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Protein

Serine/threonine-protein kinase 10

Gene

STK10

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

Functioni

Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Enzyme regulationi

Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei65ATPCurated1
Binding sitei111Inhibitor1
Binding sitei113Inhibitor1
Binding sitei117Inhibitor; via amide nitrogen1
Active sitei157Proton acceptorPROSITE-ProRule annotation1
Binding sitei175Inhibitor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi42 – 50ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • polo kinase kinase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • lymphocyte aggregation Source: Ensembl
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of lymphocyte migration Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01082-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SignaLinkiO94804.
SIGNORiO94804.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase 10 (EC:2.7.11.1)
Alternative name(s):
Lymphocyte-oriented kinase
Gene namesi
Name:STK10
Synonyms:LOK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:11388. STK10.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Testicular germ cell tumor (TGCT)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
See also OMIM:273300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023827277K → E in TGCT; somatic mutation. 2 PublicationsCorresponds to variant rs757545210dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65K → I: Loss of kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi6793.
MalaCardsiSTK10.
MIMi273300. phenotype.
OpenTargetsiENSG00000072786.
PharmGKBiPA36197.

Chemistry databases

ChEMBLiCHEMBL3981.
GuidetoPHARMACOLOGYi2211.

Polymorphism and mutation databases

BioMutaiSTK10.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866971 – 968Serine/threonine-protein kinase 10Add BLAST968

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphoserineCombined sources1
Modified residuei20PhosphoserineBy similarity1
Modified residuei191PhosphoserineCombined sources1
Modified residuei438PhosphoserineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei454PhosphoserineCombined sources1
Modified residuei485PhosphoserineCombined sources1
Modified residuei514PhosphoserineCombined sources1
Modified residuei549PhosphoserineCombined sources1
Modified residuei952PhosphothreonineCombined sources1

Post-translational modificationi

Autophosphorylates following homodimerization, leading to activation of the protein.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94804.
MaxQBiO94804.
PaxDbiO94804.
PeptideAtlasiO94804.
PRIDEiO94804.

PTM databases

iPTMnetiO94804.
PhosphoSitePlusiO94804.

Expressioni

Tissue specificityi

Highly expressed in rapidly proliferating tissues (spleen, placenta, and peripheral blood leukocytes). Also expressed in brain, heart, skeletal muscle, colon, thymus, kidney, liver, small intestine and lung.1 Publication

Gene expression databases

BgeeiENSG00000072786.
CleanExiHS_STK10.
ExpressionAtlasiO94804. baseline and differential.
GenevisibleiO94804. HS.

Organism-specific databases

HPAiCAB020840.
HPA015083.
HPA073454.

Interactioni

Subunit structurei

Homodimer; homodimerization is required for activation segment autophosphorylation.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-3951541,EBI-3951541

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112669. 7 interactors.
IntActiO94804. 1 interactor.
STRINGi9606.ENSP00000176763.

Chemistry databases

BindingDBiO94804.

Structurei

Secondary structure

1968
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 30Combined sources4
Helixi32 – 34Combined sources3
Beta strandi36 – 43Combined sources8
Beta strandi45 – 47Combined sources3
Beta strandi50 – 55Combined sources6
Turni56 – 58Combined sources3
Beta strandi61 – 67Combined sources7
Helixi75 – 87Combined sources13
Beta strandi96 – 101Combined sources6
Beta strandi106 – 111Combined sources6
Helixi118 – 125Combined sources8
Helixi131 – 150Combined sources20
Helixi160 – 162Combined sources3
Beta strandi163 – 165Combined sources3
Beta strandi171 – 173Combined sources3
Helixi177 – 187Combined sources11
Helixi196 – 198Combined sources3
Helixi201 – 208Combined sources8
Turni212 – 216Combined sources5
Helixi217 – 232Combined sources16
Turni236 – 239Combined sources4
Helixi242 – 251Combined sources10
Helixi260 – 262Combined sources3
Helixi265 – 274Combined sources10
Turni279 – 281Combined sources3
Helixi285 – 288Combined sources4
Turni292 – 296Combined sources5
Helixi301 – 314Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2J7TX-ray2.00A18-317[»]
4AOTX-ray2.33A/B18-317[»]
4BC6X-ray2.20A24-316[»]
4EQUX-ray2.00A/B18-317[»]
4USDX-ray3.05A/B18-317[»]
4USEX-ray2.65A/B18-317[»]
5AJQX-ray2.20A/B21-313[»]
ProteinModelPortaliO94804.
SMRiO94804.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94804.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 294Protein kinasePROSITE-ProRule annotationAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 224Activation segmentAdd BLAST50

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili573 – 947Sequence analysisAdd BLAST375

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi750 – 884Gln-richAdd BLAST135

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0579. Eukaryota.
ENOG410XPQN. LUCA.
GeneTreeiENSGT00810000125351.
HOGENOMiHOG000236268.
HOVERGENiHBG052712.
InParanoidiO94804.
KOiK08837.
OMAiSEEAECP.
OrthoDBiEOG091G01Y1.
PhylomeDBiO94804.
TreeFamiTF351445.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR022165. PKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF12474. PKK. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O94804-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAFANFRRIL RLSTFEKRKS REYEHVRRDL DPNEVWEIVG ELGDGAFGKV
60 70 80 90 100
YKAKNKETGA LAAAKVIETK SEEELEDYIV EIEILATCDH PYIVKLLGAY
110 120 130 140 150
YHDGKLWIMI EFCPGGAVDA IMLELDRGLT EPQIQVVCRQ MLEALNFLHS
160 170 180 190 200
KRIIHRDLKA GNVLMTLEGD IRLADFGVSA KNLKTLQKRD SFIGTPYWMA
210 220 230 240 250
PEVVMCETMK DTPYDYKADI WSLGITLIEM AQIEPPHHEL NPMRVLLKIA
260 270 280 290 300
KSDPPTLLTP SKWSVEFRDF LKIALDKNPE TRPSAAQLLE HPFVSSITSN
310 320 330 340 350
KALRELVAEA KAEVMEEIED GRDEGEEEDA VDAASTLENH TQNSSEVSPP
360 370 380 390 400
SLNADKPLEE SPSTPLAPSQ SQDSVNEPCS QPSGDRSLQT TSPPVVAPGN
410 420 430 440 450
ENGLAVPVPL RKSRPVSMDA RIQVAQEKQV AEQGGDLSPA ANRSQKASQS
460 470 480 490 500
RPNSSALETL GGEKLANGSL EPPAQAAPGP SKRDSDCSSL CTSESMDYGT
510 520 530 540 550
NLSTDLSLNK EMGSLSIKDP KLYKKTLKRT RKFVVDGVEV SITTSKIISE
560 570 580 590 600
DEKKDEEMRF LRRQELRELR LLQKEEHRNQ TQLSNKHELQ LEQMHKRFEQ
610 620 630 640 650
EINAKKKFFD TELENLERQQ KQQVEKMEQD HAVRRREEAR RIRLEQDRDY
660 670 680 690 700
TRFQEQLKLM KKEVKNEVEK LPRQQRKESM KQKMEEHTQK KQLLDRDFVA
710 720 730 740 750
KQKEDLELAM KRLTTDNRRE ICDKERECLM KKQELLRDRE AALWEMEEHQ
760 770 780 790 800
LQERHQLVKQ QLKDQYFLQR HELLRKHEKE REQMQRYNQR MIEQLKVRQQ
810 820 830 840 850
QEKARLPKIQ RSEGKTRMAM YKKSLHINGG GSAAEQREKI KQFSQQEEKR
860 870 880 890 900
QKSERLQQQQ KHENQMRDML AQCESNMSEL QQLQNEKCHL LVEHETQKLK
910 920 930 940 950
ALDESHNQNL KEWRDKLRPR KKALEEDLNQ KKREQEMFFK LSEEAECPNP
960
STPSKAAKFF PYSSADAS
Length:968
Mass (Da):112,135
Last modified:May 1, 1999 - v1
Checksum:i15E245193ECC553D
GO

Sequence cautioni

The sequence BAG51143 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62A → V in AAH70077 (PubMed:15489334).Curated1
Sequence conflicti136V → E in AAH70077 (PubMed:15489334).Curated1
Sequence conflicti317E → G in AAH70077 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041131268R → C.1 PublicationCorresponds to variant rs35826078dbSNPEnsembl.1
Natural variantiVAR_023827277K → E in TGCT; somatic mutation. 2 PublicationsCorresponds to variant rs757545210dbSNPEnsembl.1
Natural variantiVAR_041132322R → W.1 PublicationCorresponds to variant rs56214442dbSNPEnsembl.1
Natural variantiVAR_041133336T → I.1 PublicationCorresponds to variant rs55972616dbSNPEnsembl.1
Natural variantiVAR_041134467N → S.1 PublicationCorresponds to variant rs56063773dbSNPEnsembl.1
Natural variantiVAR_051671480P → L.Corresponds to variant rs34505340dbSNPEnsembl.1
Natural variantiVAR_051672520P → L.Corresponds to variant rs17074311dbSNPEnsembl.1
Natural variantiVAR_041135710M → T.1 PublicationCorresponds to variant rs34936670dbSNPEnsembl.1
Natural variantiVAR_041136853S → L.1 PublicationCorresponds to variant rs56066852dbSNPEnsembl.1
Natural variantiVAR_041137905S → T.1 PublicationCorresponds to variant rs55791916dbSNPEnsembl.1
Natural variantiVAR_051673942S → N.Corresponds to variant rs1128204dbSNPEnsembl.1
Natural variantiVAR_041138947C → Y.1 PublicationCorresponds to variant rs56355550dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015718 mRNA. Translation: BAA35073.1.
AK022960 mRNA. Translation: BAG51143.1. Different initiation.
AK313350 mRNA. Translation: BAG36152.1.
AC024561 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61439.1.
BC070077 mRNA. Translation: AAH70077.1.
AL133081 mRNA. Translation: CAB61400.1.
CCDSiCCDS34290.1.
PIRiT42687.
RefSeqiNP_005981.3. NM_005990.3.
UniGeneiHs.744005.

Genome annotation databases

EnsembliENST00000176763; ENSP00000176763; ENSG00000072786.
GeneIDi6793.
KEGGihsa:6793.
UCSCiuc003mbo.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015718 mRNA. Translation: BAA35073.1.
AK022960 mRNA. Translation: BAG51143.1. Different initiation.
AK313350 mRNA. Translation: BAG36152.1.
AC024561 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61439.1.
BC070077 mRNA. Translation: AAH70077.1.
AL133081 mRNA. Translation: CAB61400.1.
CCDSiCCDS34290.1.
PIRiT42687.
RefSeqiNP_005981.3. NM_005990.3.
UniGeneiHs.744005.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2J7TX-ray2.00A18-317[»]
4AOTX-ray2.33A/B18-317[»]
4BC6X-ray2.20A24-316[»]
4EQUX-ray2.00A/B18-317[»]
4USDX-ray3.05A/B18-317[»]
4USEX-ray2.65A/B18-317[»]
5AJQX-ray2.20A/B21-313[»]
ProteinModelPortaliO94804.
SMRiO94804.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112669. 7 interactors.
IntActiO94804. 1 interactor.
STRINGi9606.ENSP00000176763.

Chemistry databases

BindingDBiO94804.
ChEMBLiCHEMBL3981.
GuidetoPHARMACOLOGYi2211.

PTM databases

iPTMnetiO94804.
PhosphoSitePlusiO94804.

Polymorphism and mutation databases

BioMutaiSTK10.

Proteomic databases

EPDiO94804.
MaxQBiO94804.
PaxDbiO94804.
PeptideAtlasiO94804.
PRIDEiO94804.

Protocols and materials databases

DNASUi6793.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000176763; ENSP00000176763; ENSG00000072786.
GeneIDi6793.
KEGGihsa:6793.
UCSCiuc003mbo.2. human.

Organism-specific databases

CTDi6793.
DisGeNETi6793.
GeneCardsiSTK10.
HGNCiHGNC:11388. STK10.
HPAiCAB020840.
HPA015083.
HPA073454.
MalaCardsiSTK10.
MIMi273300. phenotype.
603919. gene.
neXtProtiNX_O94804.
OpenTargetsiENSG00000072786.
PharmGKBiPA36197.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0579. Eukaryota.
ENOG410XPQN. LUCA.
GeneTreeiENSGT00810000125351.
HOGENOMiHOG000236268.
HOVERGENiHBG052712.
InParanoidiO94804.
KOiK08837.
OMAiSEEAECP.
OrthoDBiEOG091G01Y1.
PhylomeDBiO94804.
TreeFamiTF351445.

Enzyme and pathway databases

BioCyciZFISH:HS01082-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SignaLinkiO94804.
SIGNORiO94804.

Miscellaneous databases

ChiTaRSiSTK10. human.
EvolutionaryTraceiO94804.
GeneWikiiSTK10.
GenomeRNAii6793.
PROiO94804.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072786.
CleanExiHS_STK10.
ExpressionAtlasiO94804. baseline and differential.
GenevisibleiO94804. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR022165. PKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF12474. PKK. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSTK10_HUMAN
AccessioniPrimary (citable) accession number: O94804
Secondary accession number(s): A6ND35
, B2R8F5, B3KMY1, Q6NSK0, Q9UIW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 165 of the entry and version 1 of the sequence. [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

Miscellaneous

Inhibition by erlotinib, an orally administered EGFR tyrosine kinase inhibitor used for treatment, enhances STK10-dependent lymphocytic responses, possibly leading to the aggravation of skin inflammation observed upon treatment by erlotinib.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.