SPY4_HUMAN
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 03-AUG-2022, entry version 168.
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};
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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; 82.
DR IntAct; Q9C004; 52.
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; Q9C004; -.
DR PeptideAtlas; Q9C004; -.
DR PRIDE; Q9C004; -.
DR ProteomicsDB; 79936; -. [Q9C004-1]
DR ProteomicsDB; 79937; -. [Q9C004-2]
DR Antibodypedia; 3761; 297 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 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; 1157681at2759; -.
DR PhylomeDB; Q9C004; -.
DR TreeFam; TF325070; -.
DR PathwayCommons; Q9C004; -.
DR SignaLink; Q9C004; -.
DR SIGNOR; Q9C004; -.
DR BioGRID-ORCS; 81848; 13 hits in 1080 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 141 other 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:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:InterPro.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; 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 InterPro; IPR030790; SPRY4.
DR PANTHER; PTHR12365:SF6; PTHR12365:SF6; 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; rare variant associated with
FT susceptibility to disease; 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
