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    DLK2 delta like non-canonical Notch ligand 2 [ Homo sapiens (human) ]

    Gene ID: 65989, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DLK2provided by HGNC
    Official Full Name
    delta like non-canonical Notch ligand 2provided by HGNC
    Primary source
    HGNC:HGNC:21113
    See related
    Ensembl:ENSG00000171462 AllianceGenome:HGNC:21113
    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
    Also known as
    DLK-2; EGFL9
    Summary
    Predicted to enable Notch binding activity. Involved in negative regulation of Notch signaling pathway. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in skin (RPKM 1.9), prostate (RPKM 1.6) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DLK2 in Genome Data Viewer
    Location:
    6p21.1
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (43450352..43456632, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (43279119..43285399, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (43418090..43424370, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375065 Neighboring gene Sharpr-MPRA regulatory region 12040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:43380603-43381102 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr6:43393233-43393754 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24600 Neighboring gene ATP binding cassette subfamily C member 10 Neighboring gene microRNA 6780b Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17230 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17229 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17231 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:43423943-43424784 Neighboring gene MPRA-validated peak5814 silencer Neighboring gene RNA, U6 small nuclear 1113, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:43445658-43446451 Neighboring gene tight junction associated protein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:43457381-43457974 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:43457975-43458569 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17232

    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. EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming. Meng F, et al. Nat Commun, 2019 Nov 6. PMID 31695034, Free PMC Article
    2. Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo. Naranjo AI, et al. Int J Mol Sci, 2022 Jan 29. PMID 35163478, Free PMC Article
    3. The novel gene EGFL9/Dlk2, highly homologous to Dlk1, functions as a modulator of adipogenesis. Nueda ML, et al. J Mol Biol, 2007 Apr 13. PMID 17320102
    4. The proteins DLK1 and DLK2 modulate NOTCH1-dependent proliferation and oncogenic potential of human SK-MEL-2 melanoma cells. Nueda ML, et al. Biochim Biophys Acta, 2014 Nov. PMID 25093684
    5. The DNA sequence and analysis of human chromosome 6. Mungall AJ, et al. Nature, 2003 Oct 23. PMID 14574404

    See all (16) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo.
      Title: Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo.
    2. EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.
      Title: EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.
    3. Studies in mouse showed that dlk2, highly homologous to dlk1 (also known as pref-1, and FA-1) appears to modulate adipogenesis in vitro in an opposite way to that of dlk1.
      Title: The novel gene EGFL9/Dlk2, highly homologous to Dlk1, functions as a modulator of adipogenesis.
    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

    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

    • MGC2487, MGC111055

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables Notch binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of Notch signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of fat cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein delta homolog 2
    Names
    EGF-like protein 9
    EGF-like-domain, multiple 9
    delta-like 2 homolog
    epidermal growth factor-like protein 9

    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_001286655.1 → NP_001273584.1  protein delta homolog 2 isoform b precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses two alternate splice sites in the central coding region, compared to variant 2. The encoded isoform (b) is shorter, compared to isoform a.
      Source sequence(s)
      AK055380, BC110320, DA332624
      UniProtKB/TrEMBL
      H0Y5P1
      Conserved Domains (1) summary
      cd00054
      Location:137 → 173
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    2. NM_001286656.2 → NP_001273585.1  protein delta homolog 2 isoform c precursor

      See identical proteins and their annotated locations for NP_001273585.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate splice site in the central coding region, compared to variant 2. The encoded isoform (c) is shorter, compared to isoform a.
      Source sequence(s)
      BC110320, BM811564
      Consensus CDS
      CCDS75461.1
      UniProtKB/TrEMBL
      Q5T3T9
      Related
      ENSP00000361563.1, ENST00000372485.5
      Conserved Domains (1) summary
      cd00054
      Location:168 → 204
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    3. NM_023932.4 → NP_076421.2  protein delta homolog 2 isoform a precursor

      See identical proteins and their annotated locations for NP_076421.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Both variants 1 and 2 encode the same isoform (a).
      Source sequence(s)
      BC110320
      Consensus CDS
      CCDS4897.1
      UniProtKB/Swiss-Prot
      B3KNZ7, Q5T3T8, Q6UY11, Q9BQ54
      Related
      ENSP00000361566.3, ENST00000372488.8
      Conserved Domains (1) summary
      cd00054
      Location:174 → 210
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    4. NM_206539.2 → NP_996262.1  protein delta homolog 2 isoform a precursor

      See identical proteins and their annotated locations for NP_996262.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (a). Both variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AK055380, AY358126
      Consensus CDS
      CCDS4897.1
      UniProtKB/Swiss-Prot
      B3KNZ7, Q5T3T8, Q6UY11, Q9BQ54
      Related
      ENSP00000349893.3, ENST00000357338.3
      Conserved Domains (1) summary
      cd00054
      Location:174 → 210
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      43450352..43456632 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419264.1 → XP_047275220.1  protein delta homolog 2 isoform X3

    2. XM_047419263.1 → XP_047275219.1  protein delta homolog 2 isoform X3

    3. XM_005249308.6 → XP_005249365.1  protein delta homolog 2 isoform X1

      Conserved Domains (1) summary
      cd00054
      Location:267 → 303
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    4. XM_011514823.4 → XP_011513125.1  protein delta homolog 2 isoform X2

      Conserved Domains (1) summary
      cd00054
      Location:236 → 272
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

    5. XM_047419265.1 → XP_047275221.1  protein delta homolog 2 isoform X4

      Related
      ENSP00000399829.1, ENST00000430324.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      43279119..43285399 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356261.1 → XP_054212236.1  protein delta homolog 2 isoform X3

    2. XM_054356258.1 → XP_054212233.1  protein delta homolog 2 isoform X1

    3. XM_054356260.1 → XP_054212235.1  protein delta homolog 2 isoform X3

    4. XM_054356259.1 → XP_054212234.1  protein delta homolog 2 isoform X2

    5. XM_054356262.1 → XP_054212237.1  protein delta homolog 2 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6UY11.1 GenPept UniProtKB/Swiss-Prot:Q6UY11

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