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Protein

Serine/threonine-protein kinase MARK2

Gene

Mark2

Organism
Mus musculus (Mouse)
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 (By similarity).By similarity

Catalytic activityi

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

Cofactori

Mg2+By similarity

Enzyme regulationi

Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-593. Inhibited by hymenialdisine (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei82ATPPROSITE-ProRule annotation1
Active sitei175Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi59 – 67ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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
PAR1 homolog
PAR1 homolog b
Short name:
Par-1b
Short name:
mPar-1b
Gene namesi
Name:Mark2
Synonyms:Emk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:99638. Mark2.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: UniProtKB
  • basal cortex Source: MGI
  • cell-cell adherens junction Source: MGI
  • lateral plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • microtubule bundle Source: UniProtKB
  • nucleus Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have no embryonic defect and are viable. They do not display obvious neuronal phenotype, possibly due to genetic redundancy with Mark1, Mark3 and Mark4. They however show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. They also show immune-cell dysfunction. As mice age, they develop splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Moreover, mice are lean, insulin hypersensitive, resistant to high-fat-diet-induced weight gain, and hypermetabolic.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863021 – 776Serine/threonine-protein kinase MARK2Add BLAST776

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40PhosphoserineBy similarity1
Modified residuei58Phosphothreonine; by autocatalysisBy similarity1
Modified residuei91Phosphoserine; by CaMK1By similarity1
Modified residuei92Phosphoserine; by CaMK1By similarity1
Modified residuei93Phosphoserine; by CaMK1By similarity1
Modified residuei208Phosphothreonine; by LKB1 and TAOK1By similarity1
Modified residuei212Phosphoserine; by GSK3-betaBy similarity1
Modified residuei274Phosphoserine; by autocatalysisBy similarity1
Modified residuei275Phosphothreonine; by autocatalysisBy similarity1
Modified residuei294Phosphothreonine; by CaMK1By similarity1
Modified residuei408PhosphoserineBy similarity1
Modified residuei409PhosphoserineBy similarity1
Modified residuei453PhosphoserineCombined sources1
Modified residuei464PhosphothreonineBy similarity1
Modified residuei483PhosphoserineCombined sources1
Modified residuei490PhosphoserineBy similarity1
Modified residuei566PhosphoserineBy similarity1
Modified residuei568PhosphoserineCombined sources1
Modified residuei589PhosphoserineBy similarity1
Modified residuei593Phosphothreonine; by PKC/PRKCZBy similarity1
Modified residuei616PhosphoserineBy similarity1
Modified residuei710PhosphoserineBy 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-593 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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ05512.
PaxDbiQ05512.
PeptideAtlasiQ05512.
PRIDEiQ05512.

PTM databases

iPTMnetiQ05512.
PhosphoSitePlusiQ05512.

Expressioni

Tissue specificityi

Highly expressed in adult kidney and testis, lower levels in heart, brain, spleen, lung and liver. Expressed in the head and neural fold in 8 dpc embryos, the limb buds, telencephalic vesicles, eyes, branchial archs and heart at 11.5 dpc, the ectoderm at 13 dpc and epiderm, hair and whisker follicles at 15 dpc.1 Publication

Gene expression databases

BgeeiENSMUSG00000024969.
CleanExiMM_MARK2.

Interactioni

Subunit structurei

Homodimer. Interacts with PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts (when phosphorylated at Thr-593) with YWHAZ. Interacts with PAK5 (By similarity). Interacts with MTCL1; the interaction is direct and increases MARK2 microtubule-binding ability (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199437. 17 interactors.
IntActiQ05512. 15 interactors.
STRINGi10090.ENSMUSP00000108969.

Structurei

3D structure databases

ProteinModelPortaliQ05512.
SMRiQ05512.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 304Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini323 – 362UBAPROSITE-ProRule annotationAdd BLAST40
Domaini727 – 776KA1PROSITE-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.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.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiQ05512.
KOiK08798.
PhylomeDBiQ05512.

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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q05512-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 FQGKKIDGPE 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 KKTTPAPSTN SVLSTSTNRS RNSPLLDRAS LGQASIQNGK
510 520 530 540 550
DSLTMPGSRA STASASAAVS AARPRQHQKS MSASVHPNKA SGLPPTESNC
560 570 580 590 600
EVPRPSTAPQ RVPVASPSAH NISSSSGAPD RTNFPRGVSS RSTFHAGQLR
610 620 630 640 650
QVRDQQNLPY GVTPASPSGH SQGRRGASGS IFSKFTSKFV RRNLNEPESK
660 670 680 690 700
DRVETLRPHV VGSGGTDKDK EEFREAKPRS LRFTWSMKTT SSMEPNEMMR
710 720 730 740 750
EIRKVLDANS CQSELHERYM LLCVHGTPGH ENFVQWEMEV CKLPRLSLNG
760 770
VRFKRISGTS MAFKNIASKI ANELKL
Length:776
Mass (Da):86,306
Last modified:January 23, 2007 - v3
Checksum:i533C8DE0B5EC507E
GO
Isoform 2 (identifier: Q05512-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-339: PDYKDPRRTELMVSMGYTR → LTTGPRDRVDGVNGLHT

Note: No experimental confirmation available.
Show »
Length:774
Mass (Da):85,798
Checksum:iA16080EE5F864414
GO
Isoform 3 (identifier: Q05512-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     502-555: Missing.

Note: No experimental confirmation available.
Show »
Length:722
Mass (Da):80,824
Checksum:iA5FF894FBA51F656
GO
Isoform 4 (identifier: Q05512-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     502-555: Missing.
     640-640: V → VRRNLSFRFA

Note: No experimental confirmation available.
Show »
Length:731
Mass (Da):81,972
Checksum:iAC87AD0A923FB943
GO

Sequence cautioni

The sequence BAC32312 differs from that shown. Reason: Frameshift at position 772.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti161 – 162SA → LH in CAA50040 (PubMed:8358177).Curated2
Sequence conflicti368L → P in CAA50040 (PubMed:8358177).Curated1
Sequence conflicti760S → Y in BAC32312 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013341321 – 339PDYKD…MGYTR → LTTGPRDRVDGVNGLHT in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_013342502 – 555Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST54
Alternative sequenceiVSP_022597640V → VRRNLSFRFA in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70764 mRNA. Translation: CAA50040.1.
AK045329 mRNA. Translation: BAC32312.1. Frameshift.
AK172444 mRNA. Translation: BAE43007.1.
BC058556 mRNA. Translation: AAH58556.1.
CCDSiCCDS37903.1. [Q05512-4]
CCDS37904.1. [Q05512-1]
CCDS50378.1. [Q05512-3]
PIRiI48609.
RefSeqiNP_001073857.1. NM_001080388.2.
NP_001073858.1. NM_001080389.2.
NP_001073859.1. NM_001080390.2.
NP_031954.2. NM_007928.3.
UniGeneiMm.258986.

Genome annotation databases

GeneIDi13728.
KEGGimmu:13728.
UCSCiuc008gks.2. mouse. [Q05512-4]
uc008gkt.2. mouse. [Q05512-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70764 mRNA. Translation: CAA50040.1.
AK045329 mRNA. Translation: BAC32312.1. Frameshift.
AK172444 mRNA. Translation: BAE43007.1.
BC058556 mRNA. Translation: AAH58556.1.
CCDSiCCDS37903.1. [Q05512-4]
CCDS37904.1. [Q05512-1]
CCDS50378.1. [Q05512-3]
PIRiI48609.
RefSeqiNP_001073857.1. NM_001080388.2.
NP_001073858.1. NM_001080389.2.
NP_001073859.1. NM_001080390.2.
NP_031954.2. NM_007928.3.
UniGeneiMm.258986.

3D structure databases

ProteinModelPortaliQ05512.
SMRiQ05512.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199437. 17 interactors.
IntActiQ05512. 15 interactors.
STRINGi10090.ENSMUSP00000108969.

PTM databases

iPTMnetiQ05512.
PhosphoSitePlusiQ05512.

Proteomic databases

MaxQBiQ05512.
PaxDbiQ05512.
PeptideAtlasiQ05512.
PRIDEiQ05512.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi13728.
KEGGimmu:13728.
UCSCiuc008gks.2. mouse. [Q05512-4]
uc008gkt.2. mouse. [Q05512-3]

Organism-specific databases

CTDi2011.
MGIiMGI:99638. Mark2.

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiQ05512.
KOiK08798.
PhylomeDBiQ05512.

Miscellaneous databases

PROiQ05512.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024969.
CleanExiMM_MARK2.

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_MOUSE
AccessioniPrimary (citable) accession number: Q05512
Secondary accession number(s): Q3T9L3, Q6PDR4, Q8BR95
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 169 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.