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Q15208 (STK38_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase 38

EC=2.7.11.1
Alternative name(s):
NDR1 protein kinase
Nuclear Dbf2-related kinase 1
Gene names
Name:STK38
Synonyms:NDR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2. Ref.1 Ref.5 Ref.7 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium. Ref.1 Ref.5 Ref.7

Enzyme 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. Ref.5 Ref.6 Ref.7 Ref.17

Subunit structure

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. Ref.6 Ref.7 Ref.9 Ref.11 Ref.12 Ref.17

Subcellular location

Nucleus. Cytoplasm Ref.1 Ref.7 Ref.9 Ref.12.

Tissue specificity

Ubiquitously expressed with highest levels observed in peripheral blood leukocytes. Ref.1 Ref.7

Post-translational modification

ISGylated Probable. Ref.8

Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B. Ref.5 Ref.9

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 465464Serine/threonine-protein kinase 38
PRO_0000086718

Regions

Domain89 – 382294Protein kinase
Domain383 – 45573AGC-kinase C-terminal
Nucleotide binding95 – 1039ATP By similarity UniProtKB O95835
Region62 – 8726Interaction with S100B

Sites

Active site2121Proton acceptor By similarity UniProtKB O95835
Binding site1181ATP Ref.1 Ref.5

Amino acid modifications

Modified residue21N-acetylalanine Ref.4
Modified residue741Phosphothreonine Ref.5
Modified residue2641Phosphoserine Ref.14
Modified residue2811Phosphoserine; by autocatalysis Ref.5
Modified residue4441Phosphothreonine; by STK24/MST3 Ref.5

Natural variations

Natural variant181E → K in a metastatic melanoma sample; somatic mutation. Ref.18
VAR_041196
Natural variant1451D → N. Ref.18
Corresponds to variant rs56005153 [ dbSNP | Ensembl ].
VAR_041197
Natural variant2671K → R. Ref.18
Corresponds to variant rs56105564 [ dbSNP | Ensembl ].
VAR_041198

Experimental info

Mutagenesis741T → A: Decreases autophosphorylation and kinase activity. Reduced binding of S100B. Ref.5
Mutagenesis1181K → A: Loss of autophosphorylation and kinase activity. Ref.1 Ref.5
Mutagenesis2811S → A: Loss of autophosphorylation and kinase activity. Ref.5
Mutagenesis4441T → A: Decreases autophosphorylation and kinase activity. Ref.5

Secondary structure

... 465
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15208 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 7262221DBFFAF83C

FASTA46554,190
        10         20         30         40         50         60 
MAMTGSTPCS SMSNHTKERV TMTKVTLENF YSNLIAQHEE REMRQKKLEK VMEEEGLKDE 

        70         80         90        100        110        120 
EKRLRRSAHA RKETEFLRLK RTRLGLEDFE SLKVIGRGAF GEVRLVQKKD TGHVYAMKIL 

       130        140        150        160        170        180 
RKADMLEKEQ VGHIRAERDI LVEADSLWVV KMFYSFQDKL NLYLIMEFLP GGDMMTLLMK 

       190        200        210        220        230        240 
KDTLTEEETQ FYIAETVLAI DSIHQLGFIH RDIKPDNLLL DSKGHVKLSD FGLCTGLKKA 

       250        260        270        280        290        300 
HRTEFYRNLN HSLPSDFTFQ NMNSKRKAET WKRNRRQLAF STVGTPDYIA PEVFMQTGYN 

       310        320        330        340        350        360 
KLCDWWSLGV IMYEMLIGYP PFCSETPQET YKKVMNWKET LTFPPEVPIS EKAKDLILRF 

       370        380        390        400        410        420 
CCEWEHRIGA PGVEEIKSNS FFEGVDWEHI RERPAAISIE IKSIDDTSNF DEFPESDILK 

       430        440        450        460 
PTVATSNHPE TDYKNKDWVF INYTYKRFEG LTARGAIPSY MKAAK 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a conserved nuclear serine/threonine protein kinase."
Millward T.A., Cron P., Hemmings B.A.
Proc. Natl. Acad. Sci. U.S.A. 92:5022-5026(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-118.
Tissue: Fetal brain.
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta and Uterus.
[4]Bienvenut W.V., Calvo F., Kolch W.
Submitted (MAR-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-17; 25-44; 51-63; 72-78; 82-97; 110-118; 122-159; 182-239; 248-266; 277-301; 334-391; 394-402 AND 437-454, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[5]"Mechanism of Ca2+-mediated regulation of NDR protein kinase through autophosphorylation and phosphorylation by an upstream kinase."
Tamaskovic R., Bichsel S.J., Rogniaux H., Stegert M.R., Hemmings B.A.
J. Biol. Chem. 278:6710-6718(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-74; SER-281 AND THR-444, MUTAGENESIS OF THR-74; LYS-118; SER-281 AND THR-444.
[6]"Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases."
Devroe E., Erdjument-Bromage H., Tempst P., Silver P.A.
J. Biol. Chem. 279:24444-24451(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH MOB1 AND MOB2.
[7]"Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein."
Bichsel S.J., Tamaskovic R., Stegert M.R., Hemmings B.A.
J. Biol. Chem. 279:35228-35235(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION, INTERACTION WITH MOB1 AND MOB2.
[8]"Identification and Herc5-mediated ISGylation of novel target proteins."
Takeuchi T., Inoue S., Yokosawa H.
Biochem. Biophys. Res. Commun. 348:473-477(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[9]"Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1."
Hirabayashi S., Nakagawa K., Sumita K., Hidaka S., Kawai T., Ikeda M., Kawata A., Ohno K., Hata Y.
Oncogene 27:4281-4292(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STK3/MST2 AND MOBKL1B, SUBCELLULAR LOCATION, PHOSPHORYLATION BY STK3/MST2.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis."
Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S.
Nature 459:455-459(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MLL5-L COMPLEX.
[12]"Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38)."
Enomoto A., Kido N., Ito M., Morita A., Matsumoto Y., Takamatsu N., Hosoi Y., Miyagawa K.
Oncogene 27:1930-1938(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP3K1 AND MAP3K2.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Structure of the Ca2+/S100B/NDR kinase peptide complex: insights into S100 target specificity and activation of the kinase."
Bhattacharya S., Large E., Heizmann C.W., Hemmings B.A., Chazin W.J.
Biochemistry 42:14416-14426(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 62-84, ENZYME REGULATION, INTERACTION WITH S100B.
[18]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-18; ASN-145 AND ARG-267.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z35102 mRNA. Translation: CAA84485.1.
Z85986 Genomic DNA. Translation: CAB39180.1.
BC012085 mRNA. Translation: AAH12085.1.
BC095413 mRNA. Translation: AAH95413.1.
CCDSCCDS4822.1.
PIRI38133.
RefSeqNP_009202.1. NM_007271.2.
XP_005248896.1. XM_005248839.1.
XP_006715051.1. XM_006714988.1.
XP_006715052.1. XM_006714989.1.
UniGeneHs.409578.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PSBNMR-C/D62-87[»]
ProteinModelPortalQ15208.
SMRQ15208. Positions 23-447.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116457. 38 interactions.
IntActQ15208. 12 interactions.
MINTMINT-1217042.
STRING9606.ENSP00000229812.

Chemistry

BindingDBQ15208.
ChEMBLCHEMBL1075155.
GuidetoPHARMACOLOGY1517.

PTM databases

PhosphoSiteQ15208.

Polymorphism databases

DMDM56749457.

Proteomic databases

MaxQBQ15208.
PaxDbQ15208.
PRIDEQ15208.

Protocols and materials databases

DNASU11329.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229812; ENSP00000229812; ENSG00000112079.
GeneID11329.
KEGGhsa:11329.
UCSCuc003omg.3. human.

Organism-specific databases

CTD11329.
GeneCardsGC06M036461.
HGNCHGNC:17847. STK38.
HPACAB004673.
MIM606964. gene.
neXtProtNX_Q15208.
PharmGKBPA38251.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG104247.
InParanoidQ15208.
KOK08790.
OMAFCCEEEH.
OrthoDBEOG7BZVS1.
PhylomeDBQ15208.
TreeFamTF105337.

Enzyme and pathway databases

SignaLinkQ15208.

Gene expression databases

BgeeQ15208.
CleanExHS_STK38.
GenevestigatorQ15208.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSTK38. human.
EvolutionaryTraceQ15208.
GeneWikiSTK38.
GenomeRNAi11329.
NextBio43035.
PROQ15208.
SOURCESearch...

Entry information

Entry nameSTK38_HUMAN
AccessionPrimary (citable) accession number: Q15208
Secondary accession number(s): Q503A1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM