Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Zinc finger FYVE domain-containing protein 9

Gene

ZFYVE9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri699 – 758FYVE-typePROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • 1-phosphatidylinositol binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: CAFA
  • serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  • endocytosis Source: UniProtKB
  • endosomal transport Source: GO_Central
  • transforming growth factor beta receptor signaling pathway Source: UniProtKB

Keywordsi

Molecular functionReceptor
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
SignaLinkiO95405
SIGNORiO95405

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ZFYVE9
Synonyms:MADHIP, SARA, SMADIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000157077.14
HGNCiHGNC:6775 ZFYVE9
MIMi603755 gene
neXtProtiNX_O95405

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi782Y → A: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi782Y → E: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi783C → A: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi783C → E: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi788P → A: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi788P → E: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi790Q → A: No effect on complex formation with SMAD2. 1 Publication1
Mutagenesisi793Q → A: No effect on complex formation with SMAD2. 1 Publication1
Mutagenesisi805V → A: Diminishes complex formation with SMAD2. 1 Publication1
Mutagenesisi805V → E: Diminishes complex formation with SMAD2. 1 Publication1

Organism-specific databases

DisGeNETi9372
OpenTargetsiENSG00000157077
PharmGKBiPA30532

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000987151 – 1425Zinc finger FYVE domain-containing protein 9Add BLAST1425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei306PhosphoserineCombined sources1
Modified residuei668PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95405
MaxQBiO95405
PaxDbiO95405
PeptideAtlasiO95405
PRIDEiO95405
ProteomicsDBi50856
50857 [O95405-2]
50858 [O95405-3]

PTM databases

iPTMnetiO95405
PhosphoSitePlusiO95405

Expressioni

Tissue specificityi

Ubiquitous. In the brain found primarily in the cerebrovascular smooth muscle cells and reactive astrocytes.

Gene expression databases

BgeeiENSG00000157077 Expressed in 188 organ(s), highest expression level in kidney
CleanExiHS_ZFYVE9
GenevisibleiO95405 HS

Organism-specific databases

HPAiCAB017702
HPA065852
HPA065862

Interactioni

Subunit structurei

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.4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114773, 43 interactors
CORUMiO95405
IntActiO95405, 40 interactors
MINTiO95405
STRINGi9606.ENSP00000287727

Structurei

Secondary structure

11425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00141
ProteinModelPortaliO95405
SMRiO95405
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95405

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni767 – 823SBDAdd BLAST57

Domaini

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.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri699 – 758FYVE-typePROSITE-ProRule annotationAdd BLAST60

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1841 Eukaryota
ENOG410XSEQ LUCA
GeneTreeiENSGT00840000129741
HOGENOMiHOG000231131
HOVERGENiHBG079085
InParanoidiO95405
KOiK04679
OMAiSQEMTNW
OrthoDBiEOG091G0VJ6
PhylomeDBiO95405
TreeFamiTF324904

Family and domain databases

Gene3Di3.30.40.10, 1 hit
4.10.720.10, 1 hit
InterProiView protein in InterPro
IPR022557 DUF3480
IPR035438 SARA/endofin
IPR024608 SARA_Smad-bd
IPR037145 SARA_Smad-bd_sf
IPR000306 Znf_FYVE
IPR017455 Znf_FYVE-rel
IPR011011 Znf_FYVE_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF11979 DUF3480, 1 hit
PF01363 FYVE, 1 hit
PF11409 SARA, 1 hit
PIRSFiPIRSF037289 SARA/endofin, 1 hit
SMARTiView protein in SMART
SM00064 FYVE, 1 hit
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS50178 ZF_FYVE, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O95405-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MENYFQAEAY NLDKVLDEFE QNEDETVSST LLDTKWNKIL DPPSHRLSFN
60 70 80 90 100
PTLASVNESA VSNESQPQLK VFSLAHSAPL TTEEEDHCAN GQDCNLNPEI
110 120 130 140 150
ATMWIDENAV AEDQLIKRNY SWDDQCSAVE VGEKKCGNLA CLPDEKNVLV
160 170 180 190 200
VAVMHNCDKR TLQNDLQDCN NYNSQSLMDA FSCSLDNENR QTDQFSFSIN
210 220 230 240 250
ESTEKDMNSE KQMDPLNRPK TEGRSVNHLC PTSSDSLASV CSPSQLKDDG
260 270 280 290 300
SIGRDPSMSA ITSLTVDSVI SSQGTDGCPA VKKQENYIPD EDLTGKISSP
310 320 330 340 350
RTDLGSPNSF SHMSEGILMK KEPAEESTTE ESLRSGLPLL LKPDMPNGSG
360 370 380 390 400
RNNDCERCSD CLVPNEVRAD ENEGYEHEET LGTTEFLNMT EHFSESQDMT
410 420 430 440 450
NWKLTKLNEM NDSQVNEEKE KFLQISQPED TNGDSGGQCV GLADAGLDLK
460 470 480 490 500
GTCISESEEC DFSTVIDTPA ANYLSNGCDS YGMQDPGVSF VPKTLPSKED
510 520 530 540 550
SVTEEKEIEE SKSECYSNIY EQRGNEATEG SGLLLNSTGD LMKKNYLHNF
560 570 580 590 600
CSQVPSVLGQ SSPKVVASLP SISVPFGGAR PKQPSNLKLQ IPKPLSDHLQ
610 620 630 640 650
NDFPANSGNN TKNKNDILGK AKLGENSATN VCSPSLGNIS NVDTNGEHLE
660 670 680 690 700
SYEAEISTRP CLALAPDSPD NDLRAGQFGI SARKPFTTLG EVAPVWVPDS
710 720 730 740 750
QAPNCMKCEA RFTFTKRRHH CRACGKVFCA SCCSLKCKLL YMDRKEARVC
760 770 780 790 800
VICHSVLMNA QAWENMMSAS SQSPNPNNPA EYCSTIPPLQ QAQASGALSS
810 820 830 840 850
PPPTVMVPVG VLKHPGAEVA QPREQRRVWF ADGILPNGEV ADAAKLTMNG
860 870 880 890 900
TSSAGTLAVS HDPVKPVTTS PLPAETDICL FSGSITQVGS PVGSAMNLIP
910 920 930 940 950
EDGLPPILIS TGVKGDYAVE EKPSQISVMQ QLEDGGPDPL VFVLNANLLS
960 970 980 990 1000
MVKIVNYVNR KCWCFTTKGM HAVGQSEIVI LLQCLPDEKC LPKDIFNHFV
1010 1020 1030 1040 1050
QLYRDALAGN VVSNLGHSFF SQSFLGSKEH GGFLYVTSTY QSLQDLVLPT
1060 1070 1080 1090 1100
PPYLFGILIQ KWETPWAKVF PIRLMLRLGA EYRLYPCPLF SVRFRKPLFG
1110 1120 1130 1140 1150
ETGHTIMNLL ADFRNYQYTL PVVQGLVVDM EVRKTSIKIP SNRYNEMMKA
1160 1170 1180 1190 1200
MNKSNEHVLA GGACFNEKAD SHLVCVQNDD GNYQTQAISI HNQPRKVTGA
1210 1220 1230 1240 1250
SFFVFSGALK SSSGYLAKSS IVEDGVMVQI TAENMDSLRQ ALREMKDFTI
1260 1270 1280 1290 1300
TCGKADAEEP QEHIHIQWVD DDKNVSKGVV SPIDGKSMET ITNVKIFHGS
1310 1320 1330 1340 1350
EYKANGKVIR WTEVFFLEND DQHNCLSDPA DHSRLTEHVA KAFCLALCPH
1360 1370 1380 1390 1400
LKLLKEDGMT KLGLRVTLDS DQVGYQAGSN GQPLPSQYMN DLDSALVPVI
1410 1420
HGGACQLSEG PVVMELIFYI LENIV
Length:1,425
Mass (Da):156,403
Last modified:August 14, 2001 - v2
Checksum:iADE5CB530C1272C6
GO
Isoform 2 (identifier: O95405-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:1,366
Mass (Da):150,348
Checksum:iC7779D54E2435CC9
GO
Isoform 3 (identifier: O95405-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     760-762: AQA → GKY
     763-1425: Missing.

Show »
Length:762
Mass (Da):83,721
Checksum:iB96C60B807CFF367
GO

Sequence cautioni

The sequence AAC99462 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD31694 differs from that shown. Reason: Frameshift at position 1243.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052985287Y → C. Corresponds to variant dbSNP:rs9803965Ensembl.1
Natural variantiVAR_052986414Q → P. Corresponds to variant dbSNP:rs3790525Ensembl.1
Natural variantiVAR_052987639I → V. Corresponds to variant dbSNP:rs11809887Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004315760 – 818Missing in isoform 2. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_004316760 – 762AQA → GKY in isoform 3. 1 Publication3
Alternative sequenceiVSP_004317763 – 1425Missing in isoform 3. 1 PublicationAdd BLAST663

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104304 mRNA Translation: AAC99462.1 Different initiation.
AF130419 mRNA Translation: AAD31694.1 Frameshift.
AF130420 mRNA Translation: AAD31695.1
AC105754 Genomic DNA No translation available.
AL513218 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06790.1
CH471059 Genomic DNA Translation: EAX06791.1
BC032680 mRNA Translation: AAH32680.1
CCDSiCCDS563.1 [O95405-1]
CCDS564.1 [O95405-2]
RefSeqiNP_004790.2, NM_004799.3 [O95405-1]
NP_015563.2, NM_007324.3 [O95405-2]
XP_011540739.1, XM_011542437.2 [O95405-1]
UniGeneiHs.532345

Genome annotation databases

EnsembliENST00000287727; ENSP00000287727; ENSG00000157077 [O95405-1]
ENST00000357206; ENSP00000349737; ENSG00000157077 [O95405-2]
ENST00000371591; ENSP00000360647; ENSG00000157077 [O95405-1]
GeneIDi9372
KEGGihsa:9372
UCSCiuc001cto.5 human [O95405-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104304 mRNA Translation: AAC99462.1 Different initiation.
AF130419 mRNA Translation: AAD31694.1 Frameshift.
AF130420 mRNA Translation: AAD31695.1
AC105754 Genomic DNA No translation available.
AL513218 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX06790.1
CH471059 Genomic DNA Translation: EAX06791.1
BC032680 mRNA Translation: AAH32680.1
CCDSiCCDS563.1 [O95405-1]
CCDS564.1 [O95405-2]
RefSeqiNP_004790.2, NM_004799.3 [O95405-1]
NP_015563.2, NM_007324.3 [O95405-2]
XP_011540739.1, XM_011542437.2 [O95405-1]
UniGeneiHs.532345

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DEVX-ray2.20B/D771-811[»]
1MK2X-ray2.74B773-810[»]
4BKWX-ray2.53A895-1425[»]
5MJYX-ray2.25E/F1-22[»]
DisProtiDP00141
ProteinModelPortaliO95405
SMRiO95405
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114773, 43 interactors
CORUMiO95405
IntActiO95405, 40 interactors
MINTiO95405
STRINGi9606.ENSP00000287727

PTM databases

iPTMnetiO95405
PhosphoSitePlusiO95405

Proteomic databases

EPDiO95405
MaxQBiO95405
PaxDbiO95405
PeptideAtlasiO95405
PRIDEiO95405
ProteomicsDBi50856
50857 [O95405-2]
50858 [O95405-3]

Protocols and materials databases

DNASUi9372
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287727; ENSP00000287727; ENSG00000157077 [O95405-1]
ENST00000357206; ENSP00000349737; ENSG00000157077 [O95405-2]
ENST00000371591; ENSP00000360647; ENSG00000157077 [O95405-1]
GeneIDi9372
KEGGihsa:9372
UCSCiuc001cto.5 human [O95405-1]

Organism-specific databases

CTDi9372
DisGeNETi9372
EuPathDBiHostDB:ENSG00000157077.14
GeneCardsiZFYVE9
H-InvDBiHIX0000582
HGNCiHGNC:6775 ZFYVE9
HPAiCAB017702
HPA065852
HPA065862
MIMi603755 gene
neXtProtiNX_O95405
OpenTargetsiENSG00000157077
PharmGKBiPA30532
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1841 Eukaryota
ENOG410XSEQ LUCA
GeneTreeiENSGT00840000129741
HOGENOMiHOG000231131
HOVERGENiHBG079085
InParanoidiO95405
KOiK04679
OMAiSQEMTNW
OrthoDBiEOG091G0VJ6
PhylomeDBiO95405
TreeFamiTF324904

Enzyme and pathway databases

ReactomeiR-HSA-2173788 Downregulation of TGF-beta receptor signaling
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-3656532 TGFBR1 KD Mutants in Cancer
SignaLinkiO95405
SIGNORiO95405

Miscellaneous databases

ChiTaRSiZFYVE9 human
EvolutionaryTraceiO95405
GeneWikiiZinc_finger_FYVE_domain-containing_protein_9
GenomeRNAii9372
PROiPR:O95405
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157077 Expressed in 188 organ(s), highest expression level in kidney
CleanExiHS_ZFYVE9
GenevisibleiO95405 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
4.10.720.10, 1 hit
InterProiView protein in InterPro
IPR022557 DUF3480
IPR035438 SARA/endofin
IPR024608 SARA_Smad-bd
IPR037145 SARA_Smad-bd_sf
IPR000306 Znf_FYVE
IPR017455 Znf_FYVE-rel
IPR011011 Znf_FYVE_PHD
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF11979 DUF3480, 1 hit
PF01363 FYVE, 1 hit
PF11409 SARA, 1 hit
PIRSFiPIRSF037289 SARA/endofin, 1 hit
SMARTiView protein in SMART
SM00064 FYVE, 1 hit
SUPFAMiSSF57903 SSF57903, 1 hit
PROSITEiView protein in PROSITE
PS50178 ZF_FYVE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiZFYV9_HUMAN
AccessioniPrimary (citable) accession number: O95405
Secondary accession number(s): Q5T0F6
, Q5T0F7, Q9UNE1, Q9Y5R7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: August 14, 2001
Last modified: November 7, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again