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    ULK3 unc-51 like kinase 3 [ Homo sapiens (human) ]

    Gene ID: 25989, updated on 14-Nov-2024

    Summary

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    Official Symbol
    ULK3provided by HGNC
    Official Full Name
    unc-51 like kinase 3provided by HGNC
    Primary source
    HGNC:HGNC:19703
    See related
    Ensembl:ENSG00000140474 MIM:613472; AllianceGenome:HGNC:19703
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in skin (RPKM 31.2), small intestine (RPKM 22.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ULK3 in Genome Data Viewer
    Location:
    15q24.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (74836118..74843156, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (72706014..72713002, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (75128459..75135497, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75112197-75113010 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75113011-75113824 Neighboring gene lectin, mannose binding 1 like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75114639-75115451 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:75118950-75119157 Neighboring gene uncharacterized LOC105370897 Neighboring gene complexin 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9808 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:75128807-75129383 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:75131867-75132014 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75134491-75135016 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:75135085-75135996 Neighboring gene microRNA 6882 Neighboring gene secretory carrier membrane protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9809 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9810 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9811 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9813 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9814 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75157901-75158832 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:75161878-75162388 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:75162904-75163889 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9815 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:75182299-75182832 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:75191053-75191552 Neighboring gene mannose phosphate isomerase Neighboring gene family with sequence similarity 219 member B

    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. Autophagy mediates the mitotic senescence transition. Young AR, et al. Genes Dev, 2009 Apr 1. PMID 19279323, Free PMC Article
    2. The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome. Goruppi S, et al. Nat Commun, 2023 Feb 16. PMID 36797248, Free PMC Article
    3. Conformational plasticity of the ULK3 kinase domain. Mathea S, et al. Biochem J, 2021 Jul 30. PMID 34190988
    4. ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins. Caballe A, et al. Elife, 2015 May 26. PMID 26011858, Free PMC Article
    5. Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway. Maloverjan A, et al. Exp Cell Res, 2010 Feb 15. PMID 19878745

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.
      Title: The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.
    2. Conformational plasticity of the ULK3 kinase domain.
      Title: Conformational plasticity of the ULK3 kinase domain.
    3. Increased ULK3 also induces autophagy, which is unlinked from GLI and CAF activation. ULK3 upregulation occurs in the CAFs of several tumor types, and ULK3 silencing suppresses the tumor-enhancing properties of these cells.
      Title: The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI.
    4. Structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for cytokinetic abscission.
      Title: ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins.
    5. First named and identified as protein kinase of the ULK family
      Title: The protein kinase complement of the human genome.
    6. Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
      Title: Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study.
    7. Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway.
      Title: Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway.
    8. serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins
      Title: Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway.
    9. Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide association study of blood pressure and hypertension.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: The IFNG (IFN-gamma) genotype predicts cytogenetic and molecular response to imatinib therapy in chronic myeloid leukemia.
    Submit: New GeneRIF Correction

    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
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
    EBI GWAS Catalog
    Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.
    EBI GWAS Catalog
    Genome-wide association study of blood pressure and hypertension.
    EBI GWAS Catalog
    Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.
    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)

    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

    • FLJ90566, DKFZp434C131

    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 IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 protein binding IPI
    Inferred from Physical Interaction
    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 TAS
    Traceable Author Statement
    more info
    		  
    enables ribosomal protein S6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in autophagosome assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in autophagy TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular senescence TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in fibroblast activation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of smoothened signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in piecemeal microautophagy of the nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of smoothened signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of autophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to starvation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in reticulophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in smoothened signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in autophagosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in ciliary tip TAS
    Traceable Author Statement
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in phagophore assembly site IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in phagophore assembly site TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in phagophore assembly site membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    serine/threonine-protein kinase ULK3
    NP_001092906.3
    NP_001271293.2
    NP_001271294.1
    NP_001398011.1
    XP_005254346.1
    XP_016877557.1
    XP_047288324.1
    XP_047288325.1
    XP_047288326.1
    XP_047288327.1
    XP_047288328.1
    XP_047288329.1
    XP_054233677.1
    XP_054233678.1
    XP_054233679.1
    XP_054233680.1
    XP_054233681.1
    XP_054233682.1
    XP_054233683.1
    XP_054233684.1

    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.

    mRNA and Protein(s)

    1. NM_001099436.4 → NP_001092906.3  serine/threonine-protein kinase ULK3 isoform a

      See identical proteins and their annotated locations for NP_001092906.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AK293181, AK299380, AL117482, BC157884
      Consensus CDS
      CCDS45305.1
      UniProtKB/Swiss-Prot
      B2RXK3, B4DFT0, B4DRQ7, D3DW68, Q6PHR2, Q9NPN5, Q9UFS4
      UniProtKB/TrEMBL
      B4DFS6
      Related
      ENSP00000400312.2, ENST00000440863.7
      Conserved Domains (4) summary
      smart00220
      Location:14 → 270
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd02684
      Location:279 → 353
      MIT_2; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This sub-family of MIT domains is found in proteins with an n-terminal serine/threonine kinase domain. The molecular function of the MIT domain is unclear.
      cd14121
      Location:18 → 269
      STKc_ULK3; Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3
      cl00299
      Location:374 → 449
      MIT; MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar ...

    2. NM_001284364.3 → NP_001271293.2  serine/threonine-protein kinase ULK3 isoform b

      See identical proteins and their annotated locations for NP_001271293.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a.
      Source sequence(s)
      AI677802, AK293181, BC157884
      Consensus CDS
      CCDS76779.1
      UniProtKB/TrEMBL
      B4DFS6
      Related
      ENSP00000456051.1, ENST00000569437.5
      Conserved Domains (4) summary
      smart00220
      Location:14 → 270
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd02684
      Location:279 → 353
      MIT_2; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This sub-family of MIT domains is found in proteins with an n-terminal serine/threonine kinase domain. The molecular function of the MIT domain is unclear.
      cd14121
      Location:18 → 269
      STKc_ULK3; Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3
      cl00299
      Location:374 → 442
      MIT; MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar ...

    3. NM_001284365.3 → NP_001271294.1  serine/threonine-protein kinase ULK3 isoform c

      See identical proteins and their annotated locations for NP_001271294.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 5' region and initiates translation from a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter than isoform a.
      Source sequence(s)
      AK293181, AL117482, BI829133
      UniProtKB/TrEMBL
      B4DDG2, B4DQN3
      Conserved Domains (4) summary
      smart00220
      Location:1 → 153
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd02684
      Location:162 → 236
      MIT_2; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This sub-family of MIT domains is found in proteins with an n-terminal serine/threonine kinase domain. The molecular function of the MIT domain is unclear.
      cl00299
      Location:257 → 332
      MIT; MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar ...
      cl21453
      Location:1 → 152
      PKc_like; Protein Kinases, catalytic domain

    4. NM_001411082.1 → NP_001398011.1  serine/threonine-protein kinase ULK3 isoform d

      Status: VALIDATED

      Source sequence(s)
      AC091230
      Consensus CDS
      CCDS92044.1
      Related
      ENSP00000457853.1, ENST00000568667.5

    RNA

    1. NR_104307.3 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) contains an alternate internal segment, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL117482
      Related
      ENST00000570276.5

    2. NR_104308.3 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) contains an alternate internal segment and uses alternate splice sites at two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AI677802, BC048289, BC056423, BI829133
      Related
      ENST00000561725.5

    3. NR_104309.3 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) contains an alternate internal segment and use an alternate splice sites at an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC056423, BI829133
      Related
      ENST00000566479.5

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      74836118..74843156 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017022068.2 → XP_016877557.1  serine/threonine-protein kinase ULK3 isoform X2

    2. XM_005254289.3 → XP_005254346.1  serine/threonine-protein kinase ULK3 isoform X1

      See identical proteins and their annotated locations for XP_005254346.1

      UniProtKB/Swiss-Prot
      Q6PHR2
      Conserved Domains (4) summary
      smart00220
      Location:46 → 281
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd02684
      Location:290 → 364
      MIT_2; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This sub-family of MIT domains is found in proteins with an n-terminal serine/threonine kinase domain. The molecular function of the MIT domain is unclear.
      cd14121
      Location:46 → 280
      STKc_ULK3; Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3
      cl00299
      Location:385 → 460
      MIT; MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar ...

    3. XM_047432373.1 → XP_047288329.1  serine/threonine-protein kinase ULK3 isoform X6

    4. XM_047432368.1 → XP_047288324.1  serine/threonine-protein kinase ULK3 isoform X2

    5. XM_047432371.1 → XP_047288327.1  serine/threonine-protein kinase ULK3 isoform X4

      Related
      ENST00000565881.5

    6. XM_047432369.1 → XP_047288325.1  serine/threonine-protein kinase ULK3 isoform X3

    7. XM_047432370.1 → XP_047288326.1  serine/threonine-protein kinase ULK3 isoform X3

    8. XM_047432372.1 → XP_047288328.1  serine/threonine-protein kinase ULK3 isoform X5

    RNA

    1. XR_007064437.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      72706014..72713002 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377703.1 → XP_054233678.1  serine/threonine-protein kinase ULK3 isoform X2

    2. XM_054377702.1 → XP_054233677.1  serine/threonine-protein kinase ULK3 isoform X1

    3. XM_054377709.1 → XP_054233684.1  serine/threonine-protein kinase ULK3 isoform X6

    4. XM_054377706.1 → XP_054233681.1  serine/threonine-protein kinase ULK3 isoform X4

    5. XM_054377704.1 → XP_054233679.1  serine/threonine-protein kinase ULK3 isoform X3

    6. XM_054377705.1 → XP_054233680.1  serine/threonine-protein kinase ULK3 isoform X3

    7. XM_054377708.1 → XP_054233683.1  serine/threonine-protein kinase ULK3 isoform X5

    8. XM_054377707.1 → XP_054233682.1  serine/threonine-protein kinase ULK3 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6PHR2.2 GenPept UniProtKB/Swiss-Prot:Q6PHR2

    Gene LinkOut

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

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