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Protein

Nucleolar protein 3

Gene

NOL3

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

Functioni

Isoform 1: May be involved in RNA splicing.1 Publication
Isoform 2: Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors (PubMed:15004034). Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:15509781). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (By similarity). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). Inhibits too myoblast differentiation through caspase inhibition (By similarity).By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi99 – 2081 PublicationAdd BLAST110

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • caspase binding Source: UniProtKB
  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  • RNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, mRNA processing, mRNA splicing

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140939-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleolar protein 3Imported
Alternative name(s):
Apoptosis repressor with CARD1 Publication
Muscle-enriched cytoplasmic protein1 Publication
Short name:
Myp1 Publication
Nucleolar protein of 30 kDa1 Publication
Short name:
Nop301 Publication
Gene namesi
Name:NOL3Imported
Synonyms:ARC1 Publication, NOP1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:7869. NOL3.

Subcellular locationi

Isoform 1 :
  • Nucleusnucleolus 1 Publication

  • Note: The SR-rich C-terminus mediates nuclear localization.1 Publication
Isoform 2 :
  • Cytoplasm 1 Publication
  • Mitochondrion By similarity
  • Sarcoplasmic reticulum By similarity
  • Membrane Curated; Lipid-anchor Curated

  • Note: Phosphorylation at Thr-149 results in translocation to mithochondria. Colocalized with mitochondria in response to oxidative stress.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: ProtInc
  • membrane Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB
  • nucleolus Source: UniProtKB
  • sarcoplasmic reticulum Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Nucleus, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Myoclonus, familial cortical (FCM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurologic condition characterized by adult onset of cortical myoclonus manifest as involuntary jerks or movements affecting the face and limbs. Affected individuals can also experience falls without seizure activity or loss of consciousness.
See also OMIM:614937
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06973121E → Q in FCM; the mutation may alter post-translational modification of the protein. 1 PublicationCorresponds to variant rs397514600dbSNPEnsembl.1
Natural variantiVAR_07264480A → T in FCM. 1 PublicationCorresponds to variant rs780601409dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi17K → R: Abolished ubiquitination in response to an apoptotic stimulus; when associated with R-68 and R-163. 1 Publication1
Mutagenesisi31L → F: Did not reduce creatine kinase release or infarct size after myocardial ischemia/reperfusion. Causes loss of mitochondrial membrane potential and nuclear condensation. Failes to prevent the increase in Bax. Interacts with BAX. 1 Publication1
Mutagenesisi68K → R: Abolished ubiquitination in response to an apoptotic stimulus; when associated with R-17 and R-163. 1 Publication1
Mutagenesisi163K → R: Abolished ubiquitination in response to an apoptotic stimulus; when associated with R-17 and R-68. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi8996.
MalaCardsiNOL3.
MIMi614937. phenotype.
OpenTargetsiENSG00000140939.
Orphaneti319189. Familial cortical myoclonus.
PharmGKBiPA31673.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001440992 – 208Nucleolar protein 3Add BLAST207

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei149Phosphothreonine; by CK2By similarity1

Post-translational modificationi

Phosphorylation at Thr-149 is required for its antiapoptotic effect by blocking death-inducing signaling complex death-inducing signaling complex (DISC) activity through the control of interaction with CASP8. Phosphorylation at Thr-149 results in translocation to mithochondria and this translocation enables the binding to CASP8. Dephosphorylated at Thr-149 by calcineurin; doesn't inhibit the association between FADD and CASP8 and the consequent apoptosis.By similarity
Polyubiquitinated by MDM2; promoting proteasomal-dependent degradation in response to apoptotic stimuli.By similarity1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO60936.
PaxDbiO60936.
PeptideAtlasiO60936.
PRIDEiO60936.

PTM databases

iPTMnetiO60936.
PhosphoSitePlusiO60936.

Expressioni

Tissue specificityi

Highly expressed in heart and skeletal muscle. Detected at low levels in placenta, liver, kidney and pancreas.

Inductioni

Protein expression decreases in hearts failure patients (PubMed:16505176) and in response to oxidative stress (PubMed:17142452).2 Publications

Gene expression databases

BgeeiENSG00000140939.
CleanExiHS_ARC.
HS_NOL3.
ExpressionAtlasiO60936. baseline and differential.
GenevisibleiO60936. HS.

Organism-specific databases

HPAiCAB009208.

Interactioni

Subunit structurei

Oligomerizes (via CARD doamin). Interacts (via CARD domain) with CASP2; inhibits CASP2 activity in a phosphorylation-dependent manner. Interacts with CASP8; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium. Interacts with TFPT; translocates NOL3 into the nucleus and negatively regulated TFPT-induced cell death (By similarity). Interacts directly (via CARD domain) with FAS and FADD (via DED domain); inhibits death-inducing signaling complex death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (By similarity). Interacts (via CARD domain) with BAX (via a C-terminal 33 residues); inhibits BAX activation and translocation and consequently cytochrome c release from mitochondria. Interacts with PPM1G; may dephosphorylate NOL3 (By similarity). Interacts (via CARD domain) with BBC3 (via BH3 domain); preventing the association of BBC3 with BCL2 and resulting in activation of CASP8 (By similarity). Interacts (via CARD domain) with BAD(via BH3 domain); preventing the association of BAD with BCL2 (By similarity). Interacts directly (via CARD domain) with TNFRSF1A; inhibits TNF-signaling pathway (By similarity). Isoform 1 binds to SFRS9/SRp30C.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-740992,EBI-740992
CASP8Q147903EBI-740992,EBI-78060
TINF2Q9BSI42EBI-740992,EBI-717399

GO - Molecular functioni

  • caspase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114477. 37 interactors.
DIPiDIP-29940N.
IntActiO60936. 10 interactors.
MINTiMINT-1462750.
STRINGi9606.ENSP00000268605.

Structurei

Secondary structure

1208
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 23Combined sources16
Helixi27 – 36Combined sources10
Helixi42 – 50Combined sources9
Helixi54 – 68Combined sources15
Helixi70 – 84Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UZ0X-ray2.40A/B1-95[»]
ProteinModelPortaliO60936.
SMRiO60936.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 95CARDPROSITE-ProRule annotationAdd BLAST92

Domaini

CARD is critical for both extrinsic and intrinsic apoptotic pathways (By similarity). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (PubMed:15004034) (By similarity). The calcium binding domain plays a protective role in calcium-mediated cell death (PubMed:15509781).By similarity2 Publications

Sequence similaritiesi

Contains 1 CARD domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410J0R1. Eukaryota.
ENOG4111BHK. LUCA.
GeneTreeiENSGT00510000049353.
HOGENOMiHOG000113820.
InParanoidiO60936.
OMAiCAQRTTR.
OrthoDBiEOG091G0U8K.
PhylomeDBiO60936.
TreeFamiTF336957.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00114. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2Curated (identifier: O60936-2) [UniParc]FASTAAdd to basket
Also known as: Myp1 Publication

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
MGNAQERPSE TIDRERKRLV ETLQADSGLL LDALLARGVL TGPEYEALDA
60 70 80 90 100
LPDAERRVRR LLLLVQGKGE AACQELLRCA QRTAGAPDPA WDWQHVGPGY
110 120 130 140 150
RDRSYDPPCP GHWTPEAPGS GTTCPGLPRA SDPDEAGGPE GSEAVQSGTP
160 170 180 190 200
EEPEPELEAE ASKEAEPEPE PEPELEPEAE AEPEPELEPE PDPEPEPDFE

ERDESEDS
Length:208
Mass (Da):22,629
Last modified:April 1, 2015 - v2
Checksum:i239EF1A143EF6168
GO
Isoform 1Curated (identifier: O60936-1) [UniParc]FASTAAdd to basket
Also known as: Nop301 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     96-208: VGPGYRDRSY...FEERDESEDS → ATGTAAMTLH...SDRRCPAHAG

Show »
Length:219
Mass (Da):24,327
Checksum:iB1CCCB199D4FEE09
GO
Isoform 3Curated (identifier: O60936-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPVLGKAGEERRATADAWGQKEEPEEETGQSVWRGRRTPSSPCWPPGPVLAEPSGGWDRAPTM

Note: No experimental confirmation available.
Show »
Length:270
Mass (Da):29,355
Checksum:iACA253B5CD21348B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06973121E → Q in FCM; the mutation may alter post-translational modification of the protein. 1 PublicationCorresponds to variant rs397514600dbSNPEnsembl.1
Natural variantiVAR_07264480A → T in FCM. 1 PublicationCorresponds to variant rs780601409dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0546071M → MPVLGKAGEERRATADAWGQ KEEPEEETGQSVWRGRRTPS SPCWPPGPVLAEPSGGWDRA PTM in isoform 3. 1 Publication1
Alternative sequenceiVSP_05751596 – 208VGPGY…ESEDS → ATGTAAMTLHAQATGRRRHP ARGPHAPGCPELQTLTRPGA LRAPRRCNPGPRRSQSQSWK LRPLKRLNRSRSQSQSWNPR LKQNQSRNWSQNRTQSPSPT SRKGTSPKIPEGQSSDRRCP AHAG in isoform 1. 1 PublicationAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043244 mRNA. Translation: AAC34993.1.
AF064598 Genomic DNA. Translation: AAC18590.1.
AF064598 Genomic DNA. Translation: AAC18591.1.
AF064599 mRNA. Translation: AAC18593.1.
AF064600 mRNA. Translation: AAC18594.1.
AK294145 mRNA. Translation: BAG57471.1.
AC074143 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83087.1.
BC012798 mRNA. Translation: AAH12798.1.
CCDSiCCDS42176.1. [O60936-2]
CCDS58473.1. [O60936-1]
CCDS61960.1. [O60936-3]
RefSeqiNP_001171986.1. NM_001185057.2. [O60936-1]
NP_001263236.1. NM_001276307.1. [O60936-2]
NP_001263238.1. NM_001276309.1. [O60936-2]
NP_001263240.1. NM_001276311.1.
NP_001263241.1. NM_001276312.1. [O60936-2]
NP_001263248.1. NM_001276319.1. [O60936-3]
NP_003937.1. NM_003946.6. [O60936-2]
XP_016879332.1. XM_017023843.1. [O60936-3]
UniGeneiHs.513667.

Genome annotation databases

EnsembliENST00000268605; ENSP00000268605; ENSG00000140939. [O60936-2]
ENST00000564053; ENSP00000457243; ENSG00000140939. [O60936-3]
ENST00000568146; ENSP00000454598; ENSG00000140939. [O60936-1]
GeneIDi8996.
KEGGihsa:8996.
UCSCiuc010vjd.4. human. [O60936-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043244 mRNA. Translation: AAC34993.1.
AF064598 Genomic DNA. Translation: AAC18590.1.
AF064598 Genomic DNA. Translation: AAC18591.1.
AF064599 mRNA. Translation: AAC18593.1.
AF064600 mRNA. Translation: AAC18594.1.
AK294145 mRNA. Translation: BAG57471.1.
AC074143 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83087.1.
BC012798 mRNA. Translation: AAH12798.1.
CCDSiCCDS42176.1. [O60936-2]
CCDS58473.1. [O60936-1]
CCDS61960.1. [O60936-3]
RefSeqiNP_001171986.1. NM_001185057.2. [O60936-1]
NP_001263236.1. NM_001276307.1. [O60936-2]
NP_001263238.1. NM_001276309.1. [O60936-2]
NP_001263240.1. NM_001276311.1.
NP_001263241.1. NM_001276312.1. [O60936-2]
NP_001263248.1. NM_001276319.1. [O60936-3]
NP_003937.1. NM_003946.6. [O60936-2]
XP_016879332.1. XM_017023843.1. [O60936-3]
UniGeneiHs.513667.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UZ0X-ray2.40A/B1-95[»]
ProteinModelPortaliO60936.
SMRiO60936.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114477. 37 interactors.
DIPiDIP-29940N.
IntActiO60936. 10 interactors.
MINTiMINT-1462750.
STRINGi9606.ENSP00000268605.

PTM databases

iPTMnetiO60936.
PhosphoSitePlusiO60936.

Proteomic databases

EPDiO60936.
PaxDbiO60936.
PeptideAtlasiO60936.
PRIDEiO60936.

Protocols and materials databases

DNASUi8996.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000268605; ENSP00000268605; ENSG00000140939. [O60936-2]
ENST00000564053; ENSP00000457243; ENSG00000140939. [O60936-3]
ENST00000568146; ENSP00000454598; ENSG00000140939. [O60936-1]
GeneIDi8996.
KEGGihsa:8996.
UCSCiuc010vjd.4. human. [O60936-2]

Organism-specific databases

CTDi8996.
DisGeNETi8996.
GeneCardsiNOL3.
HGNCiHGNC:7869. NOL3.
HPAiCAB009208.
MalaCardsiNOL3.
MIMi605235. gene.
614937. phenotype.
neXtProtiNX_O60936.
OpenTargetsiENSG00000140939.
Orphaneti319189. Familial cortical myoclonus.
PharmGKBiPA31673.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0R1. Eukaryota.
ENOG4111BHK. LUCA.
GeneTreeiENSGT00510000049353.
HOGENOMiHOG000113820.
InParanoidiO60936.
OMAiCAQRTTR.
OrthoDBiEOG091G0U8K.
PhylomeDBiO60936.
TreeFamiTF336957.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140939-MONOMER.

Miscellaneous databases

ChiTaRSiNOL3. human.
GeneWikiiNOL3.
GenomeRNAii8996.
PROiO60936.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140939.
CleanExiHS_ARC.
HS_NOL3.
ExpressionAtlasiO60936. baseline and differential.
GenevisibleiO60936. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SMARTiSM00114. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOL3_HUMAN
AccessioniPrimary (citable) accession number: O60936
Secondary accession number(s): B4DFL0, O60937
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: April 1, 2015
Last modified: November 30, 2016
This is version 143 of the entry and version 2 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 16
    Human chromosome 16: 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.