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Q5U2N4

- MKNK2_RAT

UniProt

Q5U2N4 - MKNK2_RAT

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Protein

MAP kinase-interacting serine/threonine-protein kinase 2

Gene

Mknk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli

Functioni

Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during spermatogenesis. Displays a high basal kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarity
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by CGP57380 and staurosporine.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei113 – 1131ATPPROSITE-ProRule annotation
Active sitei205 – 2051Proton acceptorPROSITE-ProRule annotation
Binding sitei209 – 2091StaurosporineBy similarity
Metal bindingi299 – 2991ZincBy similarity
Metal bindingi311 – 3111ZincBy similarity
Metal bindingi314 – 3141ZincBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi90 – 989ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. cellular response to arsenic-containing substance Source: Ensembl
  2. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  3. hemopoiesis Source: Ensembl
  4. intracellular signal transduction Source: Ensembl
  5. regulation of translation Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Translation regulation

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-interacting serine/threonine-protein kinase 2 (EC:2.7.11.1)
Alternative name(s):
MAP kinase signal-integrating kinase 2
Short name:
MAPK signal-integrating kinase 2
Short name:
Mnk2
Gene namesi
Name:Mknk2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 7

Organism-specific databases

RGDi1305728. Mknk2.

Subcellular locationi

Cytoplasm By similarity. NucleusPML body By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleolus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 459459MAP kinase-interacting serine/threonine-protein kinase 2PRO_0000226965Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei244 – 2441PhosphothreonineBy similarity
Modified residuei249 – 2491PhosphothreonineBy similarity
Modified residuei379 – 3791PhosphothreonineBy similarity
Modified residuei431 – 4311PhosphoserineBy similarity
Modified residuei434 – 4341PhosphoserineBy similarity
Modified residuei446 – 4461PhosphoserineBy similarity
Modified residuei450 – 4501PhosphothreonineBy similarity

Post-translational modificationi

Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As2O3 treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Expressioni

Gene expression databases

GenevestigatoriQ5U2N4.

Interactioni

Subunit structurei

Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ER2K. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ER2K protects it from dephosphorylation and inactivation. Interacts with ESR2 and EIF4E in the nucleus (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000039672.

Structurei

3D structure databases

ProteinModelPortaliQ5U2N4.
SMRiQ5U2N4. Positions 71-369.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini84 – 368285Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni160 – 1623Staurosporine bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi60 – 667Nuclear localization signalBy similarity
Motifi438 – 4425MAP kinase bindingBy similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120509.
HOGENOMiHOG000231140.
HOVERGENiHBG106949.
InParanoidiQ5U2N4.
KOiK04372.
OMAiVQKKTAE.
OrthoDBiEOG7SV0VB.
PhylomeDBiQ5U2N4.
TreeFamiTF314050.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
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]
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.

Q5U2N4-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVQKRTAELQ GFHRSFKGQN PFELAFTLDP AQHGDSDFSP QCEARPDMPS
60 70 80 90 100
SQPIDIPDAK KRGRKKKRCR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT
110 120 130 140 150
CVNLITNQEY AVKIIEKQLG HIRSRVFREV EMLYQCQGHR NVLELIEFFE
160 170 180 190 200
EEDRFYLVFE KMRGGSILSH IHRRRHFNEL EASVVVQDVA SALDFLHNKG
210 220 230 240 250
IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS PISTPELLTP
260 270 280 290 300
CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGHCG
310 320 330 340 350
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWSHISFA AKDLISKLLV
360 370 380 390 400
RDAKQRLSAA QVLQHPWVQG CAPENTLPTP LVLQRNSCAK DLTSFAAEAI
410 420 430 440 450
AMNRQLAQCE EDAGQDQPVL IRATSRCLQL SPPSQSKLAQ RRQRASLSAT

PVVLVGDRV
Length:459
Mass (Da):51,574
Last modified:December 7, 2004 - v1
Checksum:i7D26909FB98AC34D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC085941 mRNA. Translation: AAH85941.1.
RefSeqiNP_001011985.1. NM_001011985.1.
XP_006240945.1. XM_006240883.2.
UniGeneiRn.231923.

Genome annotation databases

EnsembliENSRNOT00000041106; ENSRNOP00000039672; ENSRNOG00000029028.
GeneIDi299618.
KEGGirno:299618.
UCSCiRGD:1305728. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC085941 mRNA. Translation: AAH85941.1 .
RefSeqi NP_001011985.1. NM_001011985.1.
XP_006240945.1. XM_006240883.2.
UniGenei Rn.231923.

3D structure databases

ProteinModelPortali Q5U2N4.
SMRi Q5U2N4. Positions 71-369.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000039672.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000041106 ; ENSRNOP00000039672 ; ENSRNOG00000029028 .
GeneIDi 299618.
KEGGi rno:299618.
UCSCi RGD:1305728. rat.

Organism-specific databases

CTDi 2872.
RGDi 1305728. Mknk2.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00770000120509.
HOGENOMi HOG000231140.
HOVERGENi HBG106949.
InParanoidi Q5U2N4.
KOi K04372.
OMAi VQKKTAE.
OrthoDBi EOG7SV0VB.
PhylomeDBi Q5U2N4.
TreeFami TF314050.

Miscellaneous databases

NextBioi 645528.
PROi Q5U2N4.

Gene expression databases

Genevestigatori Q5U2N4.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
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 ]
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

  1. "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].
    Tissue: Lung.

Entry informationi

Entry nameiMKNK2_RAT
AccessioniPrimary (citable) accession number: Q5U2N4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: December 7, 2004
Last modified: November 26, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3