Reviewed,
UniProtKB/Swiss-Prot O95405 (ZFYV9_HUMAN)
Last modified
January 19, 2010.
Version 91.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Zinc finger FYVE domain-containing protein 9 Alternative name(s): Mothers against decapentaplegic homolog-interacting protein Short name=Madh-interacting protein Smad anchor for receptor activation Receptor activation anchor Short name=hSARA Novel serine protease Short name=NSP | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1425 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in recruiting unphosphorylated forms of SMAD2/SMAD3 to the TGF-beta receptor by controlling their subcellular localization and by interacting and colocalizing with the TGF-beta receptor. Phosphorylation of SMAD2/SMAD3 induces dissociation from ZFYVE9 and formation of SMAD2/SMAD4 complexes and nuclear translocation. |
| Subunit structure | Binds SMAD2, SMAD3, and TGF-beta receptor. |
| Subcellular location | |
| 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 domain of SMAD2 or SMAD3. The FYVE-type zinc finger domain (also called double zinc finger domain) is required to maintain the normal localization of the protein but is not involved in mediating interaction with SMADs. Can bind phosphatidyl inositol-3 phosphate. |
| Sequence similarities | Contains 1 FYVE-type zinc finger. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| LRP12 | Q9Y561 | 1 | EBI-296817,EBI-296693 | |
| RHO | P08100 | 2 | EBI-296817,EBI-1394177 | |
| SMAD3 | P84022 | 1 | EBI-296817,EBI-347161 | |
| STX3 | Q13277 | 2 | EBI-296817,EBI-1394295 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O95405-1) 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. | ||||||
| Isoform 2 (identifier: O95405-2) The sequence of this isoform differs from the canonical sequence as follows: 760-818: Missing. | ||||||
| Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Ref.2 (AAD31694) sequence differs from that shown due to a frameshift in position 1243. | ||||||
| Isoform 3 (identifier: O95405-3) The sequence of this isoform differs from the canonical sequence as follows: 760-762: AQA → GKY 763-1425: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||
Molecule processing | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1425 | 1425 | Zinc finger FYVE domain-containing protein 9 | PRO_0000098715 | ||||||||||||
Regions | ||||||||||||||||
| Zinc finger | 699 – 758 | 60 | FYVE-type | |||||||||||||
| Region | 767 – 823 | 57 | SBD | |||||||||||||
Natural variations | ||||||||||||||||
| Alternative sequence | 760 – 818 | 59 | Missing in isoform 2. | VSP_004315 | ||||||||||||
| Alternative sequence | 760 – 762 | 3 | AQA → GKY in isoform 3. | VSP_004316 | ||||||||||||
| Alternative sequence | 763 – 1425 | 663 | Missing in isoform 3. | VSP_004317 | ||||||||||||
| Natural variant | 287 | 1 | Y → C: dbSNP rs9803965. | VAR_052985 | ||||||||||||
| Natural variant | 414 | 1 | Q → P: dbSNP rs3790525. | VAR_052986 | ||||||||||||
| Natural variant | 639 | 1 | I → V: dbSNP rs11809887. | VAR_052987 | ||||||||||||
Experimental info | ||||||||||||||||
| Mutagenesis | 782 | 1 | Y → A: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 782 | 1 | Y → E: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 783 | 1 | C → A: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 783 | 1 | C → E: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 788 | 1 | P → A: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 788 | 1 | P → E: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 805 | 1 | V → A: Diminishes complex formation with SMAD2. | |||||||||||||
| Mutagenesis | 805 | 1 | V → E: Diminishes complex formation with SMAD2. | |||||||||||||
Secondary structure | ||||||||||||||||
Helix Strand Turn | ||||||||||||||||
| Helix | 779 – 781 | 3 | ||||||||||||||
| Helix | 788 – 792 | 5 | ||||||||||||||
| Turn | 793 – 795 | 3 | ||||||||||||||
| Beta strand | 804 – 807 | 4 | ||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor." Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L. Cell 95:779-791(1998) [PubMed: 9865696] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Identification of a novel serine protease-like molecule in human brain." Meckelein B., Marshall D.C.L., Conn K.J., Pietropaolo M., Van Nostrand W., Abraham C.R. Brain Res. Mol. Brain Res. 55:181-197(1998) [PubMed: 9582421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3). Tissue: Fetal brain. |
| [3] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis. |
| [6] | "An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). |
| [7] | "Structural basis of Smad2 recognition by the Smad anchor for receptor activation." Wu G., Chen Y.-G., Ozdamar B., Gyuricza C.A., Chong P.A., Wrana J.L., Massague J., Shi Y. Science 287:92-97(2000) [PubMed: 10615055] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 771-811 IN COMPLEX WITH SMAD2, MUTAGENESIS. |
| [8] | "Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control." Qin B.Y., Lam S.S., Correia J.J., Lin K. Genes Dev. 16:1950-1963(2002) [PubMed: 12154125] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 773-810 IN COMPLEX WITH SMAD3. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AF104304 mRNA. Translation: AAC99462.1. Different initiation. AF130419 mRNA. Translation: AAD31694.1. Frameshift. AF130420 mRNA. Translation: AAD31695.1. AL513218, AC105754 Genomic DNA. Translation: CAI12285.1. AL513218, AC105754 Genomic DNA. Translation: CAI12286.1. CH471059 Genomic DNA. Translation: EAX06790.1. CH471059 Genomic DNA. Translation: EAX06791.1. BC032680 mRNA. Translation: AAH32680.1. | ||||||||||||||||||
| IPI | IPI00026338. IPI00030648. IPI00480079. | ||||||||||||||||||
| RefSeq | NP_004790.2. NP_015562.1. NP_015563.2. | ||||||||||||||||||
| UniGene | Hs.532345 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||
| SMR | O95405. Positions 679-762. | ||||||||||||||||||
| DisProt | DP00141. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| IntAct | O95405. 6 interactions. | ||||||||||||||||||
| STRING | O95405. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | O95405. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000287727; ENSP00000287727; ENSG00000157077; Homo sapiens. [Genome view] ENST00000371591; ENSP00000360647; ENSG00000157077; Homo sapiens. [Genome view] | ||||||||||||||||||
| GeneID | 9372. | ||||||||||||||||||
| KEGG | hsa:9372. | ||||||||||||||||||
| UCSC | uc001ctn.1. human. uc001cto.1. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 9372. | ||||||||||||||||||
| GeneCards | GC01P052380. | ||||||||||||||||||
| H-InvDB | HIX0000582. | ||||||||||||||||||
| HGNC | HGNC:6775. ZFYVE9. | ||||||||||||||||||
| MIM | 603755. gene. | ||||||||||||||||||
| PharmGKB | PA30532. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | prNOG04433. | ||||||||||||||||||
| HOGENOM | HBG283005. | ||||||||||||||||||
| HOVERGEN | O95405. | ||||||||||||||||||
| InParanoid | O95405. | ||||||||||||||||||
| OMA | KVFSLAH. | ||||||||||||||||||
| OrthoDB | EOG9R26D5. | ||||||||||||||||||
| PhylomeDB | O95405. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | tgfbrpathway. TGF-beta receptor signaling. | ||||||||||||||||||
| Reactome | REACT_6844. Signaling by TGF beta. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | O95405. | ||||||||||||||||||
| Bgee | O95405. | ||||||||||||||||||
| CleanEx | HS_ZFYVE9. | ||||||||||||||||||
| Genevestigator | O95405. | ||||||||||||||||||
| GermOnline | ENSG00000157077. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR000306. Znf_FYVE. IPR017455. Znf_FYVE-rel. IPR011011. Znf_FYVE_PHD. IPR017165. Znf_FYVE_SARA/endofin. [Graphical view] | ||||||||||||||||||
| Pfam | PF01363. FYVE. 1 hit. [Graphical view] | ||||||||||||||||||
| PIRSF | PIRSF037289. SARA/endofin. 1 hit. | ||||||||||||||||||
| SMART | SM00064. FYVE. 1 hit. [Graphical view] | ||||||||||||||||||
| PROSITE | PS50178. ZF_FYVE. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| NextBio | 35102. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | ZFYV9_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O95405 Secondary accession number(s): Q5T0F6 Q9Y5R7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


