TESK1_RAT
ID TESK1_RAT Reviewed; 628 AA.
AC Q63572;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Dual specificity testis-specific protein kinase 1;
DE EC=2.7.12.1;
DE AltName: Full=Testicular protein kinase 1;
GN Name=Tesk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Testis;
RX PubMed=8537404; DOI=10.1074/jbc.270.52.31331;
RA Toshima J., Ohashi K., Okano I., Nunoue K., Kishioka M., Kuma K.,
RA Miyata T., Hirai M., Baba T., Mizuno K.;
RT "Identification and characterization of a novel protein kinase, TESK1,
RT specifically expressed in testicular germ cells.";
RL J. Biol. Chem. 270:31331-31337(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-215, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ASP-170; TYR-201; SER-215 AND TYR-217.
RX PubMed=10207045; DOI=10.1074/jbc.274.17.12171;
RA Toshima J., Tanaka T., Mizuno K.;
RT "Dual specificity protein kinase activity of testis-specific protein kinase
RT 1 and its regulation by autophosphorylation of serine-215 within the
RT activation loop.";
RL J. Biol. Chem. 274:12171-12176(1999).
RN [4]
RP FUNCTION, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-439, AND
RP MUTAGENESIS OF ASP-170 AND SER-439.
RX PubMed=11555644; DOI=10.1074/jbc.m104620200;
RA Toshima J.Y., Toshima J., Watanabe T., Mizuno K.;
RT "Binding of 14-3-3beta regulates the kinase activity and subcellular
RT localization of testicular protein kinase 1.";
RL J. Biol. Chem. 276:43471-43481(2001).
RN [5]
RP INTERACTION WITH PARVA.
RX PubMed=15817463; DOI=10.1074/jbc.m500752200;
RA LaLonde D.P., Brown M.C., Bouverat B.P., Turner C.E.;
RT "Actopaxin interacts with TESK1 to regulate cell spreading on
RT fibronectin.";
RL J. Biol. Chem. 280:21680-21688(2005).
RN [6]
RP INTERACTION WITH SPRED1; SPRY1; SPRY2; SPRY3; SPRY4 AND SPRED2, AND
RP MUTAGENESIS OF ASP-170.
RX PubMed=17974561; DOI=10.1074/jbc.m705457200;
RA Chandramouli S., Yu C.Y., Yusoff P., Lao D.H., Leong H.F., Mizuno K.,
RA Guy G.R.;
RT "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK
RT phosphorylation downstream of receptor tyrosine kinase signaling.";
RL J. Biol. Chem. 283:1679-1691(2008).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH TAOK1 AND SPRED1, AND
RP MUTAGENESIS OF ASP-170.
RX PubMed=18216281; DOI=10.1091/mbc.e07-07-0730;
RA Johne C., Matenia D., Li X.Y., Timm T., Balusamy K., Mandelkow E.M.;
RT "Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1
RT that link the microtubule and actin cytoskeleton.";
RL Mol. Biol. Cell 19:1391-1403(2008).
RN [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY CELL ADHESION
RP AND SCIATIC NERVE CRUSH INJURY.
RX PubMed=22302232; DOI=10.1007/s12031-012-9712-x;
RA Lou D., Sun B., Wei H., Deng X., Chen H., Xu D., Li G., Xu H., Wang Y.;
RT "Spatiotemporal expression of testicular protein kinase 1 after rat sciatic
RT nerve injury.";
RL J. Mol. Neurosci. 47:180-191(2012).
CC -!- FUNCTION: Dual specificity protein kinase activity catalyzing
CC autophosphorylation and phosphorylation of exogenous substrates on both
CC serine/threonine and tyrosine residues (PubMed:10207045). Regulates the
CC cellular cytoskeleton by enhancing actin stress fiber formation via
CC phosphorylation of cofilin and by preventing microtubule breakdown via
CC inhibition of TAOK1/MARKK kinase activity (PubMed:18216281,
CC PubMed:11555644). Inhibits podocyte motility via regulation of actin
CC cytoskeletal dynamics and phosphorylation of CFL1 (By similarity).
CC Positively regulates integrin-mediated cell spreading, via
CC phosphorylation of cofilin (By similarity). Suppresses ciliogenesis via
CC multiple pathways; phosphorylation of CFL1, suppression of ciliary
CC vesicle directional trafficking to the ciliary base, and by
CC facilitating YAP1 nuclear localization where it acts as a
CC transcriptional corepressor of the TEAD4 target genes AURKA and PLK1
CC (By similarity). Probably plays a central role at and after the meiotic
CC phase of spermatogenesis (PubMed:8537404).
CC {ECO:0000250|UniProtKB:O70146, ECO:0000250|UniProtKB:Q15569,
CC ECO:0000269|PubMed:10207045, ECO:0000269|PubMed:11555644,
CC ECO:0000269|PubMed:18216281, ECO:0000269|PubMed:8537404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC -!- ACTIVITY REGULATION: Activated by autophosphorylation on Ser-215.
CC Kinase activity is inhibited by SPRED1. {ECO:0000269|PubMed:10207045,
CC ECO:0000269|PubMed:18216281}.
CC -!- SUBUNIT: Interacts (via both C- and N-termini) with SPRY4 (via C-
CC terminus); the interaction inhibits TESK1 kinase activity
CC (PubMed:17974561). Interacts with TAOK1; the interaction inhibits TAOK1
CC kinase activity (PubMed:18216281). Interacts (via C-terminus) with
CC SPRED1 (via C-terminus); the interaction inhibits TESK1 kinase activity
CC (PubMed:17974561, PubMed:18216281). Interacts (via C-terminus) with
CC PARVA/PARVIN (via C-terminus); the interaction inhibits TESK1 kinase
CC activity (PubMed:15817463). Interacts with YWHAB/14-3-3 beta; the
CC interaction is dependent on the phosphorylation of TESK1 Ser-439 and
CC inhibits TESK1 kinase activity (PubMed:11555644). Interacts with SPRY1,
CC SPRY3 and SPRED2 (PubMed:17974561). Interacts (via C-terminus) with
CC SPRY2 (via C-terminus); the interaction disrupts SPRY2 interaction with
CC PPP2CA/PP2A-C, possibly by vesicular sequestration of SPRY2
CC (PubMed:17974561). Therefore dephosphorylation of SPRY2 by the
CC serine/threonine-protein phosphatase 2A (PP2A) holoenzyme is lost,
CC inhibiting its interaction with GRB2 (PubMed:17974561).
CC {ECO:0000269|PubMed:11555644, ECO:0000269|PubMed:15817463,
CC ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18216281}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22302232}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:22302232}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q15569}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:22302232}. Note=Colocalizes with SPRY4 in vesicular
CC spots in the cytoplasm (By similarity). Localized to F-actin-rich
CC lamellipodia at the cell periphery following fibronectin-mediated cell
CC adhesion of Schwann cells (PubMed:22302232).
CC {ECO:0000250|UniProtKB:Q15569, ECO:0000269|PubMed:22302232}.
CC -!- TISSUE SPECIFICITY: Weakly expressed in sciatic nerves (at protein
CC level) (PubMed:22302232). Highly expressed in testicular germ cells
CC (PubMed:8537404, PubMed:10207045). Expressed at low levels in brain,
CC lung, heart, liver and kidney (PubMed:10207045).
CC {ECO:0000269|PubMed:10207045, ECO:0000269|PubMed:22302232,
CC ECO:0000269|PubMed:8537404}.
CC -!- INDUCTION: Induced by fibronectin-mediated cell adhesion of Schwann
CC cells (PubMed:22302232). Induced by sciatic nerve crush injury,
CC expression peaks 2 weeks post-injury and returns to normal at 4 weeks
CC post-injury in the macrophages of promyelinating Schwann tubules
CC (PubMed:22302232). {ECO:0000269|PubMed:22302232}.
CC -!- DOMAIN: The extracatalytic C-terminal part is highly rich in proline
CC residues.
CC -!- PTM: Autophosphorylated on serine and tyrosine residues.
CC {ECO:0000269|PubMed:10207045}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; D50864; BAA09460.1; -; mRNA.
DR EMBL; BC081773; AAH81773.1; -; mRNA.
DR RefSeq; NP_113766.1; NM_031578.1.
DR AlphaFoldDB; Q63572; -.
DR SMR; Q63572; -.
DR MINT; Q63572; -.
DR STRING; 10116.ENSRNOP00000023694; -.
DR iPTMnet; Q63572; -.
DR PhosphoSitePlus; Q63572; -.
DR PaxDb; Q63572; -.
DR Ensembl; ENSRNOT00000080909; ENSRNOP00000071965; ENSRNOG00000053729.
DR GeneID; 29460; -.
DR KEGG; rno:29460; -.
DR UCSC; RGD:62059; rat.
DR CTD; 7016; -.
DR RGD; 62059; Tesk1.
DR eggNOG; ENOG502QTCP; Eukaryota.
DR GeneTree; ENSGT00940000157807; -.
DR HOGENOM; CLU_018577_0_0_1; -.
DR InParanoid; Q63572; -.
DR OMA; SPPTWGD; -.
DR OrthoDB; 219904at2759; -.
DR PhylomeDB; Q63572; -.
DR TreeFam; TF318014; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-446388; Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.
DR PRO; PR:Q63572; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000053729; Expressed in testis and 19 other tissues.
DR Genevisible; Q63572; RN.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:ARUK-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:RGD.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051650; P:establishment of vesicle localization; ISS:UniProtKB.
DR GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0031953; P:negative regulation of protein autophosphorylation; IDA:ARUK-UCL.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:ARUK-UCL.
DR GO; GO:0090521; P:podocyte cell migration; ISS:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:ARUK-UCL.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0032880; P:regulation of protein localization; IDA:ARUK-UCL.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR015782; TESK1.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR PANTHER; PTHR46485:SF3; PTHR46485:SF3; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cytoplasm; Cytoskeleton; Kinase; Magnesium;
KW Manganese; Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..628
FT /note="Dual specificity testis-specific protein kinase 1"
FT /id="PRO_0000086748"
FT DOMAIN 52..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..526
FT /note="Required for interaction with YWHAB"
FT /evidence="ECO:0000269|PubMed:11555644"
FT REGION 424..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..628
FT /note="Required for interaction with SPRED1 and SPRY2.
FT Required for TESK1-mediated dephosphorylation of SPRY2 and
FT SPRY2 inhibition of ERK phosphorylation"
FT /evidence="ECO:0000269|PubMed:17974561"
FT REGION 529..626
FT /note="Required for interaction with PARVA"
FT /evidence="ECO:0000269|PubMed:15817463"
FT REGION 538..568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 170
FT /note="Proton acceptor"
FT BINDING 58..66
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 215
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10207045"
FT MOD_RES 338
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O70146"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11555644"
FT MUTAGEN 170
FT /note="D->A: Loss of kinase and autophosphorylating
FT activity. Abolishes TESK1-induced actin stress fiber
FT formation. No effect on interaction with YWHAB, SPRY2 or
FT SPRED1. No effect on TESK1-mediated dephosphorylation of
FT SPRY2."
FT /evidence="ECO:0000269|PubMed:10207045,
FT ECO:0000269|PubMed:11555644, ECO:0000269|PubMed:17974561,
FT ECO:0000269|PubMed:18216281"
FT MUTAGEN 201
FT /note="Y->A: No effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10207045"
FT MUTAGEN 215
FT /note="S->A: Loss of autophosphorylation site, loss of
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:10207045"
FT MUTAGEN 215
FT /note="S->E: Loss of autophosphorylation site, no effect on
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:10207045"
FT MUTAGEN 217
FT /note="Y->A: No effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10207045"
FT MUTAGEN 439
FT /note="S->A: Abolishes interaction with YWHAB."
FT /evidence="ECO:0000269|PubMed:11555644"
SQ SEQUENCE 628 AA; 67988 MW; F05F67FBD934B9AD CRC64;
MAGERPPLRG PGPGETPVEG PGGAGGGPGR GRPSSYRALR SAVSSLARVD DFDCAEKIGA
GFFSEVYKVR HRQSGQVMVL KMNKLPSNRS NTLREVQLMN RLRHPNILRF MGVCVHQGQL
HALTEYMNGG TLEQLLSSPE PLSWPVRLHL ALDIAQGLRY LHAKGVFHRD LTSKNCLVRR
EDGGFTAVVG DFGLAEKIPV YREGARKEPL AVVGSPYWMA PEVLRGELYD EKADVFAFGI
VLCELIARVP ADPDYLPRTE DFGLDVPAFR TLVGNDCPLP FLLLAIHCCS MEPSARAPFT
EITQHLEQIL EQLPEPTPLA KMPLAKAPLT YNQGSVPRGG PSATLPRSDP RLSRSRSDLF
LPPSPESPPS WGDNLTRVNP FSLREDLRGG KIKLLDTPCK PATPLPLVPP SPLTSTQLPL
VASPESLVQP ETPVRRCRSL PSSPELPRRM ETALPGPGPS PVGPSTEERM DCEGSSPEPE
PPGPAPQLPL AVATDNFIST CSSASQPWSA RPGPSLNNNP PAVVVNSPQG WAREPWNRAQ
HSLPRAAALE RTEPSPPPSA PREQEEGLPC PGCCLSPFSF GFLSMCPRPT PAVARYRNLN
CEAGSLLCHR GHHAKPPTPS LQLPGARS
