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

    Gene ID: 9061, updated on 28-Oct-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
    mouse all
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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. The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding. Harjes S, et al. J Mol Biol, 2005 Apr 1. PMID 15755455
    2. 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
    3. Sphingosine kinase 1 and cancer: a systematic review and meta-analysis. Zhang Y, et al. PLoS One, 2014. PMID 24587339, Free PMC Article
    4. 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
    5. 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

    See all (59) 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

      See identical proteins and their annotated locations for NP_005434.4

      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

      See identical proteins and their annotated locations for XP_011530703.1

      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

      See identical proteins and their annotated locations for XP_011530702.1

      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

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

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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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