ID   STK38_MOUSE             Reviewed;         465 AA.
AC   Q91VJ4;
DT   21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 175.
DE   RecName: Full=Serine/threonine-protein kinase 38;
DE            EC=2.7.11.1;
DE   AltName: Full=NDR1 protein kinase;
DE   AltName: Full=Nuclear Dbf2-related kinase 1;
GN   Name=Stk38 {ECO:0000312|EMBL:AAH09658.1};
GN   Synonyms=Ndr1 {ECO:0000250|UniProtKB:Q15208};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAP44997.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:AAP44997.1};
RX   PubMed=15037617; DOI=10.1074/jbc.m402472200;
RA   Stegert M.R., Tamaskovic R., Bichsel S.J., Hergovich A., Hemmings B.A.;
RT   "Regulation of NDR2 protein kinase by multi-site phosphorylation and the
RT   S100B calcium-binding protein.";
RL   J. Biol. Chem. 279:23806-23812(2004).
RN   [2] {ECO:0000312|EMBL:AAH09658.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N {ECO:0000312|EMBL:AAH09658.1};
RC   TISSUE=Mammary gland {ECO:0000312|EMBL:AAH09658.1};
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Pancreas, Spleen,
RC   and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH MICAL1.
RX   PubMed=21730291; DOI=10.1128/mcb.01389-10;
RA   Zhou Y., Adolfs Y., Pijnappel W.W., Fuller S.J., Van der Schors R.C.,
RA   Li K.W., Sugden P.H., Smit A.B., Hergovich A., Pasterkamp R.J.;
RT   "MICAL-1 is a negative regulator of MST-NDR kinase signaling and
RT   apoptosis.";
RL   Mol. Cell. Biol. 31:3603-3615(2011).
CC   -!- FUNCTION: Negative regulator of MAP3K1/2 signaling. Converts MAP3K2
CC       from its phosphorylated form to its non-phosphorylated form and
CC       inhibits autophosphorylation of MAP3K2 (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:21730291}.
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=2.7.11.1;
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=2.7.11.1;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ACTIVITY REGULATION: Activated by binding of S100B which releases
CC       autoinhibitory N-lobe interactions, enabling ATP to bind and the
CC       autophosphorylation of Ser-281. Thr-444 then undergoes calcium-
CC       dependent phosphorylation by STK24/MST3. Interactions between
CC       phosphorylated Thr-444 and the N-lobe promote additional structural
CC       changes that complete the activation of the kinase. Autoinhibition is
CC       also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-
CC       terminal of STK38.
CC   -!- SUBUNIT: Homodimeric S100B binds two molecules of STK38. Interacts with
CC       MOB1 and MOB2 (By similarity). Interacts with MAP3K1 and MAP3K2 (via
CC       the kinase catalytic domain) (By similarity). Forms a tripartite
CC       complex with MOBKL1B and STK3/MST2 (By similarity). Interacts with
CC       MICAL1; leading to inhibit the protein kinase activity by antagonizing
CC       activation by MST1/STK4 (PubMed:21730291).
CC       {ECO:0000250|UniProtKB:Q15208, ECO:0000269|PubMed:21730291}.
CC   -!- INTERACTION:
CC       Q91VJ4; Q8VDP3: Mical1; NbExp=9; IntAct=EBI-2527046, EBI-4394891;
CC       Q91VJ4; Q13043: STK4; Xeno; NbExp=2; IntAct=EBI-2527046, EBI-367376;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed at high levels in spleen, lung, thymus,
CC       brain and fat tissue. {ECO:0000269|PubMed:15037617}.
CC   -!- PTM: ISGylated. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. {ECO:0000305}.
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DR   EMBL; AY292399; AAP44997.1; -; mRNA.
DR   EMBL; BC009658; AAH09658.1; -; mRNA.
DR   CCDS; CCDS28589.1; -.
DR   RefSeq; NP_598876.1; NM_134115.2.
DR   AlphaFoldDB; Q91VJ4; -.
DR   BMRB; Q91VJ4; -.
DR   SMR; Q91VJ4; -.
DR   BioGRID; 223068; 15.
DR   IntAct; Q91VJ4; 13.
DR   MINT; Q91VJ4; -.
DR   STRING; 10090.ENSMUSP00000113657; -.
DR   iPTMnet; Q91VJ4; -.
DR   PhosphoSitePlus; Q91VJ4; -.
DR   SwissPalm; Q91VJ4; -.
DR   EPD; Q91VJ4; -.
DR   jPOST; Q91VJ4; -.
DR   MaxQB; Q91VJ4; -.
DR   PaxDb; 10090-ENSMUSP00000009138; -.
DR   PeptideAtlas; Q91VJ4; -.
DR   ProteomicsDB; 258761; -.
DR   Pumba; Q91VJ4; -.
DR   Antibodypedia; 29688; 471 antibodies from 33 providers.
DR   DNASU; 106504; -.
DR   Ensembl; ENSMUST00000009138.13; ENSMUSP00000009138.6; ENSMUSG00000024006.18.
DR   Ensembl; ENSMUST00000119274.3; ENSMUSP00000113657.2; ENSMUSG00000024006.18.
DR   Ensembl; ENSMUST00000232836.2; ENSMUSP00000156711.2; ENSMUSG00000024006.18.
DR   GeneID; 106504; -.
DR   KEGG; mmu:106504; -.
DR   UCSC; uc008bsa.1; mouse.
DR   AGR; MGI:2442572; -.
DR   CTD; 11329; -.
DR   MGI; MGI:2442572; Stk38.
DR   VEuPathDB; HostDB:ENSMUSG00000024006; -.
DR   eggNOG; KOG0605; Eukaryota.
DR   GeneTree; ENSGT00940000153544; -.
DR   HOGENOM; CLU_000288_67_0_1; -.
DR   InParanoid; Q91VJ4; -.
DR   OMA; EEIKCNS; -.
DR   OrthoDB; 988261at2759; -.
DR   PhylomeDB; Q91VJ4; -.
DR   TreeFam; TF105337; -.
DR   Reactome; R-MMU-9013418; RHOBTB2 GTPase cycle.
DR   Reactome; R-MMU-9013422; RHOBTB1 GTPase cycle.
DR   BioGRID-ORCS; 106504; 7 hits in 82 CRISPR screens.
DR   ChiTaRS; Stk38; mouse.
DR   PRO; PR:Q91VJ4; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; Q91VJ4; Protein.
DR   Bgee; ENSMUSG00000024006; Expressed in granulocyte and 267 other cell types or tissues.
DR   ExpressionAtlas; Q91VJ4; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR   GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR   GO; GO:0099173; P:postsynapse organization; ISO:MGI.
DR   GO; GO:0036211; P:protein modification process; ISO:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   CDD; cd21782; MobB_NDR1; 1.
DR   CDD; cd05628; STKc_NDR1; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR017892; Pkinase_C.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1.
DR   PANTHER; PTHR24356:SF221; SERINE_THREONINE-PROTEIN KINASE 38; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF00433; Pkinase_C; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q91VJ4; MM.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208"
FT   CHAIN           2..465
FT                   /note="Serine/threonine-protein kinase 38"
FT                   /id="PRO_0000086719"
FT   DOMAIN          89..382
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          383..455
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   REGION          62..87
FT                   /note="Interaction with S100B"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        212
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         95..103
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:O95835,
FT                   ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         118
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208,
FT                   ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208"
FT   MOD_RES         74
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208"
FT   MOD_RES         264
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         281
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208"
FT   MOD_RES         444
FT                   /note="Phosphothreonine; by STK24/MST3"
FT                   /evidence="ECO:0000250|UniProtKB:Q15208"
SQ   SEQUENCE   465 AA;  54174 MW;  00E29F8963196750 CRC64;
     MAMTGSTPCS SMSNHTKERV TMTKVTLENF YSNLIAQHEE REMRQKKLEK VMEEEGLKDE
     EKRLRRSAHA RKETEFLRLK RTRLGLEDFE SLKVIGRGAF GEVRLVQKKD TGHVYAMKIL
     RKADMLEKEQ VGHIRAERDI LVEADSLWVV KMFYSFQDKL NLYLIMEFLP GGDMMTLLMK
     KDTLTEEETQ FYIAETVLAI DSIHQLGFIH RDIKPDNLLL DSKGHVKLSD FGLCTGLKKA
     HRTEFYRNLN HSLPSDFTFQ NMNSKRKAET WKRNRRQLAF STVGTPDYIA PEVFMQTGYN
     KLCDWWSLGV IMYEMLIGYP PFCSETPQET YKKVMNWKET LTFPPEVPVS EKAKGLILRF
     CCEWEHRIGA PGVEEIKNNL FFEGVDWEHI RERPAAISIE IKSIDDTSNF DEFPESDILK
     PTVTTSSHPE TDYKNKDWVF INYTYKRFEG LTARGAIPSY MKAAK
//