ID NOL3_HUMAN Reviewed; 208 AA. AC O60936; B4DFL0; O60937; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-APR-2015, sequence version 2. DT 24-JAN-2024, entry version 190. DE RecName: Full=Nucleolar protein 3 {ECO:0000312|HGNC:HGNC:7869}; DE AltName: Full=Apoptosis repressor with CARD {ECO:0000305|PubMed:9560245}; DE AltName: Full=Muscle-enriched cytoplasmic protein {ECO:0000305|PubMed:10196175}; DE Short=Myp {ECO:0000303|PubMed:10196175}; DE AltName: Full=Nucleolar protein of 30 kDa {ECO:0000303|PubMed:10196175}; DE Short=Nop30 {ECO:0000303|PubMed:10196175}; GN Name=NOL3 {ECO:0000312|HGNC:HGNC:7869}; GN Synonyms=ARC {ECO:0000303|PubMed:9560245}, NOP GN {ECO:0000303|PubMed:10196175}; 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] (ISOFORM 2), AND INTERACTION WITH CASP2 AND RP CASP8. RX PubMed=9560245; DOI=10.1073/pnas.95.9.5156; RA Koseki T., Inohara N., Chen S., Nunez G.; RT "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that RT interacts selectively with caspases."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5156-5160(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR RP LOCATION, SUBUNIT, INTERACTION WITH SFRS9, AND FUNCTION (ISOFORM 1). RC TISSUE=Cervix carcinoma; RX PubMed=10196175; DOI=10.1074/jbc.274.16.10951; RA Stoss O., Schwaiger F.-W., Cooper T.A., Stamm S.; RT "Alternative splicing determines the intracellular localization of the RT novel nuclear protein Nop30 and its interaction with the splicing factor RT SRp30c."; RL J. Biol. Chem. 274:10951-10962(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain cortex; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; 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 [7] RP FUNCTION (ISOFORM 2), INTERACTION WITH BAX, AND DOMAIN. RX PubMed=15004034; DOI=10.1074/jbc.m400695200; RA Gustafsson A.B., Tsai J.G., Logue S.E., Crow M.T., Gottlieb R.A.; RT "Apoptosis repressor with caspase recruitment domain protects against cell RT death by interfering with Bax activation."; RL J. Biol. Chem. 279:21233-21238(2004). RN [8] RP FUNCTION (ISOFORM 2), DOMAIN, AND INTERACTION WITH CASP8. RX PubMed=15509781; DOI=10.1128/mcb.24.22.9763-9770.2004; RA Jo D.G., Jun J.I., Chang J.W., Hong Y.M., Song S., Cho D.H., Shim S.M., RA Lee H.J., Cho C., Kim D.H., Jung Y.K.; RT "Calcium binding of ARC mediates regulation of caspase 8 and cell death."; RL Mol. Cell. Biol. 24:9763-9770(2004). RN [9] RP INDUCTION. RX PubMed=16505176; DOI=10.1161/circulationaha.105.576785; RA Donath S., Li P., Willenbockel C., Al-Saadi N., Gross V., Willnow T., RA Bader M., Martin U., Bauersachs J., Wollert K.C., Dietz R., RA von Harsdorf R.; RT "Apoptosis repressor with caspase recruitment domain is required for RT cardioprotection in response to biomechanical and ischemic stress."; RL Circulation 113:1203-1212(2006). RN [10] RP INDUCTION, UBIQUITINATION, AND MUTAGENESIS OF LYS-17; LYS-68 AND LYS-163. RX PubMed=17142452; DOI=10.1074/jbc.m609186200; RA Nam Y.J., Mani K., Wu L., Peng C.F., Calvert J.W., Foo R.S., RA Krishnamurthy B., Miao W., Ashton A.W., Lefer D.J., Kitsis R.N.; RT "The apoptosis inhibitor ARC undergoes ubiquitin-proteasomal-mediated RT degradation in response to death stimuli: identification of a degradation- RT resistant mutant."; RL J. Biol. Chem. 282:5522-5528(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=25255805; DOI=10.1038/ncomms5919; RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H., RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.; RT "Global profiling of co- and post-translationally N-myristoylated proteomes RT in human cells."; RL Nat. Commun. 5:4919-4919(2014). RN [13] RP VARIANT MYOCL1 GLN-21, AND CHARACTERIZATION OF VARIANT MYOCL1 GLN-21. RX PubMed=22926851; DOI=10.1002/ana.23666; RA Russell J.F., Steckley J.L., Coppola G., Hahn A.F., Howard M.A., RA Kornberg Z., Huang A., Mirsattari S.M., Merriman B., Klein E., Choi M., RA Lee H.Y., Kirk A., Nelson-Williams C., Gibson G., Baraban S.C., RA Lifton R.P., Geschwind D.H., Fu Y.H., Ptacek L.J.; RT "Familial cortical myoclonus with a mutation in NOL3."; RL Ann. Neurol. 72:175-183(2012). RN [14] RP VARIANT MYOCL1 THR-80. RX PubMed=25138476; DOI=10.1007/s00415-014-7463-z; RA Macerollo A., Mencacci N.E., Erro R., Cordivari C., Edwards M.J., RA Wood N.W., Bhatia K.P.; RT "Screening of mutations in NOL3 in a myoclonic syndromes series."; RL J. Neurol. 261:1830-1831(2014). CC -!- FUNCTION: [Isoform 1]: May be involved in RNA splicing. CC {ECO:0000269|PubMed:10196175}. CC -!- FUNCTION: [Isoform 2]: Functions as an apoptosis repressor that blocks CC multiple modes of cell death. Inhibits extrinsic apoptotic pathways CC through two different ways. Firstly by interacting with FAS and FADD CC upon FAS activation blocking death-inducing signaling complex (DISC) CC assembly (By similarity). Secondly by interacting with CASP8 in a CC mitochondria localization- and phosphorylation-dependent manner, CC limiting the amount of soluble CASP8 available for DISC-mediated CC activation (By similarity). Inhibits intrinsic apoptotic pathway in CC response to a wide range of stresses, through its interaction with BAX CC resulting in BAX inactivation, preventing mitochondrial dysfunction and CC release of pro-apoptotic factors (PubMed:15004034). Inhibits calcium- CC mediated cell death by functioning as a cytosolic calcium buffer, CC dissociating its interaction with CASP8 and maintaining calcium CC homeostasis (PubMed:15509781). Negatively regulates oxidative stress- CC induced apoptosis by phosphorylation-dependent suppression of the CC mitochondria-mediated intrinsic pathway, by blocking CASP2 activation CC and BAX translocation (By similarity). Negatively regulates hypoxia- CC induced apoptosis in part by inhibiting the release of cytochrome c CC from mitochondria in a caspase-independent manner (By similarity). Also CC inhibits TNF-induced necrosis by preventing TNF-signaling pathway CC through TNFRSF1A interaction abrogating the recruitment of RIPK1 to CC complex I (By similarity). Finally through its role as apoptosis CC repressor, promotes vascular remodeling through inhibition of apoptosis CC and stimulation of proliferation, in response to hypoxia (By CC similarity). Inhibits too myoblast differentiation through caspase CC inhibition (By similarity). {ECO:0000250|UniProtKB:Q62881, CC ECO:0000250|UniProtKB:Q9D1X0, ECO:0000269|PubMed:15004034, CC ECO:0000269|PubMed:15509781}. CC -!- SUBUNIT: Oligomerizes (via CARD doamin). Interacts (via CARD domain) CC with CASP2; inhibits CASP2 activity in a phosphorylation-dependent CC manner. Interacts with CASP8; decreases CASP8 activity in a CC mitochondria localization- and phosphorylation-dependent manner and CC this interaction is dissociated by calcium. Interacts with TFPT; CC translocates NOL3 into the nucleus and negatively regulated TFPT- CC induced cell death (By similarity). Interacts directly (via CARD CC domain) with FAS and FADD (via DED domain); inhibits death-inducing CC signaling complex death-inducing signaling complex (DISC) assembly by CC inhibiting the increase in FAS-FADD binding induced by FAS activation CC (By similarity). Interacts (via CARD domain) with BAX (via a C-terminal CC 33 residues); inhibits BAX activation and translocation and CC consequently cytochrome c release from mitochondria. Interacts with CC PPM1G; may dephosphorylate NOL3 (By similarity). Interacts (via CARD CC domain) with BBC3 (via BH3 domain); preventing the association of BBC3 CC with BCL2 and resulting in activation of CASP8 (By similarity). CC Interacts (via CARD domain) with BAD(via BH3 domain); preventing the CC association of BAD with BCL2 (By similarity). Interacts directly (via CC CARD domain) with TNFRSF1A; inhibits TNF-signaling pathway (By CC similarity). Isoform 1 binds to SFRS9/SRp30C. CC {ECO:0000250|UniProtKB:Q62881, ECO:0000250|UniProtKB:Q9D1X0, CC ECO:0000269|PubMed:10196175, ECO:0000269|PubMed:15004034, CC ECO:0000269|PubMed:15509781, ECO:0000269|PubMed:9560245}. CC -!- INTERACTION: CC O60936; Q14790: CASP8; NbExp=3; IntAct=EBI-740992, EBI-78060; CC O60936; O60936: NOL3; NbExp=2; IntAct=EBI-740992, EBI-740992; CC O60936; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-740992, EBI-5235340; CC O60936; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-740992, EBI-717399; CC O60936; P04637: TP53; NbExp=3; IntAct=EBI-740992, EBI-366083; CC O60936; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-740992, EBI-947187; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus CC {ECO:0000269|PubMed:10196175}. Note=The SR-rich C-terminus mediates CC nuclear localization. {ECO:0000269|PubMed:10196175}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:10196175}. Mitochondrion CC {ECO:0000250|UniProtKB:Q62881}. Sarcoplasmic reticulum CC {ECO:0000250|UniProtKB:Q62881}. Membrane {ECO:0000305}; Lipid-anchor CC {ECO:0000305}. Note=Phosphorylation at Thr-149 results in translocation CC to mitochondria. Colocalized with mitochondria in response to oxidative CC stress. {ECO:0000250|UniProtKB:Q62881}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=2 {ECO:0000305}; Synonyms=Myp {ECO:0000303|PubMed:10196175}; CC IsoId=O60936-2; Sequence=Displayed; CC Name=1 {ECO:0000305}; Synonyms=Nop30 {ECO:0000303|PubMed:10196175}; CC IsoId=O60936-1; Sequence=VSP_057515; CC Name=3 {ECO:0000305}; CC IsoId=O60936-3; Sequence=VSP_054607; CC -!- TISSUE SPECIFICITY: Highly expressed in heart and skeletal muscle. CC Detected at low levels in placenta, liver, kidney and pancreas. CC -!- INDUCTION: Protein expression decreases in hearts failure patients CC (PubMed:16505176) and in response to oxidative stress CC (PubMed:17142452). {ECO:0000269|PubMed:16505176, CC ECO:0000269|PubMed:17142452}. CC -!- DOMAIN: CARD is critical for both extrinsic and intrinsic apoptotic CC pathways (By similarity). CARD domain mediates a protective effect CC against myocardial ischemia/reperfusion, oxidative stress and TNF- CC induced necrosis (PubMed:15004034). The C-terminal domain (amino acids CC 99 to 208) is involved in calcium binding and plays a protective role CC in calcium-mediated cell death (PubMed:15509781). CC {ECO:0000250|UniProtKB:Q62881, ECO:0000269|PubMed:15004034, CC ECO:0000269|PubMed:15509781}. CC -!- PTM: Phosphorylation at Thr-149 is required for its antiapoptotic CC effect by blocking death-inducing signaling complex death-inducing CC signaling complex (DISC) activity through the control of interaction CC with CASP8. Phosphorylation at Thr-149 results in translocation to CC mitochondria and this translocation enables the binding to CASP8. CC Dephosphorylated at Thr-149 by calcineurin; doesn't inhibit the CC association between FADD and CASP8 and the consequent apoptosis. CC {ECO:0000250|UniProtKB:Q62881}. CC -!- PTM: Polyubiquitinated by MDM2; promoting proteasomal-dependent CC degradation in response to apoptotic stimuli. CC {ECO:0000250|UniProtKB:Q62881, ECO:0000269|PubMed:17142452}. CC -!- DISEASE: Myoclonus, familial, 1 (MYOCL1) [MIM:614937]: An autosomal CC dominant neurologic condition characterized by adult onset of cortical CC myoclonus manifest as involuntary jerks or movements affecting the face CC and limbs. Affected individuals can also experience falls without CC seizure activity or loss of consciousness. CC {ECO:0000269|PubMed:22926851, ECO:0000269|PubMed:25138476}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41552/NOL3"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF043244; AAC34993.1; -; mRNA. DR EMBL; AF064598; AAC18590.1; -; Genomic_DNA. DR EMBL; AF064598; AAC18591.1; -; Genomic_DNA. DR EMBL; AF064599; AAC18593.1; -; mRNA. DR EMBL; AF064600; AAC18594.1; -; mRNA. DR EMBL; AK294145; BAG57471.1; -; mRNA. DR EMBL; AC074143; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471092; EAW83087.1; -; Genomic_DNA. DR EMBL; BC012798; AAH12798.1; -; mRNA. DR CCDS; CCDS42176.1; -. [O60936-2] DR CCDS; CCDS58473.1; -. [O60936-1] DR RefSeq; NP_001171986.1; NM_001185057.2. [O60936-1] DR RefSeq; NP_001263236.1; NM_001276307.1. [O60936-2] DR RefSeq; NP_001263238.1; NM_001276309.1. [O60936-2] DR RefSeq; NP_001263240.1; NM_001276311.1. DR RefSeq; NP_001263241.1; NM_001276312.1. [O60936-2] DR RefSeq; NP_001263248.1; NM_001276319.1. DR RefSeq; NP_003937.1; NM_003946.6. [O60936-2] DR RefSeq; XP_016879332.1; XM_017023843.1. DR PDB; 4UZ0; X-ray; 2.40 A; A/B=1-95. DR PDBsum; 4UZ0; -. DR AlphaFoldDB; O60936; -. DR SMR; O60936; -. DR BioGRID; 114477; 46. DR DIP; DIP-29940N; -. DR IntAct; O60936; 12. DR STRING; 9606.ENSP00000457243; -. DR iPTMnet; O60936; -. DR PhosphoSitePlus; O60936; -. DR BioMuta; NOL3; -. DR EPD; O60936; -. DR jPOST; O60936; -. DR MassIVE; O60936; -. DR MaxQB; O60936; -. DR PaxDb; 9606-ENSP00000457243; -. DR PeptideAtlas; O60936; -. DR ProteomicsDB; 4053; -. DR ProteomicsDB; 49679; -. [O60936-1] DR ProteomicsDB; 49680; -. [O60936-2] DR Pumba; O60936; -. DR Antibodypedia; 3976; 420 antibodies from 39 providers. DR DNASU; 8996; -. DR Ensembl; ENST00000564053.5; ENSP00000457243.2; ENSG00000140939.15. [O60936-2] DR Ensembl; ENST00000564992.2; ENSP00000457720.2; ENSG00000140939.15. [O60936-2] DR Ensembl; ENST00000568146.1; ENSP00000454598.1; ENSG00000140939.15. [O60936-1] DR GeneID; 8996; -. DR KEGG; hsa:8996; -. DR MANE-Select; ENST00000564992.2; ENSP00000457720.2; NM_001276309.3; NP_001263238.1. DR UCSC; uc010vjd.4; human. [O60936-2] DR AGR; HGNC:7869; -. DR CTD; 8996; -. DR DisGeNET; 8996; -. DR GeneCards; NOL3; -. DR HGNC; HGNC:7869; NOL3. DR HPA; ENSG00000140939; Low tissue specificity. DR MalaCards; NOL3; -. DR MIM; 605235; gene. DR MIM; 614937; phenotype. DR neXtProt; NX_O60936; -. DR OpenTargets; ENSG00000140939; -. DR Orphanet; 319189; Familial cortical myoclonus. DR PharmGKB; PA31673; -. DR VEuPathDB; HostDB:ENSG00000140939; -. DR eggNOG; ENOG502SR4M; Eukaryota. DR GeneTree; ENSGT00510000049353; -. DR HOGENOM; CLU_1261120_0_0_1; -. DR InParanoid; O60936; -. DR OMA; MGNSQER; -. DR OrthoDB; 5266108at2759; -. DR PhylomeDB; O60936; -. DR TreeFam; TF336957; -. DR PathwayCommons; O60936; -. DR SignaLink; O60936; -. DR SIGNOR; O60936; -. DR BioGRID-ORCS; 8996; 14 hits in 1166 CRISPR screens. DR ChiTaRS; NOL3; human. DR GeneWiki; NOL3; -. DR GenomeRNAi; 8996; -. DR Pharos; O60936; Tbio. DR PRO; PR:O60936; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O60936; Protein. DR Bgee; ENSG00000140939; Expressed in apex of heart and 201 other cell types or tissues. DR ExpressionAtlas; O60936; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:ProtInc. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0035877; F:death effector domain binding; IBA:GO_Central. DR GO; GO:0005123; F:death receptor binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0006376; P:mRNA splice site recognition; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0008380; P:RNA splicing; TAS:ProtInc. DR CDD; cd01671; CARD; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR PANTHER; PTHR22797; CARD6/NUCLEOLAR PROTEIN 3; 1. DR PANTHER; PTHR22797:SF37; NUCLEOLAR PROTEIN 3; 1. DR Pfam; PF00619; CARD; 1. DR SMART; SM00114; CARD; 1. DR SUPFAM; SSF47986; DEATH domain; 1. DR PROSITE; PS50209; CARD; 1. DR Genevisible; O60936; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Calcium; Cytoplasm; KW Disease variant; Lipoprotein; Membrane; Metal-binding; Mitochondrion; KW mRNA processing; mRNA splicing; Myristate; Nucleus; Phosphoprotein; KW Reference proteome; Sarcoplasmic reticulum; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:25255805" FT CHAIN 2..208 FT /note="Nucleolar protein 3" FT /id="PRO_0000144099" FT DOMAIN 4..95 FT /note="CARD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT REGION 107..208 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 169..208 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 149 FT /note="Phosphothreonine; by CK2" FT /evidence="ECO:0000250|UniProtKB:Q62881" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:25255805" FT VAR_SEQ 1 FT /note="M -> MPVLGKAGEERRATADAWGQKEEPEEETGQSVWRGRRTPSSPCWPPG FT PVLAEPSGGWDRAPTM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054607" FT VAR_SEQ 96..208 FT /note="VGPGYRDRSYDPPCPGHWTPEAPGSGTTCPGLPRASDPDEAGGPEGSEAVQS FT GTPEEPEPELEAEASKEAEPEPEPEPELEPEAEAEPEPELEPEPDPEPEPDFEERDESE FT DS -> ATGTAAMTLHAQATGRRRHPARGPHAPGCPELQTLTRPGALRAPRRCNPGPRR FT SQSQSWKLRPLKRLNRSRSQSQSWNPRLKQNQSRNWSQNRTQSPSPTSRKGTSPKIPEG FT QSSDRRCPAHAG (in isoform 1)" FT /evidence="ECO:0000303|PubMed:10196175" FT /id="VSP_057515" FT VARIANT 21 FT /note="E -> Q (in MYOCL1; the mutation may alter FT post-translational modification of the protein; FT dbSNP:rs397514600)" FT /evidence="ECO:0000269|PubMed:22926851" FT /id="VAR_069731" FT VARIANT 80 FT /note="A -> T (in MYOCL1; dbSNP:rs780601409)" FT /evidence="ECO:0000269|PubMed:25138476" FT /id="VAR_072644" FT MUTAGEN 17 FT /note="K->R: Abolished ubiquitination in response to an FT apoptotic stimulus; when associated with R-68 and R-163." FT /evidence="ECO:0000269|PubMed:17142452" FT MUTAGEN 31 FT /note="L->F: Did not reduce creatine kinase release or FT infarct size after myocardial ischemia/reperfusion. Causes FT loss of mitochondrial membrane potential and nuclear FT condensation. Failes to prevent the increase in Bax. FT Interacts with BAX." FT /evidence="ECO:0000269|PubMed:15004034" FT MUTAGEN 68 FT /note="K->R: Abolished ubiquitination in response to an FT apoptotic stimulus; when associated with R-17 and R-163." FT /evidence="ECO:0000269|PubMed:17142452" FT MUTAGEN 163 FT /note="K->R: Abolished ubiquitination in response to an FT apoptotic stimulus; when associated with R-17 and R-68." FT /evidence="ECO:0000269|PubMed:17142452" FT HELIX 8..23 FT /evidence="ECO:0007829|PDB:4UZ0" FT HELIX 27..36 FT /evidence="ECO:0007829|PDB:4UZ0" FT HELIX 42..50 FT /evidence="ECO:0007829|PDB:4UZ0" FT HELIX 54..68 FT /evidence="ECO:0007829|PDB:4UZ0" FT HELIX 70..84 FT /evidence="ECO:0007829|PDB:4UZ0" SQ SEQUENCE 208 AA; 22629 MW; 239EF1A143EF6168 CRC64; MGNAQERPSE TIDRERKRLV ETLQADSGLL LDALLARGVL TGPEYEALDA LPDAERRVRR LLLLVQGKGE AACQELLRCA QRTAGAPDPA WDWQHVGPGY RDRSYDPPCP GHWTPEAPGS GTTCPGLPRA SDPDEAGGPE GSEAVQSGTP EEPEPELEAE ASKEAEPEPE PEPELEPEAE AEPEPELEPE PDPEPEPDFE ERDESEDS //