Human Gene ZFYVE9 (ENST00000287727.8) from GENCODE V44
Description: Homo sapiens zinc finger FYVE-type containing 9 (ZFYVE9), transcript variant 3, mRNA. (from RefSeq NM_004799) 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: ENST00000287727.8 Gencode Gene: ENSG00000157077.16 Transcript (Including UTRs) Position: hg38 chr1:52,142,089-52,346,634 Size: 204,546 Total Exon Count: 19 Strand: + Coding Region Position: hg38 chr1:52,233,207-52,346,221 Size: 113,015 Coding Exon Count: 17
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;
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.
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.
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
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.
Biochemical and Signaling Pathways
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
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