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NEURL2 Gene

protein-coding   GIFtS: 46
GCID: GC20M044517

Neuralized E3 Ubiquitin Protein Ligase 2

(Previous names: chromosome 20 open reading frame 163, neuralized-like 2...)
(Previous symbol: C20orf163)
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Neuralized E3 Ubiquitin Protein Ligase 21 2     OZZ2
C20orf1631 2 3     OZZ-E32
Chromosome 20 Open Reading Frame 1631     Neuralized Homolog 22
Neuralized Homolog 2 (Drosophila)1     Neuralized-Like Protein 22
Neuralized-Like 2 (Drosophila)1     

External Ids:    HGNC: 161561   Entrez Gene: 1408252   Ensembl: ENSG000001242577   OMIM: 6085975   UniProtKB: Q9BR093   

Export aliases for NEURL2 gene to outside databases

Previous GC identifers: GC20M045203 GC20M043950 GC20M041259


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NEURL2 Gene:
This gene encodes a protein that is involved in the regulation of myofibril organization. This protein is likely
the adaptor component of the E3 ubiquitin ligase complex in striated muscle, and it regulates the
ubiquitin-mediated degradation of beta-catenin during myogenesis. Alternative splicing of this gene results in
multiple transcript variants. (provided by RefSeq, Jun 2013)

GeneCards Summary for NEURL2 Gene:
NEURL2 (neuralized E3 ubiquitin protein ligase 2) is a protein-coding gene. An important paralog of this gene is NEURL4.

UniProtKB/Swiss-Prot: NEUL2_HUMAN, Q9BR09
Function: Plays an important role in the process of myofiber differentiation and maturation. Probable
substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein
ligase complex, which mediates the ubiquitination of proteins. Probably contributes to catalysis through
recognition and positioning of the substrate and the ubiquitin-conjugating enzyme. During myogenesis, controls
the ubiquitination and degradation of the specific pool of CTNNB1/beta-catenin located at the sarcolemma (By
similarity)

Gene Wiki entry for NEURL2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Regulatory transcription factor binding sites in the NEURL2 gene promoter:
         TBP   NF-1/L   Nkx2-5   NF-kappaB   Tal-1beta   GATA-2   YY1   E47   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNEURL2 promoter sequence
   Search Chromatin IP Primers for NEURL2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NEURL2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13.12   Ensembl cytogenetic band:  20q13.12   HGNC cytogenetic band: 20q13.12

NEURL2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NEURL2 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20M044517:  view genomic region     (about GC identifiers)

Start:
44,517,264 bp from pter      End:
44,519,926 bp from pter
Size:
2,663 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NEUL2_HUMAN, Q9BR09 (See protein sequence)
Recommended Name: Neuralized-like protein 2  
Size: 285 amino acids; 31690 Da
Subunit: Probable component the ECS(NEURL2) E3 ubiquitin-protein ligase complex consisting of TCEB2/Elongin B,
TCEB1/Elongin C, CUL5, RBX1 and NEURL2. Interacts with CTNNB1 (By similarity)
Secondary accessions: Q3KR34

Explore the universe of human proteins at neXtProt for NEURL2: NX_Q9BR09

Explore proteomics data for NEURL2 at MOPED


See NEURL2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts): 
NP_001265464.1  NP_542787.1  

ENSEMBL proteins: 
 ENSP00000442383   ENSP00000361596  

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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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2 InterPro protein domains:
 IPR006573 Neu_Z
 IPR001496 SOCS_C

Graphical View of Domain Structure for InterPro Entry Q9BR09

ProtoNet protein and cluster: Q9BR09

1 Blocks protein domain: IPB001496 SOCS protein

UniProtKB/Swiss-Prot: NEUL2_HUMAN, Q9BR09
Domain: The SOCS domain mediates the interaction with TCEB1 and TCEB2, while the NHR domain may be involved in
ubiquitination substrate binding (By similarity)
Similarity: Contains 1 NHR (neuralized homology repeat) domain
Similarity: Contains 1 SOCS box domain


Find genes that share domains with NEURL2           About GenesLikeMe


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

     UniProtKB/Swiss-Prot Summary: NEUL2_HUMAN, Q9BR09
Function: Plays an important role in the process of myofiber differentiation and maturation. Probable
substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein
ligase complex, which mediates the ubiquitination of proteins. Probably contributes to catalysis through
recognition and positioning of the substrate and the ubiquitin-conjugating enzyme. During myogenesis, controls
the ubiquitination and degradation of the specific pool of CTNNB1/beta-catenin located at the sarcolemma (By
similarity)

     Gene Ontology (GO): 1 molecular function term:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005515protein binding ----
     
Find genes that share ontologies with NEURL2           About GenesLikeMe


Phenotypes:
     1 GenomeRNAi human phenotype for NEURL2:
 Metaphase cells 

     4 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Neurl2):
 growth/size/body  muscle  nervous system  normal 

Find genes that share phenotypes with NEURL2           About GenesLikeMe

Animal Models:
     MGI mouse knock-out Neurl2tm1Adz for NEURL2

   inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NEURL2
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(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot
NEUL2_HUMAN, Q9BR09: Cytoplasm (By similarity)
Subcellular locations from COMPARTMENTS: 

CompartmentConfidence
cytosol3
nucleus2

Gene Ontology (GO): 2 cellular component terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005927muscle tendon junction IEA--
GO:0030891VCB complex IEA--

Find genes that share ontologies with NEURL2           About GenesLikeMe


(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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UniProtKB/Swiss-Prot: NEUL2_HUMAN, Q9BR09
Pathway: Protein modification; protein ubiquitination

    Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for NEURL2
Interactions:

    GeneGlobe Interaction Network for NEURL2

STRING Interaction Network Preview (showing 5 interactants - click image to see 13)

Selected Interacting proteins for NEURL2 (Q9BR093 ENSP000003615964) via UniProtKB, MINT, STRING, and/or I2D (see all 14)

InteractantInteraction Details
GeneCardExternal ID(s)
CTNNB1P352223, ENSP000003444564I2D: score=2 STRING: ENSP00000344456
TCEB2Q153703I2D: score=1 
ATG3ENSP000002832904STRING: ENSP00000283290
OS9ENSP000003181654STRING: ENSP00000318165
RBX1ENSP000002162254STRING: ENSP00000216225
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Gene Ontology (GO): 4 biological process terms:    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0016567protein ubiquitination IEA--
GO:0030239myofibril assembly ----
GO:0035556intracellular signal transduction IEA--
GO:0045214sarcomere organization IEA--

Find genes that share ontologies with NEURL2           About GenesLikeMe



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore
   Browse drugs & compounds from Enzo Life Sciences
  Browse compounds at ApexBio 

Browse Tocris compounds for NEURL2 (NEUL2)



(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for NEURL2 gene (2 alternative transcripts): 
NM_001278535.1  NM_080749.3  

2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
ENST00000545238 ENST00000372518(uc002xqg.1)
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Selected AceView cDNA sequences (see all 26):

AW515245 AW305049 CA425681 AW298115 AJ295985 AI078253 NM_080749 AK054821 
CD674633 BC074737 BX441365 AI589199 AL844375 BX409810 BX115239 BP367504 
F34149 BX409811 AL844254 CB269672 AI097227 AA971892 F34155 AW298116 

GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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NEURL2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: GTGCACCGGC
NEURL2 Expression
About this image

NEURL2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

NEURL2 Protein Expression

UniProtKB/Swiss-Prot: NEUL2_HUMAN, Q9BR09
Tissue specificity: Expressed specifically in skeletal and cardiac muscles

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In Situ
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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for NEURL2 gene from Selected species (see all 12)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
mouse
(Mus musculus)
Mammalia Neurl21 , 5 neuralized-like 2 (Drosophila)1, 5 84.68(n)1
90.53(a)1
  2 (85.27 cM)5
4151151  NM_001082974.21  NP_001076443.11 
 1648307325 
chicken
(Gallus gallus)
Aves NEURL26
neuralized E3 ubiquitin protein ligase 2
71(a)
1 ↔ 1
20(10871289-10873861)
lizard
(Anolis carolinensis)
Reptilia NEURL26
neuralized E3 ubiquitin protein ligase 2
71(a)
1 ↔ 1
AAWZ02036849(7238-21141)
tropical clawed frog
(Xenopus tropicalis)
Amphibia LOC1004948961 neuralized-like protein 2-like 63.32(n)
68.73(a)
  100494896  XM_002932509.2  XP_002932555.2 
zebrafish
(Danio rerio)
Actinopterygii zgc:1621871 zgc:162187 61.28(n)
64.23(a)
  560768  NM_001083831.1  NP_001077300.1 
fruit fly
(Drosophila melanogaster)
Insecta CG38941 CG3894 53.23(n)
41.53(a)
  37959  NM_138119.6  NP_611963.5 


ENSEMBL Gene Tree for NEURL2 (if available)
TreeFam Gene Tree for NEURL2 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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Paralogs for NEURL2 gene
NEURL42  ENSG000002619152  
1 SIMAP similar gene for NEURL2 using alignment to 2 protein entries:     NEUL2_HUMAN (see all proteins):
NEURL4

Find genes that share paralogs with NEURL2           About GenesLikeMe



(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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3 SNPs for NEURL2    About this table                                 

Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 20 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
rs1997859911,2
C--44518247(+) TCTCT-/CTTTCTT 1 -- int10--------
rs106391821,2
C--44518258(+) CTCTC-/TCTT  
        
TCttt
1 -- int1 trp30--------
rs353423271,2,4
----see VAR_0520332 mis40--------

HapMap Linkage Disequilibrium report for NEURL2 (44517264 - 44519926 bp)

Structural Variations
     Database of Genomic Variants (DGV) 4 variations for NEURL2:    About this table    
Variant IDTypeSubtypePubMed ID
nsv833991CNV Loss17160897
nsv833990CNV Loss17160897
nsv517296CNV Loss19592680
nsv482069CNV Gain20164927

Site Specific Mutation Identification with PCR Assays
SeqTarget long-range PCR primers for resequencing NEURL2
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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 608597    OMIM disorders: --


Find genes that share disorders with NEURL2           About GenesLikeMe

Genetic Association Database (GAD): NEURL2
Human Genome Epidemiology (HuGE) Navigator: NEURL2 (1 document)

Export disorders for NEURL2 gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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PubMed articles for NEURL2 gene integrated from 10 sources:
(articles sorted by number of sources associating them with NEURL2)
    Utopia: connect your pdf to the dynamic
world of online information

  1. Neuralized-2: Expression in human and rodents and interaction with Delta-like ligands. (PubMed id 19723503)1, 3 Rullinkov G....Timmusk T. (Biochem. Biophys. Res. Commun. 2009)
  2. Candidate-gene testing for orphan limb-girdle muscular dystrophies. (PubMed id 19472918)1, 4 Aurino S....Nigro V. (Acta Myol 2008)
  3. Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation during myogenesis. (PubMed id 14960280)1, 2 Nastasi T.... D'Azzo A. (Dev. Cell 2004)
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
  6. The SOCS box: a tale of destruction and degradation. (PubMed id 12076535)1, 3 Kile B.T....Hilton D.J. (Trends Biochem. Sci. 2002)
  7. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)
  8. Ozz; a new name on the long list of beta-catenin's nemeses. (PubMed id 14992713)1 Wu G....He X. (Mol. Cell 2004)
  9. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)1 Strausberg R.L....Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002)

(in PubMed, OMIM, and NCBI Bookshelf)
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 ANDOR
Aliases
Free Text  

  Query String
PubMed
OMIM
NCBI Bookshelf
  (Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 140825 HGNC: 16156 AceView: NEURL2 Ensembl:ENSG00000124257 euGenes: HUgn140825
ECgene: NEURL2 H-InvDB: NEURL2

(According to HUGE)
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  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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NameDescription
PharmGKB entry for NEURL2 Pharmacogenomics, SNPs, Pathways

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
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Patent Information for NEURL2 gene:
Search GeneIP for patents involving NEURL2

GeneCards and IP:
Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014

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