STK38_MOUSE
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 03-AUG-2022, entry version 166.
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, and
RC 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.ENSMUSP00000009138; -.
DR iPTMnet; Q91VJ4; -.
DR PhosphoSitePlus; Q91VJ4; -.
DR EPD; Q91VJ4; -.
DR jPOST; Q91VJ4; -.
DR MaxQB; Q91VJ4; -.
DR PaxDb; Q91VJ4; -.
DR PeptideAtlas; Q91VJ4; -.
DR PRIDE; Q91VJ4; -.
DR ProteomicsDB; 258761; -.
DR Antibodypedia; 29688; 452 antibodies from 33 providers.
DR DNASU; 106504; -.
DR Ensembl; ENSMUST00000009138; ENSMUSP00000009138; ENSMUSG00000024006.
DR Ensembl; ENSMUST00000119274; ENSMUSP00000113657; ENSMUSG00000024006.
DR Ensembl; ENSMUST00000232836; ENSMUSP00000156711; ENSMUSG00000024006.
DR GeneID; 106504; -.
DR KEGG; mmu:106504; -.
DR UCSC; uc008bsa.1; mouse.
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; YTYKKSD; -.
DR OrthoDB; 759391at2759; -.
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 77 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 264 other tissues.
DR ExpressionAtlas; Q91VJ4; baseline and differential.
DR Genevisible; Q91VJ4; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; 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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
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 Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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
