Nell2 NEL-like 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nell2provided by MGI
Official Full Name: NEL-like 2provided by MGI
Primary source: MGI:MGI:1858510
See related: Ensembl:ENSMUSG00000022454 AllianceGenome:MGI:1858510
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: mel91; A330108N19Rik
Summary: Enables identical protein binding activity. Involved in commissural neuron axon guidance and fertilization. Located in extracellular region. Is expressed in several structures, including alimentary system; autopod; central nervous system; limb mesenchyme; and sensory organ. Orthologous to human NELL2 (neural EGFL like 2). [provided by Alliance of Genome Resources, Jan 2025]
Expression: Biased expression in cortex adult (RPKM 60.0), frontal lobe adult (RPKM 49.2) and 7 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 E3; 15 49.39 cM

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (95117321..95426677, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (95219440..95528796, complement)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Male mice in which Nell2 had been knocked out were infertile.
Title: NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility.
Nell2 acts as a domain-specific positional label in the dorsal lateral geniculate nucleus that discriminates contralateral and ipsilateral retinal ganglion cell axons, and it plays essential roles in the establishment of the eye-specific retinogeniculate projection
Title: Nell2 regulates the contralateral-versus-ipsilateral visual projection as a domain-specific positional cue.
Cytosolic NELL2 specifically interacts with PKC beta isotypes and inhibits PKC beta1 through direct binding to the N-terminal pseudosubstrate domain of PKC beta1.
Title: The cytosolic splicing variant of NELL2 inhibits PKCβ1 in glial cells.
These findings identify NELL2 as an axon guidance cue and establish Robo3 as a multifunctional regulator of pathfinding that simultaneously mediates NELL2 repulsion, inhibits Slit repulsion, and facilitates Netrin attraction to achieve a common guidance purpose.
Title: Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2.
NELL2 plays an important role in the regulation of neuronal differentiation via control of N-cadherin expression and cell aggregation.
Title: Neural epidermal growth factor-like like protein 2 (NELL2) promotes aggregation of embryonic carcinoma P19 cells by inducing N-cadherin expression.
Nel interacts with a range of molecules through its different domains and exerts distinct functions.
Title: Structure-function analysis of Nel, a thrombospondin-1-like glycoprotein involved in neural development and functions.
the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK
Title: Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death.
NELL2 plays an important role as a novel suppressor in long-term potentiation in vivo in the mouse dentate gyrus
Title: Enhanced long-term potentiation in vivo in dentate gyrus of NELL2-deficient mice.
NELL2 plays an important role in hippocampus-dependent spatial learning and that emotional learning does not depend critically on NELL2.
Title: Spatial learning of mice lacking a neuron-specific epidermal growth factor family protein, NELL2.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (5) 1 citation
Targeted (3) 1 citation
Transposon induced (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH125253 (e-PCR)
- UniSTS:162075

13.MMHAP79FRE7.seq (e-PCR)
- UniSTS:123184

Nell2 (e-PCR), detects polymorphism
- UniSTS:465487

R75516 (e-PCR)
- UniSTS:125550

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables heparin binding	IBA Inferred from Biological aspect of Ancestor more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
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
enables protein kinase C binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in commissural neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in commissural neuron axon guidance	ISO Inferred from Sequence Orthology more info
involved_in development of secondary female sexual characteristics	ISO Inferred from Sequence Orthology more info
involved_in fertilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neurogenesis	ISO Inferred from Sequence Orthology more info
involved_in neuron cellular homeostasis	ISO Inferred from Sequence Orthology more info
involved_in neuron cellular homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of hormone secretion	ISO Inferred from Sequence Orthology more info
involved_in regulation of growth	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: protein kinase C-binding protein NELL2

Names: NEL-like protein 2; nel-like 2 homolog

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_001289653.1 → NP_001276582.1 protein kinase C-binding protein NELL2 precursor

Status: VALIDATED

Source sequence(s)

AC109198, AC163991, AC164402

Consensus CDS

CCDS27775.1

UniProtKB/Swiss-Prot

Q61220, Q80UM5

UniProtKB/TrEMBL

A0A2R8VHV8

Related

ENSMUSP00000074751.3, ENSMUST00000075275.3

Conserved Domains (5) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain
NM_001356950.1 → NP_001343879.1 protein kinase C-binding protein NELL2 precursor

Status: VALIDATED

Source sequence(s)

AC109198, AC163991, AC164402

Consensus CDS

CCDS27775.1

UniProtKB/Swiss-Prot

Q61220, Q80UM5

UniProtKB/TrEMBL

A0A2R8VHV8

Related

ENSMUSP00000131665.2, ENSMUST00000166170.9

Conserved Domains (5) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain
NM_001356951.1 → NP_001343880.1 protein kinase C-binding protein NELL2 precursor

Status: VALIDATED

Source sequence(s)

AC109198, AC163991, AC164402

Consensus CDS

CCDS27775.1

UniProtKB/Swiss-Prot

Q61220, Q80UM5

UniProtKB/TrEMBL

A0A2R8VHV8

Related

ENSMUSP00000155490.2, ENSMUST00000229981.2

Conserved Domains (5) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

95117321..95426677 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006521163.3 → XP_006521226.1 protein kinase C-binding protein NELL2 isoform X1

UniProtKB/Swiss-Prot

Q61220, Q80UM5

UniProtKB/TrEMBL

A0A2R8VHV8

Conserved Domains (5) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain
XM_036159519.1 → XP_036015412.1 protein kinase C-binding protein NELL2 isoform X2

UniProtKB/TrEMBL

A0A2R8VHV8

Conserved Domains (6) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam00093
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:708 → 758

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain
XM_006521164.5 → XP_006521227.1 protein kinase C-binding protein NELL2 isoform X2

UniProtKB/TrEMBL

A0A2R8VHV8

Related

ENSMUSP00000155436.2, ENSMUST00000229933.2

Conserved Domains (6) summary

smart00179
Location:558 → 592

EGF_CA; Calcium-binding EGF-like domain

smart00210
Location:32 → 217

TSPN; Thrombospondin N-terminal -like domains

pfam00093
Location:277 → 333

VWC; von Willebrand factor type C domain

pfam07645
Location:605 → 636

EGF_CA; Calcium-binding EGF domain

cl17735
Location:708 → 758

VWC; von Willebrand factor type C domain

pfam12947
Location:489 → 524

EGF_3; EGF domain

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_016743.2: Suppressed sequence

Description

NM_016743.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.