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Protein

Serine/threonine-protein kinase 38

Gene

STK38

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

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 STK38.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei118ATPPROSITE-ProRule annotation2 Publications1
Active sitei212Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi95 – 103ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • cadherin binding Source: BHF-UCL
  • magnesium ion binding Source: UniProtKB
  • mitogen-activated protein kinase kinase kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cellular protein modification process Source: ProtInc
  • intracellular signal transduction Source: UniProtKB
  • negative regulation of MAP kinase activity Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • protein phosphorylation Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
SignaLinkiQ15208.
SIGNORiQ15208.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase 38 (EC:2.7.11.1)
Alternative name(s):
NDR1 protein kinase
Nuclear Dbf2-related kinase 1
Gene namesi
Name:STK38Imported
Synonyms:NDR11 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112079.8.
HGNCiHGNC:17847. STK38.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi74T → A: Decreases autophosphorylation and kinase activity. Reduced binding of S100B. 1 Publication1
Mutagenesisi118K → A: Loss of autophosphorylation and kinase activity. 2 Publications1
Mutagenesisi281S → A: Loss of autophosphorylation and kinase activity. 1 Publication1
Mutagenesisi444T → A: Decreases autophosphorylation and kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi11329.
OpenTargetsiENSG00000112079.
PharmGKBiPA38251.

Chemistry databases

ChEMBLiCHEMBL1075155.
GuidetoPHARMACOLOGYi1517.

Polymorphism and mutation databases

BioMutaiSTK38.
DMDMi56749457.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000867182 – 465Serine/threonine-protein kinase 38Add BLAST464

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei74Phosphothreonine1 Publication1
Modified residuei264PhosphoserineCombined sources1
Modified residuei281Phosphoserine; by autocatalysis1 Publication1
Modified residuei444Phosphothreonine; by STK24/MST31 Publication1

Post-translational modificationi

ISGylated.1 Publication
Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15208.
MaxQBiQ15208.
PaxDbiQ15208.
PeptideAtlasiQ15208.
PRIDEiQ15208.

PTM databases

iPTMnetiQ15208.
PhosphoSitePlusiQ15208.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels observed in peripheral blood leukocytes.2 Publications

Gene expression databases

BgeeiENSG00000112079.
CleanExiHS_STK38.
ExpressionAtlasiQ15208. baseline and differential.
GenevisibleiQ15208. HS.

Organism-specific databases

HPAiCAB004673.
HPA038623.
HPA051324.

Interactioni

Subunit structurei

Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4 (By similarity). Homodimeric S100B binds two molecules of STK38. Component of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with MOB1 and MOB2. Interacts with MAP3K1 and MAP3K2 (via the kinase catalytic domain). Forms a tripartite complex with MOBKL1B and STK3/MST2.By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • mitogen-activated protein kinase kinase kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116457. 53 interactors.
CORUMiQ15208.
IntActiQ15208. 17 interactors.
MINTiMINT-1217042.
STRINGi9606.ENSP00000229812.

Chemistry databases

BindingDBiQ15208.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi74 – 85Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PSBNMR-C/D62-87[»]
ProteinModelPortaliQ15208.
SMRiQ15208.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15208.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini89 – 382Protein kinasePROSITE-ProRule annotationImportedAdd BLAST294
Domaini383 – 455AGC-kinase C-terminalAdd BLAST73

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni62 – 87Interaction with S100B1 PublicationAdd BLAST26

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0605. Eukaryota.
ENOG410XQC0. LUCA.
GeneTreeiENSGT00760000118994.
HOGENOMiHOG000233033.
HOVERGENiHBG104247.
InParanoidiQ15208.
KOiK08790.
OMAiNHPESDY.
OrthoDBiEOG091G028J.
PhylomeDBiQ15208.
TreeFamiTF105337.

Family and domain databases

InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
SMARTiView protein in SMART
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15208-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAMTGSTPCS SMSNHTKERV TMTKVTLENF YSNLIAQHEE REMRQKKLEK
60 70 80 90 100
VMEEEGLKDE EKRLRRSAHA RKETEFLRLK RTRLGLEDFE SLKVIGRGAF
110 120 130 140 150
GEVRLVQKKD TGHVYAMKIL RKADMLEKEQ VGHIRAERDI LVEADSLWVV
160 170 180 190 200
KMFYSFQDKL NLYLIMEFLP GGDMMTLLMK KDTLTEEETQ FYIAETVLAI
210 220 230 240 250
DSIHQLGFIH RDIKPDNLLL DSKGHVKLSD FGLCTGLKKA HRTEFYRNLN
260 270 280 290 300
HSLPSDFTFQ NMNSKRKAET WKRNRRQLAF STVGTPDYIA PEVFMQTGYN
310 320 330 340 350
KLCDWWSLGV IMYEMLIGYP PFCSETPQET YKKVMNWKET LTFPPEVPIS
360 370 380 390 400
EKAKDLILRF CCEWEHRIGA PGVEEIKSNS FFEGVDWEHI RERPAAISIE
410 420 430 440 450
IKSIDDTSNF DEFPESDILK PTVATSNHPE TDYKNKDWVF INYTYKRFEG
460
LTARGAIPSY MKAAK
Length:465
Mass (Da):54,190
Last modified:November 1, 1996 - v1
Checksum:i7262221DBFFAF83C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04119618E → K in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041197145D → N1 PublicationCorresponds to variant dbSNP:rs56005153Ensembl.1
Natural variantiVAR_041198267K → R1 PublicationCorresponds to variant dbSNP:rs56105564Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z35102 mRNA. Translation: CAA84485.1.
Z85986 Genomic DNA. No translation available.
BC012085 mRNA. Translation: AAH12085.1.
BC095413 mRNA. Translation: AAH95413.1.
CCDSiCCDS4822.1.
PIRiI38133.
RefSeqiNP_001292031.1. NM_001305102.1.
NP_009202.1. NM_007271.3.
XP_006715051.1. XM_006714988.3.
XP_006715052.1. XM_006714989.3.
UniGeneiHs.409578.

Genome annotation databases

EnsembliENST00000229812; ENSP00000229812; ENSG00000112079.
GeneIDi11329.
KEGGihsa:11329.
UCSCiuc003omh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTK38_HUMAN
AccessioniPrimary (citable) accession number: Q15208
Secondary accession number(s): Q503A1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: October 25, 2017
This is version 170 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families