Q5R8M1 · STK38_PONAB
- ProteinSerine/threonine-protein kinase 38
- GeneSTK38
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids465 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2. 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.
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 (By similarity).
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Cellular Component | site of double-strand break | |
Molecular Function | ATP 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 | UFM1-modified protein reader activity | |
Biological Process | DNA damage checkpoint signaling | |
Biological Process | DNA damage response | |
Biological Process | negative regulation of MAP kinase activity | |
Biological Process | protein modification process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase 38
- EC number
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Pongo
Accessions
- Primary accessionQ5R8M1
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to DNA double-strand breaks in response to DNA damage.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000292953 | 2-465 | Serine/threonine-protein kinase 38 | |||
Sequence: AMTGSTPCSSMSNHTKERVTMTKVTLENFYSNLIAQHEEREMRQKKLEKVMEEEGLKDEEKRLRRSAHARKETEFLRLKRTRLGLEDFESLKVIGRGAFGEVRLVQKKDTGHVYAMKILRKADMLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLCTGLKKAHRTEFYRNLNHSLPSDFTFQNMNSKRKAETWKRNRRQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKVMNWKETLTFPPEVPISEKAKDLILRFCCEWEHRIGAPGVEEIKSNSFFEGVDWEHIRERPAAISIEIKSIDDTSNFDEFPESDILKPTVATSNHPETDYKNKDWVFINYTYKRFEGLTARGAIPSYMKAAK | ||||||
Modified residue | 74 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 264 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 281 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 444 | Phosphothreonine; by STK24/MST3 | ||||
Sequence: T |
Post-translational modification
ISGylated.
Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.
Keywords
- PTM
Interaction
Subunit
Homodimeric S100B binds two molecules of STK38. Interacts with MOB1 and MOB2. Interacts with MAP3K1 and MAP3K2 (via the kinase domain). Forms a tripartite complex with MOBKL1B and STK3/MST2. Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4.
Protein-protein interaction databases
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 updated2004-12-21 v1
- Checksum7262221DBFFAF83C
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I5TIU1 | A0A8I5TIU1_PONAB | STK38 | 450 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
CR859730 EMBL· GenBank· DDBJ | CAH91889.1 EMBL· GenBank· DDBJ | mRNA |