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    MARK2 microtubule affinity regulating kinase 2 [ Homo sapiens (human) ]

    Gene ID: 2011, updated on 28-Oct-2024

    Summary

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    Official Symbol
    MARK2provided by HGNC
    Official Full Name
    microtubule affinity regulating kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:3332
    See related
    Ensembl:ENSG00000072518 MIM:600526; AllianceGenome:HGNC:3332
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EMK1; EMK-1; PAR-1; Par1b; Par-1b
    Summary
    This gene encodes a member of the Par-1 family of serine/threonine protein kinases. The protein is an important regulator of cell polarity in epithelial and neuronal cells, and also controls the stability of microtubules through phosphorylation and inactivation of several microtubule-associating proteins. The protein localizes to cell membranes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]
    Expression
    Ubiquitous expression in esophagus (RPKM 11.9), colon (RPKM 10.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MARK2 in Genome Data Viewer
    Location:
    11q13.1
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (63839110..63911020)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (63828449..63900374)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (63606582..63678492)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3446 Neighboring gene spindlin interactor and repressor of chromatin binding Neighboring gene ReSE screen-validated silencer GRCh37_chr11:63598793-63599010 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:63599819-63600638 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:63605268-63606256 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4875 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3447 Neighboring gene ATP synthase membrane subunit g pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4876 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4877 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:63642729-63643230 Neighboring gene RNA, U6 small nuclear 1306, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4878 Neighboring gene tRNA-Arg (anticodon CCT) 9-1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:63670286-63671098 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:63674933-63675606 Neighboring gene Sharpr-MPRA regulatory region 844 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:63682139-63683091 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:63683713-63684376 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3448 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3449 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3450 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:63687688-63688350 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:63688351-63689011 Neighboring gene REST corepressor 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:63705477-63705977 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3451 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4879 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:63706395-63706580 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:63712515-63713444 Neighboring gene N-alpha-acetyltransferase 40, NatD catalytic subunit

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Prognosis in human melanoma: PAR-1 expression is superior to other coagulation components and VEGF. Depasquale I, et al. Histopathology, 2008 Mar. PMID 18315603
    2. Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b. Nishikawa H, et al. Sci Rep, 2016 Jul 22. PMID 27445265, Free PMC Article
    3. Microtubule affinity-regulating kinase 2 is associated with DNA damage response and cisplatin resistance in non-small cell lung cancer. Hubaux R, et al. Int J Cancer, 2015 Nov 1. PMID 25907283, Free PMC Article
    4. Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes. Slim CL, et al. PLoS Biol, 2013 Dec. PMID 24358023, Free PMC Article
    5. Natural variant of the Helicobacter pylori CagA oncoprotein that lost the ability to interact with PAR1. Hashi K, et al. Cancer Sci, 2014 Mar. PMID 24354359, Free PMC Article

    See all (190) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. N[6]-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor.
      Title: N(6)-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor.
    2. MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites.
      Title: MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites.
    3. Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase.
      Title: Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase.
    4. MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1alpha and p53 pathways.
      Title: MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1α and p53 pathways.
    5. MARK2/4 promotes Warburg effect and cell growth in non-small cell lung carcinoma through the AMPKalpha1/mTOR/HIF-1alpha signaling pathway.
      Title: MARK2/4 promotes Warburg effect and cell growth in non-small cell lung carcinoma through the AMPKα1/mTOR/HIF-1α signaling pathway.
    6. Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330-5p and upregulating MARK2.
      Title: Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330-5p and upregulating MARK2.
    7. The cell polarity kinase Par1b/MARK2 activation selects specific NF-kB transcripts via phosphorylation of core mediator Med17/TRAP80.
      Title: The cell polarity kinase Par1b/MARK2 activation selects specific NF-kB transcripts via phosphorylation of core mediator Med17/TRAP80.
    8. MARK2 phosphorylates eIF2alpha in response to proteotoxic stress.
      Title: MARK2 phosphorylates eIF2α in response to proteotoxic stress.
    9. Study shows that MARK2 is required to recentre spindles that are off-centred following actin disassembly, showing the close functional relationship between MARK2 and the actin network. These results suggest that, during both interphase and mitosis, MARK2 localizes at specialized membrane subdomains and coordinates actin and microtubule cytoskeletal changes, thus enabling normal cell division.
      Title: MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly.
    10. Par1b-inhibition by CagA contributes to DNA Double Strand Breaks in H. pylori infected human primary gastric epithelial cells.
      Title: Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells.
    Submit: New GeneRIF Correction See all GeneRIFs (44)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC99619

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables RNA binding HDA PubMed 
    enables cadherin binding HDA PubMed 
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables lipid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables tau protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables tau protein binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables tau-protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables tau-protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables tau-protein kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables tau-protein kinase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in activation of protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in autophagy of mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in axon development ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in establishment of cell polarity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in establishment of cell polarity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in establishment or maintenance of cell polarity regulating cell shape ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in establishment or maintenance of epithelial cell apical/basal polarity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in microtubule cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrion localization NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in neuron migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-serine phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in peptidyl-threonine phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of neuron projection development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein phosphorylation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of axonogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cytoskeleton organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of microtubule binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in regulation of microtubule cytoskeleton organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in actin filament IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in dendrite IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in microtubule bundle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    serine/threonine-protein kinase MARK2
    Names
    ELKL motif kinase 1
    MAP/microtubule affinity-regulating kinase 2
    PAR1 homolog b
    Ser/Thr protein kinase PAR-1B
    serine/threonine protein kinase EMK
    testicular tissue protein Li 117
    NP_001034558.2
    NP_001156768.1
    NP_001156769.1
    NP_004945.4
    NP_059672.2

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029771.1 RefSeqGene

      Range
      5183..77093
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039469.3 → NP_001034558.2  serine/threonine-protein kinase MARK2 isoform d

      See identical proteins and their annotated locations for NP_001034558.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (d).
      Source sequence(s)
      AB188493, AK225766, AP003780, BC008771, BM719402
      Consensus CDS
      CCDS53649.1
      UniProtKB/Swiss-Prot
      Q15449, Q15524, Q5XGA3, Q68A18, Q7KZI7, Q96HB3, Q96RG0
      UniProtKB/TrEMBL
      A8K2S4
      Related
      ENSP00000385751.2, ENST00000402010.8
      Conserved Domains (3) summary
      cd12201
      Location:689 → 787
      MARK2_C; C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 2
      cd14406
      Location:322 → 363
      UBA_MARK2; UBA domain found in serine/threonine-protein kinase MARK2 and similar proteins
      cd14072
      Location:52 → 304
      STKc_MARK; Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases

    2. NM_001163296.2 → NP_001156768.1  serine/threonine-protein kinase MARK2 isoform e

      See identical proteins and their annotated locations for NP_001156768.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks two alternate in-frame exons in the 3' coding region, compared to variant 4. The resulting isoform (e) lacks two internal segments, compared to isoform d.
      Source sequence(s)
      AB188493, AK225766, AP003780, BM719402
      Consensus CDS
      CCDS53650.1
      UniProtKB/TrEMBL
      A0A0A0MRU9, A0A140VJP1
      Related
      ENSP00000355091.5, ENST00000361128.9
      Conserved Domains (3) summary
      cd12201
      Location:620 → 718
      MARK2_C; C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 2
      cd14406
      Location:322 → 363
      UBA_MARK2; UBA domain found in serine/threonine-protein kinase MARK2 and similar proteins
      cd14072
      Location:52 → 304
      STKc_MARK; Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases

    3. NM_001163297.2 → NP_001156769.1  serine/threonine-protein kinase MARK2 isoform f

      See identical proteins and their annotated locations for NP_001156769.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks three alternate in-frame exons and uses an alternate in-frame splice site, compared to variant 4. The resulting isoform (f) lacks two internal segments and 1 internal residue, compared to isoform d.
      Source sequence(s)
      AK225766, AP003780, BM719402
      Consensus CDS
      CCDS53651.1
      UniProtKB/TrEMBL
      A0A0A0MRU9
      Related
      ENSP00000294247.9, ENST00000350490.11
      Conserved Domains (3) summary
      cd12201
      Location:610 → 708
      MARK2_C; C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 2
      cd14406
      Location:322 → 363
      UBA_MARK2; UBA domain found in serine/threonine-protein kinase MARK2 and similar proteins
      cd14072
      Location:52 → 304
      STKc_MARK; Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases

    4. NM_004954.5 → NP_004945.4  serine/threonine-protein kinase MARK2 isoform c

      See identical proteins and their annotated locations for NP_004945.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate in-frame exons in the 3' coding region and uses an alternate in-frame splice site in the central coding region, compared to variant 4. The resulting isoform (c) lacks two internal segments and 1 internal residue, compared to isoform d.
      Source sequence(s)
      AK225766, AP003780, BC084540, BM719402
      Consensus CDS
      CCDS8051.2
      UniProtKB/TrEMBL
      A0A0A0MRU9
      Related
      ENSP00000425765.1, ENST00000508192.5
      Conserved Domains (3) summary
      cd12201
      Location:625 → 723
      MARK2_C; C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 2
      cd14406
      Location:322 → 363
      UBA_MARK2; UBA domain found in serine/threonine-protein kinase MARK2 and similar proteins
      cd14072
      Location:52 → 304
      STKc_MARK; Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases

    5. NM_017490.4 → NP_059672.2  serine/threonine-protein kinase MARK2 isoform a

      See identical proteins and their annotated locations for NP_059672.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents use of an alternate promoter and 5' UTR, uses a downstream start codon, lacks an in-frame exon, and uses an alternate in-frame splice site, compared to variant 4. The resulting isoform (a) has a shorter N-terminus and lacks an internal segment and 1 internal residue, compared to isoform d.
      Source sequence(s)
      AK290339, AP003780, BM719402, BT007342, DA855402
      Consensus CDS
      CCDS41665.1
      UniProtKB/TrEMBL
      A8K2S4
      Related
      ENSP00000423974.2, ENST00000509502.6
      Conserved Domains (3) summary
      cd12201
      Location:646 → 744
      MARK2_C; C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 2
      cd14406
      Location:289 → 330
      UBA_MARK2; UBA domain found in serine/threonine-protein kinase MARK2 and similar proteins
      cd14072
      Location:19 → 271
      STKc_MARK; Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      63839110..63911020
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      63828449..63900374
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q7KZI7.2 GenPept UniProtKB/Swiss-Prot:Q7KZI7

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools