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UniProtKB - O95405 (ZFYV9_HUMAN)

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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
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • endocytosis Source: UniProtKB
  • transforming growth factor beta receptor signaling pathway Source: UniProtKB
View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
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
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

Show more details

GO - Molecular functioni

  • protein domain specific binding Source: CAFA
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114773, 42 interactors
CORUMiO95405
IntActiO95405, 40 interactors
MINTiO95405
STRINGi9606.ENSP00000287727

Structurei

Secondary structure

11425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 20Combined sources17
Helixi779 – 781Combined sources3
Helixi788 – 792Combined sources5
Turni793 – 795Combined sources3
Beta strandi797 – 800Combined sources4
Beta strandi804 – 807Combined sources4
Beta strandi901 – 903Combined sources3
Beta strandi907 – 909Combined sources3
Beta strandi918 – 922Combined sources5
Helixi925 – 932Combined sources8
Beta strandi940 – 945Combined sources6
Beta strandi948 – 957Combined sources10
Beta strandi960 – 970Combined sources11
Helixi971 – 973Combined sources3
Beta strandi977 – 983Combined sources7
Helixi994 – 1007Combined sources14
Beta strandi1017 – 1019Combined sources3
Beta strandi1030 – 1036Combined sources7
Beta strandi1039 – 1041Combined sources3
Beta strandi1050 – 1060Combined sources11
Turni1061 – 1063Combined sources3
Helixi1064 – 1069Combined sources6
Helixi1071 – 1082Combined sources12
Beta strandi1089 – 1091Combined sources3
Helixi1106 – 1109Combined sources4
Beta strandi1113 – 1115Combined sources3
Beta strandi1127 – 1131Combined sources5
Beta strandi1134 – 1140Combined sources7
Helixi1141 – 1143Combined sources3
Helixi1144 – 1152Combined sources9
Beta strandi1156 – 1162Combined sources7
Beta strandi1170 – 1177Combined sources8
Beta strandi1183 – 1192Combined sources10
Beta strandi1196 – 1199Combined sources4
Beta strandi1201 – 1207Combined sources7
Beta strandi1218 – 1222Combined sources5
Beta strandi1225 – 1229Combined sources5
Helixi1232 – 1243Combined sources12
Beta strandi1248 – 1250Combined sources3
Beta strandi1263 – 1270Combined sources8
Turni1282 – 1284Combined sources3
Beta strandi1291 – 1295Combined sources5
Beta strandi1302 – 1304Combined sources3
Beta strandi1307 – 1316Combined sources10
Helixi1334 – 1347Combined sources14
Helixi1348 – 1350Combined sources3
Helixi1351 – 1356Combined sources6
Beta strandi1361 – 1368Combined sources8
Beta strandi1373 – 1379Combined sources7
Helixi1386 – 1388Combined sources3
Helixi1389 – 1400Combined sources12
Beta strandi1413 – 1422Combined sources10

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
OMAiSNRYNEM
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

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: June 20, 2018
This is version 170 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

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