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    STK4 serine/threonine kinase 4 [ Homo sapiens (human) ]

    Gene ID: 6789, updated on 14-Nov-2024

    Summary

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    Official Symbol
    STK4provided by HGNC
    Official Full Name
    serine/threonine kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:11408
    See related
    Ensembl:ENSG00000101109 MIM:604965; AllianceGenome:HGNC:11408
    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
    KRS2; MST1; YSK3
    Summary
    The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process. [provided by RefSeq, Jul 2008]
    Annotation information
    Note: MST1 (Gene ID: 4485) and STK4 (Gene ID: 6789) share the MST1 symbol/alias in common. MST1 is a widely used alternative name for serine/threonine kinase 4 (STK4), which can be confused with the official symbol for macrophage stimulating 1 (MST1). [01 Jun 2018]
    Expression
    Broad expression in lymph node (RPKM 17.1), appendix (RPKM 14.6) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See STK4 in Genome Data Viewer
    Location:
    20q13.12
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (44966512..45080021)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (46702402..46815925)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (43595153..43708662)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904912 Neighboring gene translocase of outer mitochondrial membrane 34 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17941 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17942 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17943 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12951 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12952 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17944 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12953 Neighboring gene STK4 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12954 Neighboring gene potassium voltage-gated channel modifier subfamily S member 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:43743251-43743752 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:43743753-43744252 Neighboring gene WAP four-disulfide core domain 5

    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. Dimerization-induced folding of MST1 SARAH and the influence of the intrinsically unstructured inhibitory domain: low thermodynamic stability of monomer. Constantinescu Aruxandei D, et al. Biochemistry, 2011 Dec 27. PMID 22112013
    2. Mammalian sterile-like 1 kinase inhibits TGFβ and EGF‑dependent regulation of invasiveness, migration and proliferation of HEC-1-A endometrial cancer cells. Attarha S, et al. Int J Oncol, 2014 Aug. PMID 24841766
    3. Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway. Zhou Y, et al. Acta Biochim Biophys Sin (Shanghai), 2020 Aug 5. PMID 32556311
    4. The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Hergovich A, et al. Curr Biol, 2009 Nov 3. PMID 19836237
    5. A Case of STK4 Deficiency with Complications Evoking Mycobacterial Infection. Radwan N, et al. J Clin Immunol, 2020 May. PMID 32394035

    See all (235) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association Study between SNPs in MST1 and MST2 and H. pylori Infection as well as Noncardia Gastric Carcinogenesis.
      Title: Association Study between SNPs in MST1 and MST2 and H. pylori Infection as well as Noncardia Gastric Carcinogenesis.
    2. MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-kappaB signalling pathway.
      Title: MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.
    3. The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.
      Title: The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.
    4. Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.
      Title: Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.
    5. STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.
      Title: STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma.
    6. MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.
      Title: MST1 downregulates TAZ tumor suppressor protein in multiple myeloma and is a potential therapeutic target.
    7. Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review.
      Title: Hematopoietic stem cell transplantation in serine/threonine kinase 4 (STK4) deficiency: Report of two cases and literature review.
    8. Mammalian STE20-like kinase-1/2 are activated in human platelets stimulated by collagen or thrombin and play a vital role in collagen-activated platelets.
      Title: Mammalian STE20-like kinase-1/2 are activated in human platelets stimulated by collagen or thrombin and play a vital role in collagen-activated platelets.
    9. Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington's Disease and Other Neurodegenerative Disorders.
      Title: Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington's Disease and Other Neurodegenerative Disorders.
    10. LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.
      Title: LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (116)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Combined immunodeficiency due to STK4 deficiency
    MedGen: C3553943 OMIM: 614868 GeneReviews: Not available
    		Compare labs

    Variation

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    See Variation Viewer (GRCh37.p13)

    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

    • DKFZp686A2068

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables AMP-activated protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables Rho-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables eukaryotic translation initiation factor 2alpha kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS121 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AT120 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXS139 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS14 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS36 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S10 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S28 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S57 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T11 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T3 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T45 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4S1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein kinase activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    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 ribosomal protein S6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in branching involved in blood vessel morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in canonical Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell differentiation involved in embryonic placenta development IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within cell morphogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in central nervous system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in endocardium development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in extrinsic apoptotic signaling pathway via death domain receptors IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hepatocyte apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in hippo signaling TAS
    Traceable Author Statement
    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 keratinocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of epithelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neural tube formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of fat cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of hepatocyte apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within positive regulation of hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of substrate-dependent cell migration, cell attachment to substrate IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in primitive hemopoiesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein import into nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein import into nucleus IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within protein stabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein tetramerization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cell differentiation involved in embryonic placenta development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    serine/threonine-protein kinase 4
    Names
    STE20-like kinase MST1
    hippo homolog
    kinase responsive to stress 2
    mammalian STE20-like protein kinase 1
    mammalian sterile 20-like 1
    serine/threonine-protein kinase Krs-2
    NP_001339314.1
    NP_006273.1
    XP_005260589.1
    XP_011527320.1
    XP_016883520.1
    XP_016883522.1
    XP_047296381.1
    XP_047296382.1
    XP_054179906.1
    XP_054179907.1
    XP_054179908.1
    XP_054179909.1
    XP_054179910.1

    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_032172.1 RefSeqGene

      Range
      5001..118475
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_535

    mRNA and Protein(s)

    1. NM_001352385.2 → NP_001339314.1  serine/threonine-protein kinase 4 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AK027088, AL109839, BC038850, Z93016
      Consensus CDS
      CCDS86957.1
      UniProtKB/TrEMBL
      A0PJ51
      Related
      ENSP00000361887.1, ENST00000372801.5
      Conserved Domains (1) summary
      cd06612
      Location:26 → 281
      STKc_MST1_2; Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2

    2. NM_006282.5 → NP_006273.1  serine/threonine-protein kinase 4 isoform 1

      See identical proteins and their annotated locations for NP_006273.1

      Status: REVIEWED

      Source sequence(s)
      AK027088, AL597960, U60207, Z93016
      Consensus CDS
      CCDS13341.1
      UniProtKB/Swiss-Prot
      B2RCR8, Q13043, Q15802, Q4G156, Q5H982, Q6PD60, Q9BR32, Q9NTZ4
      UniProtKB/TrEMBL
      Q59FZ4
      Related
      ENSP00000361892.3, ENST00000372806.8
      Conserved Domains (3) summary
      cd06612
      Location:26 → 281
      STKc_MST1_2; Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2
      smart00220
      Location:30 → 281
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam11629
      Location:433 → 480
      Mst1_SARAH; C terminal SARAH domain of Mst1

    RNA

    1. NR_147974.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL109839, BC039023
      Related
      ENST00000487587.3

    2. NR_147975.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL109839

    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_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      44966512..45080021
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017028031.3 → XP_016883520.1  serine/threonine-protein kinase 4 isoform X1

      UniProtKB/TrEMBL
      Q59FZ4
      Conserved Domains (3) summary
      cd06612
      Location:17 → 268
      STKc_MST1_2; Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2
      smart00220
      Location:24 → 268
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam11629
      Location:420 → 467
      Mst1_SARAH; C terminal SARAH domain of Mst1

    2. XM_011529018.4 → XP_011527320.1  serine/threonine-protein kinase 4 isoform X3

      See identical proteins and their annotated locations for XP_011527320.1

      UniProtKB/TrEMBL
      A0A087WVN8, Q59FZ4
      Related
      ENSP00000479564.2, ENST00000474717.3
      Conserved Domains (3) summary
      cd06612
      Location:1 → 205
      STKc_MST1_2; Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2
      smart00220
      Location:1 → 205
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam11629
      Location:357 → 404
      Mst1_SARAH; C terminal SARAH domain of Mst1

    3. XM_047440425.1 → XP_047296381.1  serine/threonine-protein kinase 4 isoform X1

    4. XM_005260532.5 → XP_005260589.1  serine/threonine-protein kinase 4 isoform X1

      UniProtKB/TrEMBL
      Q59FZ4
      Conserved Domains (3) summary
      cd06612
      Location:17 → 268
      STKc_MST1_2; Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2
      smart00220
      Location:24 → 268
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      pfam11629
      Location:420 → 467
      Mst1_SARAH; C terminal SARAH domain of Mst1

    5. XM_017028033.2 → XP_016883522.1  serine/threonine-protein kinase 4 isoform X4

      UniProtKB/TrEMBL
      A0PJ51

    6. XM_047440426.1 → XP_047296382.1  serine/threonine-protein kinase 4 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      46702402..46815925
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054323935.1 → XP_054179910.1  serine/threonine-protein kinase 4 isoform X4

    2. XM_054323932.1 → XP_054179907.1  serine/threonine-protein kinase 4 isoform X1

    3. XM_054323931.1 → XP_054179906.1  serine/threonine-protein kinase 4 isoform X1

    4. XM_054323934.1 → XP_054179909.1  serine/threonine-protein kinase 4 isoform X3

    5. XM_054323933.1 → XP_054179908.1  serine/threonine-protein kinase 4 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13043.2 GenPept UniProtKB/Swiss-Prot:Q13043

    Gene LinkOut

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

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