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

Gene ID: 2011, updated on 7-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (63839110..63911020)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (63828449..63900374)
105.20220307 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
  • 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. MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1α and p53 pathways. Ponnusamy L, et al. J Cell Biochem, 2022 Apr. PMID 35048405
  2. MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly. Hart M, et al. Open Biol, 2019 Jun 28. PMID 31238822, Free PMC Article
  3. Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells. Zamperone A, et al. Cell Cycle, 2019 Feb. PMID 30580666, Free PMC Article
  4. Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism. Zulkipli I, et al. J Cell Biol, 2018 Sep 3. PMID 29941476, Free PMC Article
  5. Interconversion of inactive to active conformation of MARK2: Insights from molecular modeling and molecular dynamics simulation. Ahrari S, et al. Arch Biochem Biophys, 2017 Sep 15. PMID 28711359

See all (169) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. MARK2 phosphorylates eIF2alpha in response to proteotoxic stress.
    Title: MARK2 phosphorylates eIF2α in response to proteotoxic stress.
  7. 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.
  8. 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.
  9. Clustering of the CD44 extracellular domain by high-molecular-weight hyaluronan leads to recruitment of the polarity-regulating kinase PAR1b by the CD44 intracellular domain, which results in disruption of the Hippo signaling-inhibitory PAR1b-MST complex.
    Title: High-Molecular-Weight Hyaluronan Is a Hippo Pathway Ligand Directing Cell Density-Dependent Growth Inhibition via PAR1b.
  10. The authors uncovered a novel role for MARK2 in maintaining the mitotic spindle at the cell's geometric center.
    Title: Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism.
Submit: New GeneRIF Correction See all GeneRIFs (42)

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 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 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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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_2023_10

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

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