O54992 (MAPK5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
MAP kinase-activated protein kinase 5
Short name=MAPK-activated protein kinase 5
Short name=MAPKAP kinase 5
Short name=MAPKAPK-5
EC=2.7.11.1

Gene names

Name:

Mapkapk5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tumor suppressor serine/threonine-protein kinase involved 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. Ref.6 Ref.7 Ref.8 Ref.10 Ref.18 Ref.19
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.16
Enzyme regulation	Activated following phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as H2O2, arsenite, anisomycin TNF alpha and also PMA and the calcium ionophore A23187; but to a lesser extent. In vitro, activated by SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine. Ref.1 Ref.16
Subunit structure	Interacts with SQSTM1 By similarity. Interacts with ERK3/MAPK6 and ERK4/MAPK4 (via FRIEDE motif); the interaction is direct. Interacts with YWHAE; the interaction prevents phosphorylation of HSP27/HSPB1 leading to disrupt F-actin polymerization. Ref.6 Ref.7 Ref.8 Ref.12 Ref.14 Ref.15
Subcellular location	Cytoplasm. Nucleus. Note: Translocates to the cytoplasm following phosphorylation and activation. Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm. Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export. Ref.6 Ref.7 Ref.8 Ref.11 Ref.13 Ref.16 Ref.17
Tissue specificity	Expressed ubiquitously. Ref.1
Post-translational modification	Phosphorylated on Thr-182 ERK3/MAPK6 or ERK4/MAPK4; which is the regulatory phosphorylation site and is located on the T-loop/loop 12, leading to activation. Phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11 is subject to debate. Phosphorylated at Ser-115 by PKA/PRKACA, leading to localization to the cytoplasm. Autophosphorylated. Ref.1 Ref.6 Ref.7 Ref.17
Disruption phenotype	Phenotypes are different depending on reports. According to a first report, mice are viable and fertile and do not show changes in tissue morphology and behavior: they exhibit the same susceptibility to LPS-induced endotoxic shock as wild-type animals and do not show the defects in LPS-induced biosynthesis of inflammatory cytokines known to occur with Mapkapk2-deficient animals (Ref.5). According to another report, both homozygous and heterozygous mutant mice are highly susceptible to skin carcinogenesis induced by DMBA (Ref.10). According to a third report, mutant show embryonic lethality around E11 in a C57BL/6 background (Ref.6). Ref.5 Ref.6 Ref.10
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.
Caution	The role of p38 MAPK kinases is unclear in phosphorylation and activation of Mapkapk5. According to some reports, it interacts and is phosphorylated by p38-alpha/MAPK14 and p38-beta/MAPK11 (Ref.1). According to other reports, it is not activated by p38-alpha/MAPK14 and p38-beta/MAPK11 (Ref.5). An explanation for these discrepancies, might be that the interaction with p38 MAPK kinases is weak and occurs only under specific conditions.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from mutant phenotype Ref.10. Source: UniProtKB negative regulation of TOR signaling cascade Inferred from direct assay Ref.19. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of translation Inferred from sequence or structural similarity. Source: UniProtKB stress-induced premature senescence Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.7Ref.8Ref.16. Source: UniProtKB nucleus Inferred from direct assay Ref.7Ref.8Ref.16. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW p53 binding Inferred from direct assay Ref.10. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.7Ref.8Ref.10Ref.16Ref.19. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O54992-1)

Also known as: MK-5 type 1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O54992-2)

Also known as: MK-5 type 3;

The sequence of this isoform differs from the canonical sequence as follows:
     344-408: DLKVSLKPLHSVNNPILRKRKLLGTKPKDGIYIHDHENGTEDSNVALEKLRDVIAQCILPQAGKG → E

Isoform 3 (identifier: O54992-3)

Also known as: MK-5 type 4;

The sequence of this isoform differs from the canonical sequence as follows:
     13-161: Missing.

Isoform 4 (identifier: O54992-4)

Also known as: MK-5 type 5;

The sequence of this isoform differs from the canonical sequence as follows:
     13-161: Missing.
     407-408: Missing.

Isoform 5 (identifier: O54992-5)

Also known as: MK-5 type 2;

The sequence of this isoform differs from the canonical sequence as follows:
     407-408: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 473	473	MAP kinase-activated protein kinase 5		PRO_0000086297
Regions
	Domain	22 – 304	283	Protein kinase
	Nucleotide binding	28 – 36	9	ATP By similarity
	Coiled coil	409 – 440	32	Potential
Sites
	Active site	148	1	Proton acceptor By similarity
	Binding site	51	1	ATP Probable
Amino acid modifications
	Modified residue	115	1	Phosphoserine; by PKA Ref.17
	Modified residue	182	1	Phosphothreonine; by MAPK11, MAPK14, MAPK4, MAPK6 and PKA Ref.6 Ref.7
	Modified residue	212	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	13 – 161	149	Missing in isoform 3 and isoform 4.		VSP_011599
	Alternative sequence	344 – 408	65	DLKVS…QAGKG → E in isoform 2.		VSP_011600
	Alternative sequence	407 – 408	2	Missing in isoform 4 and isoform 5.		VSP_011598
Experimental info
	Mutagenesis	51	1	K → E: No p38-alpha/MAPK14-, p38-beta/MAPK11-, ERK3/MAPK6-, ERK4/MAPK4-induced activation. Ref.1 Ref.6 Ref.10 Ref.19
	Mutagenesis	51	1	K → R or M: Kinase defective mutant, abolishes activity. Ref.1 Ref.6 Ref.10 Ref.19
	Mutagenesis	115	1	S → A: Impairs shuttling to the cytoplasm. Ref.17
	Mutagenesis	115	1	S → D: Mimicks phosphorylation state, lesding to localization to the cytoplasm. Ref.17
	Mutagenesis	182	1	T → A: Impairs protein kinase activity and shuttling to the cytoplasm. Ref.6 Ref.7 Ref.10 Ref.16
	Mutagenesis	337	1	L → A: Constitutive active mutant. In a knockin model, mouse display increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explore further into the open arm on the elevated plus maze and are less active in the closed arm compared to littermate controls. Male knockin mice display no differences in anxiety, but their locomotor activity increases compared to non-transgenic littermates. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MK-5 type 1) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 45441A735075B247	FASTA	473	54,152
	10 20 30 40 50 60 MSEDSDMEKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL KILLDRPKAR 70 80 90 100 110 120 NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI VMEMMEGGEL FHRISQHRHF 130 140 150 160 170 180 TEKQASQVTK QIALALQHCH LLNIAHRDLK PENLLFKDNS LDAPVKLCDF GFAKVDQGDL 190 200 210 220 230 240 MTPQFTPYYV APQVLEAQRR HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP 250 260 270 280 290 300 FYSKHHSRTI PKDMRKKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD 310 320 330 340 350 360 HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQDLKVSLK PLHSVNNPIL 370 380 390 400 410 420 RKRKLLGTKP KDGIYIHDHE NGTEDSNVAL EKLRDVIAQC ILPQAGKGEN EDEKLNEVMQ 430 440 450 460 470 EAWKYNRECK LLRDALQSFS WNGRGFTDKV DRLKLAEVVK QVIEEQTLPH EPQ
	Isoform 2 (MK-5 type 3) [UniParc]. Checksum: 7EEAF061669A3F61	FASTA	409	47,103
	10 20 30 40 50 60 MSEDSDMEKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL KILLDRPKAR 70 80 90 100 110 120 NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI VMEMMEGGEL FHRISQHRHF 130 140 150 160 170 180 TEKQASQVTK QIALALQHCH LLNIAHRDLK PENLLFKDNS LDAPVKLCDF GFAKVDQGDL 190 200 210 220 230 240 MTPQFTPYYV APQVLEAQRR HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP 250 260 270 280 290 300 FYSKHHSRTI PKDMRKKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD 310 320 330 340 350 360 HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQEENEDEK LNEVMQEAWK 370 380 390 400 YNRECKLLRD ALQSFSWNGR GFTDKVDRLK LAEVVKQVIE EQTLPHEPQ
	Isoform 3 (MK-5 type 4) [UniParc]. Checksum: 25BF2CB86528174D	FASTA	324	37,042
	10 20 30 40 50 60 MSEDSDMEKA IKDAPVKLCD FGFAKVDQGD LMTPQFTPYY VAPQVLEAQR RHQKEKSGII 70 80 90 100 110 120 PTSPTPYTYN KSCDLWSLGV IIYVMLCGYP PFYSKHHSRT IPKDMRKKIM TGSFEFPEEE 130 140 150 160 170 180 WSQISEMAKD VVRKLLKVKP EERLTIEGVL DHPWLNSTEA LDNVLPSAQL MMDKAVVAGI 190 200 210 220 230 240 QQAHAEQLAN MRIQDLKVSL KPLHSVNNPI LRKRKLLGTK PKDGIYIHDH ENGTEDSNVA 250 260 270 280 290 300 LEKLRDVIAQ CILPQAGKGE NEDEKLNEVM QEAWKYNREC KLLRDALQSF SWNGRGFTDK 310 320 VDRLKLAEVV KQVIEEQTLP HEPQ
	Isoform 4 (MK-5 type 5) [UniParc]. Checksum: BADC2B6FEB4AEA4A	FASTA	322	36,856
	10 20 30 40 50 60 MSEDSDMEKA IKDAPVKLCD FGFAKVDQGD LMTPQFTPYY VAPQVLEAQR RHQKEKSGII 70 80 90 100 110 120 PTSPTPYTYN KSCDLWSLGV IIYVMLCGYP PFYSKHHSRT IPKDMRKKIM TGSFEFPEEE 130 140 150 160 170 180 WSQISEMAKD VVRKLLKVKP EERLTIEGVL DHPWLNSTEA LDNVLPSAQL MMDKAVVAGI 190 200 210 220 230 240 QQAHAEQLAN MRIQDLKVSL KPLHSVNNPI LRKRKLLGTK PKDGIYIHDH ENGTEDSNVA 250 260 270 280 290 300 LEKLRDVIAQ CILPQAGENE DEKLNEVMQE AWKYNRECKL LRDALQSFSW NGRGFTDKVD 310 320 RLKLAEVVKQ VIEEQTLPHE PQ
	Isoform 5 (MK-5 type 2) [UniParc]. Checksum: AC171E324E40A3D4	FASTA	471	53,967
	10 20 30 40 50 60 MSEDSDMEKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL KILLDRPKAR 70 80 90 100 110 120 NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI VMEMMEGGEL FHRISQHRHF 130 140 150 160 170 180 TEKQASQVTK QIALALQHCH LLNIAHRDLK PENLLFKDNS LDAPVKLCDF GFAKVDQGDL 190 200 210 220 230 240 MTPQFTPYYV APQVLEAQRR HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP 250 260 270 280 290 300 FYSKHHSRTI PKDMRKKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD 310 320 330 340 350 360 HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQDLKVSLK PLHSVNNPIL 370 380 390 400 410 420 RKRKLLGTKP KDGIYIHDHE NGTEDSNVAL EKLRDVIAQC ILPQAGENED EKLNEVMQEA 430 440 450 460 470 WKYNRECKLL RDALQSFSWN GRGFTDKVDR LKLAEVVKQV IEEQTLPHEP Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 kinase." Ni H., Wang X.S., Diener K., Yao Z. Biochem. Biophys. Res. Commun. 243:492-496(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF LYS-51, ENZYME REGULATION, PHOSPHORYLATION BY ERK2/MAPK1 AND MAPK14. Tissue: Spleen.
[2]	"Novel splice variants of MK5 from mouse heart." Benoit M.-J., Moise N., Mamarbachi A.M., Allen B.G. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4 AND 5).
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"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] (ISOFORM 1). Strain: FVB/N-3. Tissue: Mammary tumor.
[5]	"Elimination of protein kinase MK5/PRAK activity by targeted homologous recombination." Shi Y., Kotlyarov A., Laabeta K., Gruber A.D., Butt E., Marcus K., Meyer H.E., Friedrich A., Volk H.D., Gaestel M. Mol. Cell. Biol. 23:7732-7741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"Scaffolding by ERK3 regulates MK5 in development." Schumacher S., Laass K., Kant S., Shi Y., Visel A., Gruber A.D., Kotlyarov A., Gaestel M. EMBO J. 23:4770-4779(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION, INTERACTION WITH MAPK6, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT THR-182, MUTAGENESIS OF LYS-51 AND THR-182, DISRUPTION PHENOTYPE.
[7]	"Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway." Seternes O.M., Mikalsen T., Johansen B., Michaelsen E., Armstrong C.G., Morrice N.A., Turgeon B., Meloche S., Moens U., Keyse S.M. EMBO J. 23:4780-4791(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK6, SUBCELLULAR LOCATION, INTERACTION WITH MAPK6, PHOSPHORYLATION AT THR-182, MUTAGENESIS OF THR-182.
[8]	"Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5." Kant S., Schumacher S., Singh M.K., Kispert A., Kotlyarov A., Gaestel M. J. Biol. Chem. 281:35511-35519(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MAPK4, SUBCELLULAR LOCATION, INTERACTION WITH MAPK4.
[9]	"Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity." Gerits N., Van Belle W., Moens U. Behav. Brain Funct. 3:58-58(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LEU-337.
[10]	"PRAK is essential for ras-induced senescence and tumor suppression." Sun P., Yoshizuka N., New L., Moser B.A., Li Y., Liao R., Xie C., Chen J., Deng Q., Yamout M., Dong M.Q., Frangou C.G., Yates J.R. III, Wright P.E., Han J. Cell 128:295-308(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF TP53, DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-51 AND THR-182.
[11]	"Modulation of F-actin rearrangement by the cyclic AMP/cAMP-dependent protein kinase (PKA) pathway is mediated by MAPK-activated protein kinase 5 and requires PKA-induced nuclear export of MK5." Gerits N., Mikalsen T., Kostenko S., Shiryaev A., Johannessen M., Moens U. J. Biol. Chem. 282:37232-37243(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5." Perander M., Aberg E., Johansen B., Dreyer B., Guldvik I.J., Outzen H., Keyse S.M., Seternes O.M. Biochem. J. 411:613-622(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK4.
[13]	"Determinants that control the distinct subcellular localization of p38alpha-PRAK and p38beta-PRAK complexes." Li Q., Zhang N., Zhang D., Wang Y., Lin T., Wang Y., Zhou H., Ye Z., Zhang F., Lin S.C., Han J. J. Biol. Chem. 283:11014-11023(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5." Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L., Meloche S. J. Cell. Physiol. 217:778-788(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK4 AND MAPK6.
[15]	"Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif." Aberg E., Torgersen K.M., Johansen B., Keyse S.M., Perander M., Seternes O.M. J. Biol. Chem. 284:19392-19401(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK4 AND MAPK6.
[16]	"The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor." Kostenko S., Khan M.T., Sylte I., Moens U. Cell. Mol. Life Sci. 68:289-301(2011) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF THR-182.
[17]	"Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function." Kostenko S., Shiryaev A., Gerits N., Dumitriu G., Klenow H., Johannessen M., Moens U. Cell. Mol. Life Sci. 68:847-862(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-115, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-115.
[18]	"Distinct roles of MK2 and MK5 in cAMP/PKA- and stress/p38MAPK-induced heat shock protein 27 phosphorylation." Shiryaev A., Dumitriu G., Moens U. J. Mol. Signal. 6:4-4(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HSPB1.
[19]	"Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1." Zheng M., Wang Y.H., Wu X.N., Wu S.Q., Lu B.J., Dong M.Q., Zhang H., Sun P., Lin S.C., Guan K.L., Han J. Nat. Cell Biol. 13:263-272(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF RHEB, MUTAGENESIS OF LYS-51.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF039840 mRNA. Translation: AAC40047.1. AY533679 mRNA. Translation: AAS22330.1. AY533680 mRNA. Translation: AAS22331.2. AY533681 mRNA. Translation: AAS22332.1. AY533682 mRNA. Translation: AAS22333.1. AC155316 Genomic DNA. No translation available. BC019184 mRNA. Translation: AAH19184.1.
IPI	IPI00120068. IPI00462486. IPI00462487. IPI00462488. IPI00850634.
PIR	JC5952.
RefSeq	NP_034895.1. NM_010765.2.
UniGene	Mm.272206.
3D structure databases
ProteinModelPortal	O54992.
SMR	O54992. Positions 11-364.
ModBase	Search...
Protein-protein interaction databases
IntAct	O54992. 2 interactions.
PTM databases
PhosphoSite	O54992.
Proteomic databases
PRIDE	O54992.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031410; ENSMUSP00000031410; ENSMUSG00000029454. ENSMUST00000111782; ENSMUSP00000107412; ENSMUSG00000029454. ENSMUST00000111783; ENSMUSP00000107413; ENSMUSG00000029454. ENSMUST00000111786; ENSMUSP00000107416; ENSMUSG00000029454. ENSMUST00000153763; ENSMUSP00000119182; ENSMUSG00000029454.
GeneID	17165.
KEGG	mmu:17165.
UCSC	uc008zjq.1. mouse. uc008zjr.1. mouse. uc008zjs.1. mouse.
Organism-specific databases
CTD	8550.
MGI	MGI:1333110. Mapkapk5.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074510.
HOGENOM	HOG000233031.
HOVERGEN	HBG106948.
InParanoid	O54992.
KO	K04442.
OMA	QVTKQIA.
OrthoDB	EOG43JC4K.
Gene expression databases
ArrayExpress	O54992.
Bgee	O54992.
CleanEx	MM_MAPKAPK5.
Genevestigator	O54992.
GermOnline	ENSMUSG00000029454. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	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. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2607.
ChiTaRS	MAPKAPK5. mouse.
NextBio	291446.
SOURCE	Search...

Entry information

Entry name

MAPK5_MOUSE

Accession

Primary (citable) accession number: O54992
Secondary accession number(s): E9QQ45 , Q6QME4, Q6QME5, Q6QME6, Q6QME7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program