ID   STK38_PONAB             Reviewed;         465 AA.
AC   Q5R8M1;
DT   12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 118.
DE   RecName: Full=Serine/threonine-protein kinase 38;
DE            EC=2.7.11.1;
GN   Name=STK38;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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   -!- 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; Evidence={ECO:0000250};
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 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimeric S100B binds two molecules of STK38. Interacts with
CC       MOB1 and MOB2. Interacts with MAP3K1 and MAP3K2 (via the kinase
CC       domain). Forms a tripartite complex with MOBKL1B and STK3/MST2.
CC       Interacts with MICAL1; leading to inhibit the protein kinase activity
CC       by antagonizing activation by MST1/STK4. {ECO:0000250|UniProtKB:Q15208,
CC       ECO:0000250|UniProtKB:Q91VJ4}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
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; CR859730; CAH91889.1; -; mRNA.
DR   RefSeq; NP_001126095.1; NM_001132623.1.
DR   RefSeq; XP_009240039.1; XM_009241764.1.
DR   AlphaFoldDB; Q5R8M1; -.
DR   BMRB; Q5R8M1; -.
DR   SMR; Q5R8M1; -.
DR   STRING; 9601.ENSPPYP00000018509; -.
DR   Ensembl; ENSPPYT00000019246; ENSPPYP00000018509; ENSPPYG00000016547.
DR   GeneID; 100173048; -.
DR   KEGG; pon:100173048; -.
DR   CTD; 11329; -.
DR   eggNOG; KOG0605; Eukaryota.
DR   GeneTree; ENSGT00940000153544; -.
DR   HOGENOM; CLU_000288_67_0_1; -.
DR   InParanoid; Q5R8M1; -.
DR   OMA; YTYKKSD; -.
DR   OrthoDB; 759391at2759; -.
DR   TreeFam; TF105337; -.
DR   Proteomes; UP000001595; Chromosome 6.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR   GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IEA:Ensembl.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR   GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
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; SM00133; S_TK_X; 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   2: Evidence at transcript 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_0000292953"
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   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:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         118
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="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:0000250|UniProtKB:Q15208"
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;  54190 MW;  7262221DBFFAF83C 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 LTFPPEVPIS EKAKDLILRF
     CCEWEHRIGA PGVEEIKSNS FFEGVDWEHI RERPAAISIE IKSIDDTSNF DEFPESDILK
     PTVATSNHPE TDYKNKDWVF INYTYKRFEG LTARGAIPSY MKAAK