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O95405 (ZFYV9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc finger FYVE domain-containing protein 9
Alternative name(s):
Mothers against decapentaplegic homolog-interacting protein
Short name=Madh-interacting protein
Novel serine protease
Short name=NSP
Receptor activation anchor
Short name=hSARA
Smad anchor for receptor activation
Gene names
Name:ZFYVE9
Synonyms:MADHIP, SARA, SMADIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1425 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.8

Subunit 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. Ref.1 Ref.8

Subcellular location

Cytoplasm. Early endosome membrane Ref.1 Ref.6 Ref.8.

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.

The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P.

Sequence similarities

Contains 1 FYVE-type zinc finger.

Sequence caution

The sequence AAC99462.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAD31694.1 differs from that shown. Reason: Frameshift at position 1243.

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.
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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14251425Zinc finger FYVE domain-containing protein 9
PRO_0000098715

Regions

Zinc finger699 – 75860FYVE-type
Region767 – 82357SBD

Natural variations

Alternative sequence760 – 81859Missing in isoform 2.
VSP_004315
Alternative sequence760 – 7623AQA → GKY in isoform 3.
VSP_004316
Alternative sequence763 – 1425663Missing in isoform 3.
VSP_004317
Natural variant2871Y → C.
Corresponds to variant rs9803965 [ dbSNP | Ensembl ].
VAR_052985
Natural variant4141Q → P.
Corresponds to variant rs3790525 [ dbSNP | Ensembl ].
VAR_052986
Natural variant6391I → V.
Corresponds to variant rs11809887 [ dbSNP | Ensembl ].
VAR_052987

Experimental info

Mutagenesis7821Y → A: Diminishes complex formation with SMAD2.
Mutagenesis7821Y → E: Diminishes complex formation with SMAD2.
Mutagenesis7831C → A: Diminishes complex formation with SMAD2.
Mutagenesis7831C → E: Diminishes complex formation with SMAD2.
Mutagenesis7881P → A: Diminishes complex formation with SMAD2.
Mutagenesis7881P → E: Diminishes complex formation with SMAD2.
Mutagenesis7901Q → A: No effect on complex formation with SMAD2.
Mutagenesis7931Q → A: No effect on complex formation with SMAD2.
Mutagenesis8051V → A: Diminishes complex formation with SMAD2.
Mutagenesis8051V → E: Diminishes complex formation with SMAD2.

Secondary structure

.............................................................................................. 1425
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 14, 2001. Version 2.
Checksum: ADE5CB530C1272C6

FASTA1,425156,403
        10         20         30         40         50         60 
MENYFQAEAY NLDKVLDEFE QNEDETVSST LLDTKWNKIL DPPSHRLSFN PTLASVNESA 

        70         80         90        100        110        120 
VSNESQPQLK VFSLAHSAPL TTEEEDHCAN GQDCNLNPEI ATMWIDENAV AEDQLIKRNY 

       130        140        150        160        170        180 
SWDDQCSAVE VGEKKCGNLA CLPDEKNVLV VAVMHNCDKR TLQNDLQDCN NYNSQSLMDA 

       190        200        210        220        230        240 
FSCSLDNENR QTDQFSFSIN ESTEKDMNSE KQMDPLNRPK TEGRSVNHLC PTSSDSLASV 

       250        260        270        280        290        300 
CSPSQLKDDG SIGRDPSMSA ITSLTVDSVI SSQGTDGCPA VKKQENYIPD EDLTGKISSP 

       310        320        330        340        350        360 
RTDLGSPNSF SHMSEGILMK KEPAEESTTE ESLRSGLPLL LKPDMPNGSG RNNDCERCSD 

       370        380        390        400        410        420 
CLVPNEVRAD ENEGYEHEET LGTTEFLNMT EHFSESQDMT NWKLTKLNEM NDSQVNEEKE 

       430        440        450        460        470        480 
KFLQISQPED TNGDSGGQCV GLADAGLDLK GTCISESEEC DFSTVIDTPA ANYLSNGCDS 

       490        500        510        520        530        540 
YGMQDPGVSF VPKTLPSKED SVTEEKEIEE SKSECYSNIY EQRGNEATEG SGLLLNSTGD 

       550        560        570        580        590        600 
LMKKNYLHNF CSQVPSVLGQ SSPKVVASLP SISVPFGGAR PKQPSNLKLQ IPKPLSDHLQ 

       610        620        630        640        650        660 
NDFPANSGNN TKNKNDILGK AKLGENSATN VCSPSLGNIS NVDTNGEHLE SYEAEISTRP 

       670        680        690        700        710        720 
CLALAPDSPD NDLRAGQFGI SARKPFTTLG EVAPVWVPDS QAPNCMKCEA RFTFTKRRHH 

       730        740        750        760        770        780 
CRACGKVFCA SCCSLKCKLL YMDRKEARVC VICHSVLMNA QAWENMMSAS SQSPNPNNPA 

       790        800        810        820        830        840 
EYCSTIPPLQ QAQASGALSS PPPTVMVPVG VLKHPGAEVA QPREQRRVWF ADGILPNGEV 

       850        860        870        880        890        900 
ADAAKLTMNG TSSAGTLAVS HDPVKPVTTS PLPAETDICL FSGSITQVGS PVGSAMNLIP 

       910        920        930        940        950        960 
EDGLPPILIS TGVKGDYAVE EKPSQISVMQ QLEDGGPDPL VFVLNANLLS MVKIVNYVNR 

       970        980        990       1000       1010       1020 
KCWCFTTKGM HAVGQSEIVI LLQCLPDEKC LPKDIFNHFV QLYRDALAGN VVSNLGHSFF 

      1030       1040       1050       1060       1070       1080 
SQSFLGSKEH GGFLYVTSTY QSLQDLVLPT PPYLFGILIQ KWETPWAKVF PIRLMLRLGA 

      1090       1100       1110       1120       1130       1140 
EYRLYPCPLF SVRFRKPLFG ETGHTIMNLL ADFRNYQYTL PVVQGLVVDM EVRKTSIKIP 

      1150       1160       1170       1180       1190       1200 
SNRYNEMMKA MNKSNEHVLA GGACFNEKAD SHLVCVQNDD GNYQTQAISI HNQPRKVTGA 

      1210       1220       1230       1240       1250       1260 
SFFVFSGALK SSSGYLAKSS IVEDGVMVQI TAENMDSLRQ ALREMKDFTI TCGKADAEEP 

      1270       1280       1290       1300       1310       1320 
QEHIHIQWVD DDKNVSKGVV SPIDGKSMET ITNVKIFHGS EYKANGKVIR WTEVFFLEND 

      1330       1340       1350       1360       1370       1380 
DQHNCLSDPA DHSRLTEHVA KAFCLALCPH LKLLKEDGMT KLGLRVTLDS DQVGYQAGSN 

      1390       1400       1410       1420 
GQPLPSQYMN DLDSALVPVI HGGACQLSEG PVVMELIFYI LENIV 

« Hide

Isoform 2 [UniParc].

Checksum: C7779D54E2435CC9
Show »

FASTA1,366150,348
Isoform 3 [UniParc].

Checksum: B96C60B807CFF367
Show »

FASTA76283,721

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SMAD2; SMAD3; TGFBR1 AND TGFBR2, FUNCTION, SUBCELLULAR LOCATION.
[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] [Europe PMC] [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. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[6]"Early endosomal regulation of Smad-dependent signaling in endothelial cells."
Panopoulou E., Gillooly D.J., Wrana J.L., Zerial M., Stenmark H., Murphy C., Fotsis T.
J. Biol. Chem. 277:18046-18052(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]"Cytoplasmic PML function in TGF-beta signalling."
Lin H.K., Bergmann S., Pandolfi P.P.
Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML; SMAD2 AND SMAD3.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 771-811 IN COMPLEX WITH SMAD2, MUTAGENESIS.
[11]"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] [Europe PMC] [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.
CCDSCCDS563.1. [O95405-1]
CCDS564.1. [O95405-2]
RefSeqNP_004790.2. NM_004799.3. [O95405-1]
NP_015563.2. NM_007324.3. [O95405-2]
UniGeneHs.532345.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DEVX-ray2.20B/D771-811[»]
1MK2X-ray2.74B773-810[»]
4BKWX-ray2.53A895-1425[»]
DisProtDP00141.
ProteinModelPortalO95405.
SMRO95405. Positions 689-761, 771-811, 895-1424.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114773. 39 interactions.
IntActO95405. 37 interactions.
MINTMINT-243774.
STRING9606.ENSP00000287727.

PTM databases

PhosphoSiteO95405.

Proteomic databases

MaxQBO95405.
PaxDbO95405.
PRIDEO95405.

Protocols and materials databases

DNASU9372.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287727; ENSP00000287727; ENSG00000157077. [O95405-1]
ENST00000357206; ENSP00000349737; ENSG00000157077. [O95405-2]
ENST00000371591; ENSP00000360647; ENSG00000157077. [O95405-1]
GeneID9372.
KEGGhsa:9372.
UCSCuc001ctn.4. human. [O95405-3]
uc001cto.4. human. [O95405-1]
uc001ctp.4. human. [O95405-2]

Organism-specific databases

CTD9372.
GeneCardsGC01P052608.
H-InvDBHIX0000582.
HGNCHGNC:6775. ZFYVE9.
HPACAB017702.
MIM603755. gene.
neXtProtNX_O95405.
PharmGKBPA30532.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG283908.
HOGENOMHOG000231131.
HOVERGENHBG079085.
InParanoidO95405.
KOK04679.
OMATMWIDEN.
OrthoDBEOG7JDQWQ.
PhylomeDBO95405.
TreeFamTF324904.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkO95405.

Gene expression databases

BgeeO95405.
CleanExHS_ZFYVE9.
GenevestigatorO95405.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
4.10.720.10. 1 hit.
InterProIPR022557. 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.
[Graphical view]
PfamPF11979. DUF3480. 1 hit.
PF01363. FYVE. 1 hit.
PF11409. SARA. 1 hit.
[Graphical view]
PIRSFPIRSF037289. SARA/endofin. 1 hit.
SMARTSM00064. FYVE. 1 hit.
[Graphical view]
SUPFAMSSF57903. SSF57903. 1 hit.
PROSITEPS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95405.
GeneWikiZinc_finger_FYVE_domain-containing_protein_9.
GenomeRNAi9372.
NextBio35102.
PROO95405.
SOURCESearch...

Entry information

Entry nameZFYV9_HUMAN
AccessionPrimary (citable) accession number: O95405
Secondary accession number(s): Q5T0F6 expand/collapse secondary AC list , Q5T0F7, Q9UNE1, Q9Y5R7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: August 14, 2001
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM