Q61220 · NELL2_MOUSE
- ProteinProtein kinase C-binding protein NELL2
- GeneNell2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids819 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays multiple roles in neural tissues, regulates neuronal proliferation, survival, differentiation, polarization, as well as axon guidance and synaptic functions. Plays an important role in axon development during neuronal differentiation through the MAPK intracellular signaling pathway (By similarity) (PubMed:26586761, PubMed:32198364).
Via binding to its receptor ROBO3, plays a role in axon guidance, functioning as a repulsive axon guidance cue that contributes to commissural axon guidance to the midline (PubMed:26586761, PubMed:32198364).
Required for neuron survival through the modulation of MAPK signaling pathways too. Involved in the regulation of hypothalamic GNRH secretion and the control of puberty (By similarity).
Via binding to its receptor ROBO3, plays a role in axon guidance, functioning as a repulsive axon guidance cue that contributes to commissural axon guidance to the midline (PubMed:26586761, PubMed:32198364).
Required for neuron survival through the modulation of MAPK signaling pathways too. Involved in the regulation of hypothalamic GNRH secretion and the control of puberty (By similarity).
Epididymal-secreted protein that signals through a ROS1-pathway to regulate the epididymal initial segment (IS) maturation, sperm maturation and male fertility.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 443 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 444 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 446 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 462 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 463 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 466 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 558 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 559 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 561 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 577 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 578 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 581 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 605 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 606 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 608 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 624 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 625 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 628 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | dendrite | |
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Cellular Component | perikaryon | |
Molecular Function | calcium ion binding | |
Molecular Function | heparin binding | |
Molecular Function | identical protein binding | |
Molecular Function | protein kinase C binding | |
Biological Process | commissural neuron axon guidance | |
Biological Process | development of secondary female sexual characteristics | |
Biological Process | fertilization | |
Biological Process | neurogenesis | |
Biological Process | neuron cellular homeostasis | |
Biological Process | positive regulation of hormone secretion | |
Biological Process | regulation of growth |
Keywords
- Ligand
Names & Taxonomy
Protein names
- Recommended nameProtein kinase C-binding protein NELL2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ61220
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Detected in the epididymal lumen.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Deficient male mice exhibit infertility, impaired binding of sperm to zona pellucida, and impaired sperm migration in female genital tract. Postnatal differentiation of the initial segment (IS) of the caput epididymis is completely abolished in Nell2 deficient males and continued throughout life. Ovch2 is not secreted and Adam3 is not processed into its mature form in cauda epididymal spermatozoa, leading to inability of spermatozoa to pass through the uterotubal junction and to bind to the zona pellucida.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 451 | Strong (120-fold) reduction of affinity towards ROBO3; when associated with A-453. Reduced axon repulsive activity; when associated with A-453. | ||||
Sequence: R → A | ||||||
Mutagenesis | 453 | Strong (120-fold) reduction of affinity towards ROBO3; when associated with A-451. Reduced axon repulsive activity; when associated with A-453. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 455 | Mildly (2.4-fold) reduction of affinity towards ROBO3. Does not affect axon repulsive activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 480 | Strong (120-fold) reduction of affinity towards ROBO3; when associated with A-481. | ||||
Sequence: D → A | ||||||
Mutagenesis | 481 | Strong (120-fold) reduction of affinity towards ROBO3; when associated with A-480. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 501 | Abolishes binding to ROBO3; when associated with A-503. Abolishes axon repulsive activity; when associated with A-503. | ||||
Sequence: L → A | ||||||
Mutagenesis | 503 | Abolishes binding to ROBO3; when associated with A-503. Abolishes axon repulsive activity; when associated with A-503. | ||||
Sequence: F → A | ||||||
Mutagenesis | 512 | Mildly (2.4-fold) reduced affinity for ROBO3. Does not affect axon repulsive activity. | ||||
Sequence: V → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 23 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MHAMESRVLLRTFCVILGLGAVWG | ||||||
Chain | PRO_0000007667 | 25-819 | Protein kinase C-binding protein NELL2 | |||
Sequence: LGVDPSLQIDVLTELELGESTDGVRQVPGLHNGTKAFLFQESPRSIKASTATAERFFQKLRNKHEFTILVTLKQIHLNSGVILSIHHLDHRYLELESSGHRNEIRLHYRSGTHRPHTEVFPYILADAKWHKLSLAFSASHLILHIDCNKIYERVVEMPSTDLPLGTTFWLGQRNNAHGYFKGIMQDVHVLVMPQGFIAQCPDLNRTCPTCNDFHGLVQKIMELQDILSKTSAKLSRAEQRMNRLDQCYCERTCTVKGTTYRESESWTDGCKNCTCLNGTIQCETLVCPAPDCPPKSAPAYVDGKCCKECKSTCQFQGRSYFEGERNTVYSSSGMCVLYECKDQTMKLVENIGCPPLDCPESHQIALSHSCCKVCKGYDFCSEKHTCMENSVCRNLNDRAVCSCRDGFRALREDNAYCEDIDECAEGRHYCRENTMCVNTPGSFMCICKTGYIRIDDYSCTEHDECLTNQHNCDENALCFNTVGGHNCVCKPGYTGNGTTCKAFCKDGCRNGGACIAANVCACPQGFTGPSCETDIDECSEGFVQCDSRANCINLPGWYHCECRDGYHDNGMFAPGGESCEDIDECGTGRHSCTNDTICFNLDGGYDCRCPHGKNCTGDCVHEGKVKHTGQIWVLENDRCSVCSCQTGFVMCRRMVCDCENPTVDLSCCPECDPRLSSQCLHQNGETVYNSGDTWVQDCRQCRCLQGEVDCWPLACPEVECEFSVLPENECCPRCVTDPCQADTIRNDITKTCLDEMNVVRFTGSSWIKHGTECTLCQCKNGHLCCSVDPQCLQEL | ||||||
Glycosylation | 56 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 228 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 296 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 301 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 404↔416 | |||||
Sequence: CSEKHTCMENSVC | ||||||
Disulfide bond | 410↔425 | |||||
Sequence: CMENSVCRNLNDRAVC | ||||||
Disulfide bond | 427↔441 | |||||
Sequence: CRDGFRALREDNAYC | ||||||
Disulfide bond | 447↔460 | |||||
Sequence: CAEGRHYCRENTMC | ||||||
Disulfide bond | 454↔469 | |||||
Sequence: CRENTMCVNTPGSFMC | ||||||
Disulfide bond | 471↔483 | |||||
Sequence: CKTGYIRIDDYSC | ||||||
Disulfide bond | 489↔502 | |||||
Sequence: CLTNQHNCDENALC | ||||||
Disulfide bond | 496↔511 | |||||
Sequence: CDENALCFNTVGGHNC | ||||||
Disulfide bond | 513↔524 | |||||
Sequence: CKPGYTGNGTTC | ||||||
Glycosylation | 520 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 528↔538 | |||||
Sequence: CKDGCRNGGAC | ||||||
Disulfide bond | 532↔544 | |||||
Sequence: CRNGGACIAANVC | ||||||
Disulfide bond | 546↔555 | |||||
Sequence: CPQGFTGPSC | ||||||
Glycosylation | 551 | O-linked (GlcNAc...) threonine | ||||
Sequence: T | ||||||
Disulfide bond | 562↔575 | |||||
Sequence: CSEGFVQCDSRANC | ||||||
Disulfide bond | 569↔584 | |||||
Sequence: CDSRANCINLPGWYHC | ||||||
Disulfide bond | 586↔603 | |||||
Sequence: CRDGYHDNGMFAPGGESC | ||||||
Disulfide bond | 609↔622 | |||||
Sequence: CGTGRHSCTNDTIC | ||||||
Disulfide bond | 616↔631 | |||||
Sequence: CTNDTICFNLDGGYDC | ||||||
Glycosylation | 618 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 633↔639 | |||||
Sequence: CPHGKNC | ||||||
Glycosylation | 638 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in brain and testis but not in epididymis (PubMed:32499443).
Expressed in regions flanking the commissural axon trajectory, including the ventral horn (PubMed:26586761).
Expressed in regions flanking the commissural axon trajectory, including the ventral horn (PubMed:26586761).
Developmental stage
At 9.5 dpc expressed in the presumptive motor column in the ventral horn. At 10.5 dpc, additional sites of expression include dorsal root ganglia, the dorsal mantle layer of the spinal cord, and a triangular population of cells close to the ventricle. Expression in cells forming ventral corridor persists at 11.5 dpc.
Gene expression databases
Interaction
Subunit
Homotrimer (PubMed:32198364).
Interacts with NICOL1; this interaction triggers epididymal differentiation (PubMed:37095084).
Interacts (via EGF domains) with ROBO3 (via FN domains); binding to ROBO3 induces repulsive guidance cue for commissural axons (PubMed:26586761, PubMed:32198364).
Interacts with NICOL1; this interaction triggers epididymal differentiation (PubMed:37095084).
Interacts (via EGF domains) with ROBO3 (via FN domains); binding to ROBO3 induces repulsive guidance cue for commissural axons (PubMed:26586761, PubMed:32198364).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 67-231 | Laminin G-like | ||||
Sequence: PRSIKASTATAERFFQKLRNKHEFTILVTLKQIHLNSGVILSIHHLDHRYLELESSGHRNEIRLHYRSGTHRPHTEVFPYILADAKWHKLSLAFSASHLILHIDCNKIYERVVEMPSTDLPLGTTFWLGQRNNAHGYFKGIMQDVHVLVMPQGFIAQCPDLNRTC | ||||||
Domain | 275-334 | VWFC 1 | ||||
Sequence: RTCTVKGTTYRESESWTDGCKNCTCLNGTIQCETLVCPAPDCPPKSAPAYVDGKCCKECK | ||||||
Domain | 400-442 | EGF-like 1 | ||||
Sequence: GYDFCSEKHTCMENSVCRNLNDRAVCSCRDGFRALREDNAYCE | ||||||
Domain | 443-484 | EGF-like 2; calcium-binding | ||||
Sequence: DIDECAEGRHYCRENTMCVNTPGSFMCICKTGYIRIDDYSCT | ||||||
Domain | 485-525 | EGF-like 3; calcium-binding | ||||
Sequence: EHDECLTNQHNCDENALCFNTVGGHNCVCKPGYTGNGTTCK | ||||||
Domain | 526-556 | EGF-like 4 | ||||
Sequence: AFCKDGCRNGGACIAANVCACPQGFTGPSCE | ||||||
Domain | 558-604 | EGF-like 5; calcium-binding | ||||
Sequence: DIDECSEGFVQCDSRANCINLPGWYHCECRDGYHDNGMFAPGGESCE | ||||||
Domain | 605-640 | EGF-like 6; calcium-binding | ||||
Sequence: DIDECGTGRHSCTNDTICFNLDGGYDCRCPHGKNCT | ||||||
Domain | 701-759 | VWFC 2 | ||||
Sequence: SQCLHQNGETVYNSGDTWVQDCRQCRCLQGEVDCWPLACPEVECEFSVLPENECCPRCV |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length819
- Mass (Da)91,432
- Last updated2013-09-18 v3
- Checksum530ECD363029571D
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8VHV8 | A0A2R8VHV8_MOUSE | Nell2 | 806 | ||
Q8BM06 | Q8BM06_MOUSE | Nell2 | 858 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 81 | in Ref. 1; AAB02924 | ||||
Sequence: F → L | ||||||
Sequence conflict | 183 | in Ref. 1; AAB02924 | ||||
Sequence: S → F | ||||||
Sequence conflict | 187 | in Ref. 1; AAB02924 | ||||
Sequence: P → A | ||||||
Sequence conflict | 352 | in Ref. 1; AAB02924 | ||||
Sequence: V → A | ||||||
Sequence conflict | 423 | in Ref. 1; AAB02924 | ||||
Sequence: A → V | ||||||
Sequence conflict | 470 | in Ref. 1; AAB02924 | ||||
Sequence: I → V | ||||||
Sequence conflict | 492 | in Ref. 1; AAB02924 | ||||
Sequence: N → T | ||||||
Sequence conflict | 668 | in Ref. 1; AAB02924 | ||||
Sequence: C → W | ||||||
Sequence conflict | 687 | in Ref. 1; AAB02924 | ||||
Sequence: V → D |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U59230 EMBL· GenBank· DDBJ | AAB02924.1 EMBL· GenBank· DDBJ | mRNA | ||
AC109198 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC163991 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC164402 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC051968 EMBL· GenBank· DDBJ | AAH51968.1 EMBL· GenBank· DDBJ | mRNA |