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Protein

Serine/threonine-protein kinase 4

Gene

STK4

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

The C-terminal non-catalytic region inhibits the kinase activity, the enzyme is activated by caspase-cleavage. Homodimerization and autophosphorylation of Thr-182 is also required for full activation (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei58 – 581ATPPROSITE-ProRule annotation
Active sitei148 – 1481Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi35 – 439ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase 4 (EC:2.7.11.1)
Cleaved into the following 2 chains:
Gene namesi
Name:STK4
ORF Names:RCJMB04_17i1
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
Proteomesi
  • UP000000539 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: The caspase-cleaved form cycles between nucleus and cytoplasm.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 486486Serine/threonine-protein kinase 4PRO_0000246628Add
BLAST
Chaini1 – 325325Serine/threonine-protein kinase 4 37kDa subunitBy similarityPRO_0000413747Add
BLAST
Chaini326 – 486161Serine/threonine-protein kinase 4 18kDa subunitBy similarityPRO_0000413748Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei182 – 1821Phosphothreonine; by autocatalysisBy similarity

Post-translational modificationi

Proteolytically cleaved by caspase-3 during apoptosis at Asp-325 resulting in a 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N) (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei325 – 3262Cleavage; by caspase-3By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ5ZJK4.

Interactioni

Subunit structurei

Homodimer; mediated via the coiled-coil region.By similarity

Protein-protein interaction databases

STRINGi9031.ENSGALP00000006511.

Structurei

3D structure databases

ProteinModelPortaliQ5ZJK4.
SMRiQ5ZJK4. Positions 15-299, 430-479.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 280252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini432 – 47948SARAHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili288 – 32437Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi372 – 3776Poly-Glu

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SARAH domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0201. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000234203.
HOVERGENiHBG108518.
InParanoidiQ5ZJK4.
KOiK04411.
PhylomeDBiQ5ZJK4.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[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.
PS50951. SARAH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q5ZJK4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METVQLRNPR RQLKKLDEDS LTKQPEEVFD VLEKLGEGSY GSVFKAIHKE
60 70 80 90 100
TGQVVAIKQV PVESDLQEII KEISIMQQCD SPHVVKYYGS YFKNTDLWIV
110 120 130 140 150
MEYCGAGSVS DIIRLRNKTL TEEEIATIVQ STLKGLEYLH FMRKIHRDIK
160 170 180 190 200
AGNILLNTEG HAKLADFGVA GQLTDTMAKR NTVIGTPFWM APGVIQEIGY
210 220 230 240 250
NCVADIWSLG ITAIEMAEGK PPYADIHPMR AIFMIPTNPP PTFRKPELWS
260 270 280 290 300
DAFTDFVKQC LVKSPEQRAT AIQLLQHPFV KSAKGASILR DLINEAMDIK
310 320 330 340 350
LKRQEAQQRE LDQEDEENSE EDETDSGTMV RASGDETGTI RVVNTMSDGA
360 370 380 390 400
NTMIEHDGTL ESQLGTMVIN TEDEEEEGTM KRRDETMQPA RPSFLEYFEQ
410 420 430 440 450
KAKENQVNSF GKNVSGQTKN SSDWKVPQDG DYEFLKTWSV DELQRRLSAL
460 470 480
DPMMEQEIEE IRQKYQSKRQ PILDAIEAKK RRQQNF
Length:486
Mass (Da):55,337
Last modified:November 23, 2004 - v1
Checksum:i08C81E45F94CF3A5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ720430 mRNA. Translation: CAG32089.1.
RefSeqiNP_001026024.1. NM_001030853.1.
UniGeneiGga.15820.

Genome annotation databases

GeneIDi419187.
KEGGigga:419187.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ720430 mRNA. Translation: CAG32089.1.
RefSeqiNP_001026024.1. NM_001030853.1.
UniGeneiGga.15820.

3D structure databases

ProteinModelPortaliQ5ZJK4.
SMRiQ5ZJK4. Positions 15-299, 430-479.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9031.ENSGALP00000006511.

Proteomic databases

PaxDbiQ5ZJK4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi419187.
KEGGigga:419187.

Organism-specific databases

CTDi6789.

Phylogenomic databases

eggNOGiKOG0201. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000234203.
HOVERGENiHBG108518.
InParanoidiQ5ZJK4.
KOiK04411.
PhylomeDBiQ5ZJK4.

Miscellaneous databases

NextBioi20822285.
PROiQ5ZJK4.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[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.
PS50951. SARAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: CB.
    Tissue: Bursa of Fabricius.

Entry informationi

Entry nameiSTK4_CHICK
AccessioniPrimary (citable) accession number: Q5ZJK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: November 23, 2004
Last modified: May 11, 2016
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.