STYX_HUMAN
ID STYX_HUMAN Reviewed; 223 AA.
AC Q8WUJ0; B9EJG0; Q99850;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Serine/threonine/tyrosine-interacting protein {ECO:0000305};
DE AltName: Full=Inactive tyrosine-protein phosphatase STYX {ECO:0000305};
DE AltName: Full=Phosphoserine/threonine/tyrosine interaction protein {ECO:0000250|UniProtKB:Q60969};
GN Name=STYX {ECO:0000312|HGNC:HGNC:11447};
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 [LARGE SCALE MRNA].
RC TISSUE=Umbilical vein endothelial cell;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 116-181.
RC TISSUE=Lung;
RX PubMed=9633825;
RA Dayton M.A., Knobloch T.J.;
RT "Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung
RT fibroblast cell line WI-38.";
RL Recept. Signal Transduct. 7:241-256(1997).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184; SER-193 AND SER-201, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [6]
RP FUNCTION, LACK OF CATALYTIC ACTIVITY, INTERACTION WITH MAPK1, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF GLY-120.
RX PubMed=23847209; DOI=10.1073/pnas.1301985110;
RA Reiterer V., Fey D., Kolch W., Kholodenko B.N., Farhan H.;
RT "Pseudophosphatase STYX modulates cell-fate decisions and cell migration by
RT spatiotemporal regulation of ERK1/2.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E2934-2943(2013).
RN [7]
RP FUNCTION, INTERACTION WITH FBXW7 AND MAPK1, SUBCELLULAR LOCATION, MOTIF,
RP AND MUTAGENESIS OF 76-PHE--GLN-78; GLY-120 AND 142-LYS--ARG-144.
RX PubMed=28007894; DOI=10.15252/embj.201694795;
RA Reiterer V., Figueras-Puig C., Le Guerroue F., Confalonieri S., Vecchi M.,
RA Jalapothu D., Kanse S.M., Deshaies R.J., Di Fiore P.P., Behrends C.,
RA Farhan H.;
RT "The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits
RT SCFFBXW7 function.";
RL EMBO J. 36:260-273(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-177.
RX PubMed=18058037; DOI=10.1007/s10969-007-9036-1;
RA Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P.,
RA Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S.,
RA Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y.,
RA Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R., Sali A.,
RA Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.;
RT "Structural genomics of protein phosphatases.";
RL J. Struct. Funct. Genomics 8:121-140(2007).
CC -!- FUNCTION: Catalytically inactive phosphatase (PubMed:23847209). Acts as
CC a nuclear anchor for MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209).
CC Modulates cell-fate decisions and cell migration by spatiotemporal
CC regulation of MAPK1/MAPK3 (ERK1/ERK2) (PubMed:23847209). By binding to
CC the F-box of FBXW7, prevents the assembly of FBXW7 into the SCF E3
CC ubiquitin-protein ligase complex, and thereby inhibits degradation of
CC its substrates (PubMed:28007894). Plays a role in spermatogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q60969,
CC ECO:0000269|PubMed:23847209, ECO:0000269|PubMed:28007894}.
CC -!- SUBUNIT: Interacts with MAPK1; independently of MAPK1 phosphorylation
CC status (PubMed:23847209). Interacts with CARHSP1/Crhsp-24 (By
CC similarity). Interacts (via FQQ motif) with FBXW7 isoforms 1 (via F-box
CC domain) and 3 (via F-box domain); the interaction is direct and
CC prevents FBXW7 interaction with SKP1, a component of the SCF(FBXW7)
CC complex (PubMed:28007894). Does not interact with FBXW7 isoform 2
CC (PubMed:28007894). {ECO:0000250|UniProtKB:Q60969,
CC ECO:0000269|PubMed:23847209, ECO:0000269|PubMed:28007894}.
CC -!- INTERACTION:
CC Q8WUJ0; Q969H0: FBXW7; NbExp=10; IntAct=EBI-20979851, EBI-359574;
CC Q8WUJ0; Q969H0-1: FBXW7; NbExp=4; IntAct=EBI-20979851, EBI-6162410;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23847209,
CC ECO:0000269|PubMed:28007894}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:23847209}. Note=Predominantly localizes to the
CC nucleus. {ECO:0000269|PubMed:23847209, ECO:0000269|PubMed:28007894}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class subfamily. {ECO:0000305}.
CC -!- CAUTION: Contains a Gly residue instead of a conserved Cys residue at
CC position 120 in the dsPTPase catalytic loop which renders it
CC catalytically inactive as a phosphatase. The binding pocket is however
CC sufficiently preserved to bind phosphorylated substrates, and may
CC protect them from phosphatases. {ECO:0000269|PubMed:23847209,
CC ECO:0000305|PubMed:28007894}.
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DR EMBL; AK098195; BAC05259.1; -; mRNA.
DR EMBL; CH471078; EAW65641.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65644.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW80612.1; -; Genomic_DNA.
DR EMBL; BC020265; AAH20265.1; -; mRNA.
DR EMBL; BC146995; AAI46996.1; -; mRNA.
DR EMBL; BC146998; AAI46999.1; -; mRNA.
DR EMBL; U87169; AAB47561.1; -; mRNA.
DR CCDS; CCDS9711.1; -.
DR RefSeq; NP_001124173.1; NM_001130701.1.
DR RefSeq; NP_660294.1; NM_145251.3.
DR PDB; 2R0B; X-ray; 1.60 A; A=26-177.
DR PDBsum; 2R0B; -.
DR AlphaFoldDB; Q8WUJ0; -.
DR SMR; Q8WUJ0; -.
DR BioGRID; 112684; 86.
DR IntAct; Q8WUJ0; 52.
DR MINT; Q8WUJ0; -.
DR STRING; 9606.ENSP00000346599; -.
DR DEPOD; STYX; -.
DR GlyGen; Q8WUJ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WUJ0; -.
DR PhosphoSitePlus; Q8WUJ0; -.
DR BioMuta; STYX; -.
DR DMDM; 29840812; -.
DR EPD; Q8WUJ0; -.
DR jPOST; Q8WUJ0; -.
DR MassIVE; Q8WUJ0; -.
DR MaxQB; Q8WUJ0; -.
DR PaxDb; Q8WUJ0; -.
DR PeptideAtlas; Q8WUJ0; -.
DR PRIDE; Q8WUJ0; -.
DR ProteomicsDB; 74688; -.
DR Antibodypedia; 23899; 49 antibodies from 15 providers.
DR DNASU; 6815; -.
DR Ensembl; ENST00000354586.5; ENSP00000346599.4; ENSG00000198252.12.
DR Ensembl; ENST00000442123.6; ENSP00000403214.2; ENSG00000198252.12.
DR GeneID; 6815; -.
DR KEGG; hsa:6815; -.
DR MANE-Select; ENST00000354586.5; ENSP00000346599.4; NM_145251.4; NP_660294.1.
DR UCSC; uc001xaa.4; human.
DR CTD; 6815; -.
DR DisGeNET; 6815; -.
DR GeneCards; STYX; -.
DR HGNC; HGNC:11447; STYX.
DR HPA; ENSG00000198252; Low tissue specificity.
DR MIM; 615814; gene.
DR neXtProt; NX_Q8WUJ0; -.
DR NIAGADS; ENSG00000198252; -.
DR OpenTargets; ENSG00000198252; -.
DR PharmGKB; PA36244; -.
DR VEuPathDB; HostDB:ENSG00000198252; -.
DR eggNOG; KOG1716; Eukaryota.
DR GeneTree; ENSGT00940000154859; -.
DR HOGENOM; CLU_027074_7_1_1; -.
DR InParanoid; Q8WUJ0; -.
DR OMA; EWRYEMR; -.
DR OrthoDB; 1576308at2759; -.
DR PhylomeDB; Q8WUJ0; -.
DR TreeFam; TF350439; -.
DR PathwayCommons; Q8WUJ0; -.
DR SignaLink; Q8WUJ0; -.
DR SIGNOR; Q8WUJ0; -.
DR BioGRID-ORCS; 6815; 41 hits in 1071 CRISPR screens.
DR ChiTaRS; STYX; human.
DR EvolutionaryTrace; Q8WUJ0; -.
DR GenomeRNAi; 6815; -.
DR Pharos; Q8WUJ0; Tbio.
DR PRO; PR:Q8WUJ0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8WUJ0; protein.
DR Bgee; ENSG00000198252; Expressed in superficial temporal artery and 193 other tissues.
DR ExpressionAtlas; Q8WUJ0; baseline and differential.
DR Genevisible; Q8WUJ0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990444; F:F-box domain binding; IMP:UniProtKB.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0001691; F:pseudophosphatase activity; IMP:UniProtKB.
DR GO; GO:0045204; P:MAPK export from nucleus; IMP:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0062026; P:negative regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR SMART; SM00195; DSPc; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..223
FT /note="Serine/threonine/tyrosine-interacting protein"
FT /id="PRO_0000094950"
FT DOMAIN 28..176
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 197..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 76..78
FT /note="Interaction with FBXW7"
FT /evidence="ECO:0000269|PubMed:28007894"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MUTAGEN 76..78
FT /note="FQQ->AAA: Loss of interaction with FBXW7. Does not
FT affect interaction with MAPK1 and nuclear localization."
FT /evidence="ECO:0000269|PubMed:28007894"
FT MUTAGEN 120
FT /note="G->C: Confers phosphatase activity. Dephosphorylates
FT MAPK1. Does not affect interaction with FBXW7 and nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:23847209,
FT ECO:0000269|PubMed:28007894"
FT MUTAGEN 142..144
FT /note="KYR->AAA: Increases interaction with FBXW7."
FT /evidence="ECO:0000269|PubMed:28007894"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:2R0B"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:2R0B"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:2R0B"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2R0B"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:2R0B"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 99..111
FT /evidence="ECO:0007829|PDB:2R0B"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:2R0B"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:2R0B"
FT HELIX 161..175
FT /evidence="ECO:0007829|PDB:2R0B"
SQ SEQUENCE 223 AA; 25492 MW; D2C8D05104073EE8 CRC64;
MEDVKLEFPS LPQCKEDAEE WTYPMRREMQ EILPGLFLGP YSSAMKSKLP VLQKHGITHI
ICIRQNIEAN FIKPNFQQLF RYLVLDIADN PVENIIRFFP MTKEFIDGSL QMGGKVLVHG
NAGISRSAAF VIAYIMETFG MKYRDAFAYV QERRFCINPN AGFVHQLQEY EAIYLAKLTI
QMMSPLQIER SLSVHSGTTG SLKRTHEEED DFGTMQVATA QNG
