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

Summary

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

Location:: 4q25

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (107613666..107720234, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (110915973..111022538, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (108534822..108641390, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

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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Markers

SHGC-10924 (e-PCR)
- UniSTS:38169

G59422 (e-PCR)
- UniSTS:136733

SHGC-79878 (e-PCR)
- UniSTS:101450

SHGC-67932 (e-PCR)
- UniSTS:36712

SHGC-18786 (e-PCR)
- UniSTS:72581

D4S3101 (e-PCR)
- UniSTS:4753

SHGC-58007 (e-PCR)
- UniSTS:69787

SHGC-52884 (e-PCR)
- UniSTS:51131

SGC44586 (e-PCR)
- UniSTS:197

G54601 (e-PCR)
- UniSTS:117736

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 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

EC 2.7.1.25

EC 2.7.7.4

XP_011530702.1

EC 2.7.1.25

EC 2.7.7.4

XP_011530703.1

EC 2.7.1.25

EC 2.7.7.4

XP_054207171.1

EC 2.7.1.25

EC 2.7.7.4

XP_054207172.1

EC 2.7.1.25

EC 2.7.7.4

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)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

107613666..107720234 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_060928.1 Alternate T2T-CHM13v2.0

Range

110915973..111022538 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054351197.1 → XP_054207172.1 bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1
XM_054351196.1 → XP_054207171.1 bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 isoform X1