EKS-OTG-00323

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-OTG-00323

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
STE/STE20	348.4	2.4E-104	30	281	252

Status

Reviewed

Ensembl Protein

ENSOGAP00000005955

UniProt Accession

A4K2Q5;

Protein Name

Serine/threonine-protein kinase 4 18kDa subunit

Protein Synonyms/Alias

MST1/N; MST1/C;

Gene Name

STK4

Gene Synonyms/Alias

STK4;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSOGAG00000006656	ENSOGAP00000005955	ENSOGAT00000006659

Organism

Otolemur garnettii

Functional Description

Stress-activated, pro-apoptotic kinase which, followingcaspase-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 '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 (By similarity).

Protein Length

487

Protein Sequence
(FASTA)

METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK ETGQIVAIKQ 60

VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI VMEYCGAGSV SDIIRLRNKT 120

LTEDEIATIL QSTLKGLEYL HFMRKIHRDI KAGNILLNTE GHAKLADFGV AGQLTDTMAK 180

RNTVIGTPFW MAPEVIQEIG YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP 240

PPTFRKPELW SDNFTDFVRQ CLVKSPDQRA TATQLLQHPF VKSAKGVSIL RDLINEAMDV 300

KLKRQEAQQR EVDQDDEENS EEDELDSGTM VRAVGDEMGT VRVASTMSDG ANTMIEHDDT 360

LPSQLGTMVI NADDEEEEGT MKRRDETMQP AKPSFLEYFE QKEKENQINS FGKSVPGPLK 420

NSSDWKVPQD GDYEFLKSWT VEDLQKRLLA LDPMMEQEIE EIRQKYQSKR QPILDAIEAK 480

KRRQQNF 487

Nucleotide Sequence
(FASTA)

ATGGAGACCG TGCAGCTGAG GAACCCGCCG CGCCGGCAGC TGAAAAAGTT GGATGAAGAT 60

AGTTTAACCA AACAACCAGA AGAAGTGTTT GATGTCTTAG AGAAACTTGG AGAAGGATCC 120

TACGGCAGTG TATACAAAGC TATTCATAAA GAGACGGGTC AGATTGTTGC TATTAAGCAA 180

GTTCCTGTGG AATCAGACCT GCAGGAGATA ATCAAAGAAA TCTCTATAAT GCAACAATGT 240

GACAGCCCAC ATGTTGTCAA ATATTATGGC AGTTATTTTA AGAATACAGA CTTGTGGATT 300

GTCATGGAGT ATTGTGGGGC TGGTTCTGTG TCTGATATCA TTCGATTACG AAATAAAACG 360

TTAACAGAAG ATGAAATAGC TACAATATTG CAGTCAACTC TTAAGGGACT AGAATACCTT 420

CATTTTATGA GAAAAATACA TCGAGATATC AAGGCAGGAA ATATTTTGCT AAATACAGAA 480

GGACATGCAA AGCTTGCAGA TTTTGGGGTG GCAGGTCAAC TTACAGATAC CATGGCCAAG 540

CGGAATACAG TGATAGGAAC ACCATTTTGG ATGGCTCCAG AAGTGATTCA GGAAATTGGG 600

TACAACTGTG TAGCAGACAT CTGGTCTCTG GGAATAACTG CCATAGAAAT GGCTGAAGGG 660

AAACCCCCAT ATGCTGATAT CCACCCAATG AGGGCAATAT TCATGATTCC TACAAACCCT 720

CCTCCCACAT TCCGAAAGCC AGAGCTGTGG TCAGATAACT TCACGGATTT TGTGAGGCAG 780

TGTCTTGTGA AGAGCCCTGA CCAGAGAGCC ACAGCCACTC AGCTCCTGCA GCACCCATTT 840

GTCAAGAGTG CCAAAGGAGT GTCAATACTG CGAGACTTAA TTAATGAAGC CATGGATGTG 900

AAATTGAAAC GCCAGGAAGC CCAGCAGCGG GAAGTGGACC AGGATGATGA AGAAAACTCA 960

GAGGAGGATG AATTAGATTC TGGCACGATG GTTCGAGCAG TGGGTGATGA GATGGGCACC 1020

GTCCGAGTAG CCAGCACCAT GAGTGATGGA GCCAATACTA TGATTGAGCA TGATGACACG 1080

TTGCCATCAC AGCTGGGCAC CATGGTGATC AATGCAGATG ATGAGGAAGA GGAAGGGACT 1140

ATGAAAAGAA GGGATGAGAC TATGCAGCCT GCAAAACCAT CTTTTCTTGA ATATTTTGAA 1200

CAAAAAGAAA AGGAAAACCA GATTAACAGC TTTGGCAAGA GTGTACCTGG CCCACTGAAA 1260

AATTCTTCAG ATTGGAAAGT GCCACAAGAT GGAGACTATG AGTTTCTTAA GAGTTGGACG 1320

GTGGAGGACC TTCAGAAGAG ACTCTTGGCT CTGGACCCCA TGATGGAGCA GGAGATTGAA 1380

GAGATCCGGC AGAAGTACCA GTCCAAGCGG CAGCCAATCC TGGACGCCAT TGAGGCAAAG 1440

AAGAGGCGGC AACAGAACTT CTGA 1464

Domain Profile

S: 1     yelleeigkGalgkvylarekktgelvaikkinlekqekleelqkeisvlkklkhpnive  60

         +++le++g+G++g+vy+a +k+tg++vaik++ +e+  +l+e++keis+++++++p++v+

Q: 30    FDVLEKLGEGSYGSVYKAIHKETGQIVAIKQVPVES--DLQEIIKEISIMQQCDSPHVVK  87

         7899*******************************7..9*********************

S: 61    ylesflkeeelwlvmeylagGslsdlvkeelkselkEeqiayilrevlkaLeylHskkvi  120

         y++s++k+++lw+vmey+ +Gs+sd+++  ++++l+E++ia+il+++lk+LeylH +++i

Q: 88    YYGSYFKNTDLWIVMEYCGAGSVSDIIR-LRNKTLTEDEIATILQSTLKGLEYLHFMRKI  146

         ****************************.99*****************************

S: 121   HrdikakniLlteegeVkLsdfgvaaqlektrkkrktvvgtpywmAPEviaqeekgYdek  180

         Hrdika+niLl++eg+ kL+dfgva ql++t++kr+tv+gtp+wmAPEvi+  e gY++

Q: 147   HRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQ--EIGYNCV  204

         ***************************************************..9******

S: 181   aDiwslGItaielaegepPfkdleplkallkilkneppklkskkkfskefkefvekclqk  240

         aDiwslGItaie+aeg+pP++d++p++a+++i++n+pp++++++ +s++f++fv++cl k

Q: 205   ADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDNFTDFVRQCLVK  264

         ************************************************************

S: 241   npekRpsasellkhkFl  257

         +p++R++a++ll+h+F+

Q: 265   SPDQRATATQLLQHPFV  281

         ****************7

Domain Sequence
(FASTA)

FDVLEKLGEG SYGSVYKAIH KETGQIVAIK QVPVESDLQE IIKEISIMQQ CDSPHVVKYY 60

GSYFKNTDLW IVMEYCGAGS VSDIIRLRNK TLTEDEIATI LQSTLKGLEY LHFMRKIHRD 120

IKAGNILLNT EGHAKLADFG VAGQLTDTMA KRNTVIGTPF WMAPEVIQEI GYNCVADIWS 180

LGITAIEMAE GKPPYADIHP MRAIFMIPTN PPPTFRKPEL WSDNFTDFVR QCLVKSPDQR 240

ATATQLLQHP FV 252

Keyword

Acetylation; Apoptosis; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sorex araneus"; ?>Taeniopygia guttata"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0043539	; F:protein serine/threonine kinase activator activity
GO:0004674	; F:protein serine/threonine kinase activity
GO:0006915	; P:apoptotic process
GO:0060706	; P:cell differentiation involved in embryonic placenta development
GO:0000902	; P:cell morphogenesis
GO:0007417	; P:central nervous system development
GO:0003157	; P:endocardium development
GO:0035329	; P:hippo signaling cascade
GO:0006917	; P:induction of apoptosis
GO:0007243	; P:intracellular protein kinase cascade
GO:0030216	; P:keratinocyte differentiation
GO:0090090	; P:negative regulation of canonical Wnt receptor signaling pathway
GO:0008285	; P:negative regulation of cell proliferation
GO:0046621	; P:negative regulation of organ growth
GO:0001841	; P:neural tube formation
GO:0001569	; P:patterning of blood vessels
GO:0018105	; P:peptidyl-serine phosphorylation
GO:0060215	; P:primitive hemopoiesis
GO:0046777	; P:protein autophosphorylation

KEGG

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR011524	; SARAH.
IPR024205	; SARAH_domain.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.

Pfam

PF11629	; Mst1_SARAH; 1.
PF00069	; Pkinase; 1.

SMARTs

SM00220

; S_TKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; FALSE_NEG.
PS50951	; SARAH; 1.

Prints

Created Date

20-Feb-2013