EKS-HOS-00241

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00241

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/MAPKAPK	415.4	4.4E-124	23	304	282

Status

Reviewed

Ensembl Protein

ENSP00000202788

UniProt Accession

Q8IW41; B3KVA5; O60491; Q86X46; Q9BVX9; Q9UG86;

Protein Name

MAP kinase-activated protein kinase 5

Protein Synonyms/Alias

MAPK-activated protein kinase 5; MAPKAP kinase 5; MAPKAP-K5; MAPKAPK-5; MK-5; MK5; p38-regulated/activated protein kinase; PRAK;

Gene Name

MAPKAPK5

Gene Synonyms/Alias

MAPKAPK5; PRAK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000089022	ENSP00000202788	ENST00000202788
ENSG00000089022	ENSP00000449667	ENST00000550735
ENSG00000089022	ENSP00000448408	ENST00000553053
ENSG00000089022	ENSP00000409640	ENST00000428907
ENSG00000089022	ENSP00000448727	ENST00000547067
ENSG00000089022	ENSP00000449381	ENST00000551404
ENSG00000089022	ENSP00000449594	ENST00000546394
ENSG00000089022	ENSP00000448283	ENST00000552111

Organism

Homo sapiens

Functional Description

Tumor suppressor serine/threonine-protein kinaseinvolved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras- induced senescence and phosphorylating p53/TP53. Involved in post- transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.

Protein Length

473

Protein Sequence
(FASTA)

MSEESDMDKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL KILLDRPKAR 60

NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI VMEMMEGGEL FHRISQHRHF 120

TEKQASQVTK QIALALRHCH LLNIAHRDLK PENLLFKDNS LDAPVKLCDF GFAKIDQGDL 180

MTPQFTPYYV APQVLEAQRR HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP 240

FYSKHHSRTI PKDMRRKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD 300

HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQDLKVSLK PLHSVNNPIL 360

RKRKLLGTKP KDSVYIHDHE NGAEDSNVAL EKLRDVIAQC ILPQAGKGEN EDEKLNEVMQ 420

EAWKYNRECK LLRDTLQSFS WNGRGFTDKV DRLKLAEIVK QVIEEQTTSH ESQ 473

Nucleotide Sequence
(FASTA)

ATGTCGGAGG AGAGCGACAT GGACAAAGCC ATCAAGGAAA CTTCCATTTT AGAAGAATAC 60

AGTATCAATT GGACTCAGAA GCTGGGAGCT GGAATTAGTG GTCCAGTTAG AGTCTGTGTA 120

AAGAAATCTA CTCAAGAACG GTTTGCGCTG AAAATTCTTC TTGATCGTCC AAAAGCTAGA 180

AATGAGGTAC GTCTGCACAT GATGTGTGCC ACACACCCAA ACATAGTTCA GATTATTGAA 240

GTGTTTGCTA ACAGTGTCCA GTTTCCCCAT GAGTCCAGCC CTAGGGCCCG ACTCTTAATT 300

GTAATGGAGA TGATGGAAGG GGGAGAGCTA TTTCACAGAA TCAGCCAGCA CCGGCACTTT 360

ACAGAGAAGC AAGCCAGCCA AGTAACAAAG CAGATAGCTT TGGCTCTGCG GCACTGTCAC 420

TTGTTAAACA TTGCGCACAG AGACCTCAAG CCTGAAAATC TGCTTTTTAA GGATAACTCT 480

TTGGATGCCC CAGTGAAGTT GTGTGACTTT GGATTTGCCA AGATTGACCA AGGTGACTTG 540

ATGACACCCC AGTTCACCCC TTATTATGTA GCACCCCAGG TACTGGAGGC GCAAAGAAGG 600

CATCAGAAGG AGAAATCTGG CATCATACCT ACCTCACCGA CGCCCTACAC TTACAACAAG 660

AGCTGTGACT TGTGGTCCCT AGGGGTGATT ATCTATGTGA TGCTGTGCGG ATACCCTCCT 720

TTTTACTCCA AACACCACAG CCGGACTATC CCAAAGGATA TGCGAAGAAA GATCATGACA 780

GGCAGTTTTG AGTTCCCAGA GGAAGAGTGG AGTCAGATCT CAGAGATGGC CAAAGATGTT 840

GTGAGGAAGC TCCTGAAGGT CAAACCGGAG GAGAGACTCA CCATCGAGGG AGTGCTGGAC 900

CACCCCTGGC TCAATTCCAC CGAGGCCCTG GATAATGTGC TGCCTTCTGC TCAGCTGATG 960

ATGGACAAGG CAGTGGTTGC AGGAATCCAG CAGGCTCACG CGGAACAGTT GGCCAACATG 1020

AGAATCCAGG ATCTGAAAGT CAGCCTCAAA CCCCTGCACT CAGTGAACAA CCCCATTCTG 1080

CGGAAGAGGA AGTTACTTGG CACCAAGCCA AAGGACAGTG TCTATATCCA CGACCATGAG 1140

AATGGAGCCG AGGATTCCAA TGTTGCCTTG GAAAAACTCC GAGATGTGAT TGCTCAGTGT 1200

ATTCTCCCCC AGGCTGGTAA AGGAGAGAAT GAAGATGAGA AACTGAATGA AGTAATGCAG 1260

GAGGCTTGGA AGTATAACCG GGAATGCAAA CTCCTAAGAG ATACTCTGCA GAGCTTCAGC 1320

TGGAATGGTC GTGGATTCAC AGATAAAGTA GATCGACTAA AACTGGCAGA AATTGTGAAG 1380

CAGGTGATAG AAGAGCAAAC CACGTCCCAC GAATCCCAAT AA 1422

Domain Profile

S: 2     lteevlGeGisgkvlecvkkktgekyalkilkdrkkvrrevelhvqasghknivelidvf  61

         +++++lG+Gisg v+ cvkk+t+e++alkil dr+k+r+ev+lh+++++h+niv++i+vf

Q: 23    NWTQKLGAGISGPVRVCVKKSTQERFALKILLDRPKARNEVRLHMMCATHPNIVQIIEVF  82

         689*********************************************************

S: 62    ensfe......dekrlllvlekleGGellsriqerkaftekeasevvkdiasalkflhsk  115

         +ns++      +++rll+v+e++eGGel++ri+++++ftek+as+v+k+ia al+++h

Q: 83    ANSVQfphessPRARLLIVMEMMEGGELFHRISQHRHFTEKQASQVTKQIALALRHCHLL  142

         ****99999999************************************************

S: 116   niahrDlkpenlLyeskeknapvklcDfglaketeeeeelktpcltaeyvaPevleaeke  175

         niahrDlkpenlL+++++ +apvklcDfg+ak   ++ +l+tp++t++yvaP+vlea+++

Q: 143   NIAHRDLKPENLLFKDNSLDAPVKLCDFGFAK--IDQGDLMTPQFTPYYVAPQVLEAQRR  200

         ********************************..89***********************9

S: 176   e.............allydksCDlWslGvilyillcGypPfyskk.graiskklkeriqe  221

         +             +++y+ksCDlWslGvi+y++lcGypPfysk+ +r+i+k+++++i++

Q: 201   HqkeksgiiptsptPYTYNKSCDLWSLGVIIYVMLCGYPPFYSKHhSRTIPKDMRRKIMT  260

         99*****************************************9979*************

S: 222   gkyefPeeeWsevseeakdlirklLkrdpkerltieevlnhpwv  265

         g++efPeeeWs++se+akd++rklLk++p+erltie vl+hpw+

Q: 261   GSFEFPEEEWSQISEMAKDVVRKLLKVKPEERLTIEGVLDHPWL  304

         *******************************************6

Domain Sequence
(FASTA)

NWTQKLGAGI SGPVRVCVKK STQERFALKI LLDRPKARNE VRLHMMCATH PNIVQIIEVF 60

ANSVQFPHES SPRARLLIVM EMMEGGELFH RISQHRHFTE KQASQVTKQI ALALRHCHLL 120

NIAHRDLKPE NLLFKDNSLD APVKLCDFGF AKIDQGDLMT PQFTPYYVAP QVLEAQRRHQ 180

KEKSGIIPTS PTPYTYNKSC DLWSLGVIIY VMLCGYPPFY SKHHSRTIPK DMRRKIMTGS 240

FEFPEEEWSQ ISEMAKDVVR KLLKVKPEER LTIEGVLDHP WL 282

Keyword

Alternative splicing; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Tumor suppressor.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Echinops telfairi"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>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"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tarsius syrichta"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0004708	; F:MAP kinase kinase activity
GO:0002039	; F:p53 binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0032007	; P:negative regulation of TOR signaling cascade
GO:0046777	; P:protein autophosphorylation
GO:0007265	; P:Ras protein signal transduction
GO:0006417	; P:regulation of translation
GO:0090400	; P:stress-induced premature senescence

KEGG

hsa:8550

;

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00069

; Pkinase; 1.

SMARTs

SM00220

; S_TKc; 1.

Prosites

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

Prints

Created Date

20-Feb-2013