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PAPSS1 3'-phosphoadenosine 5'-phosphosulfate synthase 1 [ Homo sapiens (human) ]

Gene ID: 9061, updated on 19-Sep-2024

Summary

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Official Symbol
PAPSS1provided by HGNC
Official Full Name
3'-phosphoadenosine 5'-phosphosulfate synthase 1provided by HGNC
Primary source
HGNC:HGNC:8603
See related
Ensembl:ENSG00000138801 MIM:603262; AllianceGenome:HGNC:8603
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SK1; PAPSS; ATPSK1
Summary
Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[supplied by OMIM, Mar 2008]
Expression
Ubiquitous expression in endometrium (RPKM 32.6), brain (RPKM 30.3) and 25 other tissues See more
Orthologs
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Genomic context

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See PAPSS1 in Genome Data Viewer
Location:
4q25
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (107613666..107720234, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (110915973..111022538, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (108534822..108641390, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 551, pseudogene Neighboring gene uncharacterized LOC105377358 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:108626049-108626213 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21789 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15612 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21790 Neighboring gene NANOG hESC enhancer GRCh37_chr4:108655227-108655757 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:108748306-108749505 Neighboring gene sphingomyelin synthase 2 Neighboring gene CYP2U1 and SGMS2 antisense RNA 1 Neighboring gene RNA, U6 small nuclear 733, pseudogene Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:108812473-108813203 Neighboring gene uncharacterized LOC107986298 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:108827506-108828091 Neighboring gene uncharacterized LOC124900751 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:108852075-108852582 Neighboring gene cytochrome P450 family 2 subfamily U member 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. In Vivo Validation of PAPSS1 (3'-phosphoadenosine 5'-phosphosulfate synthase 1) as a Cisplatin-sensitizing Therapeutic Target. Leung AWY, et al. Clin Cancer Res, 2017 Nov 1. PMID 28790117
  2. Sphingosine kinase 1 and cancer: a systematic review and meta-analysis. Zhang Y, et al. PLoS One, 2014. PMID 24587339, Free PMC Article
  3. Role of sphingosine kinase-1 in paracrine/transcellular angiogenesis and lymphangiogenesis in vitro. Anelli V, et al. FASEB J, 2010 Aug. PMID 20335228, Free PMC Article
  4. Evidence for association with hepatocellular carcinoma at the PAPSS1 locus on chromosome 4q25 in a family-based study. Shih WL, et al. Eur J Hum Genet, 2009 Oct. PMID 19337310, Free PMC Article
  5. The host cell sulfonation pathway contributes to retroviral infection at a step coincident with provirus establishment. Bruce JW, et al. PLoS Pathog, 2008 Nov. PMID 19008949, Free PMC Article

See all (56) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Correlation of 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) expression with clinical parameters and prognosis in esophageal squamous cell carcinoma.
    Title: Correlation of 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (PAPSS1) expression with clinical parameters and prognosis in esophageal squamous cell carcinoma.
  2. The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells.
    Title: The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells.
  3. These results suggest that PAPSS1 inhibition enhances cisplatin activity in multiple preclinical model systems and that low PAPSS1 expression may serve as a biomarker for platin sensitivity in cancer patients. Developing strategies to target PAPSS1 activity in conjunction with platinum-based chemotherapy may offer an approach to improving treatment outcomes
    Title: In Vivo Validation of PAPSS1 (3'-phosphoadenosine 5'-phosphosulfate synthase 1) as a Cisplatin-sensitizing Therapeutic Target.
  4. we found that ectopic expression of oncogenic KRas and HRas in cells resulted in elevated CIB1 expression. We previously described the Ca(2+)-myristoyl switch function of CIB1, and its ability to facilitate agonist-induced plasma membrane localisation of sphingosine kinase 1 (SK1), a location where SK1 is known to elicit oncogenic signalling.
    Title: CIB1 contributes to oncogenic signalling by Ras via modulating the subcellular localisation of sphingosine kinase 1.
  5. These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity
    Title: Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation.
  6. leptin signalling links a novel SFK/ERK1/2-mediated pathway and SK1 expression.
    Title: Leptin induces upregulation of sphingosine kinase 1 in oestrogen receptor-negative breast cancer via Src family kinase-mediated, janus kinase 2-independent pathway.
  7. SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival.
    Title: Sphingosine kinase 1 and cancer: a systematic review and meta-analysis.
  8. study showed expression patterns of SULT1E1 and PAPSS in breast and endometrial tissues; the estrogen sulfation enzymes were comparatively higher in the tumorous tissues than adjacent normal tissues; overexpression of SULT1E1 and PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis
    Title: Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen-dependent cancers.
  9. Unusual localisation signals of both PAPS synthase isoforms, are described.
    Title: Human PAPS synthase isoforms are dynamically regulated enzymes with access to nucleus and cytoplasm.
  10. SK1 plays an essential role in regulating in vitro paracrine angiogenesis and lymphangiogenesis.
    Title: Role of sphingosine kinase-1 in paracrine/transcellular angiogenesis and lymphangiogenesis in vitro.
Submit: New GeneRIF Correction See all GeneRIFs (19)

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

EBI GWAS Catalog

Description
Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables adenylylsulfate kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables adenylylsulfate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables adenylylsulfate kinase activity TAS
Traceable Author Statement
more info
  
enables nucleotidyltransferase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sulfate adenylyltransferase (ATP) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables sulfate adenylyltransferase (ATP) activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables sulfate adenylyltransferase (ATP) activity TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in skeletal system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in sulfate assimilation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in sulfate assimilation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in sulfate assimilation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1
Names
3-prime-phosphoadenosine 5-prime-phosphosulfate synthase 1
PAPS synthase 1
PAPSS 1
SK 1
adenylyl-sulfate kinase
sulfate adenylyltransferase
sulfurylase kinase 1
NP_005434.4
XP_011530702.1
XP_011530703.1
XP_054207171.1
XP_054207172.1

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.

mRNA and Protein(s)

  1. NM_005443.5 → NP_005434.4  bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1

    Status: VALIDATED

    Source sequence(s)
    AU132232, BC011392, BQ437924
    Consensus CDS
    CCDS3676.1
    UniProtKB/Swiss-Prot
    O43252, O43841, O75332, Q6IAX6, Q96FB1, Q96TF4, Q9P1P9, Q9UE98
    UniProtKB/TrEMBL
    Q05BW9
    Related
    ENSP00000265174.4, ENST00000265174.5
    Conserved Domains (2) summary
    cd00517
    Location:254 → 617
    ATPS; ATP-sulfurylase
    pfam01583
    Location:51 → 205
    APS_kinase; Adenylylsulphate kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    107613666..107720234 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011532401.2 → XP_011530703.1  bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1

    UniProtKB/TrEMBL
    Q05BW9
    Conserved Domains (2) summary
    cd00517
    Location:233 → 596
    ATPS; ATP-sulfurylase
    pfam01583
    Location:30 → 184
    APS_kinase; Adenylylsulphate kinase

  2. XM_011532400.3 → XP_011530702.1  bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1

    UniProtKB/TrEMBL
    Q05BW9
    Conserved Domains (2) summary
    cd00517
    Location:233 → 596
    ATPS; ATP-sulfurylase
    pfam01583
    Location:30 → 184
    APS_kinase; Adenylylsulphate kinase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    110915973..111022538 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054351197.1 → XP_054207172.1  bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1

    UniProtKB/TrEMBL
    Q05BW9

  2. XM_054351196.1 → XP_054207171.1  bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1

    UniProtKB/TrEMBL
    Q05BW9
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43252.2 GenPept UniProtKB/Swiss-Prot:O43252

Gene LinkOut

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