Q13188 (STK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase 3
EC=2.7.11.1

Alternative name(s):
Mammalian STE20-like protein kinase 2
Short name=MST-2
STE20-like kinase MST2
Serine/threonine-protein kinase Krs-1

Cleaved into the following 2 chains:

1. Serine/threonine-protein kinase 3 36kDa subunit
   Short name=MST2/N
2. Serine/threonine-protein kinase 3 20kDa subunit
   Short name=MST2/C

Gene names

Name:	STK3
Synonyms:	KRS1, MST2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Phosphorylates NKX2-1 By similarity. Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38. Ref.1 Ref.2 Ref.11 Ref.13 Ref.14 Ref.16 Ref.20 Ref.23 Ref.24 Ref.28
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation. Ref.10 Ref.27
Subunit structure	Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation By similarity. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain). Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.20 Ref.22 Ref.24 Ref.25 Ref.27 Ref.28
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: The caspase-cleaved form cycles between nucleus and cytoplasm By similarity. Phosphorylation at Thr-117 leads to inhibition of nuclear translocation. Ref.20
Tissue specificity	Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues. Ref.1
Induction	Activity increases during mitosis. Ref.10 Ref.14 Ref.27
Post-translational modification	Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1. Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 protein kinase domain. Contains 1 SARAH domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement Ref.9. Source: UniProtKB cell differentiation involved in embryonic placenta development Inferred from electronic annotation. Source: Compara central nervous system development Inferred from electronic annotation. Source: Compara endocardium development Inferred from electronic annotation. Source: Compara hippo signaling cascade Traceable author statement Ref.18. Source: UniProtKB intracellular protein kinase cascade Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of organ growth Inferred from electronic annotation. Source: Compara neural tube formation Inferred from electronic annotation. Source: Compara positive regulation of JNK cascade Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara primitive hemopoiesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB protein dimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activator activity Inferred from direct assay PubMed 20412773. Source: BHF-UCL protein serine/threonine kinase activity Inferred from direct assay Ref.14Ref.16Ref.20Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAP	O95166	2	EBI-992580,EBI-712001
GABARAPL1	Q9H0R8	2	EBI-992580,EBI-746969
GABARAPL2	P60520	2	EBI-992580,EBI-720116
MAP1LC3B	Q9GZQ8	5	EBI-992580,EBI-373144
MAP1LC3C	Q9BXW4	2	EBI-992580,EBI-2603996
RASSF1	Q9NS23-2	3	EBI-992580,EBI-438698
RASSF5	Q8WWW0	3	EBI-992580,EBI-367390
SAV1	Q9H4B6	7	EBI-992580,EBI-1017775
STK4	Q13043	5	EBI-992580,EBI-367376

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 491	491	Serine/threonine-protein kinase 3		PRO_0000086689
	Chain	1 – 322	322	Serine/threonine-protein kinase 3 36kDa subunit		PRO_0000413713
	Chain	323 – 491	169	Serine/threonine-protein kinase 3 20kDa subunit		PRO_0000413714
Regions
	Domain	27 – 278	252	Protein kinase
	Domain	437 – 484	48	SARAH
	Nucleotide binding	33 – 41	9	ATP By similarity
	Coiled coil	287 – 328	42	Potential
	Coiled coil	442 – 475	34	Potential
	Compositional bias	308 – 314	7	Poly-Glu
	Compositional bias	370 – 375	6	Poly-Glu
Sites
	Active site	146	1	Proton acceptor By similarity
	Binding site	56	1	ATP
	Site	322 – 323	2	Cleavage; by caspase-3
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.7
	Modified residue	15	1	Phosphoserine Ref.19
	Modified residue	117	1	Phosphothreonine; by PKB/AKT1 Ref.22 Ref.25
	Modified residue	180	1	Phosphothreonine; by autocatalysis Probable
	Modified residue	316	1	Phosphoserine Ref.15 Ref.17 Ref.19 Ref.21 Ref.29
	Modified residue	336	1	Phosphothreonine Ref.19
	Modified residue	384	1	Phosphothreonine; by PKB/AKT1 Ref.22
	Modified residue	444	1	Phosphoserine Ref.15 Ref.19
Natural variations
	Natural variant	60	1	V → L in an ovarian clear cell carcinoma sample; somatic mutation. Ref.30		VAR_041122
	Natural variant	418	1	F → C. Corresponds to variant rs36047674 [ dbSNP | Ensembl ].		VAR_051670
Experimental info
	Mutagenesis	56	1	K → R: Loss of activity. Ref.13
	Mutagenesis	322	1	D → N: Resistant to proteolytic cleavage. Ref.9
	Sequence conflict	96 – 98	3	WIV → YLY in CAA80909. Ref.8
	Sequence conflict	121	1	D → Y in CAA80909. Ref.8
	Sequence conflict	203	1	D → G in CAA80909. Ref.8
	Sequence conflict	303	1	E → D in AAC50386. Ref.1
	Sequence conflict	332 – 334	3	ESV → GEC in AAC50386. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q13188 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: 84F598ED3617292C	FASTA	491	56,301
	10 20 30 40 50 60 MEQPPAPKSK LKKLSEDSLT KQPEEVFDVL EKLGEGSYGS VFKAIHKESG QVVAIKQVPV 70 80 90 100 110 120 ESDLQEIIKE ISIMQQCDSP YVVKYYGSYF KNTDLWIVME YCGAGSVSDI IRLRNKTLIE 130 140 150 160 170 180 DEIATILKST LKGLEYLHFM RKIHRDIKAG NILLNTEGHA KLADFGVAGQ LTDTMAKRNT 190 200 210 220 230 240 VIGTPFWMAP EVIQEIGYNC VADIWSLGIT SIEMAEGKPP YADIHPMRAI FMIPTNPPPT 250 260 270 280 290 300 FRKPELWSDD FTDFVKKCLV KNPEQRATAT QLLQHPFIKN AKPVSILRDL ITEAMEIKAK 310 320 330 340 350 360 RHEEQQRELE EEEENSDEDE LDSHTMVKTS VESVGTMRAT STMSEGAQTM IEHNSTMLES 370 380 390 400 410 420 DLGTMVINSE DEEEEDGTMK RNATSPQVQR PSFMDYFDKQ DFKNKSHENC NQNMHEPFPM 430 440 450 460 470 480 SKNVFPDNWK VPQDGDFDFL KNLSLEELQM RLKALDPMME REIEELRQRY TAKRQPILDA 490 MDAKKRRQQN F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a member of the MST subfamily of Ste20-like kinases." Creasy C.L., Chernoff J. Gene 167:303-306(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
[2]	"Newly identified stress-responsive protein kinases, Krs-1 and Krs-2." Taylor L.K., Wang H.C., Erikson R.L. Proc. Natl. Acad. Sci. U.S.A. 93:10099-10104(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[7]	Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-8; 13-43; 57-69; 85-91; 115-128; 133-141; 149-178; 229-256; 267-298; 329-338; 382-403; 423-451; 462-467 AND 474-485, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Mammary carcinoma.
[8]	"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans." Schultz S.J., Nigg E.A. Cell Growth Differ. 4:821-830(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-203.
[9]	"MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation." Lee K.-K., Ohyama T., Yajima N., Tsubuki S., Yonehara S. J. Biol. Chem. 276:19276-19285(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING, MUTAGENESIS OF ASP-322.
[10]	"Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1." O'Neill E., Rushworth L., Baccarini M., Kolch W. Science 306:2267-2270(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAF1, ENZYME REGULATION.
[11]	"The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1." Chan E.H.Y., Nousiainen M., Chalamalasetty R.B., Schaefer A., Nigg E.A., Sillje H.H.W. Oncogene 24:2076-2086(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SAV1, FUNCTION.
[12]	"Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis." Oh H.J., Lee K.-K., Song S.J., Jin M.S., Song M.S., Lee J.H., Im C.R., Lee J.-O., Yonehara S., Lim D.-S. Cancer Res. 66:2562-2569(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RASSF1.
[13]	"Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation." Callus B.A., Verhagen A.M., Vaux D.L. FEBS J. 273:4264-4276(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SAV1, MUTAGENESIS OF LYS-56.
[14]	"MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation." Praskova M., Xia F., Avruch J. Curr. Biol. 18:311-321(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-444, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to form the scaffold to activate nuclear Dbf2-related kinase 1." Hirabayashi S., Nakagawa K., Sumita K., Hidaka S., Kawai T., Ikeda M., Kawata A., Ohno K., Hata Y. Oncogene 27:4281-4292(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STK38 AND MOBKL1B.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling." Hergovich A., Hemmings B.A. BioFactors 35:338-345(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[19]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-316; THR-336 AND SER-444, MASS SPECTROMETRY.
[20]	"RASSF2 associates with and stabilizes the proapoptotic kinase MST2." Cooper W.N., Hesson L.B., Matallanas D., Dallol A., von Kriegsheim A., Ward R., Kolch W., Latif F. Oncogene 28:2988-2998(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RASSF2, SUBCELLULAR LOCATION.
[21]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[22]	"Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt." Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W. Cancer Res. 70:1195-1203(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-117 AND THR-384, INTERACTION WITH PKB/AKT1.
[23]	"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." Kilili G.K., Kyriakis J.M. J. Biol. Chem. 285:15076-15087(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[24]	"Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction." Mardin B.R., Lange C., Baxter J.E., Hardy T., Scholz S.R., Fry A.M., Schiebel E. Nat. Cell Biol. 12:1166-1176(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEK2.
[25]	"Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway." Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q. PLoS ONE 5:E9616-E9616(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-117, INTERACTION WITH PKB/AKT1.
[26]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]	"The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2." Guo C., Zhang X., Pfeifer G.P. J. Biol. Chem. 286:6253-6261(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RASSF1, ENZYME REGULATION.
[28]	"Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand." Park Y., Park J., Lee Y., Lim W., Oh B.C., Shin C., Kim W., Lee Y. J. Mol. Med. 89:181-191(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ESR1.
[29]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, MASS SPECTROMETRY.
[30]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-60.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U26424 mRNA. Translation: AAC50386.1. U60206 mRNA. Translation: AAB17261.1. AK291837 mRNA. Translation: BAF84526.1. AP002087 Genomic DNA. No translation available. AP003355 Genomic DNA. No translation available. AP003467 Genomic DNA. No translation available. AP003551 Genomic DNA. No translation available. CH471060 Genomic DNA. Translation: EAW91781.1. BC010640 mRNA. Translation: AAH10640.1. Z25422 mRNA. Translation: CAA80909.1.
IPI	IPI00942120.
PIR	I38212.
RefSeq	NP_006272.2. NM_006281.3.
UniGene	Hs.492333.
3D structure databases
ProteinModelPortal	Q13188.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13188. 34 interactions.
MINT	MINT-3027356.
STRING	9606.ENSP00000377867.
PTM databases
PhosphoSite	Q13188.
Polymorphism databases
DMDM	46577700.
2D gel databases
OGP	Q13188.
Proteomic databases
PaxDb	Q13188.
PRIDE	Q13188.
Protocols and materials databases
DNASU	6788.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000419617; ENSP00000390500; ENSG00000104375.
GeneID	6788.
KEGG	hsa:6788.
UCSC	uc003yip.3. human.
Organism-specific databases
CTD	6788.
GeneCards	GC08M099413.
HGNC	HGNC:11406. STK3.
HPA	CAB025316. HPA007120.
MIM	605030. gene.
neXtProt	NX_Q13188.
PharmGKB	PA36213.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000234203.
HOVERGEN	HBG108518.
InParanoid	Q13188.
KO	K04412.
Enzyme and pathway databases
BRENDA	2.7.11.1. 2681.
Reactome	REACT_111102. Signal Transduction.
SignaLink	Q13188.
Gene expression databases
ArrayExpress	Q13188.
Bgee	Q13188.
CleanEx	HS_STK3.
Genevestigator	Q13188.
GermOnline	ENSG00000104375. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR024205. Mst1_SARAH_domain. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR011524. SARAH_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF11629. Mst1_SARAH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. PS50951. SARAH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q13188.
ChEMBL	CHEMBL4708.
ChiTaRS	STK3. human.
GenomeRNAi	6788.
NextBio	26504.
PMAP-CutDB	Q13188.
SOURCE	Search...

Entry information

Entry name

STK3_HUMAN

Accession

Primary (citable) accession number: Q13188
Secondary accession number(s): A8K722 , Q15445, Q15801, Q96FM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	April 26, 2004
Last modified:	May 29, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.