ID SPY4_HUMAN Reviewed; 299 AA. AC Q9C004; A4FVB2; A4FVB3; Q6QIX2; Q9C003; DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2001, sequence version 2. DT 24-JAN-2024, entry version 175. DE RecName: Full=Protein sprouty homolog 4; DE Short=Spry-4; GN Name=SPRY4; 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 A AND C), FUNCTION, SUBCELLULAR RP LOCATION, AND INTERACTION WITH TESK1. RC TISSUE=Umbilical artery; RX PubMed=12027893; DOI=10.1046/j.1432-1033.2002.02921.x; RA Leeksma O.C., van Achterberg T.A.E., Tsumura Y., Toshima J., Eldering E., RA Kroes W.G.M., Mellink C., Spaargaren M., Mizuno K., Pannekoek H., RA de Vries C.J.M.; RT "Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual RT specificity kinase TESK1."; RL Eur. J. Biochem. 269:2546-2556(2002). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=14977631; DOI=10.1152/ajplung.00430.2003; RA Ding W., Bellusci S., Shi W., Warburton D.; RT "Genomic structure and promoter characterization of the human Sprouty4 RT gene, a novel regulator of lung morphogenesis."; RL Am. J. Physiol. 287:L52-L59(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Brain; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). 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 FUNCTION, AND INTERACTION WITH RAF1. RX PubMed=12717443; DOI=10.1038/ncb978; RA Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., RA Kuriyama M., Saito N., Shibuya M., Yoshimura A.; RT "Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to RT Raf1."; RL Nat. Cell Biol. 5:427-432(2003). RN [7] RP FUNCTION, INTERACTION WITH TESK1, AND SUBCELLULAR LOCATION. RX PubMed=15584898; DOI=10.1042/bj20041181; RA Tsumura Y., Toshima J., Leeksma O.C., Ohashi K., Mizuno K.; RT "Sprouty-4 negatively regulates cell spreading by inhibiting the kinase RT activity of testicular protein kinase."; RL Biochem. J. 387:627-637(2005). RN [8] 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, 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 [12] RP VARIANTS HH17 MET-77; ASN-82; ARG-154; TYR-186; TYR-218; MET-258 AND RP ILE-281. RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008; RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G., RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., RA Pitteloud N.; RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in RT individuals with congenital hypogonadotropic hypogonadism."; RL Am. J. Hum. Genet. 92:725-743(2013). CC -!- FUNCTION: Suppresses the insulin receptor and EGFR-transduced MAPK CC signaling pathway, but does not inhibit MAPK activation by a CC constitutively active mutant Ras (PubMed:12027893). Probably impairs CC the formation of GTP-Ras (PubMed:12027893). Inhibits Ras-independent, CC but not Ras-dependent, activation of RAF1 (PubMed:12717443). Represses CC integrin-mediated cell spreading via inhibition of TESK1-mediated CC phosphorylation of cofilin (PubMed:15584898). CC {ECO:0000269|PubMed:12027893, ECO:0000269|PubMed:12717443, CC ECO:0000269|PubMed:15584898}. CC -!- SUBUNIT: Interacts (via C-terminus) with TESK1 (via both C- and N- CC termini); the interaction inhibits TESK1 kinase activity CC (PubMed:12027893, PubMed:15584898). Interacts with RAF1 CC (PubMed:12717443). Interacts with CAV1 (via C-terminus) (By CC similarity). {ECO:0000250|UniProtKB:Q9WTP2, CC ECO:0000269|PubMed:12027893, ECO:0000269|PubMed:12717443, CC ECO:0000269|PubMed:15584898}. CC -!- INTERACTION: CC Q9C004; O43184-4: ADAM12; NbExp=3; IntAct=EBI-354861, EBI-12006944; CC Q9C004; Q86V38: ATN1; NbExp=3; IntAct=EBI-354861, EBI-11954292; CC Q9C004; P55212: CASP6; NbExp=3; IntAct=EBI-354861, EBI-718729; CC Q9C004; P22681: CBL; NbExp=9; IntAct=EBI-354861, EBI-518228; CC Q9C004; P06307: CCK; NbExp=3; IntAct=EBI-354861, EBI-6624398; CC Q9C004; P28329-3: CHAT; NbExp=3; IntAct=EBI-354861, EBI-25837549; CC Q9C004; P27658: COL8A1; NbExp=3; IntAct=EBI-354861, EBI-747133; CC Q9C004; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-354861, EBI-745535; CC Q9C004; Q02930-3: CREB5; NbExp=3; IntAct=EBI-354861, EBI-10192698; CC Q9C004; P02489: CRYAA; NbExp=3; IntAct=EBI-354861, EBI-6875961; CC Q9C004; P07339: CTSD; NbExp=3; IntAct=EBI-354861, EBI-2115097; CC Q9C004; G5E9A7: DMWD; NbExp=3; IntAct=EBI-354861, EBI-10976677; CC Q9C004; O95967: EFEMP2; NbExp=3; IntAct=EBI-354861, EBI-743414; CC Q9C004; P22607: FGFR3; NbExp=3; IntAct=EBI-354861, EBI-348399; CC Q9C004; Q14192: FHL2; NbExp=3; IntAct=EBI-354861, EBI-701903; CC Q9C004; P28799: GRN; NbExp=3; IntAct=EBI-354861, EBI-747754; CC Q9C004; P06396: GSN; NbExp=3; IntAct=EBI-354861, EBI-351506; CC Q9C004; P49639: HOXA1; NbExp=3; IntAct=EBI-354861, EBI-740785; CC Q9C004; P04792: HSPB1; NbExp=3; IntAct=EBI-354861, EBI-352682; CC Q9C004; O60333-2: KIF1B; NbExp=3; IntAct=EBI-354861, EBI-10975473; CC Q9C004; Q2WGJ6: KLHL38; NbExp=3; IntAct=EBI-354861, EBI-6426443; CC Q9C004; Q92876: KLK6; NbExp=3; IntAct=EBI-354861, EBI-2432309; CC Q9C004; Q6L8G4: KRTAP5-11; NbExp=3; IntAct=EBI-354861, EBI-11993296; CC Q9C004; P13473-2: LAMP2; NbExp=3; IntAct=EBI-354861, EBI-21591415; CC Q9C004; P61970: NUTF2; NbExp=3; IntAct=EBI-354861, EBI-591778; CC Q9C004; P32242: OTX1; NbExp=3; IntAct=EBI-354861, EBI-740446; CC Q9C004; D3DTS7: PMP22; NbExp=3; IntAct=EBI-354861, EBI-25882629; CC Q9C004; Q12837: POU4F2; NbExp=3; IntAct=EBI-354861, EBI-17236143; CC Q9C004; O60260-5: PRKN; NbExp=3; IntAct=EBI-354861, EBI-21251460; CC Q9C004; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-354861, EBI-5280197; CC Q9C004; P60891: PRPS1; NbExp=3; IntAct=EBI-354861, EBI-749195; CC Q9C004; P62826: RAN; NbExp=3; IntAct=EBI-354861, EBI-286642; CC Q9C004; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-354861, EBI-396669; CC Q9C004; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-354861, EBI-5235340; CC Q9C004; P31948: STIP1; NbExp=3; IntAct=EBI-354861, EBI-1054052; CC Q9C004; Q15569: TESK1; NbExp=4; IntAct=EBI-354861, EBI-354852; CC Q9C004; P02766: TTR; NbExp=3; IntAct=EBI-354861, EBI-711909; CC Q9C004; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-354861, EBI-741480; CC Q9C004; O95231: VENTX; NbExp=3; IntAct=EBI-354861, EBI-10191303; CC Q9C004; O76024: WFS1; NbExp=3; IntAct=EBI-354861, EBI-720609; CC Q9C004; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-354861, EBI-524753; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12027893, CC ECO:0000269|PubMed:15584898}. Cell projection, ruffle membrane CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic CC side {ECO:0000305}. Note=Found in the cytoplasm in unstimulated cells CC but is translocated to the membrane ruffles in cells stimulated with CC EGF (epidermal growth factor) (By similarity). Colocalizes with TESK1 CC in vesicular spots in the cytoplasm (PubMed:15584898). CC {ECO:0000250|UniProtKB:Q9WTP2, ECO:0000269|PubMed:15584898}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; Synonyms=Sprouty-4A; CC IsoId=Q9C004-1; Sequence=Displayed; CC Name=C; Synonyms=Sprouty-4C; CC IsoId=Q9C004-2; Sequence=VSP_006219, VSP_006220; CC -!- DOMAIN: The Cys-rich domain is responsible for the localization of the CC protein to the membrane ruffles. CC -!- DISEASE: Hypogonadotropic hypogonadism 17 with or without anosmia CC (HH17) [MIM:615266]: A disorder characterized by absent or incomplete CC sexual maturation by the age of 18 years, in conjunction with low CC levels of circulating gonadotropins and testosterone and no other CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is CC associated with non-reproductive phenotypes, such as anosmia, cleft CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related CC to the absence or hypoplasia of the olfactory bulbs and tracts. CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and CC probably results from a failure of embryonic migration of gonadotropin- CC releasing hormone-synthesizing neurons. In the presence of anosmia, CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann CC syndrome, whereas in the presence of a normal sense of smell, it has CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). CC {ECO:0000269|PubMed:23643382}. Note=The disease is caused by variants CC affecting distinct genetic loci, including the gene represented in this CC entry. Some patients carrying mutations in SPRY4 also have a CC heterozygous mutation in another HH-associated gene including DUSP6 and CC FGFR1 (PubMed:23643382). {ECO:0000269|PubMed:23643382}. CC -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK00652.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; AF227516; AAK00652.1; ALT_INIT; mRNA. DR EMBL; AF227517; AAK00653.1; -; mRNA. DR EMBL; AY538661; AAS46253.1; -; Genomic_DNA. DR EMBL; AK096464; BAC04798.1; -; mRNA. DR EMBL; AC091825; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC125095; AAI25096.1; -; mRNA. DR EMBL; BC125096; AAI25097.1; -; mRNA. DR CCDS; CCDS47296.1; -. [Q9C004-1] DR RefSeq; NP_001120968.1; NM_001127496.1. [Q9C004-1] DR RefSeq; NP_001280218.1; NM_001293289.1. [Q9C004-1] DR RefSeq; NP_001280219.1; NM_001293290.1. [Q9C004-1] DR RefSeq; NP_112226.2; NM_030964.3. DR RefSeq; XP_011535987.1; XM_011537685.2. DR RefSeq; XP_016865399.1; XM_017009910.1. [Q9C004-1] DR PDB; 3BUN; X-ray; 2.00 A; A=46-58. DR PDBsum; 3BUN; -. DR AlphaFoldDB; Q9C004; -. DR SMR; Q9C004; -. DR BioGRID; 123599; 85. DR IntAct; Q9C004; 54. DR MINT; Q9C004; -. DR STRING; 9606.ENSP00000344967; -. DR iPTMnet; Q9C004; -. DR PhosphoSitePlus; Q9C004; -. DR SwissPalm; Q9C004; -. DR BioMuta; SPRY4; -. DR DMDM; 14916719; -. DR CPTAC; CPTAC-1570; -. DR EPD; Q9C004; -. DR jPOST; Q9C004; -. DR MassIVE; Q9C004; -. DR MaxQB; Q9C004; -. DR PaxDb; 9606-ENSP00000344967; -. DR PeptideAtlas; Q9C004; -. DR ProteomicsDB; 79936; -. [Q9C004-1] DR ProteomicsDB; 79937; -. [Q9C004-2] DR Pumba; Q9C004; -. DR Antibodypedia; 3761; 322 antibodies from 32 providers. DR DNASU; 81848; -. DR Ensembl; ENST00000434127.3; ENSP00000399468.2; ENSG00000187678.10. [Q9C004-1] DR GeneID; 81848; -. DR KEGG; hsa:81848; -. DR MANE-Select; ENST00000434127.3; ENSP00000399468.2; NM_001127496.3; NP_001120968.1. DR UCSC; uc003lml.3; human. [Q9C004-1] DR AGR; HGNC:15533; -. DR CTD; 81848; -. DR DisGeNET; 81848; -. DR GeneCards; SPRY4; -. DR GeneReviews; SPRY4; -. DR HGNC; HGNC:15533; SPRY4. DR HPA; ENSG00000187678; Low tissue specificity. DR MalaCards; SPRY4; -. DR MIM; 607984; gene. DR MIM; 615266; phenotype. DR neXtProt; NX_Q9C004; -. DR OpenTargets; ENSG00000187678; -. DR Orphanet; 478; Kallmann syndrome. DR Orphanet; 363494; Non-seminomatous germ cell tumor of testis. DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism. DR PharmGKB; PA37975; -. DR VEuPathDB; HostDB:ENSG00000187678; -. DR eggNOG; ENOG502QQ4V; Eukaryota. DR GeneTree; ENSGT00950000183055; -. DR HOGENOM; CLU_077696_0_0_1; -. DR InParanoid; Q9C004; -. DR OMA; MCLVQGV; -. DR OrthoDB; 4219076at2759; -. DR PhylomeDB; Q9C004; -. DR TreeFam; TF325070; -. DR PathwayCommons; Q9C004; -. DR SignaLink; Q9C004; -. DR SIGNOR; Q9C004; -. DR BioGRID-ORCS; 81848; 15 hits in 1158 CRISPR screens. DR ChiTaRS; SPRY4; human. DR EvolutionaryTrace; Q9C004; -. DR GeneWiki; SPRY4; -. DR GenomeRNAi; 81848; -. DR Pharos; Q9C004; Tbio. DR PRO; PR:Q9C004; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9C004; Protein. DR Bgee; ENSG00000187678; Expressed in left coronary artery and 143 other cell types or tissues. DR ExpressionAtlas; Q9C004; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:UniProtKB. DR GO; GO:0048513; P:animal organ development; IBA:GO_Central. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:GO_Central. DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR IDEAL; IID00585; -. DR InterPro; IPR007875; Sprouty. DR PANTHER; PTHR12365:SF6; PROTEIN SPROUTY HOMOLOG 4; 1. DR PANTHER; PTHR12365; SPROUTY; 1. DR Pfam; PF05210; Sprouty; 1. DR PROSITE; PS51227; SPR; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; KW Cell projection; Cytoplasm; Developmental protein; Disease variant; KW Hypogonadotropic hypogonadism; Kallmann syndrome; Membrane; Phosphoprotein; KW Reference proteome. FT CHAIN 1..299 FT /note="Protein sprouty homolog 4" FT /id="PRO_0000076905" FT DOMAIN 166..273 FT /note="SPR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572" FT REGION 55..79 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 92..126 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 181..299 FT /note="Required for interaction with TESK1. Required for FT colocalization with TESK1 at vesicular spots in the FT cytoplasm and inhibition of TESK1 kinase activity, FT resulting in inhibition of cell spreading" FT /evidence="ECO:0000269|PubMed:15584898" FT COMPBIAS 92..111 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 97..106 FT /note="SSVSSSSSTS -> CSATCLPPAA (in isoform C)" FT /evidence="ECO:0000303|PubMed:12027893" FT /id="VSP_006219" FT VAR_SEQ 107..299 FT /note="Missing (in isoform C)" FT /evidence="ECO:0000303|PubMed:12027893" FT /id="VSP_006220" FT VARIANT 77 FT /note="T -> M (in HH17; phenotype consistent with Kallmann FT syndrome; dbSNP:rs774674946)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069929" FT VARIANT 82 FT /note="D -> N (in HH17; without anosmia; FT dbSNP:rs568363732)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069930" FT VARIANT 154 FT /note="K -> R (in HH17; phenotype consistent with Kallmann FT syndrome; dbSNP:rs78310959)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069931" FT VARIANT 186 FT /note="C -> Y (in HH17; phenotype consistent with Kallmann FT syndrome; dbSNP:rs148983803)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069932" FT VARIANT 218 FT /note="S -> Y (in HH17; some patients have a second FT mutation in another HH-associated gene including DUSP6 and FT FGFR1; dbSNP:rs139512218)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069933" FT VARIANT 258 FT /note="V -> M (in HH17; without anosmia; FT dbSNP:rs200364529)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069934" FT VARIANT 281 FT /note="V -> I (in HH17; without anosmia; FT dbSNP:rs142439525)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069935" FT CONFLICT 102 FT /note="S -> N (in Ref. 5; AAI25097)" FT /evidence="ECO:0000305" SQ SEQUENCE 299 AA; 32541 MW; 105F6F1BE9F7B6C3 CRC64; MEPPIPQSAP LTPNSVMVQP LLDSRMSHSR LQHPLTILPI DQVKTSHVEN DYIDNPSLAL TTGPKRTRGG APELAPTPAR CDQDVTHHWI SFSGRPSSVS SSSSTSSDQR LLDHMAPPPV ADQASPRAVR IQPKVVHCQP LDLKGPAVPP ELDKHFLLCE ACGKCKCKEC ASPRTLPSCW VCNQECLCSA QTLVNYGTCM CLVQGIFYHC TNEDDEGSCA DHPCSCSRSN CCARWSFMGA LSVVLPCLLC YLPATGCVKL AQRGYDRLRR PGCRCKHTNS VICKAASGDA KTSRPDKPF //