STK3 serine/threonine kinase 3 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: STK3provided by HGNC
Official Full Name: serine/threonine kinase 3provided by HGNC
Primary source: HGNC:11406
See related: Ensembl:ENSG00000104375; HPRD:05433; MIM:605030; Vega:OTTHUMG00000164651
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KRS1; MST2
Summary: This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Genomic context

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Location :: 8q22.2

Sequence :: Chromosome: 8; NC_000008.10 (99466859..99954799, complement)

See STK3 in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2 suggests that the conserved c-Abl-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death.
Title: Regulation of neuronal cell death by c-Abl-Hippo/MST2 signaling pathway.
The small number of tumors with co-expression of mutant K-Ras and MST2 has elevated apoptosis rates.
Title: Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras.
crystals of MST2 belonged to space group P2, with unit-cell parameters a = 62.0, b = 119.2, c = 62.0 A, alpha = 90.0, beta = 90.5, gamma = 90.0 degrees , or to space group P6(1)22, with unit-cell parameters a = 54.5, b = 54.5, c = 303.1 A
Title: Crystallization and preliminary X-ray crystallographic study of the human MST2 SARAH domain.
The mammalian ste20-like kinase mediated phosphorylation of four residues within SAV1 may be important in the induction of cell death by the MST pathway.
Title: Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death.
MST and hSAV act as novel co-regulators of ERalpha and may play an important role in breast cancer pathogenesis.
Title: Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand.
Through binding to MST1/2, RASSF1A supports maintenance of MST1/2 phosphorylation, promoting an active state of the MST kinases and favoring induction of apoptosis.
Title: The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2.
ste20-like kinase MST2 is regulated by the IGF1-Akt pathway
Title: Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway.
Study reports that two Hippo pathway components, Mst2 and the scaffold protein hSav1, directly interact with Nek2A and regulate its ability to localize to centrosomes, and phosphorylate C-Nap1 and rootletin.
Title: Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction.
studies reveal a more complex role for Mst2 than previously thought. The Mst2 --> LATS1/2 pathway, by maintaining PP2A-C levels, may, in some situations, positively affect mitogenic signaling
Title: Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylation.
hnRNP H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription.
Title: Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription.

Submit: New GeneRIF Correction See all (22)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_006272.1	NP_004681.1	LATS1	BIND	PubMed	STK3 (Mst2) phosphorylates Lats1.
NP_006272.1	NP_055387.1	LATS2	BIND	PubMed	STK3 (Mst2) phosphorylates Lats2.
NP_006272.1	NP_002871.1	RAF1	BIND	PubMed	Raf-1 interacts with MST2. This interaction was modeled on a demonstrated interaction between human Raf-1 and monkey MST2.
NP_006272.1	NP_068590.1	SAV1	BIND	PubMed	STK3 (Mst2) interacts with SAV1 (hWW45).
NP_006272.1	NP_006272.1	STK3	BIND	PubMed	STK3 (Mst2) autophosphorylates.
NP_006272.1	NP_006272.1	STK3	BIND	PubMed	MST2 interacts with MST2. This interaction was modeled on a demonstrated interaction between human MST2 and MST2 from an unspecified species.
Q13188	P42574	CASP3	HPRD	PubMed
Q13188	Q969H4	CNKSR1	HPRD	PubMed
Q13188	Q9NRM7	LATS2	HPRD	PubMed
Q13188	P04049	RAF1	HPRD	PubMed
Q13188	Q9H4B6	SAV1	HPRD	PubMed
Q13188	Q13188	STK3	HPRD	PubMed
BioGRID:112664	BioGRID:116801	ATG4B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:118001	CACYBP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:115550	CNKSR1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112664	BioGRID:114418	CPNE1	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:117107	DDAH2	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:108293	EIF4EBP1	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:127670	FREM1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:108904	GBP2	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:109316	HDAC2	BioGRID	PubMed	Negative Genetic
BioGRID:112664	BioGRID:109568	HSPE1	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:114139	KHSRP	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:114563	LATS1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:112664	BioGRID:117727	LATS2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112664	BioGRID:125700	LRRK2	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:124137	MAP1LC3A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:123565	MAP1LC3B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:110325	MBP	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:120527	MOB1A	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:124960	MOB1B	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:112664	BioGRID:117369	MOB4	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:110494	MPP1	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:110954	NRD1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112664	BioGRID:111047	ORM2	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:111782	PEX19	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:119734	PHAX	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:111362	PLK1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:111748	PTPN14	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:111797	QARS	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:111831	RAF1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:112664	BioGRID:116356	RASSF1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:112664	BioGRID:115115	RASSF2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:123689	RASSF5	BioGRID	PubMed	Affinity Capture-MS; Two-hybrid
BioGRID:112664	BioGRID:127936	RASSF6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112664	BioGRID:207877	Rassf1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:121917	SAV1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Two-hybrid
BioGRID:112664	BioGRID:112664	STK3	BioGRID	PubMed	Biochemical Activity
BioGRID:112664	BioGRID:112665	STK4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:112691	SULT2A1	BioGRID	PubMed	Two-hybrid
BioGRID:112664	BioGRID:112764	TAZ	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112664	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112664	BioGRID:118841	ZC3H7A	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Hippo signaling pathway, organism-specific biosystem (from KEGG)
Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
Hippo signaling pathway, conserved biosystem (from KEGG)
Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, organism-specific biosystem (from KEGG)
MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
MAPK signaling pathway, conserved biosystem (from KEGG)
MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by Hippo, organism-specific biosystem (from REACTOME)
Signaling by Hippo, organism-specific biosystemHuman Hippo signaling is a network of reactions that regulates cell proliferation and apoptosis, centered on a three-step kinase cascade. The cascade was discovered by analysis of Drosophila mutation...

General gene information

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Markers

SHGC-32998 (e-PCR)
- UniSTS:63250

RH103761 (e-PCR)
- UniSTS:98086

D8S1924 (e-PCR)
- UniSTS:74810

RH64860 (e-PCR)
- UniSTS:89236

G49552 (e-PCR)
- UniSTS:109222

RH38901 (e-PCR)
- UniSTS:85168

WI-20184 (e-PCR)
- UniSTS:54716

D8S2107 (e-PCR)
- UniSTS:3799

WI-18654 (e-PCR)
- UniSTS:57571

G17283 (e-PCR)
- UniSTS:33772

Homology

Homologs of the STK3 gene: The STK3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein dimerization activity	ISS Inferred from Sequence or Structural Similarity more info
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info
protein serine/threonine kinase activity	EXP Inferred from Experiment more info
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	TAS Traceable Author Statement more info	PubMed
hippo signaling cascade	IDA Inferred from Direct Assay more info
hippo signaling cascade	TAS Traceable Author Statement more info	PubMed
intracellular protein kinase cascade	IDA Inferred from Direct Assay more info	PubMed
negative regulation of canonical Wnt receptor signaling pathway	IMP Inferred from Mutant Phenotype more info
positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info
protein phosphorylation	IDA Inferred from Direct Assay more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: serine/threonine-protein kinase 3

Names: serine/threonine-protein kinase 3; MST-2; STE20-like kinase MST2; mammalian STE20-like protein kinase 2; serine/threonine-protein kinase Krs-1; serine/threonine kinase 3 (STE20 homolog, yeast); serine/threonine kinase 3 (Ste20, yeast homolog)

NP_001243241.1

EC 2.7.11.1

NP_001243242.1

EC 2.7.11.1

NP_006272.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001256312.1 → NP_001243241.1 serine/threonine-protein kinase 3 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region, and uses an alternate start codon compared to variant 1. The resulting protein (isoform 2) has a longer N-terminus compared to isoform 1.

Source sequence(s)

AK131363, AP003355

Consensus CDS

CCDS59108.1

UniProtKB/TrEMBL

B3KYA7

Related

ENSP00000429744, OTTHUMP00000227171, ENST00000523601, OTTHUMT00000379636

Conserved Domains (3) summary

cd06612
Location:51 – 306
Blast Score: 1393

STKc_MST1_2; Catalytic domain of the Protein Serine/Threonine Kinases, Mammalian Ste20-like protein kinase 1 and 2

pfam11629
Location:464 – 512
Blast Score: 230

Mst1_SARAH; C terminal SARAH domain of Mst1

smart00220
Location:55 – 306
Blast Score: 834

S_TKc; Serine/Threonine protein kinases, catalytic domain
NM_001256313.1 → NP_001243242.1 serine/threonine-protein kinase 3 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.

Source sequence(s)

AA370619, AK307787, AP002087, AP003355

Conserved Domains (2) summary

pfam11629
Location:325 – 373
Blast Score: 226

Mst1_SARAH; C terminal SARAH domain of Mst1

cl09925
Location:23 – 117
Blast Score: 505

PKc_like; Protein Kinases, catalytic domain
NM_006281.3 → NP_006272.2 serine/threonine-protein kinase 3 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AP003355, BC010640, U26424

Consensus CDS

CCDS47900.1

UniProtKB/Swiss-Prot

Q13188

Related

ENSP00000390500, OTTHUMP00000227170, ENST00000419617, OTTHUMT00000379635

Conserved Domains (3) summary

cd06612
Location:23 – 278
Blast Score: 1393

STKc_MST1_2; Catalytic domain of the Protein Serine/Threonine Kinases, Mammalian Ste20-like protein kinase 1 and 2

pfam11629
Location:436 – 484
Blast Score: 231

Mst1_SARAH; C terminal SARAH domain of Mst1

smart00220
Location:27 – 278
Blast Score: 835

S_TKc; Serine/Threonine protein kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p10 Primary Assembly

Range

99466859..99954799, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

94670086..95157575, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018919.1 Alternate CHM1_1.0

Range

99753477..100241345, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01037538.1 (27164..55892)	None
genomic	ABBA01037539.1	None
genomic	ABBA01037540.1	None
genomic	ABBA01037541.1	None
genomic	ABBA01037542.1	None
genomic	ABBA01037543.1	None
genomic	ABBA01037544.1	None
genomic	ABBA01037545.1	None
genomic	ABBA01037546.1	None
genomic	AC016877.11 (43226..154888)	None
genomic	AMYH01018918.1 (94910..465923)	None
genomic	AMYH01018919.1	None
genomic	AP002087.2 (19827..99505)	None
genomic	AP003355.2 (83886..153728)	None
genomic	AP003467.2 (15797..81600)	None
genomic	AP003551.2	None
genomic	CH471060.1	EAW91781.1
mRNA	AA370619.1	None
mRNA	AK075229.1	BAC11487.1
mRNA	AK131363.1	BAG54769.1
mRNA	AK291837.1	BAF84526.1
mRNA	AK307787.1	None
mRNA	AK312660.1	None
mRNA	BC010640.2	AAH10640.1
mRNA	U26424.1	AAC50386.1
mRNA	U60206.1	AAB17261.1
mRNA	Z25422.1	CAA80909.1