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NEBL nebulette [ Homo sapiens (human) ]

Gene ID: 10529, updated on 7-Apr-2024

Summary

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Official Symbol
NEBLprovided by HGNC
Official Full Name
nebuletteprovided by HGNC
Primary source
HGNC:HGNC:16932
See related
Ensembl:ENSG00000078114 MIM:605491; AllianceGenome:HGNC:16932
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
LASP2; LNEBL; C10orf113; bA165O3.1
Summary
This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Expression
Biased expression in heart (RPKM 103.7), thyroid (RPKM 26.9) and 7 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
10p12.31
Exon count:
41
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (20779973..21293050, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (20798520..21311782, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (21068902..21581979, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376442 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:20885982-20886482 Neighboring gene microRNA 4675 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:21045700-21046232 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:21046233-21046763 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:21105746-21106945 Neighboring gene uncharacterized LOC102725112 Neighboring gene MT-ND1 pseudogene 21 Neighboring gene Sharpr-MPRA regulatory region 670 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_11562 Neighboring gene uncharacterized LOC124902389 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3119 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:21322529-21322705 Neighboring gene eukaryotic translation initiation factor 4B pseudogene 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:21373491-21373644 Neighboring gene Sharpr-MPRA regulatory region 12489 Neighboring gene NANOG hESC enhancer GRCh37_chr10:21448091-21448641 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:21449895-21450799 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr10:21450800-21451703 Neighboring gene nucleophosmin 1 pseudogene 30 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21462498-21463388 Neighboring gene Sharpr-MPRA regulatory region 12641 Neighboring gene NEBL antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3120 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21570748-21571426 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr10:21571427-21572103 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21574449-21575208 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21575969-21576728 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:21581467-21582666 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21585759-21586559 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3121 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr10:21598312-21598930 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:21625535-21626086 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21645067-21645566 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21651599-21652196 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21652197-21652792 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:21661731-21662232 Neighboring gene RNA, U6 small nuclear 15, pseudogene Neighboring gene long intergenic non-protein coding RNA 2643

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. LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma. Yang YT, et al. Eur Rev Med Pharmacol Sci, 2020 Sep. PMID 33015783
  2. LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway. Li J, et al. Biomed Pharmacother, 2020 Jul. PMID 32325347
  3. Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells. Zhang Y, et al. J Cell Biochem, 2019 Sep. PMID 31026088
  4. Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-β-induced EMT. Zhang Y, et al. J Cell Biochem, 2019 Aug. PMID 30945341
  5. Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer. Qiu X, et al. Mol Med Rep, 2018 Feb. PMID 29257257, Free PMC Article

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.
    Title: Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition.
  2. LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/beta-catenin signaling pathway.
    Title: LASP2 inhibits trophoblast cell migration and invasion in preeclampsia through inactivation of the Wnt/β-catenin signaling pathway.
  3. LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.
    Title: LASP2 functions as a potential prognostic factor and therapeutic target in nasopharyngeal carcinoma.
  4. LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway.
    Title: LASP2 is downregulated in human liver cancer and contributes to hepatoblastoma cell malignant phenotypes through MAPK/ERK pathway.
  5. Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells.
    Title: Knockdown of LASP2 inhibits the proliferation, migration, and invasion of cervical cancer cells.
  6. Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-beta-induced EMT.
    Title: Upregulation of LASP2 inhibits pancreatic cancer cell migration and invasion through suppressing TGF-β-induced EMT.
  7. Survival analysis suggested that overexpressed NEBL in patients with colorectal cancer was associated with a positive prognosis for overall survival.
    Title: Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer.
  8. LASP2 may play a significant role in suppressing CRC progression and provided a novel biomarker for CRC therapy
    Title: LASP2 suppresses colorectal cancer progression through JNK/p38 MAPK pathway meditated epithelial-mesenchymal transition.
  9. The levels of phosphorylated FAK (Tyr397 and Tyr925) were increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA.
    Title: Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients.
  10. predisposition to multibacillary leprosy in Vietnam is associated with CUBN and NEBL common variants in the chromosome 10p13 linkage region
    Title: CUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam.
Submit: New GeneRIF Correction See all GeneRIFs (20)

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

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2011-12-21)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2011-12-21)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity.
EBI GWAS Catalog
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
EBI GWAS Catalog
GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ53769, MGC119746, MGC119747, MGC176421

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables actin filament binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables actin filament binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cytoskeletal protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cytoskeletal protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables filamin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables structural constituent of muscle NAS
Non-traceable Author Statement
more info
 PubMed 
enables tropomyosin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cardiac muscle thin filament assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cardiac muscle thin filament assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in I band NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in Z disc IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in Z disc IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in stress fiber IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
nebulette
Names
LIM and SH3 protein 2
LIM-nebulette
actin-binding Z-disk protein

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.

Genomic

  1. NG_017092.1 RefSeqGene

    Range
    5001..399215
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_411

mRNA and Protein(s)

  1. NM_001173484.2 → NP_001166955.1  nebulette isoform 3

    See identical proteins and their annotated locations for NP_001166955.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' and 3' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in a frameshift. The encoded isoform (3) is shorter and has distinct N- and C-termini, compared to isoform 1.
    Source sequence(s)
    AB209311, BC144201, BM973051, DT220372
    UniProtKB/Swiss-Prot
    O76041
    UniProtKB/TrEMBL
    Q59FZ8
    Conserved Domains (2) summary
    smart00227
    Location:98 → 128
    NEBU; The Nebulin repeat is present also in Las1
    cd09447
    Location:5 → 57
    LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)

  2. NM_001377322.1 → NP_001364251.1  nebulette isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL157398, AL359175, AL731547
    Conserved Domains (4) summary
    smart00227
    Location:98 → 128
    NEBU; The Nebulin repeat is present also in Las1
    cd09447
    Location:5 → 57
    LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)
    cd11935
    Location:244 → 301
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:67 → 94
    Nebulin; Nebulin repeat

  3. NM_001377323.1 → NP_001364252.1  nebulette isoform 5

    Status: REVIEWED

    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Conserved Domains (4) summary
    smart00227
    Location:82 → 112
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:197 → 254
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:51 → 78
    Nebulin; Nebulin repeat
    cl02475
    Location:8 → 41
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

  4. NM_001377324.1 → NP_001364253.1  nebulette isoform 6

    Status: REVIEWED

    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Conserved Domains (3) summary
    smart00227
    Location:79 → 109
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:194 → 251
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    cl02475
    Location:5 → 38
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

  5. NM_001377325.1 → NP_001364254.1  nebulette isoform 7

    Status: REVIEWED

    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Conserved Domains (4) summary
    smart00227
    Location:76 → 106
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:191 → 248
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:45 → 72
    Nebulin; Nebulin repeat
    cl02475
    Location:2 → 35
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

  6. NM_001377326.1 → NP_001364255.1  nebulette isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 9 and 10, encodes isoform 8.
    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Conserved Domains (4) summary
    smart00227
    Location:62 → 92
    NEBU; The Nebulin repeat is present also in Las1
    cl02475
    Location:1 → 21
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
    pfam00880
    Location:31 → 58
    Nebulin; Nebulin repeat
    cl17036
    Location:177 → 234
    SH3; Src Homology 3 domain superfamily

  7. NM_001377327.1 → NP_001364256.1  nebulette isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 8 and 10, encodes isoform 8.
    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Related
    ENST00000675702.1
    Conserved Domains (4) summary
    smart00227
    Location:62 → 92
    NEBU; The Nebulin repeat is present also in Las1
    cl02475
    Location:1 → 21
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
    pfam00880
    Location:31 → 58
    Nebulin; Nebulin repeat
    cl17036
    Location:177 → 234
    SH3; Src Homology 3 domain superfamily

  8. NM_001377328.1 → NP_001364257.1  nebulette isoform 8

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 8 and 9, encodes isoform 8.
    Source sequence(s)
    AL157398, AL359175, AL731547
    UniProtKB/TrEMBL
    Q8N8M3
    Related
    ENST00000675700.1
    Conserved Domains (4) summary
    smart00227
    Location:62 → 92
    NEBU; The Nebulin repeat is present also in Las1
    cl02475
    Location:1 → 21
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
    pfam00880
    Location:31 → 58
    Nebulin; Nebulin repeat
    cl17036
    Location:177 → 234
    SH3; Src Homology 3 domain superfamily

  9. NM_006393.3 → NP_006384.1  nebulette isoform 1

    See identical proteins and their annotated locations for NP_006384.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). This isoform (1) is also known as the sarcomeric isoform.
    Source sequence(s)
    AL157398
    Consensus CDS
    CCDS7134.1
    UniProtKB/Swiss-Prot
    B0YJ45, B9EIM9, E9PRX7, O76041, Q2TBD0, Q5VZT2, Q70I54, Q9UIC4
    UniProtKB/TrEMBL
    B0YJ47
    Related
    ENSP00000366326.4, ENST00000377122.9
    Conserved Domains (3) summary
    smart00227
    Location:762 → 791
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:957 → 1014
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    cl26511
    Location:294 → 712
    Neuromodulin_N; Gap junction protein N-terminal region

  10. NM_213569.2 → NP_998734.1  nebulette isoform 2

    See identical proteins and their annotated locations for NP_998734.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus compared to isoform 1. This isoform is referred to as LIM-nebulette or the non-muscle isoform.
    Source sequence(s)
    AB209311, AJ580772, BI522541, BM973051, CR744526
    Consensus CDS
    CCDS7133.1
    UniProtKB/TrEMBL
    Q8N8M3
    Related
    ENSP00000393896.2, ENST00000417816.2
    Conserved Domains (4) summary
    smart00227
    Location:98 → 128
    NEBU; The Nebulin repeat is present also in Las1
    cd09447
    Location:5 → 57
    LIM_LASP; The LIM domain of LIM and SH3 Protein (LASP)
    cd11935
    Location:213 → 270
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:67 → 94
    Nebulin; Nebulin repeat

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    20779973..21293050 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047424444.1 → XP_047280400.1  nebulette isoform X4

  2. XM_047424443.1 → XP_047280399.1  nebulette isoform X1

  3. XM_011519291.3 → XP_011517593.1  nebulette isoform X1

    See identical proteins and their annotated locations for XP_011517593.1

    UniProtKB/TrEMBL
    B0YJ47
    Conserved Domains (3) summary
    smart00227
    Location:587 → 616
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:941 → 998
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:307 → 331
    Nebulin; Nebulin repeat

  4. XM_005252342.6 → XP_005252399.1  nebulette isoform X2

    UniProtKB/TrEMBL
    B0YJ47
    Conserved Domains (3) summary
    smart00227
    Location:569 → 598
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:923 → 980
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:289 → 313
    Nebulin; Nebulin repeat

  5. XM_005252343.6 → XP_005252400.1  nebulette isoform X3

    See identical proteins and their annotated locations for XP_005252400.1

    UniProtKB/TrEMBL
    B0YJ47
    Conserved Domains (3) summary
    smart00227
    Location:603 → 632
    NEBU; The Nebulin repeat is present also in Las1
    cd11935
    Location:876 → 933
    SH3_Nebulette_C; C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2)
    pfam00880
    Location:323 → 347
    Nebulin; Nebulin repeat

RNA

  1. XR_001746995.3 RNA Sequence

  2. XR_242691.6 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    20798520..21311782 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054364489.1 → XP_054220464.1  nebulette isoform X4

  2. XM_054364486.1 → XP_054220461.1  nebulette isoform X1

  3. XM_054364485.1 → XP_054220460.1  nebulette isoform X1

  4. XM_054364487.1 → XP_054220462.1  nebulette isoform X2

  5. XM_054364488.1 → XP_054220463.1  nebulette isoform X3

RNA

  1. XR_008488154.1 RNA Sequence

  2. XR_008488155.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001010896.2: Suppressed sequence

    Description
    NM_001010896.2: This RefSeq was removed because it is now thought that this gene does not encode a protein.

  2. NM_001177483.1: Suppressed sequence

    Description
    NM_001177483.1: This RefSeq was removed because it is now thought that this gene does not encode a protein.

  3. NM_016365.1: Suppressed sequence

    Description
    NM_016365.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O76041.1 GenPept UniProtKB/Swiss-Prot:O76041

Gene LinkOut

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