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O08678

- MARK1_RAT

UniProt

O08678 - MARK1_RAT

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
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    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

    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 PublicationPROSITE-ProRule annotation
    Active sitei182 – 1821Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi66 – 749ATPBy similarityPROSITE-ProRule annotation

    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

    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:Mark1Imported
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi619882. Mark1.

    Subcellular locationi

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

    GO - Cellular componenti

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

    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 – 51PhosphothreonineBy similarity
    Modified residuei208 – 2081PhosphothreonineBy similarity
    Modified residuei215 – 2151Phosphothreonine; by LKB1 and TAOK12 Publications
    Modified residuei219 – 2191Phosphoserine; by GSK3-beta2 Publications
    Modified residuei403 – 4031PhosphoserineBy similarity
    Modified residuei588 – 5881PhosphoserineBy similarity
    Modified residuei613 – 6131Phosphothreonine; by PKC/PRKCZBy similarity
    Modified residuei666 – 6661PhosphoserineBy 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.By similarity2 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini60 – 311252Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini329 – 37042UBAPROSITE-ProRule annotationAdd
    BLAST
    Domaini744 – 79350KA1PROSITE-ProRule annotationAdd
    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.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.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

    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

    « Hide

    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-DawleyImported.
      Tissue: BrainImported.
    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: October 1, 2014
    This is version 111 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