Homo sapiens Protein: STK4 | |||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||
InnateDB Protein | IDBP-77188.6 | ||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||
Gene Symbol | STK4 | ||||||||||||||||||||||||||
Protein Name | serine/threonine kinase 4 | ||||||||||||||||||||||||||
Synonyms | KRS2; MST1; TIIAC; YSK3; | ||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||
Ensembl Protein | ENSP00000361887 | ||||||||||||||||||||||||||
InnateDB Gene | IDBG-77184 (STK4) | ||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||
Function | 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. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250, ECO:0000269PubMed:11278283, ECO:0000269PubMed:11517310, ECO:0000269PubMed:12757711, ECO:0000269PubMed:15109305, ECO:0000269PubMed:16510573, ECO:0000269PubMed:16751106, ECO:0000269PubMed:16930133, ECO:0000269PubMed:17932490, ECO:0000269PubMed:18328708, ECO:0000269PubMed:18986304, ECO:0000269PubMed:19525978, ECO:0000269PubMed:21212262, ECO:0000269PubMed:21245099, ECO:0000269PubMed:21512132, ECO:0000269PubMed:8702870, ECO:0000269PubMed:8816758}. | ||||||||||||||||||||||||||
Subcellular Localization | Cytoplasm. Nucleus. Note=The caspase-cleaved form cycles between the nucleus and cytoplasm. | ||||||||||||||||||||||||||
Disease Associations | T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations (TIIAC) [MIM:614868]: A primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. {ECO:0000269PubMed:22294732}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||||
Tissue Specificity | Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed. {ECO:0000269PubMed:17932490}. | ||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 106 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||
InterPro |
IPR000719
Protein kinase domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR011009 Protein kinase-like domain IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00069
PF07714 |
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PRINTS |
PR00109
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PIRSF | |||||||||||||||||||||||||||
SMART |
SM00220
SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||
SwissProt | Q13043 | ||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-Q13043 | ||||||||||||||||||||||||||
TrEMBL | Q9BS84 | ||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||
Entrez Gene | 6789 | ||||||||||||||||||||||||||
UniGene | Hs.700137 | ||||||||||||||||||||||||||
RefSeq | XP_005260588 | ||||||||||||||||||||||||||
HUGO | HGNC:11408 | ||||||||||||||||||||||||||
OMIM | 604965 | ||||||||||||||||||||||||||
CCDS | |||||||||||||||||||||||||||
HPRD | 05395 | ||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||
EMBL | AK315238 AL109839 BC005231 BC029511 BC058916 BC093768 CH471077 U18297 U60207 Z93016 | ||||||||||||||||||||||||||
GenPept | AAA83254 AAB17262 AAH05231 AAH29511 AAH58916 AAH93768 BAG37665 CAB07508 CAI19815 CAI95633 CAI95634 EAW75882 | ||||||||||||||||||||||||||