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

Summary

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. Predicted to be active in cytoplasm and glutamatergic synapse. [provided by Alliance of Genome Resources, Oct 2024]
Expression: Ubiquitous expression in brain (RPKM 8.6), endometrium (RPKM 7.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.2

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (40665905..40690651, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (43486573..43511317, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (41171810..41196556, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G64278 (e-PCR)
- UniSTS:158658

G34996 (e-PCR)
- UniSTS:15314

RH75304 (e-PCR)
- UniSTS:87281

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)

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
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
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