Q15208 · STK38_HUMAN

  • Protein
    Serine/threonine-protein kinase 38
  • Gene
    STK38
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Caution

Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461).
However, the corresponding article has been retracted (PubMed:24336203).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

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.

TypeIDPosition(s)Description
Binding site95-103ATP (UniProtKB | ChEBI)
Binding site118ATP (UniProtKB | ChEBI)
Active site212Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentglutamatergic synapse
Cellular Componentnucleus
Cellular Componentsite of double-strand break
Molecular FunctionATP binding
Molecular Functioncadherin binding
Molecular Functionhistone reader activity
Molecular Functionmagnesium ion binding
Molecular Functionmitogen-activated protein kinase kinase kinase binding
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Molecular Functionubiquitin-like protein reader activity
Molecular FunctionUFM1-modified protein reader activity
Biological ProcessDNA damage checkpoint signaling
Biological ProcessDNA damage response
Biological Processintracellular signal transduction
Biological Processnegative regulation of MAP kinase activity
Biological Processpostsynapse organization
Biological Processprotein modification process
Biological Processprotein phosphorylation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine/threonine-protein kinase 38
  • EC number
  • Alternative names
    • NDR1 protein kinase
    • Nuclear Dbf2-related kinase 1

Gene names

    • Name
      STK38
    • Synonyms
      NDR1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q15208
  • Secondary accessions
    • Q503A1

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
Chromosome
Note: Localizes to DNA double-strand breaks in response to DNA damage.

Keywords

Disease & Variants

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_04119618in a metastatic melanoma sample; somatic mutation
Mutagenesis74Decreases autophosphorylation and kinase activity. Reduced binding of S100B.
Mutagenesis118Loss of autophosphorylation and kinase activity.
Natural variantVAR_041197145in dbSNP:rs56005153
Natural variantVAR_041198267in dbSNP:rs56105564
Mutagenesis281Loss of autophosphorylation and kinase activity.
Mutagenesis306-311Abolished binding to ufmylated histone H4.
Mutagenesis444Decreases autophosphorylation and kinase activity.

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Modified residue2UniProtN-acetylalanine
ChainPRO_00000867182-465UniProtSerine/threonine-protein kinase 38
Modified residue (large scale data)6PRIDEPhosphoserine
Modified residue (large scale data)7PRIDEPhosphothreonine
Modified residue74UniProtPhosphothreonine
Modified residue264UniProtPhosphoserine
Modified residue (large scale data)264PRIDEPhosphoserine
Modified residue281UniProtPhosphoserine; by autocatalysis
Modified residue (large scale data)281PRIDEPhosphoserine
Modified residue (large scale data)282PRIDEPhosphothreonine
Modified residue444UniProtPhosphothreonine; by STK24/MST3
Modified residue (large scale data)452PRIDEPhosphothreonine

Post-translational modification

ISGylated.
Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.

Keywords

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).

Binary interactions

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, domain, motif.

TypeIDPosition(s)Description
Region62-87Interaction with S100B
Domain89-382Protein kinase
Motif306-311UFM1-interacting motif (UFIM)
Domain383-455AGC-kinase C-terminal

Domain

The UFM1-interacting motif (UFIM) specifically recognizes and binds ufmylated histone H4.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    465
  • Mass (Da)
    54,190
  • Last updated
    1996-11-01 v1
  • Checksum
    7262221DBFFAF83C
MAMTGSTPCSSMSNHTKERVTMTKVTLENFYSNLIAQHEEREMRQKKLEKVMEEEGLKDEEKRLRRSAHARKETEFLRLKRTRLGLEDFESLKVIGRGAFGEVRLVQKKDTGHVYAMKILRKADMLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLCTGLKKAHRTEFYRNLNHSLPSDFTFQNMNSKRKAETWKRNRRQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKVMNWKETLTFPPEVPISEKAKDLILRFCCEWEHRIGAPGVEEIKSNSFFEGVDWEHIRERPAAISIEIKSIDDTSNFDEFPESDILKPTVATSNHPETDYKNKDWVFINYTYKRFEGLTARGAIPSYMKAAK

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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