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Protein

Cell growth-regulating nucleolar protein

Gene

LYAR

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

Functioni

Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (PubMed:24495227). Also acts at the level of transcription regulation. Along with PRMT5, binds the gamma-globin (HBG1/HBG2) promoter and represses its expression (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and SNORD41 that encodes a small nucleolar RNA (PubMed:28686580). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (PubMed:25092918). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (By similarity). Prevents nucleolin/NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (By similarity).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi6Zinc 1By similarity1
Metal bindingi9Zinc 1By similarity1
Metal bindingi21Zinc 1By similarity1
Metal bindingi25Zinc 1By similarity1
Metal bindingi33Zinc 2By similarity1
Metal bindingi36Zinc 2By similarity1
Metal bindingi48Zinc 2By similarity1
Metal bindingi51Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1 – 26C2HC LYAR-type 1PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri28 – 52C2HC LYAR-type 2PROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA binding Source: UniProtKB

GO - Biological processi

  • erythrocyte development Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of phagocytosis Source: UniProtKB
  • rRNA processing Source: UniProtKB

Keywordsi

Molecular functionDNA-binding, Repressor
Biological processrRNA processing, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Cell growth-regulating nucleolar protein
Gene namesi
Name:LYAR
ORF Names:PNAS-5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000145220.13.
HGNCiHGNC:26021. LYAR.
MIMi617684. gene.
neXtProtiNX_Q9NX58.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 58Missing : Decreases the production of 28S rRNA and the formation of pre-60S particle. 1 PublicationAdd BLAST58

Organism-specific databases

DisGeNETi55646.
PharmGKBiPA162394697.

Polymorphism and mutation databases

BioMutaiLYAR.
DMDMi71153817.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000845281 – 379Cell growth-regulating nucleolar proteinAdd BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki14Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki207Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei215PhosphoserineCombined sources1
Modified residuei244PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NX58.
MaxQBiQ9NX58.
PaxDbiQ9NX58.
PeptideAtlasiQ9NX58.
PRIDEiQ9NX58.

2D gel databases

SWISS-2DPAGEiQ9NX58.

PTM databases

iPTMnetiQ9NX58.
PhosphoSitePlusiQ9NX58.
SwissPalmiQ9NX58.

Expressioni

Tissue specificityi

Predominantly expressed in testis.1 Publication

Developmental stagei

In an ex vivo erythroid culture system, highly expressed from early (preproerythroblasts) to mid (basophilic normoblasts) maturation. Markedly reduced in more mature erythroblasts (at protein level). The decrease in LYAR protein correlates with the rise of beta-globin (HBB) mRNA levels during erythroid cell differentiation.1 Publication

Inductioni

Induced by MYCN.1 Publication

Gene expression databases

BgeeiENSG00000145220.
CleanExiHS_LYAR.
ExpressionAtlasiQ9NX58. baseline and differential.
GenevisibleiQ9NX58. HS.

Organism-specific databases

HPAiHPA035881.

Interactioni

Subunit structurei

Interacts with PRMT5; this interaction is direct (PubMed:25092918). Interacts with GNL2 and RPL23A (PubMed:26203195). Interacts with nucleolin/NCL; this interaction is direct (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi120780. 74 interactors.
CORUMiQ9NX58.
IntActiQ9NX58. 110 interactors.
MINTiQ9NX58.
STRINGi9606.ENSP00000345917.

Structurei

3D structure databases

ProteinModelPortaliQ9NX58.
SMRiQ9NX58.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili175 – 219Sequence analysisAdd BLAST45

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi168 – 379Lys-richAdd BLAST212

Domaini

The N-terminal zinc-finger domains are required for the appropriate production of 28S rRNA and the formation of pre-60S particles.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1 – 26C2HC LYAR-type 1PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri28 – 52C2HC LYAR-type 2PROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2186. Eukaryota.
ENOG411081U. LUCA.
HOGENOMiHOG000006633.
HOVERGENiHBG006298.
InParanoidiQ9NX58.
KOiK15263.
OrthoDBiEOG091G0L4Z.
PhylomeDBiQ9NX58.
TreeFamiTF314925.

Family and domain databases

InterProiView protein in InterPro
IPR014898. Znf_C2H2_LYAR.
IPR036236. Znf_C2H2_sf.
PfamiView protein in Pfam
PF08790. zf-LYAR. 1 hit.
SUPFAMiSSF57667. SSF57667. 2 hits.
PROSITEiView protein in PROSITE
PS51804. ZF_C2HC_LYAR. 2 hits.

Sequencei

Sequence statusi: Complete.

Q9NX58-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVFFTCNACG ESVKKIQVEK HVSVCRNCEC LSCIDCGKDF WGDDYKNHVK
60 70 80 90 100
CISEDQKYGG KGYEGKTHKG DIKQQAWIQK ISELIKRPNV SPKVRELLEQ
110 120 130 140 150
ISAFDNVPRK KAKFQNWMKN SLKVHNESIL DQVWNIFSEA SNSEPVNKEQ
160 170 180 190 200
DQRPLHPVAN PHAEISTKVP ASKVKDAVEQ QGEVKKNKRE RKEERQKKRK
210 220 230 240 250
REKKELKLEN HQENSRNQKP KKRKKGQEAD LEAGGEEVPE ANGSAGKRSK
260 270 280 290 300
KKKQRKDSAS EEEAHVGAGK RKRRHSEVET DSKKKKMKLP EHPEGGEPED
310 320 330 340 350
DEAPAKGKFN WKGTIKAILK QAPDNEITIK KLRKKVLAQY YTVTDEHHRS
360 370
EEELLVIFNK KISKNPTFKL LKDKVKLVK
Length:379
Mass (Da):43,615
Last modified:July 19, 2005 - v2
Checksum:i45159F44C22537DB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21H → R in CAG38579 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023080151D → Y. Corresponds to variant dbSNP:rs2272739Ensembl.1
Natural variantiVAR_023081265H → R5 PublicationsCorresponds to variant dbSNP:rs7376390Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136750 mRNA. Translation: CAB66684.1.
AK000432 mRNA. Translation: BAA91162.1.
CR533548 mRNA. Translation: CAG38579.1.
CH471131 Genomic DNA. Translation: EAW82437.1.
CH471131 Genomic DNA. Translation: EAW82438.1.
CH471131 Genomic DNA. Translation: EAW82439.1.
BC015796 mRNA. Translation: AAH15796.1.
AF229835 mRNA. Translation: AAF42870.1.
CCDSiCCDS3374.1.
RefSeqiNP_001139197.1. NM_001145725.1.
NP_060286.1. NM_017816.2.
XP_011511807.1. XM_011513505.1.
XP_011511808.1. XM_011513506.2.
UniGeneiHs.425427.

Genome annotation databases

EnsembliENST00000343470; ENSP00000345917; ENSG00000145220.
ENST00000452476; ENSP00000397367; ENSG00000145220.
GeneIDi55646.
KEGGihsa:55646.
UCSCiuc003ght.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLYAR_HUMAN
AccessioniPrimary (citable) accession number: Q9NX58
Secondary accession number(s): D3DVS4, Q6FI78, Q9NYS1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: July 19, 2005
Last modified: March 28, 2018
This is version 148 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome