UniProtKB - Q7Z3S9 (NT2NA_HUMAN)
Notch homolog 2 N-terminal-like protein A
NOTCH2NLA
Functioni
Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway (PubMed:29856954, PubMed:29856955, PubMed:29561261).
Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production (PubMed:29856954).
Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect (PubMed:29856954).
Enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2 (PubMed:29856954).
Also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (By similarity).
By similarity3 PublicationsGO - Molecular functioni
- calcium ion binding Source: InterPro
- Notch binding Source: UniProtKB
GO - Biological processi
- cell differentiation Source: UniProtKB-KW
- cerebral cortex development Source: UniProtKB
- Notch signaling pathway Source: UniProtKB-KW
- positive regulation of Notch signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Developmental protein |
Biological process | Differentiation, Notch signaling pathway |
Ligand | Calcium |
Enzyme and pathway databases
PathwayCommonsi | Q7Z3S9 |
SignaLinki | Q7Z3S9 |
Names & Taxonomyi
Protein namesi | Recommended name: Notch homolog 2 N-terminal-like protein A2 PublicationsAlternative name(s): Notch homolog 2 N-terminal-like protein1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:31862, NOTCH2NLA |
MIMi | 618023, gene |
neXtProti | NX_Q7Z3S9 |
VEuPathDBi | HostDB:ENSG00000264343 |
Subcellular locationi
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Involvement in diseasei
Organism-specific databases
DisGeNETi | 388677 |
OpenTargetsi | ENSG00000264343 |
PharmGKBi | PA134983899 |
Miscellaneous databases
Pharosi | Q7Z3S9, Tbio |
Genetic variation databases
BioMutai | NOTCH2NL |
DMDMi | 74750065 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000337103 | 1 – 236 | Notch homolog 2 N-terminal-like protein AAdd BLAST | 236 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 7 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 14 ↔ 23 | PROSITE-ProRule annotation | ||
Disulfide bondi | 29 ↔ 40 | PROSITE-ProRule annotation | ||
Disulfide bondi | 34 ↔ 51 | PROSITE-ProRule annotation | ||
Disulfide bondi | 53 ↔ 62 | PROSITE-ProRule annotation | ||
Disulfide bondi | 70 ↔ 82 | PROSITE-ProRule annotation | ||
Disulfide bondi | 76 ↔ 92 | PROSITE-ProRule annotation | ||
Disulfide bondi | 94 ↔ 103 | PROSITE-ProRule annotation | ||
Disulfide bondi | 109 ↔ 120 | PROSITE-ProRule annotation | ||
Disulfide bondi | 114 ↔ 129 | PROSITE-ProRule annotation | ||
Disulfide bondi | 131 ↔ 140 | PROSITE-ProRule annotation | ||
Disulfide bondi | 147 ↔ 159 | PROSITE-ProRule annotation | ||
Disulfide bondi | 153 ↔ 168 | PROSITE-ProRule annotation | ||
Disulfide bondi | 170 ↔ 179 | PROSITE-ProRule annotation | ||
Disulfide bondi | 186 ↔ 197 | PROSITE-ProRule annotation | ||
Disulfide bondi | 191 ↔ 207 | PROSITE-ProRule annotation |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q7Z3S9 |
jPOSTi | Q7Z3S9 |
MassIVEi | Q7Z3S9 |
MaxQBi | Q7Z3S9 |
PaxDbi | Q7Z3S9 |
PeptideAtlasi | Q7Z3S9 |
PRIDEi | Q7Z3S9 |
ProteomicsDBi | 69079 [Q7Z3S9-1] 69080 [Q7Z3S9-2] 69081 [Q7Z3S9-3] |
TopDownProteomicsi | Q7Z3S9-3 [Q7Z3S9-3] |
PTM databases
GlyGeni | Q7Z3S9, 1 site |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000264343, Expressed in colon and 115 other tissues |
ExpressionAtlasi | Q7Z3S9, baseline and differential |
Genevisiblei | Q7Z3S9, HS |
Organism-specific databases
HPAi | ENSG00000264343, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q7Z3S9
GO - Molecular functioni
- Notch binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 132802, 377 interactors |
DIPi | DIP-47315N |
IntActi | Q7Z3S9, 250 interactors |
MINTi | Q7Z3S9 |
Miscellaneous databases
RNActi | Q7Z3S9, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 24 | EGF-like 1PROSITE-ProRule annotationAdd BLAST | 24 | |
Domaini | 25 – 63 | EGF-like 2PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 66 – 104 | EGF-like 3PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 105 – 141 | EGF-like 4PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 143 – 180 | EGF-like 5; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 38 | |
Domaini | 182 – 219 | EGF-like 6PROSITE-ProRule annotationAdd BLAST | 38 |
Sequence similaritiesi
Keywords - Domaini
EGF-like domain, RepeatPhylogenomic databases
eggNOGi | KOG1217, Eukaryota |
GeneTreei | ENSGT00940000167308 |
HOGENOMi | CLU_004826_3_0_1 |
InParanoidi | Q7Z3S9 |
OrthoDBi | 1033311at2759 |
PhylomeDBi | Q7Z3S9 |
Family and domain databases
InterProi | View protein in InterPro IPR001881, EGF-like_Ca-bd_dom IPR000742, EGF-like_dom IPR000152, EGF-type_Asp/Asn_hydroxyl_site IPR018097, EGF_Ca-bd_CS |
Pfami | View protein in Pfam PF00008, EGF, 3 hits PF07645, EGF_CA, 1 hit |
SMARTi | View protein in SMART SM00181, EGF, 5 hits SM00179, EGF_CA, 4 hits |
PROSITEi | View protein in PROSITE PS00010, ASX_HYDROXYL, 1 hit PS00022, EGF_1, 5 hits PS01186, EGF_2, 5 hits PS50026, EGF_3, 6 hits PS01187, EGF_CA, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MCVTYHNGTG YCKCPEGFLG EYCQHRDPCE KNRCQNGGTC VAQAMLGKAT
60 70 80 90 100
CRCASGFTGE DCQYSTSHPC FVSRPCLNGG TCHMLSRDTY ECTCQVGFTG
110 120 130 140 150
KECQWTDACL SHPCANGSTC TTVANQFSCK CLTGFTGQKC ETDVNECDIP
160 170 180 190 200
GHCQHGGTCL NLPGSYQCQC LQGFTGQYCD SLYVPCAPSP CVNGGTCRQT
210 220 230
GDFTFECNCL PETVRRGTEL WERDREVWNG KEHDEN
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A8I5KR58 | A0A8I5KR58_HUMAN | Notch homolog 2 N-terminal-like pro... | NOTCH2NLA | 273 | Annotation score: | ||
A0A8I5KUH1 | A0A8I5KUH1_HUMAN | Notch homolog 2 N-terminal-like pro... | NOTCH2NLA | 69 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 19 | L → S in BAC11381 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_043601 | 67 | S → P. Corresponds to variant dbSNP:rs10910779Ensembl. | 1 | |
Natural variantiVAR_043602 | 158 | T → I1 PublicationCorresponds to variant dbSNP:rs8002Ensembl. | 1 | |
Natural variantiVAR_043603 | 196 | T → S. Corresponds to variant dbSNP:rs4649852Ensembl. | 1 | |
Natural variantiVAR_043604 | 226 | E → Q. Corresponds to variant dbSNP:rs1053710Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_033895 | 1 | M → MCRDGYEPCVNEGM in isoform 3. 1 Publication | 1 | |
Alternative sequenceiVSP_033896 | 212 – 236 | ETVRR…EHDEN → ATWPIFPKLLSLQEKESYC in isoform 2. 1 PublicationAdd BLAST | 25 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK075065 mRNA Translation: BAC11381.1 Different initiation. BX537434 mRNA Translation: CAD97676.1 AL592307 Genomic DNA Translation: CAH73993.1 AL592307 Genomic DNA Translation: CAH73994.1 BC010154 mRNA Translation: AAH10154.3 BC019835 mRNA Translation: AAH19835.1 BC065219 mRNA Translation: AAH65219.2 BC084572 mRNA Translation: AAH84572.1 Different initiation. BC090943 mRNA Translation: AAH90943.1 |
CCDSi | CCDS72880.1 [Q7Z3S9-1] |
RefSeqi | NP_982283.2, NM_203458.4 [Q7Z3S9-1] XP_006711766.1, XM_006711703.3 XP_006726418.1, XM_006726355.3 XP_016855384.1, XM_016999895.1 XP_016855385.1, XM_016999896.1 XP_016855386.1, XM_016999897.1 XP_016855387.1, XM_016999898.1 XP_016858537.1, XM_017003048.1 XP_016858538.1, XM_017003049.1 XP_016858539.1, XM_017003050.1 XP_016858540.1, XM_017003051.1 |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK075065 mRNA Translation: BAC11381.1 Different initiation. BX537434 mRNA Translation: CAD97676.1 AL592307 Genomic DNA Translation: CAH73993.1 AL592307 Genomic DNA Translation: CAH73994.1 BC010154 mRNA Translation: AAH10154.3 BC019835 mRNA Translation: AAH19835.1 BC065219 mRNA Translation: AAH65219.2 BC084572 mRNA Translation: AAH84572.1 Different initiation. BC090943 mRNA Translation: AAH90943.1 |
CCDSi | CCDS72880.1 [Q7Z3S9-1] |
RefSeqi | NP_982283.2, NM_203458.4 [Q7Z3S9-1] XP_006711766.1, XM_006711703.3 XP_006726418.1, XM_006726355.3 XP_016855384.1, XM_016999895.1 XP_016855385.1, XM_016999896.1 XP_016855386.1, XM_016999897.1 XP_016855387.1, XM_016999898.1 XP_016858537.1, XM_017003048.1 XP_016858538.1, XM_017003049.1 XP_016858539.1, XM_017003050.1 XP_016858540.1, XM_017003051.1 |
3D structure databases
AlphaFoldDBi | Q7Z3S9 |
SMRi | Q7Z3S9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 132802, 377 interactors |
DIPi | DIP-47315N |
IntActi | Q7Z3S9, 250 interactors |
MINTi | Q7Z3S9 |
PTM databases
GlyGeni | Q7Z3S9, 1 site |
Genetic variation databases
BioMutai | NOTCH2NL |
DMDMi | 74750065 |
Proteomic databases
EPDi | Q7Z3S9 |
jPOSTi | Q7Z3S9 |
MassIVEi | Q7Z3S9 |
MaxQBi | Q7Z3S9 |
PaxDbi | Q7Z3S9 |
PeptideAtlasi | Q7Z3S9 |
PRIDEi | Q7Z3S9 |
ProteomicsDBi | 69079 [Q7Z3S9-1] 69080 [Q7Z3S9-2] 69081 [Q7Z3S9-3] |
TopDownProteomicsi | Q7Z3S9-3 [Q7Z3S9-3] |
Protocols and materials databases
Antibodypediai | 72493, 60 antibodies from 16 providers |
DNASUi | 388677 |
Genome annotation databases
Organism-specific databases
CTDi | 388677 |
DisGeNETi | 388677 |
GeneCardsi | NOTCH2NLA |
HGNCi | HGNC:31862, NOTCH2NLA |
HPAi | ENSG00000264343, Low tissue specificity |
MIMi | 618023, gene |
neXtProti | NX_Q7Z3S9 |
OpenTargetsi | ENSG00000264343 |
PharmGKBi | PA134983899 |
VEuPathDBi | HostDB:ENSG00000264343 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1217, Eukaryota |
GeneTreei | ENSGT00940000167308 |
HOGENOMi | CLU_004826_3_0_1 |
InParanoidi | Q7Z3S9 |
OrthoDBi | 1033311at2759 |
PhylomeDBi | Q7Z3S9 |
Enzyme and pathway databases
PathwayCommonsi | Q7Z3S9 |
SignaLinki | Q7Z3S9 |
Miscellaneous databases
BioGRID-ORCSi | 100996717, 0 hits in 4 CRISPR screens 100996763, 0 hits in 4 CRISPR screens 388677, 517 hits in 989 CRISPR screens |
ChiTaRSi | NOTCH2NLB, human |
Pharosi | Q7Z3S9, Tbio |
PROi | PR:Q7Z3S9 |
RNActi | Q7Z3S9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000264343, Expressed in colon and 115 other tissues |
ExpressionAtlasi | Q7Z3S9, baseline and differential |
Genevisiblei | Q7Z3S9, HS |
Family and domain databases
InterProi | View protein in InterPro IPR001881, EGF-like_Ca-bd_dom IPR000742, EGF-like_dom IPR000152, EGF-type_Asp/Asn_hydroxyl_site IPR018097, EGF_Ca-bd_CS |
Pfami | View protein in Pfam PF00008, EGF, 3 hits PF07645, EGF_CA, 1 hit |
SMARTi | View protein in SMART SM00181, EGF, 5 hits SM00179, EGF_CA, 4 hits |
PROSITEi | View protein in PROSITE PS00010, ASX_HYDROXYL, 1 hit PS00022, EGF_1, 5 hits PS01186, EGF_2, 5 hits PS50026, EGF_3, 6 hits PS01187, EGF_CA, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NT2NA_HUMAN | |
Accessioni | Q7Z3S9Primary (citable) accession number: Q7Z3S9 Secondary accession number(s): Q5BKT8 Q96FY1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 20, 2008 |
Last sequence update: | October 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 177 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families