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

    Gene ID: 81831, updated on 10-Dec-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (47077703..47143945, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (52874528..52940774, complement)
    RS_2024_09 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. Identification of signaling systems in proliferating and involuting phase infantile hemangiomas by genome-wide transcriptional profiling. Calicchio ML, et al. Am J Pathol, 2009 May. PMID 19349369, Free PMC Article
    2. 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
    3. Upregulation of NETO2 gene in colorectal cancer. Fedorova MS, et al. BMC Genet, 2017 Dec 28. PMID 29297384, Free PMC Article
    4. 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
    5. Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma. Wang X, et al. Gene, 2021 Feb 5. PMID 33157203

    See all (43) 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)

    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
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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_2024_08

    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

      UniProtKB/TrEMBL
      Q32NC3

    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

      UniProtKB/TrEMBL
      B7Z4I7

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

      UniProtKB/TrEMBL
      Q32NC3

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

      UniProtKB/TrEMBL
      Q32NC3
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NC67.1 GenPept UniProtKB/Swiss-Prot:Q8NC67

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