Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1

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O43252 (PAPS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 124. History...

Clusters with 100%, 90%, 50% identity |

Documents (7) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1
Short name=PAPS synthase 1
Short name=PAPSS 1

Alternative name(s):
Sulfurylase kinase 1
Short name=SK 1
Short name=SK1

Including the following 2 domains:

Sulfate adenylyltransferase
EC=2.7.7.4
Alternative name(s):
ATP-sulfurylase
Sulfate adenylate transferase
Short name=SAT
Adenylyl-sulfate kinase
EC=2.7.1.25
Alternative name(s):
3'-phosphoadenosine-5'-phosphosulfate synthase
APS kinase
Adenosine-5'-phosphosulfate 3'-phosphotransferase
Adenylylsulfate 3'-phosphotransferase

Gene names

Name:	PAPSS1
Synonyms:	ATPSK1, PAPSS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. Also involved in the biosynthesis of sulfated L-selectin ligands in endothelial cells.
Catalytic activity	ATP + sulfate = diphosphate + adenylyl sulfate. ATP + adenylyl sulfate = ADP + 3'-phosphoadenylyl sulfate.
Enzyme regulation	Inhibited by chlorate.
Pathway	Sulfur metabolism; sulfate assimilation.
Tissue specificity	Expressed in testis, pancreas, kidney, thymus, prostate, ovary, small intestine, colon, leukocytes and liver. Also expressed in high endothelial venules (HEV) cells and in cartilage.
Sequence similarities	In the N-terminal section; belongs to the APS kinase family. In the C-terminal section; belongs to the sulfate adenylyltransferase family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	3'-phosphoadenosine 5'-phosphosulfate biosynthetic process Traceable author statement. Source: Reactome skeletal system development Traceable author statement. Source: ProtInc sulfate assimilation Inferred from electronic annotation. Source: InterPro xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylylsulfate kinase activity Inferred from electronic annotation. Source: EC sulfate adenylyltransferase (ATP) activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 624

624

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1

PRO_0000105959

Regions

Nucleotide binding

59 – 66

ATP Potential

Region

1 – ?220

220

Adenylyl-sulfate kinase

Region

?221 – 624

404

Sulfate adenylyltransferase

Motif

521 – 525

PP-motif

Sites

Active site

133

Phosphoserine intermediate By similarity

Natural variations

Natural variant

270

L → F. Ref.2
Corresponds to variant rs1127008 [ dbSNP | Ensembl ].

VAR_014065

Natural variant

587

S → L. Ref.2 Ref.4 Ref.5
Corresponds to variant rs1127014 [ dbSNP | Ensembl ].

VAR_014064

Experimental info

Mutagenesis

425

H → A: Loss of activity. Ref.7

Mutagenesis

426

N → K: Increased activity. Ref.7

Mutagenesis

427 – 428

GH → AA: Loss of activity. Ref.7

Mutagenesis

427

G → A: 30% decrease in activity. Ref.7

Mutagenesis

428

H → A: Loss of activity. Ref.7

Sequence conflict

456

G → A in CAA71413. Ref.1

Sequence conflict

456

Missing in AAC39894. Ref.2

Sequence conflict

519 – 520

IV → MC in AAD09325. Ref.4

Secondary structure

624

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

O43252 [UniParc].

Last modified October 10, 2002. Version 2.
Checksum: A3DC9B943E68CDD6
Show »

FASTA

624

70,833

        10         20         30         40         50         60 
MEIPGSLCKK VKLSNNAQNW GMQRATNVTY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL 

        70         80         90        100        110        120 
SGAGKTTVSM ALEEYLVCHG IPCYTLDGDN IRQGLNKNLG FSPEDREENV RRIAEVAKLF 

       130        140        150        160        170        180 
ADAGLVCITS FISPYTQDRN NARQIHEGAS LPFFEVFVDA PLHVCEQRDV KGLYKKARAG 

       190        200        210        220        230        240 
EIKGFTGIDS EYEKPEAPEL VLKTDSCDVN DCVQQVVELL QERDIVPVDA SYEVKELYVP 

       250        260        270        280        290        300 
ENKLHLAKTD AETLPALKIN KVDMQWVQVL AEGWATPLNG FMREREYLQC LHFDCLLDGG 

       310        320        330        340        350        360 
VINLSVPIVL TATHEDKERL DGCTAFALMY EGRRVAILRN PEFFEHRKEE RCARQWGTTC 

       370        380        390        400        410        420 
KNHPYIKMVM EQGDWLIGGD LQVLDRVYWN DGLDQYRLTP TELKQKFKDM NADAVFAFQL 

       430        440        450        460        470        480 
RNPVHNGHAL LMQDTHKQLL ERGYRRPVLL LHPLGGWTKD DDVPLMWRMK QHAAVLEEGV 

       490        500        510        520        530        540 
LNPETTVVAI FPSPMMYAGP TEVQWHCRAR MVAGANFYIV GRDPAGMPHP ETGKDLYEPS 

       550        560        570        580        590        600 
HGAKVLTMAP GLITLEIVPF RVAAYNKKKK RMDYYDSEHH EDFEFISGTR MRKLAREGQK 

       610        620 
PPEGFMAPKA WTVLTEYYKS LEKA

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sulfation in high endothelial venules: cloning and expression of the human PAPS synthetase." Girard J.-P., Baekkevold E.S., Amalric F. FASEB J. 12:603-612(1998) [PubMed: 9576487] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Tonsil.
[2]	"Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains." Venkatachalam K.V., Akita H., Strott C.A. J. Biol. Chem. 273:19311-19320(1998) [PubMed: 9668121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PHE-270 AND LEU-587. Tissue: Fetal brain.
[3]	"cDNA cloning, expression, and characterization of the human bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase enzyme." Yanagisawa K., Sakakibara Y., Suiko M., Takami Y., Nakayama T., Nakajima H., Takayanagi K., Natori Y., Liu M.-C. Biosci. Biotechnol. Biochem. 62:1037-1040(1998) [PubMed: 9648242] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Human ATP sulfurylase/APS kinase." Deyrup A.T. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-587.
[5]	"Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2: gene cloning, characterization and chromosomal localization." Xu Z.-H., Otterness D.M., Freimuth R.R., Carlini E.J., Wood T.C., Mitchell S., Moon E., Kim U.-J., Xu J.-P., Siciliano M.J., Weinshilboum R.M. Biochem. Biophys. Res. Commun. 268:437-444(2000) [PubMed: 10679223] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT LEU-587. Tissue: Brain.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Uterus.
[7]	"Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase." Venkatachalam K.V., Fuda H., Koonin E.V., Strott C.A. J. Biol. Chem. 274:2601-2604(1999) [PubMed: 9915785] [Abstract] Cited for: MUTAGENESIS OF HIS-425; ASN-426; GLY-427 AND HIS-428.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y10387 mRNA. Translation: CAA71413.1.
U53447 Genomic DNA. Translation: AAC39894.1.
AF033026 mRNA. Translation: AAC28429.1.
AF016496 mRNA. Translation: AAD09325.1.
AF105227 mRNA. Translation: AAF40236.1.
AF097721

AF097720 Genomic DNA. Translation: AAF40235.1.
BC011392 mRNA. Translation: AAH11392.1.
BC050627 mRNA. Translation: AAH50627.1.

IPI

IPI00011619.

PIR

JW0087.

RefSeq

NP_005434.4. NM_005443.4.

UniGene

Hs.368610.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X6V	X-ray	1.75	A/B	1-624	[»]
1XJQ	X-ray	2.06	A/B	1-624	[»]
1XNJ	X-ray	1.98	A/B	1-624	[»]
2OFW	X-ray	2.05	A/B/C/D/E/F/G/H	24-225	[»]
2OFX	X-ray	1.90	A/B	25-227	[»]
2PEY	X-ray	1.88	A/B	51-226	[»]
2PEZ	X-ray	1.40	A/B	51-226	[»]
2QJF	X-ray	2.20	A/B	220-624	[»]

ProteinModelPortal

O43252.

SMR

O43252. Positions 25-623.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43252. 5 interactions.

MINT

MINT-1372331.

STRING

O43252.

PTM databases

PhosphoSite

O43252.

Proteomic databases

PeptideAtlas

O43252.

PRIDE

O43252.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265174; ENSP00000265174; ENSG00000138801.

GeneID

9061.

KEGG

hsa:9061.

UCSC

uc003hyk.1. human.

Organism-specific databases

CTD

9061.

GeneCards

GC04M108534.

H-InvDB

HIX0023078.

HGNC

HGNC:8603. PAPSS1.

MIM

603262. gene.

neXtProt

NX_O43252.

PharmGKB

PA384.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17306.

HOVERGEN

HBG053503.

InParanoid

O43252.

OMA

AQNWGMQ.

OrthoDB

EOG4VT5WR.

PhylomeDB

O43252.

Enzyme and pathway databases

BRENDA

2.7.1.25. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O43252.

Bgee

O43252.

CleanEx

HS_PAPSS1.

Genevestigator

O43252.

GermOnline

ENSG00000138801. Homo sapiens.

Family and domain databases

InterPro

IPR002891. APS_kinase_C.
IPR015947. PUA-like_domain.
IPR014729. Rossmann-like_a/b/a_fold.
IPR002650. Sulphate_adenylyltransferase.
[Graphical view]

Gene3D

G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.

K13811.

Pfam

PF01583. APS_kinase. 1 hit.
PF01747. ATP-sulfurylase. 1 hit.
[Graphical view]

SUPFAM

SSF88697. PUA-like. 1 hit.

TIGRFAMs

TIGR00455. ApsK. 1 hit.
TIGR00339. SopT. 1 hit.

ProtoNet

Search...

Other

NextBio

33955.

SOURCE

Search...

Entry information

Entry name

PAPS1_HUMAN

Accession

Primary (citable) accession number: O43252
Secondary accession number(s): O43841

Q9UE98

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	October 10, 2002
Last modified:	January 25, 2012
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.