SPRE2_HUMAN
ID SPRE2_HUMAN Reviewed; 418 AA.
AC Q7Z698; A1L3V4; B7Z5K7; D6W5F7; E9PEP0; Q2NKX6;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Sprouty-related, EVH1 domain-containing protein 2;
DE Short=Spred-2;
GN Name=SPRED2;
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), FUNCTION, SUBUNIT, INTERACTION WITH
RP SPRED1, AND PHOSPHORYLATION.
RC TISSUE=Glioblastoma;
RX PubMed=15683364; DOI=10.1042/bj20041284;
RA King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T.,
RA Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., Sarcevic B.,
RA Martin D., Lock P., Hovens C.M.;
RT "Distinct requirements for the Sprouty domain for functional activity of
RT Spred proteins.";
RL Biochem. J. 388:445-454(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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=Brain, and Ovary;
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 TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15580519; DOI=10.1007/s00418-004-0725-6;
RA Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U.,
RA Reinhard M., Schuh K.;
RT "Expression and subcellular localization of Spred proteins in mouse and
RT human tissues.";
RL Histochem. Cell Biol. 122:527-538(2004).
RN [7]
RP UBIQUITINATION, PHOSPHORYLATION AT TYR-228 AND TYR-231, AND MUTAGENESIS OF
RP TYR-228; TYR-231; TYR-240; TYR-251; TYR-264; TYR-266; TYR-268; TYR-311;
RP TYR-351 AND TYR-394.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206, 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 [9]
RP STRUCTURE BY NMR OF 1-124.
RX PubMed=15213456; DOI=10.1023/b:jnmr.0000032526.17586.8c;
RA Zimmermann J., Jarchau T., Walter U., Oschkinat H., Ball L.J.;
RT "1H, 13C and 15N resonance assignment of the human Spred2 EVH1 domain.";
RL J. Biomol. NMR 29:435-436(2004).
CC -!- FUNCTION: Negatively regulates Ras signaling pathways and downstream
CC activation of MAP kinases (PubMed:15683364). Inhibits fibroblast growth
CC factor (FGF)-induced retinal lens fiber differentiation, probably by
CC inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity).
CC Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens
CC epithelial cells (By similarity). {ECO:0000250|UniProtKB:Q924S7,
CC ECO:0000269|PubMed:15683364}.
CC -!- SUBUNIT: Homodimer and heterodimer (PubMed:15683364). Able to interact
CC with SPRED1 to form heterodimers (PubMed:15683364). Interacts with RAS
CC (By similarity). May interact with ZDHHC13 (via ANK repeats) and
CC ZDHHC17 (via ANK repeats) (By similarity). Interacts with TESK1 (By
CC similarity). {ECO:0000250|UniProtKB:Q924S7,
CC ECO:0000269|PubMed:15683364}.
CC -!- INTERACTION:
CC Q7Z698; Q92870-2: APBB2; NbExp=3; IntAct=EBI-7082156, EBI-21535880;
CC Q7Z698; P29972: AQP1; NbExp=3; IntAct=EBI-7082156, EBI-745213;
CC Q7Z698; P27797: CALR; NbExp=3; IntAct=EBI-7082156, EBI-1049597;
CC Q7Z698; P28329-3: CHAT; NbExp=3; IntAct=EBI-7082156, EBI-25837549;
CC Q7Z698; P36957: DLST; NbExp=3; IntAct=EBI-7082156, EBI-351007;
CC Q7Z698; G5E9A7: DMWD; NbExp=3; IntAct=EBI-7082156, EBI-10976677;
CC Q7Z698; P50570-2: DNM2; NbExp=3; IntAct=EBI-7082156, EBI-10968534;
CC Q7Z698; P22607: FGFR3; NbExp=3; IntAct=EBI-7082156, EBI-348399;
CC Q7Z698; P14136: GFAP; NbExp=3; IntAct=EBI-7082156, EBI-744302;
CC Q7Z698; Q53GS7: GLE1; NbExp=3; IntAct=EBI-7082156, EBI-1955541;
CC Q7Z698; P28799: GRN; NbExp=3; IntAct=EBI-7082156, EBI-747754;
CC Q7Z698; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-7082156, EBI-14103818;
CC Q7Z698; P42858: HTT; NbExp=6; IntAct=EBI-7082156, EBI-466029;
CC Q7Z698; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-7082156, EBI-22452746;
CC Q7Z698; O60333-2: KIF1B; NbExp=3; IntAct=EBI-7082156, EBI-10975473;
CC Q7Z698; Q5T749: KPRP; NbExp=3; IntAct=EBI-7082156, EBI-10981970;
CC Q7Z698; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-7082156, EBI-10176379;
CC Q7Z698; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-7082156, EBI-14065470;
CC Q7Z698; Q5T751: LCE1C; NbExp=3; IntAct=EBI-7082156, EBI-12224199;
CC Q7Z698; O14633: LCE2B; NbExp=3; IntAct=EBI-7082156, EBI-11478468;
CC Q7Z698; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-7082156, EBI-11955689;
CC Q7Z698; P02545: LMNA; NbExp=3; IntAct=EBI-7082156, EBI-351935;
CC Q7Z698; Q99750: MDFI; NbExp=3; IntAct=EBI-7082156, EBI-724076;
CC Q7Z698; P62166: NCS1; NbExp=3; IntAct=EBI-7082156, EBI-746987;
CC Q7Z698; P17568: NDUFB7; NbExp=3; IntAct=EBI-7082156, EBI-1246238;
CC Q7Z698; P19404: NDUFV2; NbExp=3; IntAct=EBI-7082156, EBI-713665;
CC Q7Z698; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-7082156, EBI-1055945;
CC Q7Z698; P29474: NOS3; NbExp=3; IntAct=EBI-7082156, EBI-1391623;
CC Q7Z698; D3DTS7: PMP22; NbExp=3; IntAct=EBI-7082156, EBI-25882629;
CC Q7Z698; P60891: PRPS1; NbExp=3; IntAct=EBI-7082156, EBI-749195;
CC Q7Z698; P47897: QARS1; NbExp=3; IntAct=EBI-7082156, EBI-347462;
CC Q7Z698; Q5RL73: RBM48; NbExp=3; IntAct=EBI-7082156, EBI-473821;
CC Q7Z698; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-7082156, EBI-396669;
CC Q7Z698; P51812: RPS6KA3; NbExp=4; IntAct=EBI-7082156, EBI-1046616;
CC Q7Z698; Q9UK32: RPS6KA6; NbExp=3; IntAct=EBI-7082156, EBI-722467;
CC Q7Z698; Q9NZD8: SPG21; NbExp=10; IntAct=EBI-7082156, EBI-742688;
CC Q7Z698; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-7082156, EBI-5235340;
CC Q7Z698; O95985: TOP3B; NbExp=4; IntAct=EBI-7082156, EBI-373403;
CC Q7Z698; Q99598: TSNAX; NbExp=3; IntAct=EBI-7082156, EBI-742638;
CC Q7Z698; P62760: VSNL1; NbExp=3; IntAct=EBI-7082156, EBI-740943;
CC Q7Z698; O76024: WFS1; NbExp=3; IntAct=EBI-7082156, EBI-720609;
CC Q7Z698; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-7082156, EBI-524753;
CC Q7Z698; P15622-3: ZNF250; NbExp=3; IntAct=EBI-7082156, EBI-10177272;
CC Q7Z698; Q96IQ9: ZNF414; NbExp=3; IntAct=EBI-7082156, EBI-744257;
CC Q7Z698; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-7082156, EBI-740727;
CC Q7Z698; Q86XF7: ZNF575; NbExp=3; IntAct=EBI-7082156, EBI-14069183;
CC Q7Z698; Q96EG3: ZNF837; NbExp=6; IntAct=EBI-7082156, EBI-11962574;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q924S7};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q924S7}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q924S7}. Cytoplasmic vesicle, secretory
CC vesicle membrane {ECO:0000269|PubMed:15580519}; Peripheral membrane
CC protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:15580519}. Note=Detected in the cytoplasm of the
CC stratum spinosum cells, where it is associated with cytoplasmic
CC vesicles that are supposed to be secretory granules.
CC {ECO:0000269|PubMed:15580519}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z698-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z698-2; Sequence=VSP_043755;
CC -!- TISSUE SPECIFICITY: Expressed in liver, skin, small intestine, salivary
CC gland and prostate. {ECO:0000269|PubMed:15580519}.
CC -!- PTM: Phosphorylated on serine and threonine residues (PubMed:15683364).
CC Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are
CC required for ubiquitination (PubMed:17094949).
CC {ECO:0000269|PubMed:15683364, ECO:0000269|PubMed:17094949}.
CC -!- PTM: Ubiquitinated; leading to degradation by the proteasome.
CC {ECO:0000269|PubMed:17094949}.
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DR EMBL; AY299090; AAP59415.1; -; mRNA.
DR EMBL; AK299079; BAH12943.1; -; mRNA.
DR EMBL; AC012370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99905.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99906.1; -; Genomic_DNA.
DR EMBL; BC111495; AAI11496.1; -; mRNA.
DR EMBL; BC130292; AAI30293.1; -; mRNA.
DR EMBL; BC136334; AAI36335.1; -; mRNA.
DR CCDS; CCDS33211.1; -. [Q7Z698-1]
DR CCDS; CCDS46308.1; -. [Q7Z698-2]
DR RefSeq; NP_001121682.1; NM_001128210.1. [Q7Z698-2]
DR RefSeq; NP_861449.2; NM_181784.2. [Q7Z698-1]
DR PDB; 2JP2; NMR; -; A=1-124.
DR PDBsum; 2JP2; -.
DR AlphaFoldDB; Q7Z698; -.
DR BMRB; Q7Z698; -.
DR SMR; Q7Z698; -.
DR BioGRID; 128344; 60.
DR IntAct; Q7Z698; 56.
DR MINT; Q7Z698; -.
DR STRING; 9606.ENSP00000348753; -.
DR iPTMnet; Q7Z698; -.
DR PhosphoSitePlus; Q7Z698; -.
DR SwissPalm; Q7Z698; -.
DR BioMuta; SPRED2; -.
DR DMDM; 110825745; -.
DR EPD; Q7Z698; -.
DR jPOST; Q7Z698; -.
DR MassIVE; Q7Z698; -.
DR MaxQB; Q7Z698; -.
DR PaxDb; Q7Z698; -.
DR PeptideAtlas; Q7Z698; -.
DR PRIDE; Q7Z698; -.
DR ProteomicsDB; 69384; -. [Q7Z698-1]
DR ProteomicsDB; 69385; -. [Q7Z698-2]
DR Antibodypedia; 30873; 148 antibodies from 29 providers.
DR DNASU; 200734; -.
DR Ensembl; ENST00000356388.9; ENSP00000348753.4; ENSG00000198369.10. [Q7Z698-1]
DR Ensembl; ENST00000443619.6; ENSP00000393697.2; ENSG00000198369.10. [Q7Z698-2]
DR GeneID; 200734; -.
DR KEGG; hsa:200734; -.
DR MANE-Select; ENST00000356388.9; ENSP00000348753.4; NM_181784.3; NP_861449.2.
DR UCSC; uc002sdr.5; human. [Q7Z698-1]
DR CTD; 200734; -.
DR DisGeNET; 200734; -.
DR GeneCards; SPRED2; -.
DR HGNC; HGNC:17722; SPRED2.
DR HPA; ENSG00000198369; Low tissue specificity.
DR MIM; 609292; gene.
DR neXtProt; NX_Q7Z698; -.
DR OpenTargets; ENSG00000198369; -.
DR Orphanet; 648; Noonan syndrome.
DR PharmGKB; PA134956365; -.
DR VEuPathDB; HostDB:ENSG00000198369; -.
DR eggNOG; KOG4590; Eukaryota.
DR GeneTree; ENSGT00940000156841; -.
DR HOGENOM; CLU_038867_1_1_1; -.
DR InParanoid; Q7Z698; -.
DR OMA; TEGHESE; -.
DR OrthoDB; 1094638at2759; -.
DR PhylomeDB; Q7Z698; -.
DR TreeFam; TF321411; -.
DR PathwayCommons; Q7Z698; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR Reactome; R-HSA-5658623; FGFRL1 modulation of FGFR1 signaling.
DR Reactome; R-HSA-6802953; RAS signaling downstream of NF1 loss-of-function variants.
DR SignaLink; Q7Z698; -.
DR BioGRID-ORCS; 200734; 27 hits in 1087 CRISPR screens.
DR ChiTaRS; SPRED2; human.
DR EvolutionaryTrace; Q7Z698; -.
DR GeneWiki; SPRED2; -.
DR GenomeRNAi; 200734; -.
DR Pharos; Q7Z698; Tbio.
DR PRO; PR:Q7Z698; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q7Z698; protein.
DR Bgee; ENSG00000198369; Expressed in sural nerve and 179 other tissues.
DR ExpressionAtlas; Q7Z698; baseline and differential.
DR Genevisible; Q7Z698; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISS:BHF-UCL.
DR GO; GO:0005173; F:stem cell factor receptor binding; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:BHF-UCL.
DR GO; GO:0090311; P:regulation of protein deacetylation; ISS:BHF-UCL.
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 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Membrane; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..418
FT /note="Sprouty-related, EVH1 domain-containing protein 2"
FT /id="PRO_0000076910"
FT DOMAIN 5..122
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 201..257
FT /note="KBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00821"
FT DOMAIN 308..416
FT /note="SPR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT REGION 127..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 228
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:17094949"
FT MOD_RES 231
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:17094949"
FT VAR_SEQ 1..9
FT /note="MTEETHPDD -> MASPGS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043755"
FT MUTAGEN 228
FT /note="Y->F: Reduces ubiquitination and CBL-induced
FT phosphorylation; when associated with F-231."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 231
FT /note="Y->F: Reduces ubiquitination and CBL-induced
FT phosphorylation; when associated with F-228."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 240
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 251
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 264
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination; when associated with F-266."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 266
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination; when associated with F-264."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 268
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 311
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 351
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT MUTAGEN 394
FT /note="Y->F: No effect on phosphorylation or
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:17094949"
FT CONFLICT 33
FT /note="Q -> R (in Ref. 2; BAH12943)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="Y -> C (in Ref. 1; AAP59415)"
FT /evidence="ECO:0000305"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 11..23
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 57..67
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:2JP2"
FT STRAND 94..104
FT /evidence="ECO:0007829|PDB:2JP2"
FT HELIX 105..123
FT /evidence="ECO:0007829|PDB:2JP2"
SQ SEQUENCE 418 AA; 47558 MW; CA4FE80C45008851 CRC64;
MTEETHPDDD SYIVRVKAVV MTRDDSSGGW FPQEGGGISR VGVCKVMHPE GNGRSGFLIH
GERQKDKLVV LECYVRKDLV YTKANPTFHH WKVDNRKFGL TFQSPADARA FDRGVRKAIE
DLIEGSTTSS STIHNEAELG DDDVFTTATD SSSNSSQKRE QPTRTISSPT SCEHRRIYTL
GHLHDSYPTD HYHLDQPMPR PYRQVSFPDD DEEIVRINPR EKIWMTGYED YRHAPVRGKY
PDPSEDADSS YVRFAKGEVP KHDYNYPYVD SSDFGLGEDP KGRGGSVIKT QPSRGKSRRR
KEDGERSRCV YCRDMFNHEE NRRGHCQDAP DSVRTCIRRV SCMWCADSML YHCMSDPEGD
YTDPCSCDTS DEKFCLRWMA LIALSFLAPC MCCYLPLRAC YHCGVMCRCC GGKHKAAA
