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O08678 (MARK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase MARK1

EC=2.7.11.1
EC=2.7.11.26
Alternative name(s):
MAP/microtubule affinity-regulating kinase 1
Gene names
Name:Mark1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length793 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Ref.1 Ref.2 Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1

ATP + [tau protein] = ADP + [tau protein] phosphate.

Cofactor

Magnesium By similarity. Ref.1

Enzyme regulation

Activated by phosphorylation on Thr-215. Inhibited by phosphorylation at Ser-219. Ref.2

Subcellular location

Cell membrane; Peripheral membrane protein By similarity. Cytoplasmcytoskeleton. Note: Appears to localize to an intracellular network. Ref.1

Tissue specificity

Highly expressed in brain and spleen and at lower levels in kidney and skeletal muscle. Ref.1

Domain

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.

The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) By similarity.

Post-translational modification

Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity By similarity. Phosphorylated at Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by GSK3-beta (GSK3B) inhibits the kinase activity. Ref.1 Ref.2

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 KA1 (kinase-associated) domain.

Contains 1 protein kinase domain.

Contains 1 UBA domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
   LigandATP-binding
Lipid-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cytoskeleton organization

Inferred from direct assay Ref.1. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

microtubule cytoskeleton organization

Inferred from direct assay Ref.1. Source: RGD

neuron migration

Inferred from direct assay Ref.3. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

cytoskeleton

Inferred from direct assay Ref.1. Source: UniProtKB

microtubule cytoskeleton

Non-traceable author statement Ref.1. Source: RGD

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.1. Source: UniProtKB

phosphatidic acid binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylserine binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.1. Source: RGD

protein serine/threonine kinase activity

Inferred from direct assay Ref.3Ref.1. Source: UniProtKB

tau-protein kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 793793Serine/threonine-protein kinase MARK1
PRO_0000086300

Regions

Domain60 – 311252Protein kinase
Domain329 – 37042UBA
Domain744 – 79350KA1
Nucleotide binding66 – 749ATP By similarity UniProtKB Q9H0K1

Sites

Active site1821Proton acceptor By similarity UniProtKB Q9H0K1
Binding site891ATP Ref.1

Amino acid modifications

Modified residue51Phosphothreonine By similarity
Modified residue2081Phosphothreonine By similarity
Modified residue2151Phosphothreonine; by LKB1 and TAOK1 Ref.1 Ref.2
Modified residue2191Phosphoserine; by GSK3-beta Ref.1 Ref.2
Modified residue4031Phosphoserine By similarity
Modified residue5881Phosphoserine By similarity
Modified residue6131Phosphothreonine; by PKC/PRKCZ By similarity
Modified residue6661Phosphoserine By similarity

Experimental info

Mutagenesis891K → R: Loss of kinase activity. Ref.1
Mutagenesis2151T → A: Abolishes activation of serine/threonine-protein kinase activity and only basal activity remains. Ref.1 Ref.2
Mutagenesis2151T → A: Loss of kinase activity. Ref.1 Ref.2
Mutagenesis2151T → E: Induces an increase of the basal serine/threonine-protein kinase activity. Ref.1 Ref.2
Mutagenesis2191S → A or E: Loss of activity. Ref.1 Ref.2
Mutagenesis2191S → A: Loss of kinase activity. Ref.1 Ref.2

Sequences

Sequence LengthMass (Da)Tools
O08678 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: C5BCCACE0BB9A0A3

FASTA79388,235
        10         20         30         40         50         60 
MSARTPLPTV NERDTENHTS VDGYTETHIP PTKSSSRQNI PRCRNSITSA TDEQPHIGNY 

        70         80         90        100        110        120 
RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIV 

       130        140        150        160        170        180 
KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR AKFRQIVSAV QYCHQKCIVH 

       190        200        210        220        230        240 
RDLKAENLLL DADMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV 

       250        260        270        280        290        300 
WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRVPFYM STDCENLLKK LLVLNPIKRG 

       310        320        330        340        350        360 
SLEQIMKDRW MNVGHEEEEL KPYSEPELDL NDAKRIDIMV TMGFARDEIN DALVSQKYDE 

       370        380        390        400        410        420 
VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR 

       430        440        450        460        470        480 
RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWDKDTARR LGSTTVGSKS EVTASPLVGP 

       490        500        510        520        530        540 
DRKKSSAGPS NNVYSGGSMT RRNTYVCERS TDRYAALQNG RDSSLTEMSA SSMSSTGSTV 

       550        560        570        580        590        600 
ASAGPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT AQRVPAASPS AHSISASTPD 

       610        620        630        640        650        660 
RTRFPRGSSS RSTFHGEQLR ERRSAAYSGP PASPSHDTAA LAHARRGTST GIISKITSKF 

       670        680        690        700        710        720 
VRRDPSEGEA SGRTDTARGS SGEPKDKEEG KEAKPRSLRF TWSMKTTSSM DPNDMVREIR 

       730        740        750        760        770        780 
KVLDANTCDY EQRERFLLFC VHGDARQDSL VQWEMEVCKL PRLSLNGVRF KRISGTSIAF 

       790 
KNIASKIANE LKL 

« Hide

References

[1]"MARK - a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption."
Drewes G., Ebneth A., Preuss U., Mandelkow E.-M., Mandelkow E.
Cell 89:297-308(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-215 AND SER-219, MUTAGENESIS OF LYS-89; THR-215 AND SER-219.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1."
Timm T., Li X.Y., Biernat J., Jiao J., Mandelkow E., Vandekerckhove J., Mandelkow E.M.
EMBO J. 22:5090-5101(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-215 AND SER-219, MUTAGENESIS OF THR-215 AND SER-219.
[3]"Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons."
Schaar B.T., Kinoshita K., McConnell S.K.
Neuron 41:203-213(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF DCX.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z83868 mRNA. Translation: CAB06294.1.
RefSeqNP_446399.1. NM_053947.1.
UniGeneRn.21430.

3D structure databases

ProteinModelPortalO08678.
SMRO08678. Positions 54-371, 697-793.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250617. 1 interaction.
STRING10116.ENSRNOP00000003198.

PTM databases

PhosphoSiteO08678.

Proteomic databases

PRIDEO08678.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID117016.
KEGGrno:117016.
UCSCRGD:619882. rat.

Organism-specific databases

CTD4139.
RGD619882. Mark1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233025.
HOVERGENHBG052453.
InParanoidO08678.
KOK08798.
PhylomeDBO08678.

Gene expression databases

ArrayExpressO08678.
GenevestigatorO08678.

Family and domain databases

Gene3D3.30.310.80. 1 hit.
InterProIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]
PfamPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50032. 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]
ProtoNetSearch...

Other

NextBio619755.

Entry information

Entry nameMARK1_RAT
AccessionPrimary (citable) accession number: O08678
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families