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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei65 – 651ATPCurated
Binding sitei111 – 1111Inhibitor
Binding sitei113 – 1131Inhibitor
Binding sitei117 – 1171Inhibitor; via amide nitrogen
Active sitei157 – 1571Proton acceptorPROSITE-ProRule annotation
Binding sitei175 – 1751Inhibitor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi42 – 509ATPPROSITE-ProRule annotation

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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti277 – 2771K → E in TGCT; somatic mutation. 2 Publications
Corresponds to variant rs757545210 [ dbSNP | Ensembl ].
VAR_023827

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi65 – 651K → I: Loss of kinase activity. 1 Publication

Organism-specific databases

MalaCardsiSTK10.
MIMi273300. phenotype.
PharmGKBiPA36197.

Chemistry

ChEMBLiCHEMBL3981.
GuidetoPHARMACOLOGYi2211.

Polymorphism and mutation databases

BioMutaiSTK10.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 968968Serine/threonine-protein kinase 10PRO_0000086697Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei13 – 131PhosphoserineCombined sources
Modified residuei20 – 201PhosphoserineBy similarity
Modified residuei191 – 1911PhosphoserineCombined sources
Modified residuei438 – 4381PhosphoserineCombined sources
Modified residuei450 – 4501PhosphoserineCombined sources
Modified residuei454 – 4541PhosphoserineCombined sources
Modified residuei485 – 4851PhosphoserineCombined sources
Modified residuei514 – 5141PhosphoserineCombined sources
Modified residuei549 – 5491PhosphoserineCombined sources
Modified residuei952 – 9521PhosphothreonineCombined sources

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.
PhosphoSiteiO94804.

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 interactions.
IntActiO94804. 1 interaction.
STRINGi9606.ENSP00000176763.

Chemistry

BindingDBiO94804.

Structurei

Secondary structure

1
968
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi27 – 304Combined sources
Helixi32 – 343Combined sources
Beta strandi36 – 438Combined sources
Beta strandi45 – 473Combined sources
Beta strandi50 – 556Combined sources
Turni56 – 583Combined sources
Beta strandi61 – 677Combined sources
Helixi75 – 8713Combined sources
Beta strandi96 – 1016Combined sources
Beta strandi106 – 1116Combined sources
Helixi118 – 1258Combined sources
Helixi131 – 15020Combined sources
Helixi160 – 1623Combined sources
Beta strandi163 – 1653Combined sources
Beta strandi171 – 1733Combined sources
Helixi177 – 18711Combined sources
Helixi196 – 1983Combined sources
Helixi201 – 2088Combined sources
Turni212 – 2165Combined sources
Helixi217 – 23216Combined sources
Turni236 – 2394Combined sources
Helixi242 – 25110Combined sources
Helixi260 – 2623Combined sources
Helixi265 – 27410Combined sources
Turni279 – 2813Combined sources
Helixi285 – 2884Combined sources
Turni292 – 2965Combined sources
Helixi301 – 31414Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 24-316.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94804.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 294259Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni175 – 22450Activation segmentAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili573 – 947375Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi750 – 884135Gln-richAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti62 – 621A → V in AAH70077 (PubMed:15489334).Curated
Sequence conflicti136 – 1361V → E in AAH70077 (PubMed:15489334).Curated
Sequence conflicti317 – 3171E → G in AAH70077 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti268 – 2681R → C.1 Publication
Corresponds to variant rs35826078 [ dbSNP | Ensembl ].
VAR_041131
Natural varianti277 – 2771K → E in TGCT; somatic mutation. 2 Publications
Corresponds to variant rs757545210 [ dbSNP | Ensembl ].
VAR_023827
Natural varianti322 – 3221R → W.1 Publication
Corresponds to variant rs56214442 [ dbSNP | Ensembl ].
VAR_041132
Natural varianti336 – 3361T → I.1 Publication
Corresponds to variant rs55972616 [ dbSNP | Ensembl ].
VAR_041133
Natural varianti467 – 4671N → S.1 Publication
Corresponds to variant rs56063773 [ dbSNP | Ensembl ].
VAR_041134
Natural varianti480 – 4801P → L.
Corresponds to variant rs34505340 [ dbSNP | Ensembl ].
VAR_051671
Natural varianti520 – 5201P → L.
Corresponds to variant rs17074311 [ dbSNP | Ensembl ].
VAR_051672
Natural varianti710 – 7101M → T.1 Publication
Corresponds to variant rs34936670 [ dbSNP | Ensembl ].
VAR_041135
Natural varianti853 – 8531S → L.1 Publication
Corresponds to variant rs56066852 [ dbSNP | Ensembl ].
VAR_041136
Natural varianti905 – 9051S → T.1 Publication
Corresponds to variant rs55791916 [ dbSNP | Ensembl ].
VAR_041137
Natural varianti942 – 9421S → N.
Corresponds to variant rs1128204 [ dbSNP | Ensembl ].
VAR_051673
Natural varianti947 – 9471C → Y.1 Publication
Corresponds to variant rs56355550 [ dbSNP | Ensembl ].
VAR_041138

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
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. Positions 24-316.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112669. 7 interactions.
IntActiO94804. 1 interaction.
STRINGi9606.ENSP00000176763.

Chemistry

BindingDBiO94804.
ChEMBLiCHEMBL3981.
GuidetoPHARMACOLOGYi2211.

PTM databases

iPTMnetiO94804.
PhosphoSiteiO94804.

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

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 162 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.