ID   SPRE3_HUMAN             Reviewed;         410 AA.
AC   Q2MJR0; Q2MJR1;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-FEB-2006, sequence version 1.
DT   24-JAN-2024, entry version 131.
DE   RecName: Full=Sprouty-related, EVH1 domain-containing protein 3;
DE            Short=Spred-3;
GN   Name=SPRED3; Synonyms=EVE-3;
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] (ISOFORMS 1 AND 2), AND ALTERNATIVE SPLICING.
RC   TISSUE=Liver;
RX   PubMed=16478641; DOI=10.1016/j.jhep.2005.10.031;
RA   King J.A.J., Corcoran N.M., D'Abaco G.M., Straffon A.F., Smith C.T.,
RA   Poon C.L.C., Buchert M., I S.T.T., Hall N.E., Lock P., Hovens C.M.;
RT   "Eve-3: a liver enriched suppressor of Ras/MAPK signaling.";
RL   J. Hepatol. 44:758-767(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [3]
RP   PHOSPHORYLATION, AND UBIQUITINATION.
RX   PubMed=17094949; DOI=10.1016/j.bbrc.2006.10.150;
RA   Lock P., I S.T.T., Straffon A.F., Schieb H., Hovens C.M., Stylli S.S.;
RT   "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-
RT   mediated ubiquitination.";
RL   Biochem. Biophys. Res. Commun. 351:1018-1023(2006).
RN   [4]
RP   INTERACTION WITH ZDHHC17.
RX   PubMed=24705354; DOI=10.1093/hmg/ddu137;
RA   Butland S.L., Sanders S.S., Schmidt M.E., Riechers S.P., Lin D.T.,
RA   Martin D.D., Vaid K., Graham R.K., Singaraja R.R., Wanker E.E.,
RA   Conibear E., Hayden M.R.;
RT   "The palmitoyl acyltransferase HIP14 shares a high proportion of
RT   interactors with huntingtin: implications for a role in the pathogenesis of
RT   Huntington's disease.";
RL   Hum. Mol. Genet. 23:4142-4160(2014).
CC   -!- FUNCTION: Tyrosine kinase substrate that inhibits growth-factor-
CC       mediated activation of MAP kinase (By similarity). Inhibits fibroblast
CC       growth factor (FGF)-induced retinal lens fiber differentiation,
CC       probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By
CC       similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition
CC       in lens epithelial cells (By similarity).
CC       {ECO:0000250|UniProtKB:Q6P6N5}.
CC   -!- SUBUNIT: Interacts with palmitoyltransferase ZDHHC17/HIP14; the
CC       interaction leads to palmitoylation of SPRED3.
CC       {ECO:0000269|PubMed:24705354}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6P6N5};
CC       Peripheral membrane protein {ECO:0000250|UniProtKB:Q6P6N5}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q2MJR0-1; Sequence=Displayed;
CC       Name=2; Synonyms=EVE-3;
CC         IsoId=Q2MJR0-2; Sequence=VSP_042949, VSP_042950;
CC   -!- PTM: Phosphorylated on tyrosine. {ECO:0000269|PubMed:17094949}.
CC   -!- PTM: Palmitoylated by ZDHHC17/HIP14. {ECO:0000250|UniProtKB:Q6P6N5}.
CC   -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:17094949}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; DQ323927; ABC54711.1; -; mRNA.
DR   EMBL; DQ323928; ABC54712.1; -; mRNA.
DR   EMBL; AC005789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS42560.1; -. [Q2MJR0-1]
DR   RefSeq; NP_001035987.1; NM_001042522.2. [Q2MJR0-1]
DR   RefSeq; XP_006723282.1; XM_006723219.3.
DR   AlphaFoldDB; Q2MJR0; -.
DR   SMR; Q2MJR0; -.
DR   BioGRID; 134352; 1.
DR   STRING; 9606.ENSP00000345405; -.
DR   iPTMnet; Q2MJR0; -.
DR   PhosphoSitePlus; Q2MJR0; -.
DR   BioMuta; SPRED3; -.
DR   DMDM; 110816429; -.
DR   jPOST; Q2MJR0; -.
DR   MassIVE; Q2MJR0; -.
DR   PaxDb; 9606-ENSP00000345405; -.
DR   PeptideAtlas; Q2MJR0; -.
DR   ProteomicsDB; 61394; -. [Q2MJR0-1]
DR   ProteomicsDB; 61395; -. [Q2MJR0-2]
DR   Antibodypedia; 30059; 80 antibodies from 21 providers.
DR   DNASU; 399473; -.
DR   Ensembl; ENST00000338502.8; ENSP00000345405.4; ENSG00000188766.13. [Q2MJR0-1]
DR   Ensembl; ENST00000586301.6; ENSP00000466568.1; ENSG00000188766.13. [Q2MJR0-1]
DR   Ensembl; ENST00000691638.1; ENSP00000510478.1; ENSG00000188766.13. [Q2MJR0-1]
DR   GeneID; 399473; -.
DR   KEGG; hsa:399473; -.
DR   MANE-Select; ENST00000691638.1; ENSP00000510478.1; NM_001394336.1; NP_001381265.1.
DR   UCSC; uc002oim.5; human. [Q2MJR0-1]
DR   AGR; HGNC:31041; -.
DR   CTD; 399473; -.
DR   GeneCards; SPRED3; -.
DR   HGNC; HGNC:31041; SPRED3.
DR   HPA; ENSG00000188766; Tissue enhanced (brain, pituitary gland).
DR   MIM; 609293; gene.
DR   neXtProt; NX_Q2MJR0; -.
DR   OpenTargets; ENSG00000188766; -.
DR   PharmGKB; PA134871045; -.
DR   VEuPathDB; HostDB:ENSG00000188766; -.
DR   eggNOG; KOG4590; Eukaryota.
DR   GeneTree; ENSGT00940000161445; -.
DR   HOGENOM; CLU_038867_1_1_1; -.
DR   InParanoid; Q2MJR0; -.
DR   OrthoDB; 3031266at2759; -.
DR   PhylomeDB; Q2MJR0; -.
DR   PathwayCommons; Q2MJR0; -.
DR   Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR   Reactome; R-HSA-6802953; RAS signaling downstream of NF1 loss-of-function variants.
DR   BioGRID-ORCS; 399473; 9 hits in 1142 CRISPR screens.
DR   GeneWiki; SPRED3; -.
DR   GenomeRNAi; 399473; -.
DR   Pharos; Q2MJR0; Tbio.
DR   PRO; PR:Q2MJR0; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q2MJR0; Protein.
DR   Bgee; ENSG00000188766; Expressed in kidney epithelium and 170 other cell types or tissues.
DR   ExpressionAtlas; Q2MJR0; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR   GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; ISS:UniProtKB.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR   CDD; cd10574; EVH1_SPRED-like; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR023337; KBD.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR041937; SPRE_EVH1.
DR   InterPro; IPR007875; Sprouty.
DR   InterPro; IPR000697; WH1/EVH1_dom.
DR   PANTHER; PTHR11202:SF19; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN 3; 1.
DR   PANTHER; PTHR11202; SPROUTY-RELATED, EVH1 DOMAIN-CONTAINING PROTEIN FAMILY MEMBER; 1.
DR   Pfam; PF05210; Sprouty; 1.
DR   Pfam; PF00568; WH1; 1.
DR   SMART; SM00461; WH1; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS51488; KBD; 1.
DR   PROSITE; PS51227; SPR; 1.
DR   PROSITE; PS50229; WH1; 1.
DR   Genevisible; Q2MJR0; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Lipoprotein; Membrane; Methylation;
KW   Palmitate; Phosphoprotein; Reference proteome; Ubl conjugation.
FT   CHAIN           1..410
FT                   /note="Sprouty-related, EVH1 domain-containing protein 3"
FT                   /id="PRO_0000247431"
FT   DOMAIN          1..113
FT                   /note="WH1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT   DOMAIN          195..244
FT                   /note="KBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00821"
FT   DOMAIN          296..407
FT                   /note="SPR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT   REGION          117..210
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          258..288
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        117..158
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        172..193
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        260..283
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         240
FT                   /note="Asymmetric dimethylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P6N5"
FT   MOD_RES         248
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6P6N5"
FT   VAR_SEQ         142..152
FT                   /note="SHVDSDSSSSH -> LSQYFRHMLCP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16478641"
FT                   /id="VSP_042949"
FT   VAR_SEQ         153..410
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16478641"
FT                   /id="VSP_042950"
SQ   SEQUENCE   410 AA;  42670 MW;  5086B02CAA11BDFF CRC64;
     MVRVRAVVMA RDDSSGGWLP VGGGGLSQVS VCRVRGARPE GGARQGHYVI HGERLRDQKT
     TLECTLKPGL VYNKVNPIFH HWSLGDCKFG LTFQSPAEAD EFQKSLLAAL AALGRGSLTP
     SSSSSSSSPS QDTAETPCPL TSHVDSDSSS SHSRQETPPS AAAAPIITME SASGFGPTTP
     PQRRRSSAQS YPPLLPFTGI PEPSEPLAGA GGLGWGGRGY EDYRRSGPPA PLALSTCVVR
     FAKTGALRGA ALGPPAALPA PLTEAAPPAP PARPPPGPGP SSAPAKASPE AEEAARCVHC
     RALFRRRADG RGGRCAEAPD PGRLLVRRLS CLWCAESLLY HCLSDAEGDF SDPCACEPGH
     PRPAARWAAL AALSLAVPCL CCYAPLRACH WVAARCGCAG CGGRHEEAAR
//