Q15208 · STK38_HUMAN
- ProteinSerine/threonine-protein kinase 38
- GeneSTK38
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids465 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441).
Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441).
Acts as an ufmylation 'reader' in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation (PubMed:32537488).
Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441).
Acts as an ufmylation 'reader' in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation (PubMed:32537488).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | glutamatergic synapse | |
Cellular Component | nucleus | |
Cellular Component | site of double-strand break | |
Molecular Function | ATP binding | |
Molecular Function | cadherin binding | |
Molecular Function | histone reader activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | mitogen-activated protein kinase kinase kinase binding | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Molecular Function | ubiquitin-like protein reader activity | |
Molecular Function | UFM1-modified protein reader activity | |
Biological Process | DNA damage checkpoint signaling | |
Biological Process | DNA damage response | |
Biological Process | intracellular signal transduction | |
Biological Process | negative regulation of MAP kinase activity | |
Biological Process | postsynapse organization | |
Biological Process | protein modification process | |
Biological Process | protein phosphorylation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase 38
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ15208
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to DNA double-strand breaks in response to DNA damage.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041196 | 18 | in a metastatic melanoma sample; somatic mutation | |||
Sequence: E → K | ||||||
Mutagenesis | 74 | Decreases autophosphorylation and kinase activity. Reduced binding of S100B. | ||||
Sequence: T → A | ||||||
Mutagenesis | 118 | Loss of autophosphorylation and kinase activity. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_041197 | 145 | in dbSNP:rs56005153 | |||
Sequence: D → N | ||||||
Natural variant | VAR_041198 | 267 | in dbSNP:rs56105564 | |||
Sequence: K → R | ||||||
Mutagenesis | 281 | Loss of autophosphorylation and kinase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 306-311 | Abolished binding to ufmylated histone H4. | ||||
Sequence: WSLGVI → ASAGAA | ||||||
Mutagenesis | 444 | Decreases autophosphorylation and kinase activity. | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 394 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000086718 | 2-465 | UniProt | Serine/threonine-protein kinase 38 | |||
Sequence: AMTGSTPCSSMSNHTKERVTMTKVTLENFYSNLIAQHEEREMRQKKLEKVMEEEGLKDEEKRLRRSAHARKETEFLRLKRTRLGLEDFESLKVIGRGAFGEVRLVQKKDTGHVYAMKILRKADMLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLCTGLKKAHRTEFYRNLNHSLPSDFTFQNMNSKRKAETWKRNRRQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKVMNWKETLTFPPEVPISEKAKDLILRFCCEWEHRIGAPGVEEIKSNSFFEGVDWEHIRERPAAISIEIKSIDDTSNFDEFPESDILKPTVATSNHPETDYKNKDWVFINYTYKRFEGLTARGAIPSYMKAAK | |||||||
Modified residue (large scale data) | 6 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 7 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 74 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 264 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 264 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 281 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 281 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 282 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 444 | UniProt | Phosphothreonine; by STK24/MST3 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 452 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
ISGylated.
Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed with highest levels observed in peripheral blood leukocytes.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimeric S100B binds two molecules of STK38 (PubMed:14661952).
Interacts with MOB1 and MOB2 (PubMed:15067004, PubMed:15197186).
Interacts with MAP3K1 and MAP3K2 (via the kinase catalytic domain) (PubMed:17906693).
Forms a tripartite complex with MOBKL1B and STK3/MST2 (PubMed:18362890).
Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4 (By similarity).
Interacts with MOB1 and MOB2 (PubMed:15067004, PubMed:15197186).
Interacts with MAP3K1 and MAP3K2 (via the kinase catalytic domain) (PubMed:17906693).
Forms a tripartite complex with MOBKL1B and STK3/MST2 (PubMed:18362890).
Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q15208 | ARRB1 P49407 | 3 | EBI-458376, EBI-743313 | |
BINARY | Q15208 | ARRB2 P32121 | 3 | EBI-458376, EBI-714559 | |
BINARY | Q15208 | BANP Q8N9N5-2 | 3 | EBI-458376, EBI-11524452 | |
BINARY | Q15208 | CAV1 Q03135 | 3 | EBI-458376, EBI-603614 | |
BINARY | Q15208 | HSP90AB1 P08238 | 2 | EBI-458376, EBI-352572 | |
BINARY | Q15208 | MOB1A Q9H8S9 | 3 | EBI-458376, EBI-748229 | |
BINARY | Q15208 | MOB2 Q70IA6 | 4 | EBI-458376, EBI-2558739 | |
BINARY | Q15208 | NCK1 P16333 | 3 | EBI-458376, EBI-389883 | |
BINARY | Q15208 | PEBP1 P30086 | 3 | EBI-458376, EBI-716384 | |
XENO | Q15208 | S100B P02638 | 3 | EBI-458376, EBI-458452 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 62-87 | Interaction with S100B | ||||
Sequence: KRLRRSAHARKETEFLRLKRTRLGLE | ||||||
Domain | 89-382 | Protein kinase | ||||
Sequence: FESLKVIGRGAFGEVRLVQKKDTGHVYAMKILRKADMLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLCTGLKKAHRTEFYRNLNHSLPSDFTFQNMNSKRKAETWKRNRRQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKVMNWKETLTFPPEVPISEKAKDLILRFCCEWEHRIGAPGVEEIKSNSFF | ||||||
Motif | 306-311 | UFM1-interacting motif (UFIM) | ||||
Sequence: WSLGVI | ||||||
Domain | 383-455 | AGC-kinase C-terminal | ||||
Sequence: EGVDWEHIRERPAAISIEIKSIDDTSNFDEFPESDILKPTVATSNHPETDYKNKDWVFINYTYKRFEGLTARG |
Domain
The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated histone H4.
Sequence similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length465
- Mass (Da)54,190
- Last updated1996-11-01 v1
- Checksum7262221DBFFAF83C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z35102 EMBL· GenBank· DDBJ | CAA84485.1 EMBL· GenBank· DDBJ | mRNA | ||
Z85986 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC012085 EMBL· GenBank· DDBJ | AAH12085.1 EMBL· GenBank· DDBJ | mRNA | ||
BC095413 EMBL· GenBank· DDBJ | AAH95413.1 EMBL· GenBank· DDBJ | mRNA |