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NELL2 neural EGFL like 2 [ Homo sapiens (human) ]

Gene ID: 4753, updated on 27-Nov-2024

Summary

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Official Symbol
NELL2provided by HGNC
Official Full Name
neural EGFL like 2provided by HGNC
Primary source
HGNC:HGNC:7751
See related
Ensembl:ENSG00000184613 MIM:602320; AllianceGenome:HGNC:7751
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
NRP2
Summary
The protein encoded by this gene is a glycoprotein containing several von Willebrand factor C domains and epidermal growth factor (EGF)-like domains. The encoded protein acts as a homotrimer and is found in the cytoplasm. Several variants encoding a few different isoforms exist, and at least one isoform appears to be a secreted protein. Studies in mouse suggest that this protein plays a role in neural cell growth and differentiation as well as in oncogenesis. [provided by RefSeq, Feb 2009]
Expression
Biased expression in brain (RPKM 55.4), duodenum (RPKM 9.0) and 5 other tissues See more
Orthologs
mouse all
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Genomic context

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See NELL2 in Genome Data Viewer
Location:
12q12
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (44508275..44921848, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (44466949..44872599, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (44902058..45307772, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene transmembrane protein 117 Neighboring gene IQ motif containing F1 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:44702016-44702516 Neighboring gene uncharacterized LOC124902922 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6221 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6222 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6223 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:44860659-44860854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:44896667-44897166 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:44896165-44896666 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:45270221-45270722 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:45270723-45271222 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_28669 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6224 Neighboring gene uncharacterized LOC105369742 Neighboring gene Rac GTPase activating protein 1 pseudogene 1 Neighboring gene DBX2 antisense RNA 1 Neighboring gene developing brain homeobox 2

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. In vitro guidance of retinal axons by a tectal lamina-specific glycoprotein Nel. Jiang Y, et al. Mol Cell Neurosci, 2009 Jun. PMID 19249368, Free PMC Article
  2. iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis. Yang Y, et al. Int J Mol Med, 2015 May. PMID 25760060
  3. NELL2 modulates cell proliferation and apoptosis via ERK pathway in the development of benign prostatic hyperplasia. Liu J, et al. Clin Sci (Lond), 2021 Jul 16. PMID 34195782
  4. The neuronal EGF-related genes NELL1 and NELL2 are expressed in hemopoietic cells and developmentally regulated in the B lineage. Luce MJ, et al. Gene, 1999 Apr 29. PMID 10231576
  5. NELL2 function in the protection of cells against endoplasmic reticulum stress. Kim DY, et al. Mol Cells, 2015. PMID 25537860, Free PMC Article

See all (37) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding.
    Title: Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding.
  2. NELL2 modulates cell proliferation and apoptosis via ERK pathway in the development of benign prostatic hyperplasia.
    Title: NELL2 modulates cell proliferation and apoptosis via ERK pathway in the development of benign prostatic hyperplasia.
  3. Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2.
    Title: Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2.
  4. results suggest that Robo2 functions as a receptor for NELL1/2, particularly under circumstances where Robo2 undergoes proteolytic digestion
    Title: Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2.
  5. CSF NELL2 is a potential diagnostic biomarker for TBM.
    Title: iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis.
  6. CpG islands in the NELL1 and NELL2 promoters are hypermethylated in renal cell carcinoma.NELL1 and NELL2 protein expression is downregulated in clear cell renal carcinoma.
    Title: Expression and regulatory effects on cancer cell behavior of NELL1 and NELL2 in human renal cell carcinoma.
  7. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
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)

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 calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables heparin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables identical protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase C binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in commissural neuron axon guidance IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in fertilization ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in neuron cellular homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular region ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
protein kinase C-binding protein NELL2
Names
NEL-like protein 2
NEL-related protein 2
neural epidermal growth factor-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.

mRNA and Protein(s)

  1. NM_001145107.2 → NP_001138579.1  protein kinase C-binding protein NELL2 isoform a

    See identical proteins and their annotated locations for NP_001138579.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AC079033, AK299733, D83018, DB316660
    Consensus CDS
    CCDS44863.1
    UniProtKB/TrEMBL
    B7Z625
    Related
    ENSP00000416341.2, ENST00000437801.6
    Conserved Domains (5) summary
    smart00179
    Location:605 → 639
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:79 → 264
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:652 → 683
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:536 → 571
    EGF_3; EGF domain
    cl17735
    Location:324 → 380
    VWC; von Willebrand factor type C domain

  2. NM_001145108.2 → NP_001138580.1  protein kinase C-binding protein NELL2 isoform b precursor

    See identical proteins and their annotated locations for NP_001138580.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode isoform b.
    Source sequence(s)
    AL527608, BC020544, DA307194, DB316660
    Consensus CDS
    CCDS8746.1
    UniProtKB/Swiss-Prot
    B7Z2U7, B7Z5Q4, B7Z9J5, B7Z9U3, Q96JS2, Q99435
    UniProtKB/TrEMBL
    B7Z625
    Related
    ENSP00000390680.2, ENST00000429094.7
    Conserved Domains (5) summary
    smart00179
    Location:555 → 589
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:29 → 214
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:602 → 633
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:486 → 521
    EGF_3; EGF domain
    cl17735
    Location:274 → 330
    VWC; von Willebrand factor type C domain

  3. NM_001145109.2 → NP_001138581.1  protein kinase C-binding protein NELL2 isoform c precursor

    See identical proteins and their annotated locations for NP_001138581.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    AK299277, D83018, DB316660
    Consensus CDS
    CCDS44864.1
    UniProtKB/TrEMBL
    F8VVB6
    Related
    ENSP00000378866.2, ENST00000395487.6
    Conserved Domains (5) summary
    smart00179
    Location:554 → 588
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:28 → 213
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:601 → 632
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:485 → 520
    EGF_3; EGF domain
    cl17735
    Location:273 → 329
    VWC; von Willebrand factor type C domain

  4. NM_001145110.2 → NP_001138582.1  protein kinase C-binding protein NELL2 isoform d

    See identical proteins and their annotated locations for NP_001138582.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (d) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    AC079033, AK295125, AK316058, D83018, DB316660
    Consensus CDS
    CCDS53781.1
    UniProtKB/TrEMBL
    B7Z625
    Related
    ENSP00000327988.4, ENST00000333837.8
    Conserved Domains (5) summary
    smart00179
    Location:578 → 612
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:52 → 237
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:625 → 656
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:509 → 544
    EGF_3; EGF domain
    cl17735
    Location:297 → 353
    VWC; von Willebrand factor type C domain

  5. NM_006159.2 → NP_006150.1  protein kinase C-binding protein NELL2 isoform b precursor

    See identical proteins and their annotated locations for NP_006150.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode isoform b.
    Source sequence(s)
    D83018, DA307194, DB316660
    Consensus CDS
    CCDS8746.1
    UniProtKB/Swiss-Prot
    B7Z2U7, B7Z5Q4, B7Z9J5, B7Z9U3, Q96JS2, Q99435
    UniProtKB/TrEMBL
    B7Z625
    Related
    ENSP00000394612.2, ENST00000452445.6
    Conserved Domains (5) summary
    smart00179
    Location:555 → 589
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:29 → 214
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:602 → 633
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:486 → 521
    EGF_3; EGF domain
    cl17735
    Location:274 → 330
    VWC; von Willebrand factor type C domain

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    44508275..44921848 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011538396.2 → XP_011536698.1  protein kinase C-binding protein NELL2 isoform X1

    See identical proteins and their annotated locations for XP_011536698.1

    UniProtKB/Swiss-Prot
    B7Z2U7, B7Z5Q4, B7Z9J5, B7Z9U3, Q96JS2, Q99435
    UniProtKB/TrEMBL
    B7Z625
    Conserved Domains (5) summary
    smart00179
    Location:555 → 589
    EGF_CA; Calcium-binding EGF-like domain
    smart00210
    Location:29 → 214
    TSPN; Thrombospondin N-terminal -like domains
    pfam07645
    Location:602 → 633
    EGF_CA; Calcium-binding EGF domain
    pfam12947
    Location:486 → 521
    EGF_3; EGF domain
    cl17735
    Location:274 → 330
    VWC; von Willebrand factor type C domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    44466949..44872599 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372112.1 → XP_054228087.1  protein kinase C-binding protein NELL2 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99435.1 GenPept UniProtKB/Swiss-Prot:Q99435

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