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Q7KZI7 (MARK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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=Par1b
Gene names
Name:MARK2
Synonyms:EMK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length788 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.22 Ref.27

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.10

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

Cofactor

Magnesium By similarity. Ref.10

Enzyme regulation

Inhibited by PAK7/PAK5; inhibition is independent of the kinase activity of PAK7/PAK5 By similarity. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-596. Inhibited by hymenialdisine. Specifically inhibited by the H.pylori CagA peptide FPLKRHDKVDDLSK that mimics host substrates and binds to the kinase substrate-binding site. Ref.8 Ref.10

Subunit structure

Homodimer. Interacts with PAK7/PAK5; leading to inhibit the protein kinase activity By similarity. Interacts with MTCL1 isoform 1;the interaction is direct and increases MARK2 microtubule-binding ability. Interacts (when phosphorylated at Thr-596) with YWHAZ. In case of infection, interacts with H.pylori CagA, leading to inhibit kinase activity and junctional and polarity defects. Ref.13 Ref.18 Ref.33

Subcellular location

Cell membrane; Peripheral membrane protein. Cytoplasm. Lateral cell membrane. Cytoplasmcytoskeleton. 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. Ref.12 Ref.13 Ref.33

Tissue specificity

High levels of expression in heart, brain, skeletal muscle and pancreas, lower levels observed in lung, liver and kidney. Ref.1

Domain

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. Ref.23

The KA1 domain mediates binding to phospholipids and targeting to membranes By similarity. Ref.23

Post-translational modification

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-596 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. Ref.10 Ref.12 Ref.13

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 KA1 (kinase-associated) domain.

Contains 1 protein kinase domain.

Contains 1 UBA domain.

Sequence caution

The sequence AAK82368.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processDifferentiation
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
   Coding sequence diversityAlternative promoter usage
Alternative splicing
   LigandATP-binding
Lipid-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

establishment of cell polarity

Inferred from direct assay Ref.8. Source: UniProtKB

establishment or maintenance of epithelial cell apical/basal polarity

Inferred from direct assay Ref.13. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay Ref.10. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from direct assay Ref.8. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.10. Source: UniProtKB

regulation of axonogenesis

Inferred from mutant phenotype Ref.27. Source: UniProtKB

regulation of cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentactin filament

Inferred from direct assay Ref.33. Source: UniProtKB

basal cortex

Inferred from electronic annotation. Source: Ensembl

lateral plasma membrane

Inferred from direct assay Ref.33. Source: UniProtKB

membrane

Inferred from mutant phenotype Ref.10. Source: UniProtKB

microtubule bundle

Inferred from direct assay Ref.33. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay Ref.33. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay Ref.10. Source: UniProtKB

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from direct assay Ref.10. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.15Ref.16PubMed 17442826Ref.27Ref.33. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.10Ref.15Ref.16Ref.27. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 16 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7KZI7-1)

Also known as: Alpha;

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.
Note: Produced by alternative promoter usage. No experimental confirmation available.
Isoform 2 Ref.1 (identifier: Q7KZI7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.
Note: Produced by alternative splicing of isoform 6.
Isoform 3 Ref.1 (identifier: Q7KZI7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 6.
Isoform 4 Ref.6 (identifier: Q7KZI7-4)

Also known as: Par-1Balpha;

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 1.
Isoform 5 Ref.3 (identifier: Q7KZI7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.
     654-668: Missing.
Note: Produced by alternative splicing of isoform 1.
Isoform 6 (identifier: Q7KZI7-6)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
Note: Produced by alternative promoter usage. No experimental confirmation available.
Isoform 7 (identifier: Q7KZI7-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.
Isoform 8 (identifier: Q7KZI7-8)

The sequence of this isoform differs from the canonical sequence as follows:
     644-652: Missing.
Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.
Isoform 9 (identifier: Q7KZI7-9)

The sequence of this isoform differs from the canonical sequence as follows:
     505-558: Missing.
Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.
Isoform 10 (identifier: Q7KZI7-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     505-558: Missing.
     654-668: Missing.
Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.
Isoform 11 (identifier: Q7KZI7-11)

The sequence of this isoform differs from the canonical sequence as follows:
     654-668: Missing.
Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.
Isoform 12 (identifier: Q7KZI7-12)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     654-668: Missing.
Note: Produced by alternative splicing of isoform 6. No experimental confirmation available.
Isoform 13 (identifier: Q7KZI7-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     412-412: Missing.
     505-558: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 6. Contains a phosphoserine at position 376.
Isoform 14 (identifier: Q7KZI7-14)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     412-412: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 6. Contains a phosphoserine at position 376.
Isoform 15 (identifier: Q7KZI7-15)

The sequence of this isoform differs from the canonical sequence as follows:
     412-412: Missing.
     505-558: Missing.
     645-668: Missing.
Note: Produced by alternative splicing of isoform 1. Contains a phosphoserine at position 409.
Isoform 16 (identifier: Q7KZI7-16)

The sequence of this isoform differs from the canonical sequence as follows:
     412-412: Missing.
     505-558: Missing.
     644-652: Missing.
Note: Produced by alternative splicing of isoform 1. Contains a phosphoserine at position 409.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 788788Serine/threonine-protein kinase MARK2
PRO_0000086301

Regions

Domain53 – 304252Protein kinase
Domain323 – 36240UBA
Domain739 – 78850KA1
Nucleotide binding59 – 679ATP By similarity Ref.3

Sites

Active site1751Proton acceptor By similarity Ref.3
Binding site821ATP By similarity UniProtKB O08678

Amino acid modifications

Modified residue401Phosphoserine Ref.32
Modified residue581Phosphothreonine; by autocatalysis By similarity
Modified residue911Phosphoserine; by CaMK1 By similarity
Modified residue921Phosphoserine; by CaMK1 By similarity
Modified residue931Phosphoserine; by CaMK1 By similarity
Modified residue2081Phosphothreonine; by LKB1 and TAOK1 Ref.10 Ref.26
Modified residue2121Phosphoserine; by GSK3-beta By similarity UniProtKB O08678
Modified residue2741Phosphoserine; by autocatalysis By similarity
Modified residue2751Phosphothreonine; by autocatalysis By similarity
Modified residue2941Phosphothreonine; by CaMK1 By similarity
Modified residue4091Phosphoserine Ref.21 Ref.24 Ref.26
Modified residue4561Phosphoserine Ref.17 Ref.19 Ref.20 Ref.21 Ref.26
Modified residue4861Phosphoserine Ref.14 Ref.19 Ref.21 Ref.26 Ref.32
Modified residue4931Phosphoserine Ref.21
Modified residue5691Phosphoserine Ref.24
Modified residue5961Phosphothreonine; by PKC/PRKCZ Ref.12 Ref.13
Modified residue6191Phosphoserine Ref.32
Modified residue7221Phosphoserine Ref.26

Natural variations

Alternative sequence1 – 3333Missing in isoform 2, isoform 3, isoform 6, isoform 7, isoform 10, isoform 12, isoform 13 and isoform 14. Ref.1
VSP_051705
Alternative sequence4121Missing in isoform 13, isoform 14, isoform 15 and isoform 16.
VSP_039872
Alternative sequence505 – 55854Missing in isoform 2, isoform 4, isoform 5, isoform 7, isoform 9, isoform 10, isoform 13, isoform 15 and isoform 16. Ref.1 Ref.3 Ref.6
VSP_051706
Alternative sequence644 – 6529Missing in isoform 3, isoform 4, isoform 7, isoform 8, isoform 13, isoform 14 and isoform 16. Ref.1 Ref.6
VSP_051707
Alternative sequence645 – 66824Missing in isoform 15.
VSP_041853
Alternative sequence654 – 66815Missing in isoform 5, isoform 11, isoform 10 and isoform 12. Ref.1 Ref.6
VSP_051708

Experimental info

Mutagenesis2081T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.10
Mutagenesis5961T → A: Loss of membrane dissociation and binding to YWHAZ. Ref.12 Ref.13
Sequence conflict1921A → G in CAA80914. Ref.7
Sequence conflict2361L → C in CAA80914. Ref.7
Sequence conflict389 – 3902PS → QF in CAA66229. Ref.1

Secondary structure

............................................. 788
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) [UniParc].

Last modified April 12, 2005. Version 2.
Checksum: F307BF4DDB543A70

FASTA78887,911
        10         20         30         40         50         60 
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 

        70         80         90        100        110        120 
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 

       130        140        150        160        170        180 
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 

       190        200        210        220        230        240 
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 

       250        260        270        280        290        300 
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 

       310        320        330        340        350        360 
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 

       370        380        390        400        410        420 
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 

       430        440        450        460        470        480 
NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 

       490        500        510        520        530        540 
NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP 

       550        560        570        580        590        600 
NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG 

       610        620        630        640        650        660 
QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRNLNEPE 

       670        680        690        700        710        720 
SKDRVETLRP HVVGSGGNDK EKEEFREAKP RSLRFTWSMK TTSSMEPNEM MREIRKVLDA 

       730        740        750        760        770        780 
NSCQSELHEK YMLLCMHGTP GHEDFVQWEM EVCKLPRLSL NGVRFKRISG TSMAFKNIAS 


KIANELKL 

« Hide

Isoform 2 [UniParc].

Checksum: 3D68318CFDCA31EE
Show »

FASTA70178,851
Isoform 3 [UniParc].

Checksum: 58F2BBE10943C90F
Show »

FASTA74683,184
Isoform 4 (Par-1Balpha) [UniParc].

Checksum: D676331938A84716
Show »

FASTA72581,280
Isoform 5 [UniParc].

Checksum: EC39154CF73E9858
Show »

FASTA71980,647
Isoform 6 (Beta) [UniParc].

Checksum: 493CD8C6DC3A4C06
Show »

FASTA75584,333
Isoform 7 [UniParc].

Checksum: 4BD9AA1F872638A6
Show »

FASTA69277,702
Isoform 8 [UniParc].

Checksum: 5AF7014EB5639857
Show »

FASTA77986,762
Isoform 9 [UniParc].

Checksum: 60D126D3C8967186
Show »

FASTA73482,429
Isoform 10 [UniParc].

Checksum: 9389E28076FDDAF8
Show »

FASTA68677,069
Isoform 11 [UniParc].

Checksum: 0378FF0433C4D901
Show »

FASTA77386,129
Isoform 12 [UniParc].

Checksum: 6220FC8C1A308548
Show »

FASTA74082,551
Isoform 13 [UniParc].

Checksum: 2216B4AE7BCF31BE
Show »

FASTA69177,631
Isoform 14 [UniParc].

Checksum: 54CA1DAF4B6E02CF
Show »

FASTA74583,113
Isoform 15 [UniParc].

Checksum: F30B3AB6B60B3621
Show »

FASTA70979,427
Isoform 16 [UniParc].

Checksum: 9D8FB211F5B08149
Show »

FASTA72481,209

References

« Hide 'large scale' references
[1]"Human serine/threonine protein kinase EMK1: genome structure and cDNA cloning of isoforms produced by alternative splicing."
Espinosa L., Navarro E.
Cytogenet. Cell Genet. 81:278-282(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY.
Tissue: Colon.
[2]Sugiyama A., Inoue H., Oka M.
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
Tissue: Kidney.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-755 (ISOFORM 1).
Tissue: Kidney and Placenta.
[6]"PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling."
Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J., Williams L.T.
Nat. Cell Biol. 3:628-636(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-788 (ISOFORM 4), FUNCTION.
[7]"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans."
Schultz S.J., Nigg E.A.
Cell Growth Differ. 4:821-830(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 190-237.
[8]"Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity."
Biernat J., Wu Y.Z., Timm T., Zheng-Fischhofer Q., Mandelkow E., Meijer L., Mandelkow E.M.
Mol. Biol. Cell 13:4013-4028(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[9]"Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients."
Hueso M., Beltran V., Moreso F., Ciriero E., Fulladosa X., Grinyo J.M., Seron D., Navarro E.
Biochim. Biophys. Acta 1689:58-65(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE PROMOTER USAGE.
[10]"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-208, MUTAGENESIS OF THR-208.
[11]"Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells."
Cohen D., Rodriguez-Boulan E., Musch A.
Proc. Natl. Acad. Sci. U.S.A. 101:13792-13797(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity."
Hurov J.B., Watkins J.L., Piwnica-Worms H.
Curr. Biol. 14:736-741(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-596, MUTAGENESIS OF THR-596, SUBCELLULAR LOCATION.
[13]"aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity."
Suzuki A., Hirata M., Kamimura K., Maniwa R., Yamanaka T., Mizuno K., Kishikawa M., Hirose H., Amano Y., Izumi N., Miwa Y., Ohno S.
Curr. Biol. 14:1425-1435(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-596, MUTAGENESIS OF THR-596, INTERACTION WITH YWHAZ.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells."
Ducharme N.A., Hales C.M., Lapierre L.A., Ham A.J., Oztan A., Apodaca G., Goldenring J.R.
Mol. Biol. Cell 17:3625-3637(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RAB11FIP2.
[16]"New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases."
Dequiedt F., Martin M., Von Blume J., Vertommen D., Lecomte E., Mari N., Heinen M.F., Bachmann M., Twizere J.C., Huang M.C., Rider M.H., Piwnica-Worms H., Seufferlein T., Kettmann R.
Mol. Cell. Biol. 26:7086-7102(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC7.
[17]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity."
Saadat I., Higashi H., Obuse C., Umeda M., Murata-Kamiya N., Saito Y., Lu H., Ohnishi N., Azuma T., Suzuki A., Ohno S., Hatakeyama M.
Nature 447:330-333(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH H.PYLORI CAGA.
[19]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456 AND SER-486, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[21]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409; SER-456; SER-486 AND SER-493, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2."
Jansson D., Ng A.C., Fu A., Depatie C., Al Azzabi M., Screaton R.A.
Proc. Natl. Acad. Sci. U.S.A. 105:10161-10166(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CRTC2.
[23]"The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation."
Jaleel M., Villa F., Deak M., Toth R., Prescott A.R., Van Aalten D.M., Alessi D.R.
Biochem. J. 394:545-555(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN UBA.
[24]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409 (ISOFORMS 15 AND 16), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-208; SER-409; SER-456; SER-486 AND SER-722, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 (ISOFORMS 13 AND 14), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation."
Yoshimura Y., Terabayashi T., Miki H.
Mol. Cell. Biol. 30:2206-2219(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF KIF13B.
[28]"The tau of MARK: a polarized view of the cytoskeleton."
Matenia D., Mandelkow E.M.
Trends Biochem. Sci. 34:332-342(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[29]"Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases."
Marx A., Nugoor C., Panneerselvam S., Mandelkow E.
FASEB J. 24:1637-1648(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[30]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-486 AND SER-619, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"The novel PAR-1-binding protein MTCL1 has crucial roles in organizing microtubules in polarizing epithelial cells."
Sato Y., Akitsu M., Amano Y., Yamashita K., Ide M., Shimada K., Yamashita A., Hirano H., Arakawa N., Maki T., Hayashi I., Ohno S., Suzuki A.
J. Cell Sci. 126:4671-4683(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MTCL1, SUBCELLULAR LOCATION.
[34]"Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates."
Nesic D., Miller M.C., Quinkert Z.T., Stein M., Chait B.T., Stebbins C.E.
Nat. Struct. Mol. Biol. 17:130-132(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 49-363 IN COMPLEX WITH H.PYLORI CAGA PEPTIDE INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X97630 mRNA. Translation: CAA66229.1.
AB188493 mRNA. Translation: BAD37141.1.
BT007342 mRNA. Translation: AAP36006.1.
AP003780 Genomic DNA. No translation available.
BC008771 mRNA. Translation: AAH08771.2.
BC084540 mRNA. Translation: AAH84540.1.
AF387638 mRNA. Translation: AAK82368.1. Different initiation.
Z25427 mRNA. Translation: CAA80914.1.
CCDSCCDS41665.1. [Q7KZI7-14]
CCDS53649.1. [Q7KZI7-1]
CCDS53650.1. [Q7KZI7-5]
CCDS53651.1. [Q7KZI7-15]
CCDS8051.2. [Q7KZI7-16]
PIRG01025.
I38217.
RefSeqNP_001034558.2. NM_001039469.2. [Q7KZI7-1]
NP_001156768.1. NM_001163296.1. [Q7KZI7-5]
NP_001156769.1. NM_001163297.1. [Q7KZI7-15]
NP_004945.4. NM_004954.4. [Q7KZI7-16]
NP_059672.2. NM_017490.3. [Q7KZI7-14]
XP_006718504.1. XM_006718441.1. [Q7KZI7-8]
XP_006718506.1. XM_006718443.1. [Q7KZI7-11]
XP_006718509.1. XM_006718446.1. [Q7KZI7-4]
UniGeneHs.567261.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3IECX-ray2.20A/B/C/D49-363[»]
ProteinModelPortalQ7KZI7.
SMRQ7KZI7. Positions 19-363, 689-788.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108326. 52 interactions.
DIPDIP-31321N.
IntActQ7KZI7. 33 interactions.
MINTMINT-1149196.
STRING9606.ENSP00000389184.

Chemistry

BindingDBQ7KZI7.
ChEMBLCHEMBL3831.
GuidetoPHARMACOLOGY2098.

PTM databases

PhosphoSiteQ7KZI7.

Polymorphism databases

DMDM62510922.

Proteomic databases

MaxQBQ7KZI7.
PaxDbQ7KZI7.
PRIDEQ7KZI7.

Protocols and materials databases

DNASU2011.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315032; ENSP00000326632; ENSG00000072518. [Q7KZI7-8]
ENST00000350490; ENSP00000294247; ENSG00000072518. [Q7KZI7-15]
ENST00000361128; ENSP00000355091; ENSG00000072518. [Q7KZI7-5]
ENST00000377809; ENSP00000367040; ENSG00000072518. [Q7KZI7-11]
ENST00000377810; ENSP00000367041; ENSG00000072518. [Q7KZI7-13]
ENST00000402010; ENSP00000385751; ENSG00000072518. [Q7KZI7-1]
ENST00000408948; ENSP00000386128; ENSG00000072518. [Q7KZI7-13]
ENST00000413835; ENSP00000389184; ENSG00000072518. [Q7KZI7-9]
ENST00000508192; ENSP00000425765; ENSG00000072518. [Q7KZI7-16]
ENST00000509502; ENSP00000423974; ENSG00000072518. [Q7KZI7-14]
ENST00000513765; ENSP00000421075; ENSG00000072518. [Q7KZI7-6]
GeneID2011.
KEGGhsa:2011.
UCSCuc001nxv.4. human. [Q7KZI7-16]
uc001nxw.3. human. [Q7KZI7-1]
uc001nxx.3. human. [Q7KZI7-5]
uc001nxy.3. human. [Q7KZI7-15]
uc001nxz.4. human. [Q7KZI7-14]

Organism-specific databases

CTD2011.
GeneCardsGC11P063606.
HGNCHGNC:3332. MARK2.
HPAHPA038790.
MIM600526. gene.
neXtProtNX_Q7KZI7.
PharmGKBPA35047.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG052453.
InParanoidQ7KZI7.
KOK08798.
OMAHERYMLL.
OrthoDBEOG79CXXX.
PhylomeDBQ7KZI7.
TreeFamTF315213.

Enzyme and pathway databases

SignaLinkQ7KZI7.

Gene expression databases

ArrayExpressQ7KZI7.
BgeeQ7KZI7.
CleanExHS_MARK2.
GenevestigatorQ7KZI7.

Family and domain databases

Gene3D3.30.310.80. 1 hit.
InterProIPR028375. 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]
PfamPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50032. 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]
ProtoNetSearch...

Other

ChiTaRSMARK2. human.
EvolutionaryTraceQ7KZI7.
GeneWikiMARK2.
GenomeRNAi2011.
NextBio8141.
PROQ7KZI7.
SOURCESearch...

Entry information

Entry nameMARK2_HUMAN
AccessionPrimary (citable) accession number: Q7KZI7
Secondary accession number(s): Q15449 expand/collapse secondary AC list , Q15524, Q5XGA3, Q68A18, Q96HB3, Q96RG0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: July 9, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM