InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MARK2

Summary

InnateDB Protein

IDBP-485089.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MARK2

Protein Name

MAP/microtubule affinity-regulating kinase 2

Synonyms

EMK-1; EMK1; PAR-1; Par-1b; Par1b;

Species

Homo sapiens

Ensembl Protein

ENSP00000423974

InnateDB Gene

IDBG-52754 (MARK2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11433294, ECO:0000269PubMed:12429843, ECO:0000269PubMed:14976552, ECO:0000269PubMed:15158914, ECO:0000269PubMed:15324659, ECO:0000269PubMed:15365179, ECO:0000269PubMed:16775013, ECO:0000269PubMed:16980613, ECO:0000269PubMed:18626018, ECO:0000269PubMed:20194617}.

Subcellular Localization

Cell membrane; Peripheral membrane protein. Cytoplasm. Lateral cell membrane. Cytoplasm, cytoskeleton. Note=Phosphorylation at Thr-596 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm.

Disease Associations

Tissue Specificity

High levels of expression in heart, brain, skeletal muscle and pancreas, lower levels observed in lung, liver and kidney. {ECO:0000269PubMed:9730619}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 79 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	79 [view]
Protein-Protein	79 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008289	lipid binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0044822	poly(A) RNA binding
GO:0050321	tau-protein kinase activity

Biological Process

GO:0001764	neuron migration
GO:0006468	protein phosphorylation
GO:0010976	positive regulation of neuron projection development
GO:0016055	Wnt signaling pathway
GO:0030010	establishment of cell polarity
GO:0035556	intracellular signal transduction
GO:0045197	establishment or maintenance of epithelial cell apical/basal polarity
GO:0046777	protein autophosphorylation
GO:0050770	regulation of axonogenesis
GO:0051493	regulation of cytoskeleton organization

Cellular Component

GO:0005884	actin filament
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016328	lateral plasma membrane
GO:0097427	microtubule bundle

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001772 Kinase associated domain 1 (KA1)
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR028375 KA1 domain/Ssp2 C-terminal domain

PFAM

PF00069
PF07714
PF02149

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00165
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt