containing 9 (ZFYVE9) gene, encodes complete protein.
KJ892759 - Synthetic construct Homo sapiens clone ccsbBroadEn_02153 ZFYVE9 gene, encodes complete protein.
AB209125 - Homo sapiens mRNA for zinc finger, FYVE domain containing 9 isoform 3 variant protein.
AB384409 - Synthetic construct DNA, clone: pF1KSDB3800, Homo sapiens ZFYVE9 gene for zinc finger FYVE domain-containing protein 9, complete cds, without stop codon, in Flexi system.
JD127676 - Sequence 108700 from Patent EP1572962.
JD555439 - Sequence 536463 from Patent EP1572962.
CU689478 - Synthetic construct Homo sapiens gateway clone IMAGE:100020565 5' read ZFYVE9 mRNA.
JD186018 - Sequence 167042 from Patent EP1572962.
JD322884 - Sequence 303908 from Patent EP1572962.
JD214845 - Sequence 195869 from Patent EP1572962.
JD371506 - Sequence 352530 from Patent EP1572962.
JD530193 - Sequence 511217 from Patent EP1572962.
JD292914 - Sequence 273938 from Patent EP1572962.
JD326724 - Sequence 307748 from Patent EP1572962.
JD303630 - Sequence 284654 from Patent EP1572962.
JD040401 - Sequence 21425 from Patent EP1572962.
JD040014 - Sequence 21038 from Patent EP1572962.
JD083706 - Sequence 64730 from Patent EP1572962.
JD349370 - Sequence 330394 from Patent EP1572962.
JD277383 - Sequence 258407 from Patent EP1572962.
JD053603 - Sequence 34627 from Patent EP1572962.
JD425528 - Sequence 406552 from Patent EP1572962.
JD351160 - Sequence 332184 from Patent EP1572962.
JD351159 - Sequence 332183 from Patent EP1572962.
JD364079 - Sequence 345103 from Patent EP1572962.
JD362228 - Sequence 343252 from Patent EP1572962.
JD353070 - Sequence 334094 from Patent EP1572962.
JD258809 - Sequence 239833 from Patent EP1572962.
JD152330 - Sequence 133354 from Patent EP1572962.
JD256834 - Sequence 237858 from Patent EP1572962.
JD407654 - Sequence 388678 from Patent EP1572962.
JD213287 - Sequence 194311 from Patent EP1572962.
JD213288 - Sequence 194312 from Patent EP1572962.
JD059660 - Sequence 40684 from Patent EP1572962.
JD541241 - Sequence 522265 from Patent EP1572962.
JD274563 - Sequence 255587 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04144 - Endocytosis
hsa04350 - TGF-beta signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_tgfbPathway - TGF beta signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein O95405 (Reactome details) participates in the following event(s):

R-HSA-170835 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3
R-HSA-178189 SMAD7 recruits GADD34:PP1 to phosphorylated TGFBR
R-NUL-2167890 Smad7 recruits GADD34:PP1CC to phosphorylated TGF-beta receptor complex
R-HSA-3702153 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 MH2 domain mutants
R-HSA-3713560 An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3 phosphorylation motif mutants
R-HSA-178178 PP1 dephosphorylates TGFBR1
R-NUL-2167872 PP1CC dephosphorylates TGFBR1
R-HSA-170850 Phosphorylated SMAD2/3 dissociates from TGFBR
R-HSA-3702186 Phosphorylated SMAD2/3 MH2 domain mutants dissociate from TGFBR
R-HSA-170868 Activated type I receptor phosphorylates SMAD2/3 directly
R-HSA-3702184 Activated type I receptor phosphorylates SMAD2/3 MH2 domain mutants directly
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-170834 Signaling by TGF-beta Receptor Complex
R-HSA-3656534 Loss of Function of TGFBR1 in Cancer
R-HSA-3304349 Loss of Function of SMAD2/3 in Cancer
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-3304351 Signaling by TGF-beta Receptor Complex in Cancer
R-HSA-162582 Signal Transduction
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: AF104304, ENST00000371591.1, MADHIP, O95405, Q5T0F6, Q5T0F7, Q9UNE1, Q9Y5R7, SARA, SMADIP, uc057gnt.1, uc057gnt.2, ZFYV9_HUMAN
UCSC ID: ENST00000371591.2
RefSeq Accession: NM_004799
Protein: O95405 (aka ZFYV9_HUMAN or ZFV9_HUMAN)
CCDS: CCDS563.1, CCDS564.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.