MAP kinase-activated protein kinase 5

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

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

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General annotation (Comments)

Function	Mediates stress-induced small heat shock protein 27 phosphorylation By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	In vivo, p38 alpha and beta-dependent phosphorylation increases PRAK activity By similarity. In vitro, ERK also activates MAPKAPK5. 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 By similarity. Ref.1
Subunit structure	Interacts with SQSTM1 By similarity.
Subcellular location	Cytoplasm Probable. Nucleus By similarity. Note: Also observed in the nucleus By similarity.
Tissue specificity	Expressed ubiquitously. Ref.1
Post-translational modification	Phosphorylated on Thr-182; which is the regulatory phosphorylation site and is located on the T-loop/loop 12 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.

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Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSPB1	P04792	1	EBI-1202132,EBI-352682	From a different organism.
Tp53	P02340	1	EBI-1202132,EBI-474016

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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.

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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 By similarity

Amino acid modifications

Modified residue

182

1

Phosphothreonine By similarity

Modified residue

214

1

Phosphothreonine 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-/ERK-induced activation. Ref.1

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (MK-5 type 1) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 45441A735075B247 Show »	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 « Hide
Isoform 2 (MK-5 type 3). Checksum: 7EEAF061669A3F61 Show »	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 « Hide
Isoform 3 (MK-5 type 4). Checksum: 25BF2CB86528174D Show »	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 « Hide
Isoform 4 (MK-5 type 5). Checksum: BADC2B6FEB4AEA4A Show »	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 « Hide
Isoform 5 (MK-5 type 2). Checksum: AC171E324E40A3D4 Show »	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 « Hide

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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: 9480836] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF LYS-51, ENZYME REGULATION. 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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N-3. Tissue: Mammary tumor.
+	Additional computationally mapped references.

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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. BC019184 mRNA. Translation: AAH19184.1.
IPI	IPI00120068. IPI00462486. IPI00462487. IPI00462488. IPI00850634.
PIR	JC5952.
RefSeq	NP_034895.1. XP_001479292.1.
UniGene	Mm.272206
3D structure databases
SMR	O54992. Positions 11-362.
ModBase	Search...
Protein-protein interaction databases
IntAct	O54992. 2 interactions.
STRING	O54992.
PTM databases
PhosphoSite	O54992.
Proteomic databases
PRIDE	O54992.
Genome annotation databases
Ensembl	ENSMUST00000031410; ENSMUSP00000031410; ENSMUSG00000029454; Mus musculus. [Genome view] ENSMUST00000111786; ENSMUSP00000107416; ENSMUSG00000029454; Mus musculus. [Genome view] ENSMUST00000111787; ENSMUSP00000107417; ENSMUSG00000029454; Mus musculus. [Genome view]
GeneID	17165.
KEGG	mmu:100047833. mmu:17165.
UCSC	uc008zjq.1. mouse. uc008zjr.1. mouse. uc008zjs.1. mouse.
Organism-specific databases
CTD	17165.
MGI	MGI:1333110. Mapkapk5.
Phylogenomic databases
eggNOG	roNOG12773.
HOGENOM	HBG755340.
HOVERGEN	O54992.
InParanoid	O54992.
OMA	EYSINWT.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Gene expression databases
ArrayExpress	O54992.
Bgee	O54992.
CleanEx	MM_MAPKAPK5.
Genevestigator	O54992.
GermOnline	ENSMUSG00000029454. Mus musculus.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_prot_kinase-like. IPR011009. Kinase-like_dom. IPR020646. MAP_kin-act_prot_kinase. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
PANTHER	PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. PTHR22982:SF22. MAP_kin-act_prot_kinase. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	291446.
SOURCE	Search...

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Entry information

Entry name

MAPK5_MOUSE

Accession

Primary (citable) accession number: O54992
Secondary accession number(s): Q6QME4

Q6QME7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	June 1, 1998
Last modified:	February 9, 2010
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents