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Protein

Nuclear valosin-containing protein-like

Gene

NVL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). May play a role in 60S ribosomal subunit biogenesis (PubMed:15469983, PubMed:16782053).3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi305 – 312ATP1 Publication8
Nucleotide bindingi622 – 629ATP1 Publication8

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • preribosome binding Source: UniProtKB

GO - Biological processi

  • positive regulation of telomerase activity Source: UniProtKB
  • ribosome biogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ribosome biogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143748-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear valosin-containing protein-like
Short name:
NVLp
Short name:
Nuclear VCP-like protein
Gene namesi
Name:NVL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:8070. NVL.

Subcellular locationi

Isoform 2 :
Isoform 1 :

GO - Cellular componenti

  • membrane Source: UniProtKB
  • mitochondrion Source: HPA
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • telomerase holoenzyme complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51 – 52KR → AA: Loss of nucleolar localization and interaction with RPL5. 1 Publication2
Mutagenesisi85 – 86KR → AA: Decreased nuclear localization. Complete loss of nuclear localization; when associated with 218-A--A-220 and 230-A--A-232. 1 Publication2
Mutagenesisi218 – 220KRK → AAA: Decreased nuclear localization; when associated with 230-A--A-232. Complete loss of nuclear localization; when associated with 85-A-A-86 and 230-A--A-232. 1 Publication3
Mutagenesisi230 – 232RKK → AAA: Decreased nuclear localization when associated with 218-A--A-220. Complete loss of nuclear localization; when associated with 85-A-A-86 and 218-A--A-220. 1 Publication3
Mutagenesisi311K → M: Loss of ATP-binding. Significant reduction in interaction with TERT and in telomerase activity. Loss of interaction with SKIV2L2. 1 Publication2 Publications1
Mutagenesisi628K → M: Loss of ATP-binding. No effect on interaction with TERT, SKIV2L2 and RPL5 and on telomerase activity. Significant reduction in the level of the 60S ribosomal subunit. 1 Publication3 Publications1

Organism-specific databases

DisGeNETi4931.
OpenTargetsiENSG00000143748.
PharmGKBiPA31857.

Polymorphism and mutation databases

BioMutaiNVL.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000845881 – 856Nuclear valosin-containing protein-likeAdd BLAST856

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70N6-acetyllysineBy similarity1
Modified residuei134PhosphoserineCombined sources1
Modified residuei138PhosphothreonineCombined sources1
Modified residuei156N6-acetyllysineBy similarity1
Modified residuei191PhosphoserineBy similarity1
Modified residuei211PhosphoserineCombined sources1
Modified residuei215PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO15381.
MaxQBiO15381.
PaxDbiO15381.
PeptideAtlasiO15381.
PRIDEiO15381.

2D gel databases

SWISS-2DPAGEO15381.

PTM databases

iPTMnetiO15381.
PhosphoSitePlusiO15381.

Expressioni

Tissue specificityi

Widely expressed. Highest level of expression in heart, placenta, skeletal muscle, pancreas and retina.1 Publication

Gene expression databases

BgeeiENSG00000143748.
CleanExiHS_NVL.
ExpressionAtlasiO15381. baseline and differential.
GenevisibleiO15381. HS.

Organism-specific databases

HPAiHPA028207.
HPA028219.
HPA028224.
HPA028654.

Interactioni

Subunit structurei

Interacts with NCL/nucleolin. Isoform 1 and isoform 2 interact with TERT and isoform 1 exhibits a higher binding affinity for TERT compared to isoform 2. Isoform 1 interacts with SKIV2L2 in an ATP-dependent manner. Isoform 1 interacts with RPL5 in an ATP-dependent manner.5 Publications

Protein-protein interaction databases

BioGridi110985. 39 interactors.
IntActiO15381. 22 interactors.
MINTiMINT-1423251.
STRINGi9606.ENSP00000281701.

Structurei

Secondary structure

1856
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi585 – 597Combined sources13
Helixi599 – 602Combined sources4
Helixi604 – 609Combined sources6
Beta strandi616 – 623Combined sources8
Helixi628 – 638Combined sources11
Beta strandi642 – 647Combined sources6
Turni648 – 651Combined sources4
Helixi657 – 672Combined sources16
Beta strandi675 – 681Combined sources7
Turni684 – 686Combined sources3
Helixi701 – 710Combined sources10
Beta strandi718 – 725Combined sources8
Helixi727 – 729Combined sources3
Helixi732 – 735Combined sources4
Beta strandi742 – 745Combined sources4
Helixi751 – 761Combined sources11
Turni762 – 769Combined sources8
Helixi776 – 780Combined sources5
Helixi784 – 786Combined sources3
Helixi790 – 808Combined sources19
Helixi825 – 832Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X8AX-ray2.60A574-845[»]
ProteinModelPortaliO15381.
SMRiO15381.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15381.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 220Interaction with RPL51 PublicationAdd BLAST220

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi49 – 52Nucleolar localization signal1 Publication4
Motifi85 – 88Nuclear localization signal1 Publication4
Motifi218 – 232Nuclear localization signal1 PublicationAdd BLAST15

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0733. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000079239.
HOGENOMiHOG000223225.
HOVERGENiHBG001226.
InParanoidiO15381.
KOiK14571.
OMAiNDEYYEP.
OrthoDBiEOG091G024K.
PhylomeDBiO15381.
TreeFamiTF314681.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR031996. NVL2_nucleolin-bd.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00004. AAA. 2 hits.
PF16725. Nucleolin_bd. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00674. AAA. 2 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15381-1) [UniParc]FASTAAdd to basket
Also known as: NVLp.2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKPRPAGFVD NKLKQRVIQY LTSNKCGKYV DIGVLASDLQ RVYSIDYGRR
60 70 80 90 100
KRNAFRIQVE KVFSIISSEK ELKNLTELED EHLAKRARQG EEDNEYTESY
110 120 130 140 150
SDDDSSMEDY PDPQSANHMN SSLLSLYRKG NPDSVSNTPE MEQRETTSST
160 170 180 190 200
PRISSKTGSI PLKTPAKDSE GGWFIDKTPS VKKDSFFLDL SCEKSNPKKP
210 220 230 240 250
ITEIQDSKDS SLLESDMKRK GKLKNKGSKR KKEDLQEVDG EIEAVLQKKA
260 270 280 290 300
KARGLEFQIS NVKFEDVGGN DMTLKEVCKM LIHMRHPEVY HHLGVVPPRG
310 320 330 340 350
VLLHGPPGCG KTLLAHAIAG ELDLPILKVA APEIVSGVSG ESEQKLRELF
360 370 380 390 400
EQAVSNAPCI IFIDEIDAIT PKREVASKDM ERRIVAQLLT CMDDLNNVAA
410 420 430 440 450
TARVLVIGAT NRPDSLDPAL RRAGRFDREI CLGIPDEASR ERILQTLCRK
460 470 480 490 500
LRLPQAFDFC HLAHLTPGFV GADLMALCRE AAMCAVNRVL MKLQEQQKKN
510 520 530 540 550
PEMEDLPSKG VQEERLGTEP TSETQDELQR LLGLLRDQDP LSEEQMQGLC
560 570 580 590 600
IELNDFIVAL SSVQPSAKRE GFVTVPNVTW ADIGALEDIR EELTMAILAP
610 620 630 640 650
VRNPDQFKAL GLVTPAGVLL AGPPGCGKTL LAKAVANESG LNFISVKGPE
660 670 680 690 700
LLNMYVGESE RAVRQVFQRA KNSAPCVIFF DEVDALCPRR SDRETGASVR
710 720 730 740 750
VVNQLLTEMD GLEARQQVFI MAATNRPDII DPAILRPGRL DKTLFVGLPP
760 770 780 790 800
PADRLAILKT ITKNGTKPPL DADVNLEAIA GDLRCDCYTG ADLSALVREA
810 820 830 840 850
SICALRQEMA RQKSGNEKGE LKVSHKHFEE AFKKVRSSIS KKDQIMYERL

QESLSR
Length:856
Mass (Da):95,051
Last modified:January 1, 1998 - v1
Checksum:i7A8B373FCAFB99B7
GO
Isoform 2 (identifier: O15381-2) [UniParc]FASTAAdd to basket
Also known as: NVLp.1

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.

Show »
Length:750
Mass (Da):82,746
Checksum:i56AF88DF9129D618
GO
Isoform 3 (identifier: O15381-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.
     115-205: Missing.

Note: No experimental confirmation available.
Show »
Length:659
Mass (Da):72,733
Checksum:i0728D502901260F5
GO
Isoform 4 (identifier: O15381-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.
     320-320: G → GAECSGMITAHCSFDFSGSNDPPASASQ

Show »
Length:667
Mass (Da):73,280
Checksum:iE46F119F9E1C345A
GO
Isoform 5 (identifier: O15381-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-205: Missing.

Show »
Length:765
Mass (Da):85,038
Checksum:iA34DEE65ED8A82D6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048109295V → I.Corresponds to variant rs12084919dbSNPEnsembl.1
Natural variantiVAR_015890359C → G.1 Publication1
Natural variantiVAR_048110404V → I.Corresponds to variant rs34631151dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0453341 – 216Missing in isoform 4. 1 PublicationAdd BLAST216
Alternative sequenceiVSP_0077711 – 106Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST106
Alternative sequenceiVSP_007772115 – 205Missing in isoform 3 and isoform 5. 2 PublicationsAdd BLAST91
Alternative sequenceiVSP_045335320G → GAECSGMITAHCSFDFSGSN DPPASASQ in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68140 mRNA. Translation: AAB70457.1.
U78772 mRNA. Translation: AAB70460.1.
AK297396 mRNA. Translation: BAG59836.1.
AK298244 mRNA. Translation: BAG60510.1.
AC092809 Genomic DNA. No translation available.
BC012105 mRNA. Translation: AAH12105.1.
CCDSiCCDS1541.1. [O15381-1]
CCDS1542.1. [O15381-2]
CCDS58062.1. [O15381-4]
CCDS58063.1. [O15381-5]
RefSeqiNP_001230075.1. NM_001243146.1. [O15381-4]
NP_001230076.1. NM_001243147.1. [O15381-5]
NP_002524.2. NM_002533.3. [O15381-1]
NP_996671.1. NM_206840.2. [O15381-2]
UniGeneiHs.497867.

Genome annotation databases

EnsembliENST00000281701; ENSP00000281701; ENSG00000143748. [O15381-1]
ENST00000340871; ENSP00000341362; ENSG00000143748. [O15381-4]
ENST00000391875; ENSP00000375747; ENSG00000143748. [O15381-2]
ENST00000469075; ENSP00000417826; ENSG00000143748. [O15381-5]
ENST00000469968; ENSP00000419420; ENSG00000143748. [O15381-3]
ENST00000482491; ENSP00000417213; ENSG00000143748. [O15381-4]
GeneIDi4931.
KEGGihsa:4931.
UCSCiuc001hok.4. human. [O15381-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68140 mRNA. Translation: AAB70457.1.
U78772 mRNA. Translation: AAB70460.1.
AK297396 mRNA. Translation: BAG59836.1.
AK298244 mRNA. Translation: BAG60510.1.
AC092809 Genomic DNA. No translation available.
BC012105 mRNA. Translation: AAH12105.1.
CCDSiCCDS1541.1. [O15381-1]
CCDS1542.1. [O15381-2]
CCDS58062.1. [O15381-4]
CCDS58063.1. [O15381-5]
RefSeqiNP_001230075.1. NM_001243146.1. [O15381-4]
NP_001230076.1. NM_001243147.1. [O15381-5]
NP_002524.2. NM_002533.3. [O15381-1]
NP_996671.1. NM_206840.2. [O15381-2]
UniGeneiHs.497867.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X8AX-ray2.60A574-845[»]
ProteinModelPortaliO15381.
SMRiO15381.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110985. 39 interactors.
IntActiO15381. 22 interactors.
MINTiMINT-1423251.
STRINGi9606.ENSP00000281701.

PTM databases

iPTMnetiO15381.
PhosphoSitePlusiO15381.

Polymorphism and mutation databases

BioMutaiNVL.

2D gel databases

SWISS-2DPAGEO15381.

Proteomic databases

EPDiO15381.
MaxQBiO15381.
PaxDbiO15381.
PeptideAtlasiO15381.
PRIDEiO15381.

Protocols and materials databases

DNASUi4931.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281701; ENSP00000281701; ENSG00000143748. [O15381-1]
ENST00000340871; ENSP00000341362; ENSG00000143748. [O15381-4]
ENST00000391875; ENSP00000375747; ENSG00000143748. [O15381-2]
ENST00000469075; ENSP00000417826; ENSG00000143748. [O15381-5]
ENST00000469968; ENSP00000419420; ENSG00000143748. [O15381-3]
ENST00000482491; ENSP00000417213; ENSG00000143748. [O15381-4]
GeneIDi4931.
KEGGihsa:4931.
UCSCiuc001hok.4. human. [O15381-1]

Organism-specific databases

CTDi4931.
DisGeNETi4931.
GeneCardsiNVL.
HGNCiHGNC:8070. NVL.
HPAiHPA028207.
HPA028219.
HPA028224.
HPA028654.
MIMi602426. gene.
neXtProtiNX_O15381.
OpenTargetsiENSG00000143748.
PharmGKBiPA31857.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0733. Eukaryota.
COG0464. LUCA.
GeneTreeiENSGT00570000079239.
HOGENOMiHOG000223225.
HOVERGENiHBG001226.
InParanoidiO15381.
KOiK14571.
OMAiNDEYYEP.
OrthoDBiEOG091G024K.
PhylomeDBiO15381.
TreeFamiTF314681.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143748-MONOMER.

Miscellaneous databases

ChiTaRSiNVL. human.
EvolutionaryTraceiO15381.
GeneWikiiNVL_(gene).
GenomeRNAii4931.
PROiO15381.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143748.
CleanExiHS_NVL.
ExpressionAtlasiO15381. baseline and differential.
GenevisibleiO15381. HS.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR031996. NVL2_nucleolin-bd.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00004. AAA. 2 hits.
PF16725. Nucleolin_bd. 1 hit.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00674. AAA. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNVL_HUMAN
AccessioniPrimary (citable) accession number: O15381
Secondary accession number(s): B4DMC4, B4DP98, Q96EM7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2003
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.