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O08678

- MARK1_RAT

UniProt

O08678 - MARK1_RAT

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Protein

Serine/threonine-protein kinase MARK1

Gene
Mark1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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 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).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication
ATP + [tau protein] = ADP + [tau protein] phosphate.

Cofactori

Magnesium By similarity.1 Publication

Enzyme regulationi

Activated by phosphorylation on Thr-215. Inhibited by phosphorylation at Ser-219.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei89 – 891ATP1 Publication
Active sitei182 – 1821Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi66 – 749ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. phosphatidic acid binding Source: UniProtKB
  4. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  5. phosphatidylserine binding Source: UniProtKB
  6. protein kinase activity Source: RGD
  7. protein serine/threonine kinase activity Source: UniProtKB
  8. tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  1. cytoskeleton organization Source: UniProtKB
  2. intracellular signal transduction Source: UniProtKB
  3. microtubule cytoskeleton organization Source: RGD
  4. neuron migration Source: UniProtKB
  5. protein phosphorylation Source: UniProtKB
  6. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Wnt signaling pathway

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Mark1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi619882. Mark1.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoskeleton Source: UniProtKB
  3. microtubule cytoskeleton Source: RGD
  4. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi89 – 891K → R: Loss of kinase activity. 1 Publication
Mutagenesisi215 – 2151T → A: Abolishes activation of serine/threonine-protein kinase activity and only basal activity remains. 2 Publications
Mutagenesisi215 – 2151T → A: Loss of kinase activity. 2 Publications
Mutagenesisi215 – 2151T → E: Induces an increase of the basal serine/threonine-protein kinase activity. 2 Publications
Mutagenesisi219 – 2191S → A or E: Loss of activity. 2 Publications
Mutagenesisi219 – 2191S → A: Loss of kinase activity. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 793793Serine/threonine-protein kinase MARK1PRO_0000086300Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51Phosphothreonine By similarity
Modified residuei208 – 2081Phosphothreonine By similarity
Modified residuei215 – 2151Phosphothreonine; by LKB1 and TAOK12 Publications
Modified residuei219 – 2191Phosphoserine; by GSK3-beta2 Publications
Modified residuei403 – 4031Phosphoserine By similarity
Modified residuei588 – 5881Phosphoserine By similarity
Modified residuei613 – 6131Phosphothreonine; by PKC/PRKCZ By similarity
Modified residuei666 – 6661Phosphoserine By similarity

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiO08678.

PTM databases

PhosphoSiteiO08678.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiO08678.
GenevestigatoriO08678.

Interactioni

Protein-protein interaction databases

BioGridi250617. 1 interaction.
STRINGi10116.ENSRNOP00000003198.

Structurei

3D structure databases

ProteinModelPortaliO08678.
SMRiO08678. Positions 54-371, 697-793.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini60 – 311252Protein kinaseAdd
BLAST
Domaini329 – 37042UBAAdd
BLAST
Domaini744 – 79350KA1Add
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 UBA domain.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiO08678.
KOiK08798.
PhylomeDBiO08678.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. 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]
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 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.

O08678-1 [UniParc]FASTAAdd to Basket

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MSARTPLPTV NERDTENHTS VDGYTETHIP PTKSSSRQNI PRCRNSITSA    50
TDEQPHIGNY RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS 100
LQKLFREVRI MKILNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA 150
HGRMKEKEAR AKFRQIVSAV QYCHQKCIVH RDLKAENLLL DADMNIKIAD 200
FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV WSLGVILYTL 250
VSGSLPFDGQ NLKELRERVL RGKYRVPFYM STDCENLLKK LLVLNPIKRG 300
SLEQIMKDRW MNVGHEEEEL KPYSEPELDL NDAKRIDIMV TMGFARDEIN 350
DALVSQKYDE VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST 400
LQSPAHLKVQ RSISANQKQR RFSDHAGPSI PPAVSYTKRP QANSVESEQK 450
EEWDKDTARR LGSTTVGSKS EVTASPLVGP DRKKSSAGPS NNVYSGGSMT 500
RRNTYVCERS TDRYAALQNG RDSSLTEMSA SSMSSTGSTV ASAGPSARPR 550
HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT AQRVPAASPS AHSISASTPD 600
RTRFPRGSSS RSTFHGEQLR ERRSAAYSGP PASPSHDTAA LAHARRGTST 650
GIISKITSKF VRRDPSEGEA SGRTDTARGS SGEPKDKEEG KEAKPRSLRF 700
TWSMKTTSSM DPNDMVREIR KVLDANTCDY EQRERFLLFC VHGDARQDSL 750
VQWEMEVCKL PRLSLNGVRF KRISGTSIAF KNIASKIANE LKL 793
Length:793
Mass (Da):88,235
Last modified:July 1, 1997 - v1
Checksum:iC5BCCACE0BB9A0A3
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z83868 mRNA. Translation: CAB06294.1.
RefSeqiNP_446399.1. NM_053947.1.
UniGeneiRn.21430.

Genome annotation databases

GeneIDi117016.
KEGGirno:117016.
UCSCiRGD:619882. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z83868 mRNA. Translation: CAB06294.1 .
RefSeqi NP_446399.1. NM_053947.1.
UniGenei Rn.21430.

3D structure databases

ProteinModelPortali O08678.
SMRi O08678. Positions 54-371, 697-793.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 250617. 1 interaction.
STRINGi 10116.ENSRNOP00000003198.

PTM databases

PhosphoSitei O08678.

Proteomic databases

PRIDEi O08678.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 117016.
KEGGi rno:117016.
UCSCi RGD:619882. rat.

Organism-specific databases

CTDi 4139.
RGDi 619882. Mark1.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233025.
HOVERGENi HBG052453.
InParanoidi O08678.
KOi K08798.
PhylomeDBi O08678.

Miscellaneous databases

NextBioi 619755.

Gene expression databases

ArrayExpressi O08678.
Genevestigatori O08678.

Family and domain databases

Gene3Di 3.30.310.80. 1 hit.
InterProi IPR028375. 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 ]
Pfami PF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view ]
SUPFAMi SSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS50032. 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 ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiMARK1_RAT
AccessioniPrimary (citable) accession number: O08678
Entry historyi
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 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

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