NVL_HUMAN
ID NVL_HUMAN Reviewed; 856 AA.
AC O15381; B4DMC4; B4DP98; Q96EM7;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Nuclear valosin-containing protein-like {ECO:0000305};
DE Short=NVLp;
DE Short=Nuclear VCP-like protein;
GN Name=NVL {ECO:0000312|HGNC:HGNC:8070};
GN Synonyms=NVL2 {ECO:0000303|PubMed:28416111};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT GLY-359,
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=9286697; DOI=10.1006/geno.1997.4856;
RA Germain-Lee E.L., Obie C., Valle D.;
RT "NVL: a new member of the AAA family of ATPases localized to the nucleus.";
RL Genomics 44:22-34(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), INTERACTION WITH RPL5,
RP NUCLEOLAR LOCALIZATION SIGNAL, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS
RP OF 51-LYS-ARG-52; 85-LYS-LYS-86; 218-LYS--LYS-220; 230-ARG--LYS-232 AND
RP LYS-628.
RX PubMed=15469983; DOI=10.1091/mbc.e04-08-0692;
RA Nagahama M., Hara Y., Seki A., Yamazoe T., Kawate Y., Shinohara T.,
RA Hatsuzawa K., Tani K., Tagaya M.;
RT "NVL2 is a nucleolar AAA-ATPase that interacts with ribosomal protein L5
RT through its nucleolar localization sequence.";
RL Mol. Biol. Cell 15:5712-5723(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MTREX, AND MUTAGENESIS OF
RP LYS-311 AND LYS-628.
RX PubMed=16782053; DOI=10.1016/j.bbrc.2006.06.017;
RA Nagahama M., Yamazoe T., Hara Y., Tani K., Tsuji A., Tagaya M.;
RT "The AAA-ATPase NVL2 is a component of pre-ribosomal particles that
RT interacts with the DExD/H-box RNA helicase DOB1.";
RL Biochem. Biophys. Res. Commun. 346:1075-1082(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134 AND THR-138, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134; THR-138; SER-211 AND
RP SER-215, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH NCL/NUCLEOLIN.
RX PubMed=21474449; DOI=10.1074/jbc.m110.174680;
RA Fujiwara Y., Fujiwara K., Goda N., Iwaya N., Tenno T., Shirakawa M.,
RA Hiroaki H.;
RT "Structure and function of the N-terminal nucleolin binding domain of
RT nuclear valosin-containing protein-like 2 (NVL2) harboring a nucleolar
RT localization signal.";
RL J. Biol. Chem. 286:21732-21741(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TERT, MUTAGENESIS OF
RP LYS-311 AND LYS-628, AND ATP-BINDING.
RX PubMed=22226966; DOI=10.1016/j.bbrc.2011.12.101;
RA Her J., Chung I.K.;
RT "The AAA-ATPase NVL2 is a telomerase component essential for holoenzyme
RT assembly.";
RL Biochem. Biophys. Res. Commun. 417:1086-1092(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134 AND THR-138, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP FUNCTION, MUTAGENESIS OF GLU-365; LYS-628 AND GLU-682, AND INTERACTION WITH
RP MTREX.
RX PubMed=26166824; DOI=10.1016/j.bbrc.2015.07.032;
RA Yoshikatsu Y., Ishida Y., Sudo H., Yuasa K., Tsuji A., Nagahama M.;
RT "NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and
RT is involved in pre-rRNA processing.";
RL Biochem. Biophys. Res. Commun. 464:780-786(2015).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-365 AND GLU-682.
RX PubMed=26456651; DOI=10.1016/j.bbrc.2015.09.160;
RA Hiraishi N., Ishida Y., Nagahama M.;
RT "AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar
RT protein WDR74.";
RL Biochem. Biophys. Res. Commun. 467:534-540(2015).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-208, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [18]
RP FUNCTION, INTERACTION WITH WDR74, AND MUTAGENESIS OF GLU-365 AND GLU-682.
RX PubMed=28416111; DOI=10.1016/j.str.2017.03.008;
RA Lo Y.H., Romes E.M., Pillon M.C., Sobhany M., Stanley R.E.;
RT "Structural Analysis Reveals Features of Ribosome Assembly Factor
RT Nsa1/WDR74 Important for Localization and Interaction with Rix7/NVL2.";
RL Structure 25:762-772(2017).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF GLU-365 AND GLU-682.
RX PubMed=29107693; DOI=10.1016/j.bbrc.2017.10.148;
RA Hiraishi N., Ishida Y.I., Sudo H., Nagahama M.;
RT "WDR74 participates in an early cleavage of the pre-rRNA processing pathway
RT in cooperation with the nucleolar AAA-ATPase NVL2.";
RL Biochem. Biophys. Res. Commun. 495:116-123(2018).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 574-845 IN COMPLEX WITH PHOSPHATE.
RG Structural genomics consortium (SGC);
RT "Human nuclear valosin containing protein like (NVL), C-terminal AAA-ATPase
RT domain.";
RL Submitted (MAR-2010) to the PDB data bank.
RN [21] {ECO:0007744|PDB:6RO1}
RP X-RAY CRYSTALLOGRAPHY (3.07 ANGSTROMS) OF 167-216 IN COMPLEXES WITH MTREX
RP AND ATP, INTERACTION WITH MTREX, AND MUTAGENESIS OF TRP-173; ILE-175 AND
RP ASP-176.
RX PubMed=31358741; DOI=10.1038/s41467-019-11339-x;
RA Lingaraju M., Johnsen D., Schlundt A., Langer L.M., Basquin J., Sattler M.,
RA Heick Jensen T., Falk S., Conti E.;
RT "The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using
RT distinct arch-interacting motifs.";
RL Nat. Commun. 10:3393-3393(2019).
CC -!- FUNCTION: Participates in the assembly of the telomerase holoenzyme and
CC effecting of telomerase activity via its interaction with TERT
CC (PubMed:22226966). Involved in both early and late stages of the pre-
CC rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates
CC 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983,
CC PubMed:16782053, PubMed:29107693, PubMed:26456651). Catalyzes the
CC release of specific assembly factors, such as WDR74, from pre-60S
CC ribosomal particles through the ATPase activity (PubMed:29107693,
CC PubMed:26456651, PubMed:28416111). {ECO:0000269|PubMed:15469983,
CC ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966,
CC ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651,
CC ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:29107693}.
CC -!- SUBUNIT: Interacts with NCL/nucleolin (PubMed:21474449). Isoform 1 and
CC isoform 2 interact with TERT and isoform 1 exhibits a higher binding
CC affinity for TERT compared to isoform 2 (PubMed:22226966). Isoform 1
CC interacts with MTREX in an ATP-dependent manner; the interaction is
CC required to associate NVL with nuclear RNA exosome (PubMed:26166824,
CC PubMed:31358741, PubMed:16782053). Isoform 1 interacts with RPL5 in an
CC ATP-dependent manner (PubMed:15469983). Interacts with WDR74 (through
CC WDR repeats); the interaction is independent of RNA or pre-60S ribosome
CC particles (PubMed:28416111). {ECO:0000269|PubMed:15469983,
CC ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:21474449,
CC ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26166824,
CC ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:31358741}.
CC -!- INTERACTION:
CC O15381-5; P54253: ATXN1; NbExp=3; IntAct=EBI-18577082, EBI-930964;
CC O15381-5; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-18577082, EBI-25840379;
CC O15381-5; Q01658: DR1; NbExp=3; IntAct=EBI-18577082, EBI-750300;
CC O15381-5; Q00403: GTF2B; NbExp=3; IntAct=EBI-18577082, EBI-389564;
CC O15381-5; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-18577082, EBI-1054873;
CC O15381-5; P04792: HSPB1; NbExp=3; IntAct=EBI-18577082, EBI-352682;
CC O15381-5; O43464: HTRA2; NbExp=3; IntAct=EBI-18577082, EBI-517086;
CC O15381-5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-18577082, EBI-10975473;
CC O15381-5; P19404: NDUFV2; NbExp=3; IntAct=EBI-18577082, EBI-713665;
CC O15381-5; P35240-4: NF2; NbExp=3; IntAct=EBI-18577082, EBI-1014514;
CC O15381-5; P29474: NOS3; NbExp=3; IntAct=EBI-18577082, EBI-1391623;
CC O15381-5; D3DTS7: PMP22; NbExp=3; IntAct=EBI-18577082, EBI-25882629;
CC O15381-5; P41219: PRPH; NbExp=3; IntAct=EBI-18577082, EBI-752074;
CC O15381-5; P60891: PRPS1; NbExp=3; IntAct=EBI-18577082, EBI-749195;
CC O15381-5; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-18577082, EBI-396669;
CC O15381-5; P78317: RNF4; NbExp=3; IntAct=EBI-18577082, EBI-2340927;
CC O15381-5; P37840: SNCA; NbExp=3; IntAct=EBI-18577082, EBI-985879;
CC O15381-5; Q13148: TARDBP; NbExp=6; IntAct=EBI-18577082, EBI-372899;
CC O15381-5; P09936: UCHL1; NbExp=3; IntAct=EBI-18577082, EBI-714860;
CC O15381-5; O76024: WFS1; NbExp=3; IntAct=EBI-18577082, EBI-720609;
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:15469983}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus
CC {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:15469983,
CC ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26456651,
CC ECO:0000269|PubMed:9286697}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:15469983}. Note=Expressed predominantly in the
CC nucleolus. Associates with pre-ribosomal particles in the nucleus.
CC {ECO:0000269|PubMed:16782053}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=NVLp.2;
CC IsoId=O15381-1; Sequence=Displayed;
CC Name=2; Synonyms=NVLp.1;
CC IsoId=O15381-2; Sequence=VSP_007771;
CC Name=3;
CC IsoId=O15381-3; Sequence=VSP_007771, VSP_007772;
CC Name=4;
CC IsoId=O15381-4; Sequence=VSP_045334, VSP_045335;
CC Name=5;
CC IsoId=O15381-5; Sequence=VSP_007772;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest level of expression in
CC heart, placenta, skeletal muscle, pancreas and retina.
CC {ECO:0000269|PubMed:9286697}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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DR EMBL; U68140; AAB70457.1; -; mRNA.
DR EMBL; U78772; AAB70460.1; -; mRNA.
DR EMBL; AK297396; BAG59836.1; -; mRNA.
DR EMBL; AK298244; BAG60510.1; -; mRNA.
DR EMBL; AC092809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012105; AAH12105.1; -; mRNA.
DR CCDS; CCDS1541.1; -. [O15381-1]
DR CCDS; CCDS1542.1; -. [O15381-2]
DR CCDS; CCDS58062.1; -. [O15381-4]
DR CCDS; CCDS58063.1; -. [O15381-5]
DR RefSeq; NP_001230075.1; NM_001243146.1. [O15381-4]
DR RefSeq; NP_001230076.1; NM_001243147.1. [O15381-5]
DR RefSeq; NP_002524.2; NM_002533.3. [O15381-1]
DR RefSeq; NP_996671.1; NM_206840.2. [O15381-2]
DR PDB; 2X8A; X-ray; 2.60 A; A=574-845.
DR PDB; 6RO1; X-ray; 3.07 A; B=167-216.
DR PDBsum; 2X8A; -.
DR PDBsum; 6RO1; -.
DR AlphaFoldDB; O15381; -.
DR SMR; O15381; -.
DR BioGRID; 110985; 136.
DR IntAct; O15381; 63.
DR MINT; O15381; -.
DR STRING; 9606.ENSP00000281701; -.
DR GlyGen; O15381; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15381; -.
DR MetOSite; O15381; -.
DR PhosphoSitePlus; O15381; -.
DR BioMuta; NVL; -.
DR SWISS-2DPAGE; O15381; -.
DR EPD; O15381; -.
DR jPOST; O15381; -.
DR MassIVE; O15381; -.
DR MaxQB; O15381; -.
DR PaxDb; O15381; -.
DR PeptideAtlas; O15381; -.
DR PRIDE; O15381; -.
DR ProteomicsDB; 4595; -.
DR ProteomicsDB; 4771; -.
DR ProteomicsDB; 48620; -. [O15381-1]
DR ProteomicsDB; 48621; -. [O15381-2]
DR ProteomicsDB; 48622; -. [O15381-3]
DR Antibodypedia; 34637; 223 antibodies from 27 providers.
DR DNASU; 4931; -.
DR Ensembl; ENST00000281701.11; ENSP00000281701.6; ENSG00000143748.18. [O15381-1]
DR Ensembl; ENST00000340871.8; ENSP00000341362.4; ENSG00000143748.18. [O15381-4]
DR Ensembl; ENST00000391875.6; ENSP00000375747.2; ENSG00000143748.18. [O15381-2]
DR Ensembl; ENST00000469075.5; ENSP00000417826.1; ENSG00000143748.18. [O15381-5]
DR Ensembl; ENST00000469968.5; ENSP00000419420.2; ENSG00000143748.18. [O15381-3]
DR Ensembl; ENST00000482491.5; ENSP00000417213.2; ENSG00000143748.18. [O15381-4]
DR GeneID; 4931; -.
DR KEGG; hsa:4931; -.
DR MANE-Select; ENST00000281701.11; ENSP00000281701.6; NM_002533.4; NP_002524.2.
DR UCSC; uc001hok.4; human. [O15381-1]
DR CTD; 4931; -.
DR DisGeNET; 4931; -.
DR GeneCards; NVL; -.
DR HGNC; HGNC:8070; NVL.
DR HPA; ENSG00000143748; Low tissue specificity.
DR MIM; 602426; gene.
DR neXtProt; NX_O15381; -.
DR OpenTargets; ENSG00000143748; -.
DR PharmGKB; PA31857; -.
DR VEuPathDB; HostDB:ENSG00000143748; -.
DR eggNOG; KOG0733; Eukaryota.
DR GeneTree; ENSGT00570000079239; -.
DR HOGENOM; CLU_000688_12_3_1; -.
DR InParanoid; O15381; -.
DR OMA; RQVFMRA; -.
DR OrthoDB; 194195at2759; -.
DR PhylomeDB; O15381; -.
DR TreeFam; TF314681; -.
DR PathwayCommons; O15381; -.
DR SignaLink; O15381; -.
DR BioGRID-ORCS; 4931; 766 hits in 1084 CRISPR screens.
DR ChiTaRS; NVL; human.
DR EvolutionaryTrace; O15381; -.
DR GeneWiki; NVL_(gene); -.
DR GenomeRNAi; 4931; -.
DR Pharos; O15381; Tbio.
DR PRO; PR:O15381; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O15381; protein.
DR Bgee; ENSG00000143748; Expressed in sural nerve and 118 other tissues.
DR ExpressionAtlas; O15381; baseline and differential.
DR Genevisible; O15381; HS.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:1990275; F:preribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:UniProtKB.
DR GO; GO:1904749; P:regulation of protein localization to nucleolus; IDA:UniProtKB.
DR GO; GO:0042273; P:ribosomal large subunit biogenesis; IDA:UniProtKB.
DR GO; GO:0042254; P:ribosome biogenesis; IMP:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; IDA:UniProtKB.
DR Gene3D; 1.10.10.2010; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR038100; NLV2_N_sf.
DR InterPro; IPR031996; NVL2_nucleolin-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00004; AAA; 2.
DR Pfam; PF17862; AAA_lid_3; 2.
DR Pfam; PF16725; Nucleolin_bd; 1.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00674; AAA; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ribosome biogenesis; Ubl conjugation.
FT CHAIN 1..856
FT /note="Nuclear valosin-containing protein-like"
FT /id="PRO_0000084588"
FT REGION 1..220
FT /note="Interaction with RPL5"
FT /evidence="ECO:0000269|PubMed:15469983"
FT REGION 84..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 267..474
FT /note="Interaction with WDR74"
FT /evidence="ECO:0000269|PubMed:28416111"
FT REGION 496..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 49..52
FT /note="Nucleolar localization signal"
FT /evidence="ECO:0000269|PubMed:15469983"
FT MOTIF 85..88
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:15469983"
FT MOTIF 218..232
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:15469983"
FT COMPBIAS 110..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..512
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 305..312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:22226966"
FT BINDING 622..629
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:22226966"
FT MOD_RES 70
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBY8"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 156
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBY8"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBY8"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..216
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045334"
FT VAR_SEQ 1..106
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9286697"
FT /id="VSP_007771"
FT VAR_SEQ 115..205
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_007772"
FT VAR_SEQ 320
FT /note="G -> GAECSGMITAHCSFDFSGSNDPPASASQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045335"
FT VARIANT 295
FT /note="V -> I (in dbSNP:rs12084919)"
FT /id="VAR_048109"
FT VARIANT 359
FT /note="C -> G"
FT /evidence="ECO:0000269|PubMed:9286697"
FT /id="VAR_015890"
FT VARIANT 404
FT /note="V -> I (in dbSNP:rs34631151)"
FT /id="VAR_048110"
FT MUTAGEN 51..52
FT /note="KR->AA: Loss of nucleolar localization and
FT interaction with RPL5."
FT /evidence="ECO:0000269|PubMed:15469983"
FT MUTAGEN 85..86
FT /note="KR->AA: Decreased nuclear localization. Complete
FT loss of nuclear localization; when associated with 218-A--
FT A-220 and 230-A--A-232."
FT /evidence="ECO:0000269|PubMed:15469983"
FT MUTAGEN 173
FT /note="W->A: Abolishes binding to MTREX."
FT /evidence="ECO:0000269|PubMed:31358741"
FT MUTAGEN 175
FT /note="I->E: Impairs binding to MTREX."
FT /evidence="ECO:0000269|PubMed:31358741"
FT MUTAGEN 176
FT /note="D->A: Impairs the binding of MTREX."
FT /evidence="ECO:0000269|PubMed:31358741"
FT MUTAGEN 218..220
FT /note="KRK->AAA: Decreased nuclear localization; when
FT associated with 230-A--A-232. Complete loss of nuclear
FT localization; when associated with 85-A-A-86 and 230-A--A-
FT 232."
FT /evidence="ECO:0000269|PubMed:15469983"
FT MUTAGEN 230..232
FT /note="RKK->AAA: Decreased nuclear localization when
FT associated with 218-A--A-220. Complete loss of nuclear
FT localization; when associated with 85-A-A-86 and 218-A--A-
FT 220."
FT /evidence="ECO:0000269|PubMed:15469983"
FT MUTAGEN 311
FT /note="K->M: Loss of ATP-binding. Significant reduction in
FT interaction with TERT and in telomerase activity. Loss of
FT interaction with MTREX."
FT /evidence="ECO:0000269|PubMed:16782053,
FT ECO:0000269|PubMed:22226966, ECO:0000305|PubMed:22226966"
FT MUTAGEN 365
FT /note="E->Q: Decreases 60S ribosomes synthesis. Strongly
FT decreases 60S ribosomal subunit synthesis, enhances
FT interaction with WDR74 and increases association of WDR74
FT and MTREX as well as induces partial migration of WDR74 to
FT the nucleoplasm; when associated with Q-682."
FT /evidence="ECO:0000269|PubMed:26166824,
FT ECO:0000269|PubMed:26456651"
FT MUTAGEN 628
FT /note="K->M: Loss of ATP-binding. No effect on interaction
FT with TERT, MTREX and RPL5 and on telomerase activity.
FT Significant reduction in the level of the 60S ribosomal
FT subunit."
FT /evidence="ECO:0000269|PubMed:15469983,
FT ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966,
FT ECO:0000269|PubMed:26166824, ECO:0000305|PubMed:22226966"
FT MUTAGEN 682
FT /note="E->Q: Decreases 60S ribosomes synthesis. Strongly
FT decreases 60S ribosomal subunit synthesis, enhances
FT interaction with WDR74 and increases association of WDR74
FT and MTREX as well as induces partial migration of WDR74 to
FT the nucleoplasm; when associated with Q-365."
FT /evidence="ECO:0000269|PubMed:26166824,
FT ECO:0000269|PubMed:26456651"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:6RO1"
FT HELIX 585..597
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 599..602
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 604..609
FT /evidence="ECO:0007829|PDB:2X8A"
FT STRAND 616..623
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 628..638
FT /evidence="ECO:0007829|PDB:2X8A"
FT STRAND 642..647
FT /evidence="ECO:0007829|PDB:2X8A"
FT TURN 648..651
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 657..672
FT /evidence="ECO:0007829|PDB:2X8A"
FT STRAND 675..681
FT /evidence="ECO:0007829|PDB:2X8A"
FT TURN 684..686
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 701..710
FT /evidence="ECO:0007829|PDB:2X8A"
FT STRAND 718..725
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 727..729
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 732..735
FT /evidence="ECO:0007829|PDB:2X8A"
FT STRAND 742..745
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 751..761
FT /evidence="ECO:0007829|PDB:2X8A"
FT TURN 762..769
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 776..780
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 784..786
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 790..808
FT /evidence="ECO:0007829|PDB:2X8A"
FT HELIX 825..832
FT /evidence="ECO:0007829|PDB:2X8A"
SQ SEQUENCE 856 AA; 95051 MW; 7A8B373FCAFB99B7 CRC64;
MKPRPAGFVD NKLKQRVIQY LTSNKCGKYV DIGVLASDLQ RVYSIDYGRR KRNAFRIQVE
KVFSIISSEK ELKNLTELED EHLAKRARQG EEDNEYTESY SDDDSSMEDY PDPQSANHMN
SSLLSLYRKG NPDSVSNTPE MEQRETTSST PRISSKTGSI PLKTPAKDSE GGWFIDKTPS
VKKDSFFLDL SCEKSNPKKP ITEIQDSKDS SLLESDMKRK GKLKNKGSKR KKEDLQEVDG
EIEAVLQKKA KARGLEFQIS NVKFEDVGGN DMTLKEVCKM LIHMRHPEVY HHLGVVPPRG
VLLHGPPGCG KTLLAHAIAG ELDLPILKVA APEIVSGVSG ESEQKLRELF EQAVSNAPCI
IFIDEIDAIT PKREVASKDM ERRIVAQLLT CMDDLNNVAA TARVLVIGAT NRPDSLDPAL
RRAGRFDREI CLGIPDEASR ERILQTLCRK LRLPQAFDFC HLAHLTPGFV GADLMALCRE
AAMCAVNRVL MKLQEQQKKN PEMEDLPSKG VQEERLGTEP TSETQDELQR LLGLLRDQDP
LSEEQMQGLC IELNDFIVAL SSVQPSAKRE GFVTVPNVTW ADIGALEDIR EELTMAILAP
VRNPDQFKAL GLVTPAGVLL AGPPGCGKTL LAKAVANESG LNFISVKGPE LLNMYVGESE
RAVRQVFQRA KNSAPCVIFF DEVDALCPRR SDRETGASVR VVNQLLTEMD GLEARQQVFI
MAATNRPDII DPAILRPGRL DKTLFVGLPP PADRLAILKT ITKNGTKPPL DADVNLEAIA
GDLRCDCYTG ADLSALVREA SICALRQEMA RQKSGNEKGE LKVSHKHFEE AFKKVRSSIS
KKDQIMYERL QESLSR
