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NETO2 neuropilin and tolloid like 2 [ Homo sapiens (human) ]

Gene ID: 81831, updated on 3-Apr-2024

Summary

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Official Symbol
NETO2provided by HGNC
Official Full Name
neuropilin and tolloid like 2provided by HGNC
Primary source
HGNC:HGNC:14644
See related
Ensembl:ENSG00000171208 MIM:607974; AllianceGenome:HGNC:14644
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
BTCL2; NEOT2
Summary
This gene encodes a predicted transmembrane protein containing two extracellular CUB domains followed by a low-density lipoprotein class A (LDLa) domain. A similar gene in rats encodes a protein that modulates glutamate signaling in the brain by regulating kainate receptor function. Expression of this gene may be a biomarker for proliferating infantile hemangiomas. A pseudogene of this gene is located on the long arm of chromosome 8. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]
Expression
Broad expression in spleen (RPKM 8.8), brain (RPKM 6.7) and 17 other tissues See more
Orthologs
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Genomic context

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See NETO2 in Genome Data Viewer
Location:
16q12.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (47077703..47143945, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (52874528..52940774, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (47111614..47177856, complement)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:46993862-46994528 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:46999088-46999813 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7439 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10783 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10782 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7443 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7442 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7441 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:47025988-47026488 Neighboring gene DNAJA2 divergent transcript Neighboring gene DnaJ heat shock protein family (Hsp40) member A2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7444 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7445 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10784 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10785 Neighboring gene MPRA-validated peak2576 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:47112757-47113521 Neighboring gene small nucleolar RNA U13 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7446 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7447 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7448 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7449 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7450 Neighboring gene ITFG1 antisense RNA 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:47200827-47201756 Neighboring gene ribosomal protein L23a pseudogene 72 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:47213953-47214504 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:47214505-47215056 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:47215057-47215608 Neighboring gene integrin alpha FG-GAP repeat containing 1 Neighboring gene MPRA-validated peak2577 silencer Neighboring gene proteasome 20S subunit beta 5 pseudogene

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. Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma. Wang X, et al. Gene, 2021 Feb 5. PMID 33157203
  2. Reducing NETO2 expression prevents human nasopharyngeal carcinoma (NPC) progression by suppressing metastasis and inducing apoptosis. He AR, et al. Biochem Biophys Res Commun, 2019 May 28. PMID 30975469
  3. NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients. Liu JY, et al. Cell Death Dis, 2019 Feb 15. PMID 30770791, Free PMC Article
  4. Upregulation of NETO2 gene in colorectal cancer. Fedorova MS, et al. BMC Genet, 2017 Dec 28. PMID 29297384, Free PMC Article
  5. Upregulation of NETO2 expression correlates with tumor progression and poor prognosis in colorectal carcinoma. Hu L, et al. BMC Cancer, 2015 Dec 23. PMID 26699544, Free PMC Article

See all (38) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NETO2 promotes melanoma progression via activation of the Ca[2+]/CaMKII signaling pathway.
    Title: NETO2 promotes melanoma progression via activation of the Ca(2+)/CaMKII signaling pathway.
  2. Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth.
    Title: Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth.
  3. Kainate receptor modulation by NETO2.
    Title: Kainate receptor modulation by NETO2.
  4. NETO2 promotes esophageal cancer progression by inducing proliferation and metastasis via PI3K/AKT and ERK pathway.
    Title: NETO2 promotes esophageal cancer progression by inducing proliferation and metastasis via PI3K/AKT and ERK pathway.
  5. Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma.
    Title: Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma.
  6. NETO2 expression is up-regulated in Nasopharyngeal carcinoma (NPC) clinical specimens and cell lines. NETO2 down-regulation reduces proliferation, migration and invasion in irradiated NPC cell lines.
    Title: Reducing NETO2 expression prevents human nasopharyngeal carcinoma (NPC) progression by suppressing metastasis and inducing apoptosis.
  7. NETO2 promotes invasion and metastasis of gastric cancer cells and represents a novel prognostic indicator as well as a potential therapeutic target in gastric cancer.
    Title: NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients.
  8. upregulation of NETO2 gene is first stipulated by the isoform 1 (NM_018092.4), and the probable mechanism of its activation is associated with the increased expression of SAP30 transcription factor.
    Title: [Transcription Factor SAP30 Is Involved in the Activation of NETO2 Gene Expression in Clear Cell Renal Cell Carcinoma].
  9. NETO2 may be involved in colorectal cancer progression, but is not directly associated with epithelial-mesenchymal transition
    Title: Upregulation of NETO2 gene in colorectal cancer.
  10. Results suggested that the extracellular N-terminal region including the two CUB domains was largely responsible for the distinct regulatory effects of Neto1 and Neto2 on the desensitization properties of GluK1 homomeric receptors
    Title: The auxiliary subunits Neto1 and Neto2 have distinct, subunit-dependent effects at recombinant GluK1- and GluK2-containing kainate receptors.
Submit: New GeneRIF Correction See all GeneRIFs (13)

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

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ10430, FLJ14724, FLJ90456

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ionotropic glutamate receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in neurotransmitter receptor localization to postsynaptic specialization membrane IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in postsynaptic density IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in postsynaptic density membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
neuropilin and tolloid-like protein 2
Names
brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 2
neuropilin (NRP) and tolloid (TLL)-like 2

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.

Genomic

  1. NG_047201.2 RefSeqGene

    Range
    5000..71242
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001201477.2 → NP_001188406.1  neuropilin and tolloid-like protein 2 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC007338, AY358718, BC108727, DA117339
    Consensus CDS
    CCDS58460.1
    UniProtKB/Swiss-Prot
    Q8NC67
    UniProtKB/TrEMBL
    Q32NC3
    Related
    ENSP00000306726.5, ENST00000303155.9
    Conserved Domains (2) summary
    cd00041
    Location:45 → 158
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00112
    Location:290 → 324
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

  2. NM_018092.5 → NP_060562.3  neuropilin and tolloid-like protein 2 isoform 1 precursor

    See identical proteins and their annotated locations for NP_060562.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC007338, AK074937
    Consensus CDS
    CCDS10727.1
    UniProtKB/Swiss-Prot
    J3KNF1, Q7Z381, Q8NC67, Q8ND51, Q96SP4, Q9NVY8
    Related
    ENSP00000455169.1, ENST00000562435.6
    Conserved Domains (2) summary
    cd00041
    Location:45 → 158
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00112
    Location:297 → 331
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

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_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    47077703..47143945 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006721291.2 → XP_006721354.1  neuropilin and tolloid-like protein 2 isoform X2

    Conserved Domains (1) summary
    cd00041
    Location:45 → 158
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

  2. XM_006721289.2 → XP_006721352.1  neuropilin and tolloid-like protein 2 isoform X1

    See identical proteins and their annotated locations for XP_006721352.1

    Conserved Domains (1) summary
    cd00041
    Location:45 → 158
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

  3. XM_017023740.2 → XP_016879229.1  neuropilin and tolloid-like protein 2 isoform X3

    UniProtKB/TrEMBL
    B7Z4I7
    Related
    ENSP00000454213.1, ENST00000562559.5
    Conserved Domains (2) summary
    cd00041
    Location:69 → 155
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00112
    Location:161 → 195
    LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

  4. XM_047434728.1 → XP_047290684.1  neuropilin and tolloid-like protein 2 isoform X5

  5. XM_006721292.2 → XP_006721355.1  neuropilin and tolloid-like protein 2 isoform X4

    UniProtKB/TrEMBL
    Q32NC3
    Conserved Domains (1) summary
    cd00041
    Location:45 → 158
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    52874528..52940774 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054314071.1 → XP_054170046.1  neuropilin and tolloid-like protein 2 isoform X2

  2. XM_054314070.1 → XP_054170045.1  neuropilin and tolloid-like protein 2 isoform X1

  3. XM_054314072.1 → XP_054170047.1  neuropilin and tolloid-like protein 2 isoform X3

  4. XM_054314074.1 → XP_054170049.1  neuropilin and tolloid-like protein 2 isoform X5

  5. XM_054314073.1 → XP_054170048.1  neuropilin and tolloid-like protein 2 isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8NC67.1 GenPept UniProtKB/Swiss-Prot:Q8NC67

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