PUS1 pseudouridine synthase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PUS1provided by HGNC
Official Full Name: pseudouridine synthase 1provided by HGNC
Primary source: HGNC:HGNC:15508
See related: Ensembl:ENSG00000177192 MIM:608109; AllianceGenome:HGNC:15508
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MLASA1
Summary: This gene encodes a pseudouridine synthase that converts uridine to pseudouridine once it has been incorporated into an RNA molecule. The encoded enzyme may play an essential role in tRNA function and in stabilizing the secondary and tertiary structure of many RNAs. A mutation in this gene has been linked to mitochondrial myopathy and sideroblastic anemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]
Expression: Ubiquitous expression in appendix (RPKM 5.5), lymph node (RPKM 5.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.33

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (131929276..131945896)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (131977320..131993946)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (132413821..132430441)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs.
Title: Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs.
Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.
Title: Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.
These results demonstrate a structure-dependent mode of mRNA target recognition by a conserved pseudouridine synthase and implicate modulation of RNA structure as the probable mechanism to regulate mRNA pseudouridylation.
Title: mRNA structure determines modification by pseudouridine synthase 1.
results show that the NTD of ERalpha and AR contains a novel RBM that directly binds SRA, and that STR5 can serve as a novel class of RNA inhibitor of ERalpha and AR signaling by interfering with Pus1p-mediated SRA pseudouridylation
Title: A small RNA derived from RNA coactivator SRA blocks steroid receptor signaling via inhibition of Pus1p-mediated pseudouridylation of SRA: evidence of a novel RNA binding domain in the N-terminus of steroid receptors.
Investigation of the sequence and structural requirements for hPus1p activity on human tRNASer.
Title: Pseudouridine synthase 1: a site-specific synthase without strict sequence recognition requirements.
We identified one novel homozygous null mutation in a familial case. It predicts a nonsense mutation at glutamine 154 (Q154X) that would lead to a protein lacking the 266 C-terminal amino acids
Title: Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations.
Three residues (R116, Y173, R267) that correspond to amino acids known to compose the active site of TruA, a bacterial Psi synthase that is homologous to Pus1p, were mutated in human Pus1p.
Title: Partial activity is seen with many substitutions of highly conserved active site residues in human Pseudouridine synthase 1.
Missense mutation in pseudouridine synthase 1 causes mitochondrial myopathy and sideroblastic anemia
Title: Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA).
MLASA is associated with absent or greatly reduced tRNA pseudouridylation at specific sites, implicating this pathway in its molecular pathogenesis.
Title: Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation.
A new homozygous stop mutation (E220X)predicts a protein missing 208/427 amino acid residues on the C terminus. The nuclear isoform has an N-terminal extension absent in the mature mitochondrial isoform.
Title: Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA).

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Myopathy, lactic acidosis, and sideroblastic anemia 1 MedGen: C4551958 OMIM: 600462 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables pseudouridine synthase activity	EXP Inferred from Experiment more info	PubMed
enables pseudouridine synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables pseudouridine synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables pseudouridine synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables steroid receptor RNA activator RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables tRNA binding	IDA Inferred from Direct Assay more info	PubMed
enables tRNA pseudouridine(38-40) synthase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in RNA splicing	IEA Inferred from Electronic Annotation more info
involved_in mRNA processing	IEA Inferred from Electronic Annotation more info
involved_in mRNA pseudouridine synthesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in mRNA pseudouridine synthesis	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial tRNA pseudouridine synthesis	TAS Traceable Author Statement more info
involved_in tRNA pseudouridine synthesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in tRNA pseudouridine synthesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: pseudouridylate synthase 1 homolog

Names: mitochondrial tRNA pseudouridine synthase A; pseudouridylate synthase 1; tRNA pseudouridine synthase 1; tRNA pseudouridine synthase A, mitochondrial; tRNA pseudouridine(38-40) synthase; tRNA pseudouridylate synthase I; tRNA uridine isomerase I

NP_001002019.1

EC 5.4.99.12

NP_001002020.1

EC 5.4.99.12

NP_079491.2

EC 5.4.99.12

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013039.2 RefSeqGene

Range

5002..21622

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001002019.3 → NP_001002019.1 pseudouridylate synthase 1 homolog isoform 2

See identical proteins and their annotated locations for NP_001002019.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2).

Source sequence(s)

AC131009, AF116238, AI566545, BM923133, BX340929

Consensus CDS

CCDS31928.1

UniProtKB/TrEMBL

E5KMT6, G8JLB3

Conserved Domains (2) summary

cd02568
Location:60 → 312

PseudoU_synth_PUS1_PUS2; Pseudouridine synthase, PUS1/ PUS2 like

COG0101
Location:56 → 335

TruA; tRNA U38,U39,U40 pseudouridine synthase TruA [Translation, ribosomal structure and biogenesis]
NM_001002020.3 → NP_001002020.1 pseudouridylate synthase 1 homolog isoform 2

See identical proteins and their annotated locations for NP_001002020.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2).

Source sequence(s)

AC131009, AI566545, BC002901, CB118952

Consensus CDS

CCDS31928.1

UniProtKB/TrEMBL

E5KMT6, G8JLB3

Related

ENSP00000392451.2, ENST00000443358.6

Conserved Domains (2) summary

cd02568
Location:60 → 312

PseudoU_synth_PUS1_PUS2; Pseudouridine synthase, PUS1/ PUS2 like

COG0101
Location:56 → 335

TruA; tRNA U38,U39,U40 pseudouridine synthase TruA [Translation, ribosomal structure and biogenesis]
NM_025215.6 → NP_079491.2 pseudouridylate synthase 1 homolog isoform 1

See identical proteins and their annotated locations for NP_079491.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC131009, AI566545, AK074659

Consensus CDS

CCDS9275.2

UniProtKB/Swiss-Prot

A8K877, B3KQC1, Q8WYT2, Q9BU44, Q9Y606

UniProtKB/TrEMBL

E5KMT5, G8JLB3

Related

ENSP00000365837.3, ENST00000376649.8

Conserved Domains (2) summary

cd02568
Location:88 → 340

PseudoU_synth_PUS1_PUS2; Pseudouridine synthase, PUS1/ PUS2 like

COG0101
Location:84 → 363

TruA; tRNA U38,U39,U40 pseudouridine synthase TruA [Translation, ribosomal structure and biogenesis]