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NUMBL NUMB like endocytic adaptor protein [ Homo sapiens (human) ]

Gene ID: 9253, updated on 5-Mar-2024

Summary

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Official Symbol
NUMBLprovided by HGNC
Official Full Name
NUMB like endocytic adaptor proteinprovided by HGNC
Primary source
HGNC:HGNC:8061
See related
Ensembl:ENSG00000105245 MIM:604018; AllianceGenome:HGNC:8061
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
NBL; CAG3A; CTG3a; NUMBR; NUMB-R; TNRC23; NUMBLIKE
Summary
Involved in cytokine-mediated signaling pathway and protein metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in brain (RPKM 8.6), endometrium (RPKM 7.2) and 25 other tissues See more
Orthologs
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Genomic context

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See NUMBL in Genome Data Viewer
Location:
19q13.2
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (40665905..40690651, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (43486573..43511317, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (41171810..41196556, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10634 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10635 Neighboring gene SH3KBP1 binding protein 1 Neighboring gene Sharpr-MPRA regulatory region 6117 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14657 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10636 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41108540-41109063 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10637 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10638 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10639 Neighboring gene Sharpr-MPRA regulatory region 12022 Neighboring gene latent transforming growth factor beta binding protein 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10640 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14658 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41119811-41120358 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14659 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41128498-41129138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14660 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41136805-41137395 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:41142798-41142919 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:41153389-41154370 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14661 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10641 Neighboring gene Sharpr-MPRA regulatory region 4590 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41194847-41195786 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10642 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41196725-41197662 Neighboring gene coenzyme Q8B Neighboring gene RNA, U6 small nuclear 195, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10644 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10645 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41224841-41225542 Neighboring gene inositol-trisphosphate 3-kinase C

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. Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy. García-Heredia JM, et al. Oncotarget, 2016 Sep 27. PMID 27613838, Free PMC Article
  2. Numblike regulates proliferation, apoptosis, and invasion of lung cancer cell. Yingjie L, et al. Tumour Biol, 2013 Oct. PMID 23681800
  3. Regulation of lung cancer metastasis by Klf4-Numb-like signaling. Vaira V, et al. Cancer Res, 2013 Apr 15. PMID 23440423, Free PMC Article
  4. Mutation and copy number analysis of LNX1 and Numbl in nervous system tumors. Blom T, et al. Cancer Genet Cytogenet, 2008 Oct 15. PMID 18940473
  5. SLC8A1 antisense RNA 1 suppresses papillary thyroid cancer malignant progression via the FUS RNA binding protein (FUS)/NUMB like endocytic adaptor protein (Numbl) axis. Xin Y, et al. Bioengineered, 2022 May. PMID 35599603, Free PMC Article

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SLC8A1 antisense RNA 1 suppresses papillary thyroid cancer malignant progression via the FUS RNA binding protein (FUS)/NUMB like endocytic adaptor protein (Numbl) axis.
    Title: SLC8A1 antisense RNA 1 suppresses papillary thyroid cancer malignant progression via the FUS RNA binding protein (FUS)/NUMB like endocytic adaptor protein (Numbl) axis.
  2. NumbL can act as an independent tumor suppressor inhibiting the Notch pathway and regulating the cancer stem cell pool
    Title: Numb-like (NumbL) downregulation increases tumorigenicity, cancer stem cell-like properties and resistance to chemotherapy.
  3. let-7c inhibits Notch and progression markers but up-regulates Numbl in pancreatic cancer treated with quercetin
    Title: Up-regulation of microRNA let-7c by quercetin inhibits pancreatic cancer progression by activation of Numbl.
  4. investigations revealed that NUMB and NUMBL interacted with small GTPase Rab7 to transition ERBB2 from early to late endosome for degradation.
    Title: Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation.
  5. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis
    Title: Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis.
  6. Numb/Numbl control VEGF receptor endocytosis, signaling, and recycling in endothelial cells, which promotes the angiogenic growth of blood vessels.
    Title: Regulation of vascular endothelial growth factor receptor function in angiogenesis by numb and numb-like.
  7. Numbl might be involved in the inhibition of growth, proliferation, and invasion of 95-D lung cancer cells.
    Title: Numblike regulates proliferation, apoptosis, and invasion of lung cancer cell.
  8. Numbl-Klf4 signaling is critical to maintain multiple nodes of metastatic progression, including persistence of cancer-initiating cells.
    Title: Regulation of lung cancer metastasis by Klf4-Numb-like signaling.
  9. data suggest that Numbl regulates glioma cell migration and invasion by abrogating TRAF5-induced activation of NF-KappaB
    Title: Numbl inhibits glioma cell migration and invasion by suppressing TRAF5-mediated NF-κB activation.
  10. NUMBL interacts with TRAF6 and promotes the degradation of TRAF6 in vivo, leading to the inhibition of NF-kappaB signaling pathway.
    Title: NUMBL interacts with TRAF6 and promotes the degradation of TRAF6.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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
A genome-wide association study identifies three new risk loci for Kawasaki disease.
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

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of numb homolog (Drosophila)-like (NUMBL) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Go to the HIV-1, Human Interaction Database

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in adherens junction organization IEA
Inferred from Electronic Annotation
more info
  
involved_in axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in cytokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in lateral ventricle development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in neuroblast division in subventricular zone ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of neurogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
numb-like protein
Names
numb homolog-like
numb-related protein

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_001289979.2 → NP_001276908.1  numb-like protein isoform b

    See identical proteins and their annotated locations for NP_001276908.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream start codon, compared to variant 1. The encoded protein (isoform b) has a shorter N-terminus, compared to isoform a.
    Source sequence(s)
    AC010412, BC144583, HY111715
    Consensus CDS
    CCDS77298.1
    UniProtKB/TrEMBL
    A0A0C4DGH3, B7Z5W0
    Related
    ENSP00000472400.1, ENST00000598779.5
    Conserved Domains (3) summary
    cd01268
    Location:23 → 157
    PTB_Numb; Numb Phosphotyrosine-binding (PTB) domain
    pfam06311
    Location:246 → 330
    NumbF; NUMB domain
    cl25764
    Location:348 → 516
    PAT1; Topoisomerase II-associated protein PAT1

  2. NM_001289980.2 → NP_001276909.1  numb-like protein isoform b

    See identical proteins and their annotated locations for NP_001276909.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) ) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from a downstream start codon, compared to variant 1. The encoded protein (isoform b) has a shorter N-terminus, compared to isoform a.
    Source sequence(s)
    AC010412, AK299484, DC374917
    Consensus CDS
    CCDS77298.1
    UniProtKB/TrEMBL
    A0A0C4DGH3, B7Z5W0
    Related
    ENSP00000442759.1, ENST00000540131.5
    Conserved Domains (3) summary
    cd01268
    Location:23 → 157
    PTB_Numb; Numb Phosphotyrosine-binding (PTB) domain
    pfam06311
    Location:246 → 330
    NumbF; NUMB domain
    cl25764
    Location:348 → 516
    PAT1; Topoisomerase II-associated protein PAT1

  3. NM_004756.5 → NP_004747.1  numb-like protein isoform a

    See identical proteins and their annotated locations for NP_004747.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).
    Source sequence(s)
    AC010412, AK289398
    Consensus CDS
    CCDS12561.1
    UniProtKB/Swiss-Prot
    Q7Z4J9, Q9Y6R0
    UniProtKB/TrEMBL
    A8K033
    Related
    ENSP00000252891.3, ENST00000252891.8
    Conserved Domains (2) summary
    cd01268
    Location:64 → 198
    PTB_Numb; Numb Phosphotyrosine-binding (PTB) domain
    pfam06311
    Location:287 → 371
    NumbF; NUMB domain

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_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    40665905..40690651 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    43486573..43511317 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y6R0.1 GenPept UniProtKB/Swiss-Prot:Q9Y6R0

Gene LinkOut

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