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Protein

Serine/threonine-protein kinase MARK1

Gene

Mark1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Mg2+By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei89ATPPROSITE-ProRule annotation1 Publication1
Active sitei182Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi66 – 74ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • phosphatidic acid binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • phosphatidylserine binding Source: UniProtKB
  • protein kinase activity Source: RGD
  • protein serine/threonine kinase activity Source: UniProtKB
  • tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  • cytoskeleton organization Source: UniProtKB
  • establishment of cell polarity Source: InterPro
  • intracellular signal transduction Source: UniProtKB
  • microtubule cytoskeleton organization Source: RGD
  • neuron migration Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processWnt signaling pathway
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi619882 Mark1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi89K → R: Loss of kinase activity. 1 Publication1
Mutagenesisi215T → A: Abolishes activation of serine/threonine-protein kinase activity and only basal activity remains. 2 Publications1
Mutagenesisi215T → A: Loss of kinase activity. 2 Publications1
Mutagenesisi215T → E: Induces an increase of the basal serine/threonine-protein kinase activity. 2 Publications1
Mutagenesisi219S → A or E: Loss of activity. 2 Publications1
Mutagenesisi219S → A: Loss of kinase activity. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863001 – 793Serine/threonine-protein kinase MARK1Add BLAST793

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphothreonineBy similarity1
Modified residuei208PhosphothreonineBy similarity1
Modified residuei215Phosphothreonine; by LKB1 and TAOK12 Publications1
Modified residuei219Phosphoserine; by GSK3-beta2 Publications1
Modified residuei382PhosphoserineBy similarity1
Modified residuei390PhosphoserineBy similarity1
Modified residuei393PhosphoserineBy similarity1
Modified residuei403PhosphoserineBy similarity1
Modified residuei423PhosphoserineBy similarity1
Modified residuei444PhosphoserineCombined sources1
Modified residuei475PhosphoserineBy similarity1
Modified residuei588PhosphoserineBy similarity1
Modified residuei613Phosphothreonine; by PKC/PRKCZBy similarity1
Modified residuei666PhosphoserineBy similarity1

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

PaxDbiO08678
PRIDEiO08678

PTM databases

iPTMnetiO08678
PhosphoSitePlusiO08678

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSRNOG00000002339
ExpressionAtlasiO08678 baseline and differential
GenevisibleiO08678 RN

Interactioni

Protein-protein interaction databases

BioGridi250617, 1 interactor
STRINGi10116.ENSRNOP00000003198

Structurei

3D structure databases

ProteinModelPortaliO08678
SMRiO08678
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini60 – 311Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini329 – 370UBAPROSITE-ProRule annotationAdd BLAST42
Domaini744 – 793KA1PROSITE-ProRule annotationAdd BLAST50

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

Phylogenomic databases

eggNOGiKOG0586 Eukaryota
ENOG410XNQ0 LUCA
GeneTreeiENSGT00900000140806
HOGENOMiHOG000233025
HOVERGENiHBG052453
InParanoidiO08678
KOiK08798
OMAiLPRCRNS
OrthoDBiEOG091G0D1E
PhylomeDBiO08678

Family and domain databases

InterProiView protein in InterPro
IPR028375 KA1/Ssp2_C
IPR001772 KA1_dom
IPR011009 Kinase-like_dom_sf
IPR033627 MARK1
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
PANTHERiPTHR24346:SF21 PTHR24346:SF21, 1 hit
PfamiView protein in Pfam
PF02149 KA1, 1 hit
PF00069 Pkinase, 1 hit
PF00627 UBA, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00165 UBA, 1 hit
SUPFAMiSSF103243 SSF103243, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

Sequencei

Sequence statusi: Complete.

O08678-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSARTPLPTV NERDTENHTS VDGYTETHIP PTKSSSRQNI PRCRNSITSA
60 70 80 90 100
TDEQPHIGNY RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS
110 120 130 140 150
LQKLFREVRI MKILNHPNIV KLFEVIETEK TLYLVMEYAS GGEVFDYLVA
160 170 180 190 200
HGRMKEKEAR AKFRQIVSAV QYCHQKCIVH RDLKAENLLL DADMNIKIAD
210 220 230 240 250
FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV WSLGVILYTL
260 270 280 290 300
VSGSLPFDGQ NLKELRERVL RGKYRVPFYM STDCENLLKK LLVLNPIKRG
310 320 330 340 350
SLEQIMKDRW MNVGHEEEEL KPYSEPELDL NDAKRIDIMV TMGFARDEIN
360 370 380 390 400
DALVSQKYDE VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST
410 420 430 440 450
LQSPAHLKVQ RSISANQKQR RFSDHAGPSI PPAVSYTKRP QANSVESEQK
460 470 480 490 500
EEWDKDTARR LGSTTVGSKS EVTASPLVGP DRKKSSAGPS NNVYSGGSMT
510 520 530 540 550
RRNTYVCERS TDRYAALQNG RDSSLTEMSA SSMSSTGSTV ASAGPSARPR
560 570 580 590 600
HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT AQRVPAASPS AHSISASTPD
610 620 630 640 650
RTRFPRGSSS RSTFHGEQLR ERRSAAYSGP PASPSHDTAA LAHARRGTST
660 670 680 690 700
GIISKITSKF VRRDPSEGEA SGRTDTARGS SGEPKDKEEG KEAKPRSLRF
710 720 730 740 750
TWSMKTTSSM DPNDMVREIR KVLDANTCDY EQRERFLLFC VHGDARQDSL
760 770 780 790
VQWEMEVCKL PRLSLNGVRF KRISGTSIAF KNIASKIANE LKL
Length:793
Mass (Da):88,235
Last modified:July 1, 1997 - v1
Checksum:iC5BCCACE0BB9A0A3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z83868 mRNA Translation: CAB06294.1
RefSeqiNP_446399.1, NM_053947.1
UniGeneiRn.21430

Genome annotation databases

EnsembliENSRNOT00000003198; ENSRNOP00000003198; ENSRNOG00000002339
GeneIDi117016
KEGGirno:117016
UCSCiRGD:619882 rat

Similar proteinsi

Entry informationi

Entry nameiMARK1_RAT
AccessioniPrimary (citable) accession number: O08678
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: July 1, 1997
Last modified: May 23, 2018
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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