SPRE3_HUMAN
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 03-AUG-2022, entry version 123.
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}.
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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. [Q2MJR0-1]
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; Q2MJR0; -.
DR PeptideAtlas; Q2MJR0; -.
DR PRIDE; Q2MJR0; -.
DR Antibodypedia; 30059; 77 antibodies from 20 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 CTD; 399473; -.
DR GeneCards; SPRED3; -.
DR HGNC; HGNC:31041; SPRED3.
DR HPA; ENSG00000188766; Group enriched (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 OMA; TRTKVGG; -.
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 1064 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 tissues.
DR ExpressionAtlas; Q2MJR0; baseline and differential.
DR Genevisible; Q2MJR0; HS.
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; -; 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 Pfam; PF05210; Sprouty; 1.
DR Pfam; PF00568; WH1; 1.
DR SMART; SM00461; WH1; 1.
DR PROSITE; PS51488; KBD; 1.
DR PROSITE; PS51227; SPR; 1.
DR PROSITE; PS50229; WH1; 1.
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
