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NVL nuclear VCP like [ Homo sapiens (human) ]

Gene ID: 4931, updated on 3-Apr-2024

Summary

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Official Symbol
NVLprovided by HGNC
Official Full Name
nuclear VCP likeprovided by HGNC
Primary source
HGNC:HGNC:8070
See related
Ensembl:ENSG00000143748 MIM:602426; AllianceGenome:HGNC:8070
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
NVL2
Summary
This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. Two encoded proteins, described as major and minor isoforms, have been localized to distinct regions of the nucleus. The largest encoded protein (major isoform) has been localized to the nucleolus and shown to participate in ribosome biosynthesis (PMID: 15469983, 16782053), while the minor isoform has been localized to the nucleoplasmin. [provided by RefSeq, Aug 2011]
Expression
Ubiquitous expression in skin (RPKM 7.5), lymph node (RPKM 5.1) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
1q42.11
Exon count:
28
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (224227345..224330172, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (223416266..223519053, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (224415047..224517874, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:224370121-224370951 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:224370952-224371781 Neighboring gene Sharpr-MPRA regulatory region 9300 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2602 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1850 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2603 Neighboring gene delta 4-desaturase, sphingolipid 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1851 Neighboring gene uncharacterized LOC101927143 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_5412 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:224402200-224402893 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:224405308-224405505 Neighboring gene uncharacterized LOC101927164 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2604 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:224442412-224443337 Neighboring gene Sharpr-MPRA regulatory region 1236 Neighboring gene microRNA 320b-2 Neighboring gene MPRA-validated peak721 silencer Neighboring gene RNA, U6 small nuclear 1008, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2605 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2606 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2608 Neighboring gene Sharpr-MPRA regulatory region 12366 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:224523487-224523975 Neighboring gene small nucleolar RNA U13 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:224527150-224527870 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:224528593-224529312 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2609 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:224544931-224545431 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2611 Neighboring gene cornichon family member 4

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. The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population. Wang M, et al. Prog Neuropsychopharmacol Biol Psychiatry, 2015 Oct 1. PMID 25891250
  2. Structure and function of the N-terminal nucleolin binding domain of nuclear valosin-containing protein-like 2 (NVL2) harboring a nucleolar localization signal. Fujiwara Y, et al. J Biol Chem, 2011 Jun 17. PMID 21474449, Free PMC Article
  3. Interactome analysis of the Tudor domain-containing protein SPF30 which associates with the MTR4-exosome RNA-decay machinery under the regulation of AAA-ATPase NVL2. Ishida YI, et al. Int J Biochem Cell Biol, 2021 Mar. PMID 33422691
  4. NVL: a new member of the AAA family of ATPases localized to the nucleus. Germain-Lee EL, et al. Genomics, 1997 Aug 15. PMID 9286697
  5. The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using distinct arch-interacting motifs. Lingaraju M, et al. Nat Commun, 2019 Jul 29. PMID 31358741, Free PMC Article

See all (79) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Interactome analysis of the Tudor domain-containing protein SPF30 which associates with the MTR4-exosome RNA-decay machinery under the regulation of AAA-ATPase NVL2.
    Title: Interactome analysis of the Tudor domain-containing protein SPF30 which associates with the MTR4-exosome RNA-decay machinery under the regulation of AAA-ATPase NVL2.
  2. Data show that the nuclear exosome adaptors nuclear valosin-containing protein-like (NVL) and zinc finger, CCHC domain containing 8 protein (ZCCHC8) bind the Mtr4 exosome RNA helicase (MTR4) KOW domain on a surface.
    Title: The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using distinct arch-interacting motifs.
  3. knockdown of WDR74 leads to significant defects in the pre-rRNA cleavage within the internal transcribed spacer 1, occurring in an early stage of the processing pathway. When the dissociation of WDR74 from the MTR4-containing exonuclease complex was impaired upon expression of mutant NVL2, the same processing defect, with partial migration of WDR74 from the nucleolus towards the nucleoplasm, was observed.
    Title: WDR74 participates in an early cleavage of the pre-rRNA processing pathway in cooperation with the nucleolar AAA-ATPase NVL2.
  4. Results indicated that the NVL gene may contain overlapping common genetic risk factors for major depressive disorder and schizophrenia in the Han Chinese population
    Title: The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.
  5. results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis
    Title: AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74.
  6. suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex
    Title: NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing.
  7. these findings suggest that NVL2 is essential for telomerase biogenesis and provides an alternative approach for inhibiting telomerase activity in cancer.
    Title: The AAA-ATPase NVL2 is a telomerase component essential for holoenzyme assembly.
  8. NVL2 might facilitate the dissociation and recycling of nucleolin, thereby promoting efficient ribosome biogenesis
    Title: Structure and function of the N-terminal nucleolin binding domain of nuclear valosin-containing protein-like 2 (NVL2) harboring a nucleolar localization signal.
  9. Observational study of gene-disease association. (HuGE Navigator)
    Title: Association of genetic variants with hemorrhagic stroke in Japanese individuals.
  10. interaction of NVL2 with ribosomal protein L5 is ATP-dependent and likely contributes to the nucleolar translocation of NVL2
    Title: NVL2 is a nucleolar AAA-ATPase that interacts with ribosomal protein L5 through its nucleolar localization sequence.
Submit: New GeneRIF Correction See all GeneRIFs (11)

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

EBI GWAS Catalog

Description
Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.
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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables ATP hydrolysis activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA binding HDA PubMed 
enables preribosome binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables preribosome binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in positive regulation of protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of telomerase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of telomerase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in rRNA processing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of protein localization to nucleolus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ribosomal large subunit biogenesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ribosomal large subunit biogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ribosome biogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ribosome biogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in membrane HDA PubMed 
part_of nuclear exosome (RNase complex) IDA
Inferred from Direct Assay
more info
 PubMed 
colocalizes_with nucleolus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleolus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of telomerase holoenzyme complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
nuclear valosin-containing protein-like
Names
NVLp

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_029641.1 RefSeqGene

    Range
    5018..107845
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243146.2 → NP_001230075.1  nuclear valosin-containing protein-like isoform 3

    See identical proteins and their annotated locations for NP_001230075.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three alternate coding exons in the 5' coding region, uses a downstream initiation codon, and contains an alternate in-frame exon, compared to variant 1. The resulting protein (isoform 3) is shorter and has a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC092809, AK297396, BP284587, BU683548
    Consensus CDS
    CCDS58062.1
    UniProtKB/Swiss-Prot
    O15381
    Related
    ENSP00000341362.4, ENST00000340871.8
    Conserved Domains (3) summary
    COG0464
    Location:68 → 663
    SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]
    pfam00004
    Location:429 → 559
    AAA; ATPase family associated with various cellular activities (AAA)
    cl21455
    Location:409 → 445
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  2. NM_001243147.2 → NP_001230076.1  nuclear valosin-containing protein-like isoform 4

    See identical proteins and their annotated locations for NP_001230076.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC092809, AK298244, BP284587, BU683548
    Consensus CDS
    CCDS58063.1
    UniProtKB/TrEMBL
    B4DLM8
    Related
    ENSP00000417826.1, ENST00000469075.5
    Conserved Domains (5) summary
    COG0464
    Location:193 → 761
    SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]
    pfam00004
    Location:527 → 657
    AAA; ATPase family associated with various cellular activities (AAA)
    pfam16725
    Location:2 → 72
    Nucleolin_bd; Nucleolin binding domain
    cl11522
    Location:75 → 125
    Tom22; Mitochondrial import receptor subunit Tom22
    cl21455
    Location:507 → 543
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  3. NM_002533.4 → NP_002524.2  nuclear valosin-containing protein-like isoform 1

    See identical proteins and their annotated locations for NP_002524.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1, also known as NVL.2 or the major isoform).
    Source sequence(s)
    AC092809, AK293923, BP284587, BU683548, U68140
    Consensus CDS
    CCDS1541.1
    UniProtKB/Swiss-Prot
    B4DMC4, B4DP98, O15381, Q96EM7
    UniProtKB/TrEMBL
    B4DLM8
    Related
    ENSP00000281701.6, ENST00000281701.11
    Conserved Domains (4) summary
    COG0464
    Location:284 → 852
    SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]
    pfam00004
    Location:618 → 748
    AAA; ATPase family associated with various cellular activities (AAA)
    pfam16725
    Location:2 → 72
    Nucleolin_bd; Nucleolin binding domain
    cl21455
    Location:598 → 634
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  4. NM_206840.3 → NP_996671.1  nuclear valosin-containing protein-like isoform 2

    See identical proteins and their annotated locations for NP_996671.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon and uses a downstream start codon compared to variant 1. The resulting protein (isoform 2, also known as NVL.1 or the minor isoform) is shorter and has a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC092809, AK293923, BP284587, BU683548, U78772
    Consensus CDS
    CCDS1542.1
    UniProtKB/TrEMBL
    B4DLM8
    Related
    ENSP00000375747.2, ENST00000391875.6
    Conserved Domains (1) summary
    cl27568
    Location:137 → 750
    TIP49; TIP49 C-terminus

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    224227345..224330172 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017001383.2 → XP_016856872.1  nuclear valosin-containing protein-like isoform X5

    UniProtKB/TrEMBL
    B4DLM8

  2. XM_011544196.1 → XP_011542498.1  nuclear valosin-containing protein-like isoform X4

    UniProtKB/TrEMBL
    B4DLM8
    Conserved Domains (4) summary
    COG0464
    Location:284 → 879
    SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]
    pfam00004
    Location:645 → 775
    AAA; ATPase family associated with various cellular activities (AAA)
    pfam16725
    Location:2 → 72
    Nucleolin_bd; Nucleolin binding domain
    cl21455
    Location:625 → 661
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  3. XM_017001379.2 → XP_016856868.1  nuclear valosin-containing protein-like isoform X2

    UniProtKB/TrEMBL
    B4DLM8

  4. XM_017001378.2 → XP_016856867.1  nuclear valosin-containing protein-like isoform X1

    UniProtKB/TrEMBL
    B4DLM8

  5. XM_047421613.1 → XP_047277569.1  nuclear valosin-containing protein-like isoform X7

  6. XM_017001380.3 → XP_016856869.1  nuclear valosin-containing protein-like isoform X3

    UniProtKB/TrEMBL
    B4DLM8

  7. XM_047421631.1 → XP_047277587.1  nuclear valosin-containing protein-like isoform X12

  8. XM_047421621.1 → XP_047277577.1  nuclear valosin-containing protein-like isoform X10

  9. XM_047421618.1 → XP_047277574.1  nuclear valosin-containing protein-like isoform X8

  10. XM_017001384.2 → XP_016856873.1  nuclear valosin-containing protein-like isoform X6

    UniProtKB/TrEMBL
    B4DLM8

  11. XM_047421637.1 → XP_047277593.1  nuclear valosin-containing protein-like isoform X14

  12. XM_047421635.1 → XP_047277591.1  nuclear valosin-containing protein-like isoform X13

  13. XM_047421626.1 → XP_047277582.1  nuclear valosin-containing protein-like isoform X11

  14. XM_017001385.3 → XP_016856874.1  nuclear valosin-containing protein-like isoform X9

    UniProtKB/TrEMBL
    B4DLM8

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    223416266..223519053 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054336810.1 → XP_054192785.1  nuclear valosin-containing protein-like isoform X5

  2. XM_054336809.1 → XP_054192784.1  nuclear valosin-containing protein-like isoform X4

  3. XM_054336807.1 → XP_054192782.1  nuclear valosin-containing protein-like isoform X2

  4. XM_054336806.1 → XP_054192781.1  nuclear valosin-containing protein-like isoform X1

  5. XM_054336812.1 → XP_054192787.1  nuclear valosin-containing protein-like isoform X7

  6. XM_054336808.1 → XP_054192783.1  nuclear valosin-containing protein-like isoform X3

  7. XM_054336817.1 → XP_054192792.1  nuclear valosin-containing protein-like isoform X12

  8. XM_054336815.1 → XP_054192790.1  nuclear valosin-containing protein-like isoform X10

  9. XM_054336813.1 → XP_054192788.1  nuclear valosin-containing protein-like isoform X8

  10. XM_054336811.1 → XP_054192786.1  nuclear valosin-containing protein-like isoform X6

  11. XM_054336819.1 → XP_054192794.1  nuclear valosin-containing protein-like isoform X14

  12. XM_054336818.1 → XP_054192793.1  nuclear valosin-containing protein-like isoform X13

  13. XM_054336816.1 → XP_054192791.1  nuclear valosin-containing protein-like isoform X11

  14. XM_054336814.1 → XP_054192789.1  nuclear valosin-containing protein-like isoform X9

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O15381.1 GenPept UniProtKB/Swiss-Prot:O15381

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