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Protein

Serine/threonine-protein kinase MARK2

Gene

Mark2

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

Functioni

Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity
ATP + [tau protein] = ADP + [tau protein] phosphate.

Cofactori

Mg2+By similarity

Enzyme regulationi

Inhibited by hymenialdisine (By similarity). Activated by phosphorylation on Thr-208 by STK11/LKB1 and TAOK1. Inhibited by phosphorylation at Ser-212 or Thr-539. Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei82ATPPROSITE-ProRule annotationBy similarity1
Active sitei175Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi59 – 67ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • lipid binding Source: UniProtKB-KW
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • tau-protein kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase MARK2 (EC:2.7.11.1, EC:2.7.11.26)
Alternative name(s):
ELKL motif kinase 1
Short name:
EMK-1
MAP/microtubule affinity-regulating kinase 2
Gene namesi
Name:Mark2Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi708483. Mark2.

Subcellular locationi

  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
  • Cytoplasm By similarity
  • Lateral cell membrane By similarity
  • Cytoplasmcytoskeleton By similarity

  • Note: Phosphorylation at Thr-539 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm.By similarity

GO - Cellular componenti

  • actin filament Source: UniProtKB
  • cytoplasm Source: UniProtKB-SubCell
  • lateral plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • microtubule bundle Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi82K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi91 – 93SSS → AAA: Loss of phosphorylation by CaMK1, decrease in kinase activity and ability to promote neurite outgrowth; when associated with A-294. 1 Publication3
Mutagenesisi208T → A: Abolishes activation of serine/threonine-protein kinase activity and only basal activity remains. 3 Publications1
Mutagenesisi208T → E: Phosphomimetic mutant that leads to activation but not in presence of GSK3-beta. 3 Publications1
Mutagenesisi212S → A: Loss of activity; neither activated by TAOK1 nor by STK11/LKB1. 3 Publications1
Mutagenesisi294T → A: Loss of phosphorylation by CaMK1, decrease in kinase activity and ability to promote neurite outgrowth; when associated with 91-A--A-93. 1 Publication1
Mutagenesisi539T → A: Abolishes phosphorylation by PKC/PRKCZ. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863031 – 722Serine/threonine-protein kinase MARK2Add BLAST722

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40PhosphoserineBy similarity1
Modified residuei58Phosphothreonine; by autocatalysis1 Publication1
Modified residuei91Phosphoserine; by CaMK11 Publication1
Modified residuei92Phosphoserine; by CaMK11 Publication1
Modified residuei93Phosphoserine; by CaMK11 Publication1
Modified residuei208Phosphothreonine; by LKB1 and TAOK11 Publication1
Modified residuei212Phosphoserine; by GSK3-beta3 Publications1
Modified residuei274Phosphoserine; by autocatalysis1 Publication1
Modified residuei275Phosphothreonine; by autocatalysis1 Publication1
Modified residuei294Phosphothreonine; by CaMK11 Publication1
Modified residuei408PhosphoserineCombined sources1
Modified residuei409PhosphoserineCombined sources1
Modified residuei453PhosphoserineCombined sources1
Modified residuei464PhosphothreonineBy similarity1
Modified residuei483PhosphoserineCombined sources1
Modified residuei490PhosphoserineBy similarity1
Modified residuei512PhosphoserineBy similarity1
Modified residuei514PhosphoserineBy similarity1
Modified residuei535PhosphoserineBy similarity1
Modified residuei539Phosphothreonine; by PKC/PRKCZ1 Publication1
Modified residuei562PhosphoserineBy similarity1
Modified residuei656PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-539 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm.5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO08679.
PRIDEiO08679.

PTM databases

iPTMnetiO08679.
PhosphoSitePlusiO08679.

Expressioni

Gene expression databases

BgeeiENSRNOG00000021184.
ExpressionAtlasiO08679. baseline and differential.
GenevisibleiO08679. RN.

Interactioni

Subunit structurei

Homodimer. Interacts (when phosphorylated at Thr-539) with YWHAZ. Interacts with MTCL1; the interaction is direct and increases MARK2 microtubule-binding ability (By similarity). Interacts with PAK5; leading to inhibit the protein kinase activity.By similarity2 Publications

Protein-protein interaction databases

DIPiDIP-29029N.
STRINGi10116.ENSRNOP00000028763.

Structurei

Secondary structure

1722
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 61Combined sources9
Beta strandi63 – 72Combined sources10
Turni73 – 75Combined sources3
Beta strandi78 – 85Combined sources8
Helixi86 – 88Combined sources3
Helixi91 – 106Combined sources16
Beta strandi115 – 120Combined sources6
Beta strandi122 – 130Combined sources9
Helixi137 – 144Combined sources8
Helixi149 – 168Combined sources20
Helixi178 – 180Combined sources3
Beta strandi181 – 183Combined sources3
Beta strandi189 – 191Combined sources3
Beta strandi194 – 196Combined sources3
Beta strandi202 – 205Combined sources4
Turni208 – 211Combined sources4
Helixi213 – 215Combined sources3
Helixi219 – 222Combined sources4
Helixi229 – 245Combined sources17
Helixi255 – 264Combined sources10
Helixi275 – 284Combined sources10
Helixi289 – 291Combined sources3
Helixi295 – 298Combined sources4
Helixi302 – 305Combined sources4
Helixi326 – 334Combined sources9
Helixi339 – 347Combined sources9
Helixi353 – 361Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Y8GX-ray2.50A/B39-364[»]
1ZMUX-ray2.90A/B39-364[»]
1ZMVX-ray3.10A/B39-364[»]
1ZMWX-ray2.80A/B39-364[»]
2R0IX-ray2.20A/B39-364[»]
2WZJX-ray2.79A/B/C/D/E/F39-364[»]
ProteinModelPortaliO08679.
SMRiO08679.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08679.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 304Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini323 – 362UBAPROSITE-ProRule annotationAdd BLAST40
Domaini673 – 722KA1PROSITE-ProRule annotationAdd BLAST50

Domaini

The KA1 domain mediates binding to phospholipids and targeting to membranes.By similarity
The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity).By similarity

Sequence similaritiesi

Contains 1 KA1 (kinase-associated) domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00790000122947.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiO08679.
KOiK08798.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR033624. MARK/par1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PANTHERiPTHR24346. PTHR24346. 1 hit.
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08679-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMLRGRNS ATSADEQPHI
60 70 80 90 100
GNYRLLKTIG KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE
110 120 130 140 150
VRIMKVLNHP NIVKLFEVIE TEKTLYLVME YASGGEVFDY LVAHGRMKEK
160 170 180 190 200
EARAKFRQIV SAVQYCHQKF IVHRDLKAEN LLLDADMNIK IADFGFSNEF
210 220 230 240 250
TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL YTLVSGSLPF
260 270 280 290 300
DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
310 320 330 340 350
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR
360 370 380 390 400
YNEVMATYLL LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS
410 420 430 440 450
ANPKQRRSSD QAVPAIPTSN SYSKKTQSNN AENKRPEEET GRKASSTAKV
460 470 480 490 500
PASPLPGLDR KKTTPTPSTN SVLSTSTNRS RNSPLLDRAS LGQASIQNGK
510 520 530 540 550
DSTAPQRVPV ASPSAHNISS SSGAPDRTNF PRGVSSRSTF HAGQLRQVRD
560 570 580 590 600
QQNLPFGVTP ASPSGHSQGR RGASGSIFSK FTSKFVRRNL NEPESKDRVE
610 620 630 640 650
TLRPHVVGGG GTDKEKEEFR EAKPRSLRFT WSMKTTSSME PNEMMREIRK
660 670 680 690 700
VLDANSCQSE LHERYMLLCV HGTPGHENFV QWEMEVCKLP RLSLNGVRFK
710 720
RISGTSMAFK NIASKIANEL KL
Length:722
Mass (Da):80,872
Last modified:July 1, 1997 - v1
Checksum:i2CBAFD1C38007ECC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z83869 mRNA. Translation: CAB06295.1.
RefSeqiNP_067731.1. NM_021699.1.
UniGeneiRn.42926.

Genome annotation databases

EnsembliENSRNOT00000028763; ENSRNOP00000028763; ENSRNOG00000021184.
GeneIDi60328.
KEGGirno:60328.
UCSCiRGD:708483. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z83869 mRNA. Translation: CAB06295.1.
RefSeqiNP_067731.1. NM_021699.1.
UniGeneiRn.42926.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Y8GX-ray2.50A/B39-364[»]
1ZMUX-ray2.90A/B39-364[»]
1ZMVX-ray3.10A/B39-364[»]
1ZMWX-ray2.80A/B39-364[»]
2R0IX-ray2.20A/B39-364[»]
2WZJX-ray2.79A/B/C/D/E/F39-364[»]
ProteinModelPortaliO08679.
SMRiO08679.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-29029N.
STRINGi10116.ENSRNOP00000028763.

PTM databases

iPTMnetiO08679.
PhosphoSitePlusiO08679.

Proteomic databases

PaxDbiO08679.
PRIDEiO08679.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028763; ENSRNOP00000028763; ENSRNOG00000021184.
GeneIDi60328.
KEGGirno:60328.
UCSCiRGD:708483. rat.

Organism-specific databases

CTDi2011.
RGDi708483. Mark2.

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00790000122947.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiO08679.
KOiK08798.

Miscellaneous databases

EvolutionaryTraceiO08679.
PROiO08679.

Gene expression databases

BgeeiENSRNOG00000021184.
ExpressionAtlasiO08679. baseline and differential.
GenevisibleiO08679. RN.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR033624. MARK/par1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PANTHERiPTHR24346. PTHR24346. 1 hit.
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMARK2_RAT
AccessioniPrimary (citable) accession number: O08679
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: July 1, 1997
Last modified: November 2, 2016
This is version 138 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.