Full text data of OXSR1
OXSR1
(KIAA1101, OSR1)
[Confidence: high (present in two of the MS resources)]
Serine/threonine-protein kinase OSR1; 2.7.11.1 (Oxidative stress-responsive 1 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein kinase OSR1; 2.7.11.1 (Oxidative stress-responsive 1 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00010080
IPI00010080 Oxidative-stress responsive 1 ATP binding,protein serine/threonine kinase activity, protein-tyrosine kinase activity, protein amino acid phosphorylation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00010080 Oxidative-stress responsive 1 ATP binding,protein serine/threonine kinase activity, protein-tyrosine kinase activity, protein amino acid phosphorylation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
O95747
ID OXSR1_HUMAN Reviewed; 527 AA.
AC O95747; Q3LR53; Q7Z501; Q9UPQ1;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Serine/threonine-protein kinase OSR1;
DE EC=2.7.11.1;
DE AltName: Full=Oxidative stress-responsive 1 protein;
GN Name=OXSR1; Synonyms=KIAA1101, OSR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ILE-304.
RC TISSUE=Skeletal muscle;
RX PubMed=10083736; DOI=10.1007/s100380050121;
RA Tamari M., Daigo Y., Nakamura Y.;
RT "Isolation and characterization of a novel serine threonine kinase
RT gene on chromosome 3p22-21.3.";
RL J. Hum. Genet. 44:116-120(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-304 AND THR-425.
RG NIEHS SNPs program;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 172-527.
RA Ding J.B., Yu L., Gong R.M., Mao N.H., Han X.F., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homologous to
RT human DCHT mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AUTOPHOSPHORYLATION, ENZYME REGULATION, INTERACTION WITH
RP PAK1, AND MUTAGENESIS OF LYS-46.
RX PubMed=14707132; DOI=10.1074/jbc.M313562200;
RA Chen W., Yazicioglu M., Cobb M.H.;
RT "Characterization of OSR1, a member of the mammalian Ste20p/germinal
RT center kinase subfamily.";
RL J. Biol. Chem. 279:11129-11136(2004).
RN [7]
RP INTERACTION WITH RELL1; RELL2 AND RELT, AND MUTAGENESIS OF LYS-46.
RX PubMed=16389068; DOI=10.1016/j.bbrc.2005.12.033;
RA Cusick J.K., Xu L.-G., Bin L.-H., Han K.-J., Shu H.-B.;
RT "Identification of RELT homologues that associate with RELT and are
RT phosphorylated by OSR1.";
RL Biochem. Biophys. Res. Commun. 340:535-543(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-427, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-427, AND
RP MASS SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-347, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=22361696; DOI=10.1016/j.jprot.2012.01.030;
RA Stadler C., Hjelmare M., Neumann B., Jonasson K., Pepperkok R.,
RA Uhlen M., Lundberg E.;
RT "Systematic validation of antibody binding and protein subcellular
RT localization using siRNA and confocal microscopy.";
RL J. Proteomics 75:2236-2251(2012).
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-304 AND SER-433.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Regulates downstream kinases in response to
CC environmental stress. May also have a function in regulating the
CC actin cytoskeleton.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: By autophosphorylation on threonine.
CC -!- SUBUNIT: Binds to and phosphorylates PAK1. Interacts with chloride
CC channel proteins SLC12A6 isoform 2, SLC12A1 and SLC12A2 but not
CC with SLC12A4 and SLC12A7, possibly establishing sensor/signaling
CC modules that initiate the cellular response to environmental
CC stress. Binds to and phosphorylates RELL1, RELL2 AND RELT.
CC -!- INTERACTION:
CC Q9Y376:CAB39; NbExp=3; IntAct=EBI-620853, EBI-306905;
CC P55011:SLC12A2; NbExp=2; IntAct=EBI-620853, EBI-2801449;
CC Q9H4A3:WNK1; NbExp=2; IntAct=EBI-620853, EBI-457907;
CC Q96J92:WNK4; NbExp=11; IntAct=EBI-620853, EBI-766352;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissue examined.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97192.1; Type=Erroneous initiation;
CC Sequence=BAA83053.2; Type=Frameshift; Positions=63;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/oxsr1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB017642; BAA75674.1; -; mRNA.
DR EMBL; AB029024; BAA83053.2; ALT_FRAME; mRNA.
DR EMBL; DQ201638; ABA27097.1; -; Genomic_DNA.
DR EMBL; BC008726; AAH08726.1; -; mRNA.
DR EMBL; AF087893; AAP97192.1; ALT_INIT; mRNA.
DR RefSeq; NP_005100.1; NM_005109.2.
DR UniGene; Hs.475970; -.
DR PDB; 2V3S; X-ray; 1.70 A; A/B=433-527.
DR PDB; 2VWI; X-ray; 2.15 A; A/B/C/D=1-303.
DR PDB; 3DAK; X-ray; 2.25 A; A/B/C/D=6-295.
DR PDBsum; 2V3S; -.
DR PDBsum; 2VWI; -.
DR PDBsum; 3DAK; -.
DR ProteinModelPortal; O95747; -.
DR SMR; O95747; 7-358, 433-527.
DR IntAct; O95747; 10.
DR MINT; MINT-5207465; -.
DR STRING; 9606.ENSP00000311713; -.
DR BindingDB; O95747; -.
DR ChEMBL; CHEMBL1163104; -.
DR GuidetoPHARMACOLOGY; 2132; -.
DR PhosphoSite; O95747; -.
DR PaxDb; O95747; -.
DR PeptideAtlas; O95747; -.
DR PRIDE; O95747; -.
DR DNASU; 9943; -.
DR Ensembl; ENST00000311806; ENSP00000311713; ENSG00000172939.
DR GeneID; 9943; -.
DR KEGG; hsa:9943; -.
DR UCSC; uc003chy.3; human.
DR CTD; 9943; -.
DR GeneCards; GC03P038183; -.
DR HGNC; HGNC:8508; OXSR1.
DR HPA; CAB017181; -.
DR HPA; HPA008237; -.
DR MIM; 604046; gene.
DR neXtProt; NX_O95747; -.
DR PharmGKB; PA134973207; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234204; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; O95747; -.
DR KO; K08835; -.
DR OMA; EPQANRS; -.
DR PhylomeDB; O95747; -.
DR SignaLink; O95747; -.
DR ChiTaRS; OXSR1; human.
DR EvolutionaryTrace; O95747; -.
DR GeneWiki; OXSR1; -.
DR GenomeRNAi; 9943; -.
DR NextBio; 37516; -.
DR PRO; PR:O95747; -.
DR ArrayExpress; O95747; -.
DR Bgee; O95747; -.
DR CleanEx; HS_OSR1; -.
DR CleanEx; HS_OXSR1; -.
DR Genevestigator; O95747; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 527 Serine/threonine-protein kinase OSR1.
FT /FTId=PRO_0000086456.
FT DOMAIN 17 291 Protein kinase.
FT NP_BIND 23 31 ATP (By similarity).
FT ACT_SITE 146 146 Proton acceptor (By similarity).
FT BINDING 46 46 ATP.
FT MOD_RES 339 339 Phosphoserine.
FT MOD_RES 347 347 Phosphoserine.
FT MOD_RES 427 427 Phosphoserine.
FT VARIANT 304 304 T -> I (in dbSNP:rs6599079).
FT /FTId=VAR_023232.
FT VARIANT 425 425 S -> T (in dbSNP:rs35295772).
FT /FTId=VAR_025181.
FT VARIANT 433 433 P -> S (in a metastatic melanoma sample;
FT somatic mutation).
FT /FTId=VAR_040969.
FT MUTAGEN 46 46 K->A: Loss of autophosphorylation and
FT kinase activity.
FT MUTAGEN 46 46 K->M: Loss of RELT, RELL1 and RELL2
FT phosphorylation. Retention of some
FT autophosphorylation activity may be due
FT to complex formation with other
FT endogenous kinases in the assay.
FT CONFLICT 316 316 K -> R (in Ref. 5; AAP97192).
FT CONFLICT 325 325 S -> G (in Ref. 5; AAP97192).
FT CONFLICT 363 363 K -> R (in Ref. 5; AAP97192).
FT HELIX 14 16
FT STRAND 18 24
FT STRAND 31 35
FT HELIX 37 39
FT STRAND 42 46
FT TURN 50 54
FT HELIX 57 69
FT STRAND 78 86
FT STRAND 88 93
FT HELIX 100 109
FT TURN 110 115
FT HELIX 120 139
FT HELIX 149 151
FT STRAND 152 154
FT STRAND 160 162
FT HELIX 166 170
FT HELIX 195 202
FT HELIX 207 222
FT TURN 226 229
FT HELIX 232 234
FT HELIX 235 240
FT TURN 247 250
FT HELIX 254 257
FT HELIX 262 271
FT HELIX 276 278
FT HELIX 282 286
FT HELIX 289 293
FT STRAND 434 441
FT STRAND 447 454
FT TURN 456 458
FT HELIX 461 470
FT HELIX 476 478
FT HELIX 479 491
FT TURN 493 495
FT STRAND 497 502
FT HELIX 504 506
FT STRAND 507 511
FT HELIX 515 517
FT STRAND 519 526
SQ SEQUENCE 527 AA; 58022 MW; B46EC934E95A3A1F CRC64;
MSEDSSALPW SINRDDYELQ EVIGSGATAV VQAAYCAPKK EKVAIKRINL EKCQTSMDEL
LKEIQAMSQC HHPNIVSYYT SFVVKDELWL VMKLLSGGSV LDIIKHIVAK GEHKSGVLDE
STIATILREV LEGLEYLHKN GQIHRDVKAG NILLGEDGSV QIADFGVSAF LATGGDITRN
KVRKTFVGTP CWMAPEVMEQ VRGYDFKADI WSFGITAIEL ATGAAPYHKY PPMKVLMLTL
QNDPPSLETG VQDKEMLKKY GKSFRKMISL CLQKDPEKRP TAAELLRHKF FQKAKNKEFL
QEKTLQRAPT ISERAKKVRR VPGSSGRLHK TEDGGWEWSD DEFDEESEEG KAAISQLRSP
RVKESISNSE LFPTTDPVGT LLQVPEQISA HLPQPAGQIA TQPTQVSLPP TAEPAKTAQA
LSSGSGSQET KIPISLVLRL RNSKKELNDI RFEFTPGRDT AEGVSQELIS AGLVDGRDLV
IVAANLQKIV EEPQSNRSVT FKLASGVEGS DIPDDGKLIG FAQLSIS
//
ID OXSR1_HUMAN Reviewed; 527 AA.
AC O95747; Q3LR53; Q7Z501; Q9UPQ1;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Serine/threonine-protein kinase OSR1;
DE EC=2.7.11.1;
DE AltName: Full=Oxidative stress-responsive 1 protein;
GN Name=OXSR1; Synonyms=KIAA1101, OSR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ILE-304.
RC TISSUE=Skeletal muscle;
RX PubMed=10083736; DOI=10.1007/s100380050121;
RA Tamari M., Daigo Y., Nakamura Y.;
RT "Isolation and characterization of a novel serine threonine kinase
RT gene on chromosome 3p22-21.3.";
RL J. Hum. Genet. 44:116-120(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-304 AND THR-425.
RG NIEHS SNPs program;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 172-527.
RA Ding J.B., Yu L., Gong R.M., Mao N.H., Han X.F., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homologous to
RT human DCHT mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AUTOPHOSPHORYLATION, ENZYME REGULATION, INTERACTION WITH
RP PAK1, AND MUTAGENESIS OF LYS-46.
RX PubMed=14707132; DOI=10.1074/jbc.M313562200;
RA Chen W., Yazicioglu M., Cobb M.H.;
RT "Characterization of OSR1, a member of the mammalian Ste20p/germinal
RT center kinase subfamily.";
RL J. Biol. Chem. 279:11129-11136(2004).
RN [7]
RP INTERACTION WITH RELL1; RELL2 AND RELT, AND MUTAGENESIS OF LYS-46.
RX PubMed=16389068; DOI=10.1016/j.bbrc.2005.12.033;
RA Cusick J.K., Xu L.-G., Bin L.-H., Han K.-J., Shu H.-B.;
RT "Identification of RELT homologues that associate with RELT and are
RT phosphorylated by OSR1.";
RL Biochem. Biophys. Res. Commun. 340:535-543(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-427, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-427, AND
RP MASS SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-347, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339 AND SER-427, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=22361696; DOI=10.1016/j.jprot.2012.01.030;
RA Stadler C., Hjelmare M., Neumann B., Jonasson K., Pepperkok R.,
RA Uhlen M., Lundberg E.;
RT "Systematic validation of antibody binding and protein subcellular
RT localization using siRNA and confocal microscopy.";
RL J. Proteomics 75:2236-2251(2012).
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-304 AND SER-433.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Regulates downstream kinases in response to
CC environmental stress. May also have a function in regulating the
CC actin cytoskeleton.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: By autophosphorylation on threonine.
CC -!- SUBUNIT: Binds to and phosphorylates PAK1. Interacts with chloride
CC channel proteins SLC12A6 isoform 2, SLC12A1 and SLC12A2 but not
CC with SLC12A4 and SLC12A7, possibly establishing sensor/signaling
CC modules that initiate the cellular response to environmental
CC stress. Binds to and phosphorylates RELL1, RELL2 AND RELT.
CC -!- INTERACTION:
CC Q9Y376:CAB39; NbExp=3; IntAct=EBI-620853, EBI-306905;
CC P55011:SLC12A2; NbExp=2; IntAct=EBI-620853, EBI-2801449;
CC Q9H4A3:WNK1; NbExp=2; IntAct=EBI-620853, EBI-457907;
CC Q96J92:WNK4; NbExp=11; IntAct=EBI-620853, EBI-766352;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissue examined.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97192.1; Type=Erroneous initiation;
CC Sequence=BAA83053.2; Type=Frameshift; Positions=63;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/oxsr1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB017642; BAA75674.1; -; mRNA.
DR EMBL; AB029024; BAA83053.2; ALT_FRAME; mRNA.
DR EMBL; DQ201638; ABA27097.1; -; Genomic_DNA.
DR EMBL; BC008726; AAH08726.1; -; mRNA.
DR EMBL; AF087893; AAP97192.1; ALT_INIT; mRNA.
DR RefSeq; NP_005100.1; NM_005109.2.
DR UniGene; Hs.475970; -.
DR PDB; 2V3S; X-ray; 1.70 A; A/B=433-527.
DR PDB; 2VWI; X-ray; 2.15 A; A/B/C/D=1-303.
DR PDB; 3DAK; X-ray; 2.25 A; A/B/C/D=6-295.
DR PDBsum; 2V3S; -.
DR PDBsum; 2VWI; -.
DR PDBsum; 3DAK; -.
DR ProteinModelPortal; O95747; -.
DR SMR; O95747; 7-358, 433-527.
DR IntAct; O95747; 10.
DR MINT; MINT-5207465; -.
DR STRING; 9606.ENSP00000311713; -.
DR BindingDB; O95747; -.
DR ChEMBL; CHEMBL1163104; -.
DR GuidetoPHARMACOLOGY; 2132; -.
DR PhosphoSite; O95747; -.
DR PaxDb; O95747; -.
DR PeptideAtlas; O95747; -.
DR PRIDE; O95747; -.
DR DNASU; 9943; -.
DR Ensembl; ENST00000311806; ENSP00000311713; ENSG00000172939.
DR GeneID; 9943; -.
DR KEGG; hsa:9943; -.
DR UCSC; uc003chy.3; human.
DR CTD; 9943; -.
DR GeneCards; GC03P038183; -.
DR HGNC; HGNC:8508; OXSR1.
DR HPA; CAB017181; -.
DR HPA; HPA008237; -.
DR MIM; 604046; gene.
DR neXtProt; NX_O95747; -.
DR PharmGKB; PA134973207; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234204; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; O95747; -.
DR KO; K08835; -.
DR OMA; EPQANRS; -.
DR PhylomeDB; O95747; -.
DR SignaLink; O95747; -.
DR ChiTaRS; OXSR1; human.
DR EvolutionaryTrace; O95747; -.
DR GeneWiki; OXSR1; -.
DR GenomeRNAi; 9943; -.
DR NextBio; 37516; -.
DR PRO; PR:O95747; -.
DR ArrayExpress; O95747; -.
DR Bgee; O95747; -.
DR CleanEx; HS_OSR1; -.
DR CleanEx; HS_OXSR1; -.
DR Genevestigator; O95747; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1 527 Serine/threonine-protein kinase OSR1.
FT /FTId=PRO_0000086456.
FT DOMAIN 17 291 Protein kinase.
FT NP_BIND 23 31 ATP (By similarity).
FT ACT_SITE 146 146 Proton acceptor (By similarity).
FT BINDING 46 46 ATP.
FT MOD_RES 339 339 Phosphoserine.
FT MOD_RES 347 347 Phosphoserine.
FT MOD_RES 427 427 Phosphoserine.
FT VARIANT 304 304 T -> I (in dbSNP:rs6599079).
FT /FTId=VAR_023232.
FT VARIANT 425 425 S -> T (in dbSNP:rs35295772).
FT /FTId=VAR_025181.
FT VARIANT 433 433 P -> S (in a metastatic melanoma sample;
FT somatic mutation).
FT /FTId=VAR_040969.
FT MUTAGEN 46 46 K->A: Loss of autophosphorylation and
FT kinase activity.
FT MUTAGEN 46 46 K->M: Loss of RELT, RELL1 and RELL2
FT phosphorylation. Retention of some
FT autophosphorylation activity may be due
FT to complex formation with other
FT endogenous kinases in the assay.
FT CONFLICT 316 316 K -> R (in Ref. 5; AAP97192).
FT CONFLICT 325 325 S -> G (in Ref. 5; AAP97192).
FT CONFLICT 363 363 K -> R (in Ref. 5; AAP97192).
FT HELIX 14 16
FT STRAND 18 24
FT STRAND 31 35
FT HELIX 37 39
FT STRAND 42 46
FT TURN 50 54
FT HELIX 57 69
FT STRAND 78 86
FT STRAND 88 93
FT HELIX 100 109
FT TURN 110 115
FT HELIX 120 139
FT HELIX 149 151
FT STRAND 152 154
FT STRAND 160 162
FT HELIX 166 170
FT HELIX 195 202
FT HELIX 207 222
FT TURN 226 229
FT HELIX 232 234
FT HELIX 235 240
FT TURN 247 250
FT HELIX 254 257
FT HELIX 262 271
FT HELIX 276 278
FT HELIX 282 286
FT HELIX 289 293
FT STRAND 434 441
FT STRAND 447 454
FT TURN 456 458
FT HELIX 461 470
FT HELIX 476 478
FT HELIX 479 491
FT TURN 493 495
FT STRAND 497 502
FT HELIX 504 506
FT STRAND 507 511
FT HELIX 515 517
FT STRAND 519 526
SQ SEQUENCE 527 AA; 58022 MW; B46EC934E95A3A1F CRC64;
MSEDSSALPW SINRDDYELQ EVIGSGATAV VQAAYCAPKK EKVAIKRINL EKCQTSMDEL
LKEIQAMSQC HHPNIVSYYT SFVVKDELWL VMKLLSGGSV LDIIKHIVAK GEHKSGVLDE
STIATILREV LEGLEYLHKN GQIHRDVKAG NILLGEDGSV QIADFGVSAF LATGGDITRN
KVRKTFVGTP CWMAPEVMEQ VRGYDFKADI WSFGITAIEL ATGAAPYHKY PPMKVLMLTL
QNDPPSLETG VQDKEMLKKY GKSFRKMISL CLQKDPEKRP TAAELLRHKF FQKAKNKEFL
QEKTLQRAPT ISERAKKVRR VPGSSGRLHK TEDGGWEWSD DEFDEESEEG KAAISQLRSP
RVKESISNSE LFPTTDPVGT LLQVPEQISA HLPQPAGQIA TQPTQVSLPP TAEPAKTAQA
LSSGSGSQET KIPISLVLRL RNSKKELNDI RFEFTPGRDT AEGVSQELIS AGLVDGRDLV
IVAANLQKIV EEPQSNRSVT FKLASGVEGS DIPDDGKLIG FAQLSIS
//
MIM
604046
*RECORD*
*FIELD* NO
604046
*FIELD* TI
*604046 OXIDATIVE STRESS-RESPONSIVE 1; OXSR1
;;OSR1
*FIELD* TX
CLONING
The 3p22-p21.3 chromosomal region is one of 3 regions of 3p that is
read morecommonly deleted in various carcinomas. By analyzing a cloned segment
from this region, Tamari et al. (1999) identified OXSR1, which they
designated OSR1, because the predicted 527-amino acid protein shares 39%
identity with Ste20/oxidant stress-response kinase-1 (STK25; 602255).
Northern blot analysis detected a 4.6-kb major transcript in all tissues
tested. A less abundant 7.5-kb mRNA was detected in heart and skeletal
muscle.
Using RT-PCR, Chen et al. (2004) isolated an OXSR1 cDNA from HeLa cell
RNA. The deduced 527-amino acid protein has a calculated molecular mass
of 58 kD. OXSR1 contains an N-terminal Ste20-like serine/threonine
kinase domain and 2 C-terminal regions, designated PF1 and PF2,
conserved with other members of the germinal center kinase (GCK) VI
subfamily of Ste20 kinases, such as SPAK (STK39; 607648). At the end of
the PF1 domain, OXSR1 has a putative caspase-3 (CASP3; 600636) cleavage
site. Western blot analysis detected Oxsr1 at an apparent molecular mass
of 58 kD in all mouse tissues examined except thymus. Cell fractionation
and immunofluorescence analysis of HeLa cells showed that OXSR1 was
distributed throughout the cell.
GENE FUNCTION
Chen et al. (2004) found that OXSR1 could phosphorylate a test substrate
and itself. Of the potential regulators surveyed, endogenous OXSR1 was
activated only by osmotic stresses, notably sorbitol and, to a lesser
extent, NaCl. A 2-hybrid screen identified PAK1 (602590) as an OXSR1
target protein. OXSR1 phosphorylated thr84 within the N-terminal
regulatory domain of PAK1. Replacement of thr84 with gln reduced
activation of PAK1 by an active form of the small G protein CDC42
(116952), suggesting that phosphorylation by OXSR1 modulates the G
protein sensitivity of PAK.
By yeast 2-hybrid analysis of Jurkat human T cells and
immunoprecipitation analysis of human embryonic kidney cells and HeLa
cells, Anselmo et al. (2006) showed that OXSR1 and WNK1 (605232)
interacted through conserved C-terminal motifs. OSR1 was phosphorylated
in a WNK1-dependent manner, and depletion of WNK1 from HeLa cells with
small interfering RNA reduced OXSR1 kinase activity. Depletion of either
WNK1 or OXSR1 reduced Na-K-Cl cotransporter (NKCC; see 600839) activity,
suggesting that WNK1 and OSR1 are required for NKCC function.
GENE STRUCTURE
Tamari et al. (1999) determined that the OXSR1 gene contains 18 exons
and spans approximately 90 kb.
MAPPING
Daigo et al. (1999) reported that the OXSR1 gene is located between the
OCTL1 (604047) and MYD88 (602170) genes on chromosome 3p22-p21.3.
*FIELD* RF
1. Anselmo, A. N.; Earnest, S.; Chen, W.; Juang, Y.-C.; Kim, S. C.;
Zhao, Y.; Cobb, M. H.: WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter
in HeLa cells. Proc. Nat. Acad. Sci. 103: 10883-10888, 2006.
2. Chen, W.; Yazicioglu, M.; Cobb, M. H.: Characterization of OSR1,
a member of the mammalian Ste20p/germinal center kinase subfamily. J.
Biol. Chem. 279: 11129-11136, 2004.
3. Daigo, Y.; Isomura, M.; Nishiwaki, T.; Tamari, M.; Ishikawa, S.;
Kai, M.; Murata, Y.; Takeuchi, K.; Yamane, Y.; Hayashi, R.; Minami,
M.; Fujino, M. A.; Hojo, Y.; Uchiyama, I.; Takagi, T.; Nakamura, Y.
: Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3. DNA
Res. 6: 37-44, 1999.
4. Tamari, M.; Daigo, Y.; Nakamura, Y.: Isolation and characterization
of a novel serine threonine kinase gene on chromosome 3q22-21.3. J.
Hum. Genet. 44: 116-120, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2006
*FIELD* CD
Rebekah S. Rasooly: 7/22/1999
*FIELD* ED
wwang: 08/03/2007
mgross: 10/5/2006
terry: 10/3/2006
alopez: 7/22/1999
*RECORD*
*FIELD* NO
604046
*FIELD* TI
*604046 OXIDATIVE STRESS-RESPONSIVE 1; OXSR1
;;OSR1
*FIELD* TX
CLONING
The 3p22-p21.3 chromosomal region is one of 3 regions of 3p that is
read morecommonly deleted in various carcinomas. By analyzing a cloned segment
from this region, Tamari et al. (1999) identified OXSR1, which they
designated OSR1, because the predicted 527-amino acid protein shares 39%
identity with Ste20/oxidant stress-response kinase-1 (STK25; 602255).
Northern blot analysis detected a 4.6-kb major transcript in all tissues
tested. A less abundant 7.5-kb mRNA was detected in heart and skeletal
muscle.
Using RT-PCR, Chen et al. (2004) isolated an OXSR1 cDNA from HeLa cell
RNA. The deduced 527-amino acid protein has a calculated molecular mass
of 58 kD. OXSR1 contains an N-terminal Ste20-like serine/threonine
kinase domain and 2 C-terminal regions, designated PF1 and PF2,
conserved with other members of the germinal center kinase (GCK) VI
subfamily of Ste20 kinases, such as SPAK (STK39; 607648). At the end of
the PF1 domain, OXSR1 has a putative caspase-3 (CASP3; 600636) cleavage
site. Western blot analysis detected Oxsr1 at an apparent molecular mass
of 58 kD in all mouse tissues examined except thymus. Cell fractionation
and immunofluorescence analysis of HeLa cells showed that OXSR1 was
distributed throughout the cell.
GENE FUNCTION
Chen et al. (2004) found that OXSR1 could phosphorylate a test substrate
and itself. Of the potential regulators surveyed, endogenous OXSR1 was
activated only by osmotic stresses, notably sorbitol and, to a lesser
extent, NaCl. A 2-hybrid screen identified PAK1 (602590) as an OXSR1
target protein. OXSR1 phosphorylated thr84 within the N-terminal
regulatory domain of PAK1. Replacement of thr84 with gln reduced
activation of PAK1 by an active form of the small G protein CDC42
(116952), suggesting that phosphorylation by OXSR1 modulates the G
protein sensitivity of PAK.
By yeast 2-hybrid analysis of Jurkat human T cells and
immunoprecipitation analysis of human embryonic kidney cells and HeLa
cells, Anselmo et al. (2006) showed that OXSR1 and WNK1 (605232)
interacted through conserved C-terminal motifs. OSR1 was phosphorylated
in a WNK1-dependent manner, and depletion of WNK1 from HeLa cells with
small interfering RNA reduced OXSR1 kinase activity. Depletion of either
WNK1 or OXSR1 reduced Na-K-Cl cotransporter (NKCC; see 600839) activity,
suggesting that WNK1 and OSR1 are required for NKCC function.
GENE STRUCTURE
Tamari et al. (1999) determined that the OXSR1 gene contains 18 exons
and spans approximately 90 kb.
MAPPING
Daigo et al. (1999) reported that the OXSR1 gene is located between the
OCTL1 (604047) and MYD88 (602170) genes on chromosome 3p22-p21.3.
*FIELD* RF
1. Anselmo, A. N.; Earnest, S.; Chen, W.; Juang, Y.-C.; Kim, S. C.;
Zhao, Y.; Cobb, M. H.: WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter
in HeLa cells. Proc. Nat. Acad. Sci. 103: 10883-10888, 2006.
2. Chen, W.; Yazicioglu, M.; Cobb, M. H.: Characterization of OSR1,
a member of the mammalian Ste20p/germinal center kinase subfamily. J.
Biol. Chem. 279: 11129-11136, 2004.
3. Daigo, Y.; Isomura, M.; Nishiwaki, T.; Tamari, M.; Ishikawa, S.;
Kai, M.; Murata, Y.; Takeuchi, K.; Yamane, Y.; Hayashi, R.; Minami,
M.; Fujino, M. A.; Hojo, Y.; Uchiyama, I.; Takagi, T.; Nakamura, Y.
: Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3. DNA
Res. 6: 37-44, 1999.
4. Tamari, M.; Daigo, Y.; Nakamura, Y.: Isolation and characterization
of a novel serine threonine kinase gene on chromosome 3q22-21.3. J.
Hum. Genet. 44: 116-120, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2006
*FIELD* CD
Rebekah S. Rasooly: 7/22/1999
*FIELD* ED
wwang: 08/03/2007
mgross: 10/5/2006
terry: 10/3/2006
alopez: 7/22/1999