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P31152

- MK04_HUMAN

UniProt

P31152 - MK04_HUMAN

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Protein

Mitogen-activated protein kinase 4

Gene

MAPK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle By similarity.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-186.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATPPROSITE-ProRule annotation
Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: ProtInc
  3. protein homodimerization activity Source: UniProtKB
  4. protein kinase binding Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. MAPK cascade Source: GOC
  3. protein phosphorylation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 2681.
SignaLinkiP31152.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 4 (EC:2.7.11.24)
Short name:
MAP kinase 4
Short name:
MAPK 4
Alternative name(s):
Extracellular signal-regulated kinase 4
Short name:
ERK-4
MAP kinase isoform p63
Short name:
p63-MAPK
Gene namesi
Name:MAPK4
Synonyms:ERK4, PRKM4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:6878. MAPK4.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity
Note: Translocates to the cytoplasm following interaction with MAPKAPK5.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30623.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 587587Mitogen-activated protein kinase 4PRO_0000186254Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei186 – 1861Phosphoserine; by PAK1, PAK2 and PAK32 Publications

Post-translational modificationi

Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP31152.
PaxDbiP31152.
PRIDEiP31152.

PTM databases

PhosphoSiteiP31152.

Expressioni

Tissue specificityi

High expression in heart and brain.

Gene expression databases

BgeeiP31152.
CleanExiHS_MAPK4.
ExpressionAtlasiP31152. baseline and differential.
GenevestigatoriP31152.

Organism-specific databases

HPAiCAB025868.
HPA007461.

Interactioni

Subunit structurei

Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5 By similarity.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HSP90AB1P082382EBI-3906061,EBI-352572

Protein-protein interaction databases

BioGridi111582. 15 interactions.
IntActiP31152. 11 interactions.
STRINGi9606.ENSP00000383234.

Structurei

3D structure databases

ProteinModelPortaliP31152.
SMRiP31152. Positions 13-316.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 312293Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi186 – 1883SEG motif
Motifi328 – 3336FRIEDE motif

Domaini

The FRIEDE motif is required for docking MAPKAPK5.By similarity
In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiP31152.
KOiK06855.
OMAiRCQDASE.
PhylomeDBiP31152.
TreeFamiTF105098.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01771. ERK3ERK4MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P31152-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK
60 70 80 90 100
IALSDARSMK HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV
110 120 130 140 150
AYIVQEYMET DLARLLEQGT LAEEHAKLFM YQLLRGLKYI HSANVLHRDL
160 170 180 190 200
KPANIFISTE DLVLKIGDFG LARIVDQHYS HKGYLSEGLV TKWYRSPRLL
210 220 230 240 250
LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GAHELEQMQL ILETIPVIRE
260 270 280 290 300
EDKDELLRVM PSFVSSTWEV KRPLRKLLPE VNSEAIDFLE KILTFNPMDR
310 320 330 340 350
LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AANQSQLSNW
360 370 380 390 400
DTCSSRYPVS LSSDLEWRPD RCQDASEVQR DPRAGSAPLA EDVQVDPRKD
410 420 430 440 450
SHSSSERFLE QSHSSMERAF EADYGRSCDY KVGSPSYLDK LLWRDNKPHH
460 470 480 490 500
YSEPKLILDL SHWKQAAGAP PTATGLADTG AREDEPASLF LEIAQWVKST
510 520 530 540 550
QGGPEHASPP ADDPERRLSA SPPGRPAPVD GGASPQFDLD VFISRALKLC
560 570 580
TKPEDLPDNK LGDLNGACIP EHPGDLVQTE AFSKERW
Length:587
Mass (Da):65,922
Last modified:November 25, 2008 - v2
Checksum:i71DB32D1E63EF8EE
GO

Sequence cautioni

The sequence CAA42411.1 differs from that shown. Reason: Frameshift at several positions.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti220 – 2201A → S in AAH50299. (PubMed:15489334)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti38 – 381V → M.2 Publications
Corresponds to variant rs3752087 [ dbSNP | Ensembl ].
VAR_042254
Natural varianti371 – 3711R → P.1 Publication
Corresponds to variant rs3752089 [ dbSNP | Ensembl ].
VAR_042255

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X59727 mRNA. Translation: CAA42411.1. Frameshift.
AK295058 mRNA. Translation: BAG58107.1.
AC012433 Genomic DNA. No translation available.
AC090395 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW62976.1.
CH471096 Genomic DNA. Translation: EAW62977.1.
BC050299 mRNA. Translation: AAH50299.1.
BC117216 mRNA. Translation: AAI17217.1.
CCDSiCCDS42437.1.
PIRiS23429.
RefSeqiNP_001278968.1. NM_001292039.1.
NP_001278969.1. NM_001292040.1.
NP_002738.2. NM_002747.3.
XP_005258356.1. XM_005258299.1.
UniGeneiHs.433728.

Genome annotation databases

EnsembliENST00000400384; ENSP00000383234; ENSG00000141639.
ENST00000587800; ENSP00000467343; ENSG00000141639.
GeneIDi5596.
KEGGihsa:5596.
UCSCiuc002lev.3. human.

Polymorphism databases

DMDMi215274102.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X59727 mRNA. Translation: CAA42411.1 . Frameshift.
AK295058 mRNA. Translation: BAG58107.1 .
AC012433 Genomic DNA. No translation available.
AC090395 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW62976.1 .
CH471096 Genomic DNA. Translation: EAW62977.1 .
BC050299 mRNA. Translation: AAH50299.1 .
BC117216 mRNA. Translation: AAI17217.1 .
CCDSi CCDS42437.1.
PIRi S23429.
RefSeqi NP_001278968.1. NM_001292039.1.
NP_001278969.1. NM_001292040.1.
NP_002738.2. NM_002747.3.
XP_005258356.1. XM_005258299.1.
UniGenei Hs.433728.

3D structure databases

ProteinModelPortali P31152.
SMRi P31152. Positions 13-316.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111582. 15 interactions.
IntActi P31152. 11 interactions.
STRINGi 9606.ENSP00000383234.

Chemistry

BindingDBi P31152.
ChEMBLi CHEMBL5759.
GuidetoPHARMACOLOGYi 2091.

PTM databases

PhosphoSitei P31152.

Polymorphism databases

DMDMi 215274102.

Proteomic databases

MaxQBi P31152.
PaxDbi P31152.
PRIDEi P31152.

Protocols and materials databases

DNASUi 5596.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000400384 ; ENSP00000383234 ; ENSG00000141639 .
ENST00000587800 ; ENSP00000467343 ; ENSG00000141639 .
GeneIDi 5596.
KEGGi hsa:5596.
UCSCi uc002lev.3. human.

Organism-specific databases

CTDi 5596.
GeneCardsi GC18P048125.
H-InvDB HIX0027373.
HGNCi HGNC:6878. MAPK4.
HPAi CAB025868.
HPA007461.
MIMi 176949. gene.
neXtProti NX_P31152.
PharmGKBi PA30623.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074298.
HOGENOMi HOG000233020.
HOVERGENi HBG104376.
InParanoidi P31152.
KOi K06855.
OMAi RCQDASE.
PhylomeDBi P31152.
TreeFami TF105098.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 2681.
SignaLinki P31152.

Miscellaneous databases

GeneWikii MAPK4.
GenomeRNAii 5596.
NextBioi 21720.
PROi P31152.
SOURCEi Search...

Gene expression databases

Bgeei P31152.
CleanExi HS_MAPK4.
ExpressionAtlasi P31152. baseline and differential.
Genevestigatori P31152.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01771. ERK3ERK4MAPK.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Heterogeneous expression of four MAP kinase isoforms in human tissues."
    Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J.
    FEBS Lett. 304:170-178(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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].
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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], VARIANT MET-38.
    Tissue: Brain and Cerebellum.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway."
    Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L., Thibault P., Meloche S.
    J. Biol. Chem. 286:6470-6478(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-186.
  8. "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: VARIANTS [LARGE SCALE ANALYSIS] MET-38 AND PRO-371.

Entry informationi

Entry nameiMK04_HUMAN
AccessioniPrimary (citable) accession number: P31152
Secondary accession number(s): A1A4C4, Q0VG04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 25, 2008
Last modified: October 29, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3