ID   ZFYV9_HUMAN             Reviewed;        1425 AA.
AC   O95405; Q5T0F6; Q5T0F7; Q9UNE1; Q9Y5R7;
DT   14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   14-AUG-2001, sequence version 2.
DT   24-JAN-2024, entry version 201.
DE   RecName: Full=Zinc finger FYVE domain-containing protein 9;
DE   AltName: Full=Mothers against decapentaplegic homolog-interacting protein;
DE            Short=Madh-interacting protein;
DE   AltName: Full=Novel serine protease;
DE            Short=NSP;
DE   AltName: Full=Receptor activation anchor;
DE            Short=hSARA;
DE   AltName: Full=Smad anchor for receptor activation;
GN   Name=ZFYVE9; Synonyms=MADHIP, SARA, SMADIP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SMAD2; SMAD3;
RP   TGFBR1 AND TGFBR2, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9865696; DOI=10.1016/s0092-8674(00)81701-8;
RA   Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L.;
RT   "SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.";
RL   Cell 95:779-791(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC   TISSUE=Fetal brain;
RX   PubMed=9582421; DOI=10.1016/s0169-328x(97)00366-5;
RA   Meckelein B., Marshall D.C.L., Conn K.J., Pietropaolo M., Van Nostrand W.,
RA   Abraham C.R.;
RT   "Identification of a novel serine protease-like molecule in human brain.";
RL   Brain Res. Mol. Brain Res. 55:181-197(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=11877415; DOI=10.1074/jbc.m107983200;
RA   Panopoulou E., Gillooly D.J., Wrana J.L., Zerial M., Stenmark H.,
RA   Murphy C., Fotsis T.;
RT   "Early endosomal regulation of Smad-dependent signaling in endothelial
RT   cells.";
RL   J. Biol. Chem. 277:18046-18052(2002).
RN   [7]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML; SMAD2 AND SMAD3.
RX   PubMed=15356634; DOI=10.1038/nature02783;
RA   Lin H.K., Bergmann S., Pandolfi P.P.;
RT   "Cytoplasmic PML function in TGF-beta signalling.";
RL   Nature 431:205-211(2004).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 771-811 IN COMPLEX WITH SMAD2, AND
RP   MUTAGENESIS.
RX   PubMed=10615055; DOI=10.1126/science.287.5450.92;
RA   Wu G., Chen Y.-G., Ozdamar B., Gyuricza C.A., Chong P.A., Wrana J.L.,
RA   Massague J., Shi Y.;
RT   "Structural basis of Smad2 recognition by the Smad anchor for receptor
RT   activation.";
RL   Science 287:92-97(2000).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 773-810 IN COMPLEX WITH SMAD3.
RX   PubMed=12154125; DOI=10.1101/gad.1002002;
RA   Qin B.Y., Lam S.S., Correia J.J., Lin K.;
RT   "Smad3 allostery links TGF-beta receptor kinase activation to
RT   transcriptional control.";
RL   Genes Dev. 16:1950-1963(2002).
CC   -!- FUNCTION: Early endosomal protein that functions to recruit SMAD2/SMAD3
CC       to intracellular membranes and to the TGF-beta receptor. Plays a
CC       significant role in TGF-mediated signaling by regulating the
CC       subcellular location of SMAD2 and SMAD3 and modulating the
CC       transcriptional activity of the SMAD3/SMAD4 complex. Possibly
CC       associated with TGF-beta receptor internalization.
CC       {ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:9865696}.
CC   -!- SUBUNIT: Interacts (via the SBD region) with SMAD2; the interaction
CC       recruits SMAD2 to the TGF-beta receptor and is disrupted by
CC       phosphorylation of SMAD2 upon TGF-beta receptor activation. Interacts
CC       with SMAD3. Interacts with TGFBR1 and TGFBR2; the interaction recruits
CC       SMAD2 to the TGF-beta receptor. Interacts with PML.
CC       {ECO:0000269|PubMed:10615055, ECO:0000269|PubMed:12154125,
CC       ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:9865696}.
CC   -!- INTERACTION:
CC       O95405; Q9Y561: LRP12; NbExp=2; IntAct=EBI-296817, EBI-296693;
CC       O95405; P62136: PPP1CA; NbExp=3; IntAct=EBI-296817, EBI-357253;
CC       O95405; P36873: PPP1CC; NbExp=5; IntAct=EBI-296817, EBI-356283;
CC       O95405; P08100: RHO; NbExp=2; IntAct=EBI-296817, EBI-1394177;
CC       O95405; Q15796: SMAD2; NbExp=6; IntAct=EBI-296817, EBI-1040141;
CC       O95405; P84022: SMAD3; NbExp=5; IntAct=EBI-296817, EBI-347161;
CC       O95405; Q13277: STX3; NbExp=3; IntAct=EBI-296817, EBI-1394295;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O95405-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95405-2; Sequence=VSP_004315;
CC       Name=3;
CC         IsoId=O95405-3; Sequence=VSP_004316, VSP_004317;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. In the brain found primarily in the
CC       cerebrovascular smooth muscle cells and reactive astrocytes.
CC   -!- DOMAIN: The SMAD binding domain (SBD) interacts with the MH2 domains of
CC       SMAD2 or SMAD3.
CC   -!- DOMAIN: The FYVE-type zinc finger is necessary and sufficient for its
CC       localization into early endosomes and mediates the association with
CC       PI3P.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC99462.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAD31694.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF104304; AAC99462.1; ALT_INIT; mRNA.
DR   EMBL; AF130419; AAD31694.1; ALT_FRAME; mRNA.
DR   EMBL; AF130420; AAD31695.1; -; mRNA.
DR   EMBL; AC105754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL513218; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471059; EAX06790.1; -; Genomic_DNA.
DR   EMBL; CH471059; EAX06791.1; -; Genomic_DNA.
DR   EMBL; BC032680; AAH32680.1; -; mRNA.
DR   CCDS; CCDS563.1; -. [O95405-1]
DR   CCDS; CCDS564.1; -. [O95405-2]
DR   RefSeq; NP_004790.2; NM_004799.3. [O95405-1]
DR   RefSeq; NP_015563.2; NM_007324.3. [O95405-2]
DR   RefSeq; XP_011540739.1; XM_011542437.2. [O95405-1]
DR   PDB; 1DEV; X-ray; 2.20 A; B/D=771-811.
DR   PDB; 1MK2; X-ray; 2.74 A; B=773-810.
DR   PDB; 4BKW; X-ray; 2.53 A; A=895-1425.
DR   PDB; 5MJY; X-ray; 2.25 A; E/F=1-22.
DR   PDBsum; 1DEV; -.
DR   PDBsum; 1MK2; -.
DR   PDBsum; 4BKW; -.
DR   PDBsum; 5MJY; -.
DR   AlphaFoldDB; O95405; -.
DR   SMR; O95405; -.
DR   BioGRID; 114773; 105.
DR   CORUM; O95405; -.
DR   IntAct; O95405; 56.
DR   MINT; O95405; -.
DR   STRING; 9606.ENSP00000287727; -.
DR   GlyCosmos; O95405; 1 site, 1 glycan.
DR   GlyGen; O95405; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O95405; -.
DR   PhosphoSitePlus; O95405; -.
DR   SwissPalm; O95405; -.
DR   BioMuta; ZFYVE9; -.
DR   EPD; O95405; -.
DR   jPOST; O95405; -.
DR   MassIVE; O95405; -.
DR   MaxQB; O95405; -.
DR   PaxDb; 9606-ENSP00000287727; -.
DR   PeptideAtlas; O95405; -.
DR   ProteomicsDB; 50856; -. [O95405-1]
DR   ProteomicsDB; 50857; -. [O95405-2]
DR   ProteomicsDB; 50858; -. [O95405-3]
DR   Pumba; O95405; -.
DR   Antibodypedia; 32995; 152 antibodies from 25 providers.
DR   DNASU; 9372; -.
DR   Ensembl; ENST00000287727.8; ENSP00000287727.3; ENSG00000157077.16. [O95405-1]
DR   Ensembl; ENST00000357206.6; ENSP00000349737.2; ENSG00000157077.16. [O95405-2]
DR   Ensembl; ENST00000371591.2; ENSP00000360647.1; ENSG00000157077.16. [O95405-1]
DR   GeneID; 9372; -.
DR   KEGG; hsa:9372; -.
DR   MANE-Select; ENST00000287727.8; ENSP00000287727.3; NM_004799.4; NP_004790.2.
DR   UCSC; uc001cto.5; human. [O95405-1]
DR   AGR; HGNC:6775; -.
DR   CTD; 9372; -.
DR   DisGeNET; 9372; -.
DR   GeneCards; ZFYVE9; -.
DR   HGNC; HGNC:6775; ZFYVE9.
DR   HPA; ENSG00000157077; Low tissue specificity.
DR   MIM; 603755; gene.
DR   neXtProt; NX_O95405; -.
DR   OpenTargets; ENSG00000157077; -.
DR   PharmGKB; PA30532; -.
DR   VEuPathDB; HostDB:ENSG00000157077; -.
DR   eggNOG; KOG1841; Eukaryota.
DR   GeneTree; ENSGT00940000154290; -.
DR   HOGENOM; CLU_004326_1_0_1; -.
DR   InParanoid; O95405; -.
DR   OMA; IPPNCGG; -.
DR   OrthoDB; 3061552at2759; -.
DR   PhylomeDB; O95405; -.
DR   TreeFam; TF324904; -.
DR   PathwayCommons; O95405; -.
DR   Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling. [O95405-1]
DR   Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. [O95405-1]
DR   Reactome; R-HSA-3304356; SMAD2/3 Phosphorylation Motif Mutants in Cancer. [O95405-1]
DR   Reactome; R-HSA-3656532; TGFBR1 KD Mutants in Cancer. [O95405-1]
DR   SignaLink; O95405; -.
DR   SIGNOR; O95405; -.
DR   BioGRID-ORCS; 9372; 15 hits in 1161 CRISPR screens.
DR   ChiTaRS; ZFYVE9; human.
DR   EvolutionaryTrace; O95405; -.
DR   GeneWiki; Zinc_finger_FYVE_domain-containing_protein_9; -.
DR   GenomeRNAi; 9372; -.
DR   Pharos; O95405; Tbio.
DR   PRO; PR:O95405; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O95405; Protein.
DR   Bgee; ENSG00000157077; Expressed in calcaneal tendon and 162 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005769; C:early endosome; NAS:UniProtKB.
DR   GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR   GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR   GO; GO:0006897; P:endocytosis; NAS:UniProtKB.
DR   GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR   CDD; cd15729; FYVE_endofin; 1.
DR   Gene3D; 3.30.500.40; -; 1.
DR   Gene3D; 3.30.1360.220; Domain of unknown function (DUF3480), N-terminal subdomain; 1.
DR   Gene3D; 4.10.720.10; Smad anchor for receptor activation, Smad-binding domain; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   IDEAL; IID00112; -.
DR   InterPro; IPR022557; SARA-like_C.
DR   InterPro; IPR024608; SARA-like_SBD.
DR   InterPro; IPR035438; SARA/endofin.
DR   InterPro; IPR037145; SARA_Smad-bd_sf.
DR   InterPro; IPR000306; Znf_FYVE.
DR   InterPro; IPR017455; Znf_FYVE-rel.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR46319; ZINC FINGER FYVE DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR46319:SF2; ZINC FINGER FYVE DOMAIN-CONTAINING PROTEIN 9; 1.
DR   Pfam; PF01363; FYVE; 1.
DR   Pfam; PF11409; SARA; 1.
DR   Pfam; PF11979; SARA_C; 1.
DR   PIRSF; PIRSF037289; SARA/endofin; 1.
DR   SMART; SM01421; DUF3480; 1.
DR   SMART; SM00064; FYVE; 1.
DR   SMART; SM01422; SARA; 1.
DR   SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR   PROSITE; PS50178; ZF_FYVE; 1.
DR   Genevisible; O95405; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Endosome; Membrane;
KW   Metal-binding; Phosphoprotein; Receptor; Reference proteome; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..1425
FT                   /note="Zinc finger FYVE domain-containing protein 9"
FT                   /id="PRO_0000098715"
FT   ZN_FING         699..758
FT                   /note="FYVE-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   REGION          201..255
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          291..352
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          767..823
FT                   /note="SBD"
FT   COMPBIAS        204..218
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        226..246
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        299..313
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         705
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         708
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         721
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         724
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         729
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         732
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         750
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   BINDING         753
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT   MOD_RES         306
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         668
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         760..818
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9582421"
FT                   /id="VSP_004315"
FT   VAR_SEQ         760..762
FT                   /note="AQA -> GKY (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9582421"
FT                   /id="VSP_004316"
FT   VAR_SEQ         763..1425
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9582421"
FT                   /id="VSP_004317"
FT   VARIANT         287
FT                   /note="Y -> C (in dbSNP:rs9803965)"
FT                   /id="VAR_052985"
FT   VARIANT         414
FT                   /note="Q -> P (in dbSNP:rs3790525)"
FT                   /id="VAR_052986"
FT   VARIANT         639
FT                   /note="I -> V (in dbSNP:rs11809887)"
FT                   /id="VAR_052987"
FT   MUTAGEN         782
FT                   /note="Y->A: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         782
FT                   /note="Y->E: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         783
FT                   /note="C->A: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         783
FT                   /note="C->E: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         788
FT                   /note="P->A: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         788
FT                   /note="P->E: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         790
FT                   /note="Q->A: No effect on complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         793
FT                   /note="Q->A: No effect on complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         805
FT                   /note="V->A: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   MUTAGEN         805
FT                   /note="V->E: Diminishes complex formation with SMAD2."
FT                   /evidence="ECO:0000269|PubMed:10615055"
FT   HELIX           4..20
FT                   /evidence="ECO:0007829|PDB:5MJY"
FT   HELIX           779..781
FT                   /evidence="ECO:0007829|PDB:1DEV"
FT   HELIX           788..792
FT                   /evidence="ECO:0007829|PDB:1DEV"
FT   TURN            793..795
FT                   /evidence="ECO:0007829|PDB:1DEV"
FT   STRAND          797..800
FT                   /evidence="ECO:0007829|PDB:1MK2"
FT   STRAND          804..807
FT                   /evidence="ECO:0007829|PDB:1DEV"
FT   STRAND          901..903
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          907..909
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          918..922
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           925..932
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          940..945
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          948..957
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          960..970
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           971..973
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          977..983
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           994..1007
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1017..1019
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1030..1036
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1039..1041
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1050..1060
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   TURN            1061..1063
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1064..1069
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1071..1082
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1089..1091
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1106..1109
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1113..1115
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1127..1131
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1134..1140
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1141..1143
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1144..1152
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1156..1162
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1170..1177
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1183..1192
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1196..1199
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1201..1207
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1218..1222
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1225..1229
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1232..1243
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1248..1250
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1263..1270
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   TURN            1282..1284
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1291..1295
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1302..1304
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1307..1316
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1334..1347
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1348..1350
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1351..1356
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1361..1368
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1373..1379
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1386..1388
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   HELIX           1389..1400
FT                   /evidence="ECO:0007829|PDB:4BKW"
FT   STRAND          1413..1422
FT                   /evidence="ECO:0007829|PDB:4BKW"
SQ   SEQUENCE   1425 AA;  156403 MW;  ADE5CB530C1272C6 CRC64;
     MENYFQAEAY NLDKVLDEFE QNEDETVSST LLDTKWNKIL DPPSHRLSFN PTLASVNESA
     VSNESQPQLK VFSLAHSAPL TTEEEDHCAN GQDCNLNPEI ATMWIDENAV AEDQLIKRNY
     SWDDQCSAVE VGEKKCGNLA CLPDEKNVLV VAVMHNCDKR TLQNDLQDCN NYNSQSLMDA
     FSCSLDNENR QTDQFSFSIN ESTEKDMNSE KQMDPLNRPK TEGRSVNHLC PTSSDSLASV
     CSPSQLKDDG SIGRDPSMSA ITSLTVDSVI SSQGTDGCPA VKKQENYIPD EDLTGKISSP
     RTDLGSPNSF SHMSEGILMK KEPAEESTTE ESLRSGLPLL LKPDMPNGSG RNNDCERCSD
     CLVPNEVRAD ENEGYEHEET LGTTEFLNMT EHFSESQDMT NWKLTKLNEM NDSQVNEEKE
     KFLQISQPED TNGDSGGQCV GLADAGLDLK GTCISESEEC DFSTVIDTPA ANYLSNGCDS
     YGMQDPGVSF VPKTLPSKED SVTEEKEIEE SKSECYSNIY EQRGNEATEG SGLLLNSTGD
     LMKKNYLHNF CSQVPSVLGQ SSPKVVASLP SISVPFGGAR PKQPSNLKLQ IPKPLSDHLQ
     NDFPANSGNN TKNKNDILGK AKLGENSATN VCSPSLGNIS NVDTNGEHLE SYEAEISTRP
     CLALAPDSPD NDLRAGQFGI SARKPFTTLG EVAPVWVPDS QAPNCMKCEA RFTFTKRRHH
     CRACGKVFCA SCCSLKCKLL YMDRKEARVC VICHSVLMNA QAWENMMSAS SQSPNPNNPA
     EYCSTIPPLQ QAQASGALSS PPPTVMVPVG VLKHPGAEVA QPREQRRVWF ADGILPNGEV
     ADAAKLTMNG TSSAGTLAVS HDPVKPVTTS PLPAETDICL FSGSITQVGS PVGSAMNLIP
     EDGLPPILIS TGVKGDYAVE EKPSQISVMQ QLEDGGPDPL VFVLNANLLS MVKIVNYVNR
     KCWCFTTKGM HAVGQSEIVI LLQCLPDEKC LPKDIFNHFV QLYRDALAGN VVSNLGHSFF
     SQSFLGSKEH GGFLYVTSTY QSLQDLVLPT PPYLFGILIQ KWETPWAKVF PIRLMLRLGA
     EYRLYPCPLF SVRFRKPLFG ETGHTIMNLL ADFRNYQYTL PVVQGLVVDM EVRKTSIKIP
     SNRYNEMMKA MNKSNEHVLA GGACFNEKAD SHLVCVQNDD GNYQTQAISI HNQPRKVTGA
     SFFVFSGALK SSSGYLAKSS IVEDGVMVQI TAENMDSLRQ ALREMKDFTI TCGKADAEEP
     QEHIHIQWVD DDKNVSKGVV SPIDGKSMET ITNVKIFHGS EYKANGKVIR WTEVFFLEND
     DQHNCLSDPA DHSRLTEHVA KAFCLALCPH LKLLKEDGMT KLGLRVTLDS DQVGYQAGSN
     GQPLPSQYMN DLDSALVPVI HGGACQLSEG PVVMELIFYI LENIV
//