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Protein

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

Gene

PAPSS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. May have a important role in skeletogenesis during postnatal growth (By similarity).By similarity

Catalytic activityi

ATP + sulfate = diphosphate + adenylyl sulfate.
ATP + adenylyl sulfate = ADP + 3'-phosphoadenylyl sulfate.

Pathwayi: sulfate assimilation

This protein is involved in the pathway sulfate assimilation, which is part of Sulfur metabolism.
View all proteins of this organism that are known to be involved in the pathway sulfate assimilation and in Sulfur metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei91Adenylyl sulfateBy similarity1
Binding sitei161Adenylyl sulfateBy similarity1
Binding sitei197ATP 1; via carbonyl oxygenCombined sources1 Publication1
Binding sitei553ATP 2; via amide nitrogen and carbonyl oxygenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi52 – 57ATP 1Combined sources1 Publication6
Nucleotide bindingi409 – 412ATP 2By similarity4
Nucleotide bindingi511 – 515ATP 2By similarity5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Multifunctional enzyme, Nucleotidyltransferase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS07544-MONOMER
BRENDAi2.7.1.25 2681
ReactomeiR-HSA-174362 Transport and synthesis of PAPS
R-HSA-2408550 Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3560796 Defective PAPSS2 causes SEMD-PA
SABIO-RKiO95340
UniPathwayi
UPA00097

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2
Short name:
PAPS synthase 2
Short name:
PAPSS 2
Alternative name(s):
Sulfurylase kinase 2
Short name:
SK 2
Short name:
SK2
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 namesi
Name:PAPSS2
Synonyms:ATPSK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000198682.12
HGNCiHGNC:8604 PAPSS2
MIMi603005 gene
neXtProtiNX_O95340

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Brachyolmia type 4 with mild epiphyseal and metaphyseal changes (BCYM4)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM4 is an autosomal recessive form with mild epiphyseal and metaphyseal changes. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some BCYM4 patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.
See also OMIM:612847
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07302643C → Y in BCYM4; reduces strongly PAPS synthase activity. 1 Publication1
Natural variantiVAR_06304948T → R in BCYM4; patient with premature pubarche and hyperandrogenism; results in partial loss of activity; increases ubiquitin-dependent protein instability. 2 PublicationsCorresponds to variant dbSNP:rs121908951EnsemblClinVar.1
Natural variantiVAR_07302776L → Q in BCYM4; reduces strongly PAPS synthase activity. 1 Publication1
Natural variantiVAR_073029270G → D in BCYM4; increases ubiquitin-dependent protein instability. 1 PublicationCorresponds to variant dbSNP:rs138943074EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi9060
MalaCardsiPAPSS2
MIMi612847 phenotype
OpenTargetsiENSG00000198682
Orphaneti448242 Autosomal recessive brachyolmia
93282 Spondyloepimetaphyseal dysplasia, PAPSS2 type
PharmGKBiPA383

Polymorphism and mutation databases

BioMutaiPAPSS2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001059611 – 614Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2Add BLAST614

Proteomic databases

EPDiO95340
PaxDbiO95340
PeptideAtlasiO95340
PRIDEiO95340
ProteomicsDBi50808
50809 [O95340-2]
TopDownProteomicsiO95340-1 [O95340-1]

PTM databases

iPTMnetiO95340
PhosphoSitePlusiO95340
SwissPalmiO95340

Expressioni

Tissue specificityi

Expressed in cartilage and adrenal gland.1 Publication

Gene expression databases

BgeeiENSG00000198682 Expressed in 215 organ(s), highest expression level in metanephros
CleanExiHS_PAPSS2
ExpressionAtlasiO95340 baseline and differential
GenevisibleiO95340 HS

Organism-specific databases

HPAiHPA071224

Interactioni

Protein-protein interaction databases

BioGridi114521, 17 interactors
IntActiO95340, 4 interactors
STRINGi9606.ENSP00000406157

Structurei

Secondary structure

1614
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95340
SMRiO95340
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95340

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 215Adenylyl-sulfate kinaseCuratedAdd BLAST215
Regioni79 – 82Adenylyl sulfate bindingBy similarity4
Regioni96 – 99Adenylyl sulfate bindingBy similarity4
Regioni122 – 123Adenylyl sulfate bindingBy similarity2
Regioni174 – 175Adenylyl sulfate bindingBy similarity2
Regioni224 – 614Sulfate adenylyltransferaseCuratedAdd BLAST391

Sequence similaritiesi

In the N-terminal section; belongs to the APS kinase family.Curated
In the C-terminal section; belongs to the sulfate adenylyltransferase family.Curated

Phylogenomic databases

eggNOGiKOG0635 Eukaryota
KOG4238 Eukaryota
COG0529 LUCA
COG2046 LUCA
GeneTreeiENSGT00390000009613
HOVERGENiHBG053503
KOiK13811
OMAiQHPYIKM
OrthoDBiEOG091G07ZR
PhylomeDBiO95340
TreeFamiTF313143

Family and domain databases

CDDicd02027 APSK, 1 hit
cd00517 ATPS, 1 hit
Gene3Di3.40.50.620, 1 hit
HAMAPiMF_00065 Adenylyl_sulf_kinase, 1 hit
InterProiView protein in InterPro
IPR002891 APS_kinase
IPR025980 ATP-Sase_PUA-like_dom
IPR027417 P-loop_NTPase
IPR015947 PUA-like_sf
IPR014729 Rossmann-like_a/b/a_fold
IPR024951 Sulfurylase_cat_dom
IPR002650 Sulphate_adenylyltransferase
PfamiView protein in Pfam
PF01747 ATP-sulfurylase, 1 hit
PF14306 PUA_2, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
SSF88697 SSF88697, 1 hit
TIGRFAMsiTIGR00455 apsK, 1 hit
TIGR00339 sopT, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform A (identifier: O95340-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSGIKKQKTE NQQKSTNVVY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL
60 70 80 90 100
SGAGKTTISF ALEEYLVSHA IPCYSLDGDN VRHGLNRNLG FSPGDREENI
110 120 130 140 150
RRIAEVAKLF ADAGLVCITS FISPFAKDRE NARKIHESAG LPFFEIFVDA
160 170 180 190 200
PLNICESRDV KGLYKRARAG EIKGFTGIDS DYEKPETPER VLKTNLSTVS
210 220 230 240 250
DCVHQVVELL QEQNIVPYTI IKDIHELFVP ENKLDHVRAE AETLPSLSIT
260 270 280 290 300
KLDLQWVQVL SEGWATPLKG FMREKEYLQV MHFDTLLDDG VINMSIPIVL
310 320 330 340 350
PVSAEDKTRL EGCSKFVLAH GGRRVAILRD AEFYEHRKEE RCSRVWGTTC
360 370 380 390 400
TKHPHIKMVM ESGDWLVGGD LQVLEKIRWN DGLDQYRLTP LELKQKCKEM
410 420 430 440 450
NADAVFAFQL RNPVHNGHAL LMQDTRRRLL ERGYKHPVLL LHPLGGWTKD
460 470 480 490 500
DDVPLDWRMK QHAAVLEEGV LDPKSTIVAI FPSPMLYAGP TEVQWHCRSR
510 520 530 540 550
MIAGANFYIV GRDPAGMPHP ETKKDLYEPT HGGKVLSMAP GLTSVEIIPF
560 570 580 590 600
RVAAYNKAKK AMDFYDPARH NEFDFISGTR MRKLAREGEN PPDGFMAPKA
610
WKVLTDYYRS LEKN
Length:614
Mass (Da):69,501
Last modified:April 16, 2002 - v2
Checksum:i52F4B6D972DDA91E
GO
Isoform B (identifier: O95340-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     288-288: D → DGMALP

Show »
Length:619
Mass (Da):69,970
Checksum:iD4268D03982283E6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti166R → K in AAD38423 (Ref. 2) Curated1
Sequence conflicti361E → G in AAK00296 (Ref. 3) Curated1
Sequence conflicti426R → C in AAC64583 (PubMed:9771708).Curated1
Sequence conflicti567P → L in AAD38423 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02913610E → K Significant decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs17173698EnsemblClinVar.1
Natural variantiVAR_07302643C → Y in BCYM4; reduces strongly PAPS synthase activity. 1 Publication1
Natural variantiVAR_06304948T → R in BCYM4; patient with premature pubarche and hyperandrogenism; results in partial loss of activity; increases ubiquitin-dependent protein instability. 2 PublicationsCorresponds to variant dbSNP:rs121908951EnsemblClinVar.1
Natural variantiVAR_07302776L → Q in BCYM4; reduces strongly PAPS synthase activity. 1 Publication1
Natural variantiVAR_073028183E → K Polymorphism; similar PAPS synthase activity as the wild-type. 1 PublicationCorresponds to variant dbSNP:rs774709274Ensembl.1
Natural variantiVAR_073029270G → D in BCYM4; increases ubiquitin-dependent protein instability. 1 PublicationCorresponds to variant dbSNP:rs138943074EnsemblClinVar.1
Natural variantiVAR_029137281M → L1 PublicationCorresponds to variant dbSNP:rs45624631Ensembl.1
Natural variantiVAR_022077291V → M Significant decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs45467596Ensembl.1
Natural variantiVAR_029138432R → K1 PublicationCorresponds to variant dbSNP:rs17129133Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001259288D → DGMALP in isoform B. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091242 mRNA Translation: AAC64583.1
AF074331 mRNA Translation: AAD38423.1
AF313907 mRNA Translation: AAK00296.1
AF160509
, AF160503, AF160504, AF160505, AF160506, AF160507, AF160508 Genomic DNA Translation: AAF40307.2
AF173365 mRNA Translation: AAF12761.1
AF150754 mRNA Translation: AAF20366.2
BC009894 mRNA Translation: AAH09894.1
CCDSiCCDS44453.1 [O95340-2]
CCDS7385.1 [O95340-1]
RefSeqiNP_001015880.1, NM_001015880.1 [O95340-2]
NP_004661.2, NM_004670.3 [O95340-1]
UniGeneiHs.524491

Genome annotation databases

EnsembliENST00000361175; ENSP00000354436; ENSG00000198682 [O95340-1]
ENST00000456849; ENSP00000406157; ENSG00000198682 [O95340-2]
GeneIDi9060
KEGGihsa:9060
UCSCiuc001kew.4 human [O95340-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091242 mRNA Translation: AAC64583.1
AF074331 mRNA Translation: AAD38423.1
AF313907 mRNA Translation: AAK00296.1
AF160509
, AF160503, AF160504, AF160505, AF160506, AF160507, AF160508 Genomic DNA Translation: AAF40307.2
AF173365 mRNA Translation: AAF12761.1
AF150754 mRNA Translation: AAF20366.2
BC009894 mRNA Translation: AAH09894.1
CCDSiCCDS44453.1 [O95340-2]
CCDS7385.1 [O95340-1]
RefSeqiNP_001015880.1, NM_001015880.1 [O95340-2]
NP_004661.2, NM_004670.3 [O95340-1]
UniGeneiHs.524491

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AX4X-ray2.50A/B/C/D21-218[»]
ProteinModelPortaliO95340
SMRiO95340
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114521, 17 interactors
IntActiO95340, 4 interactors
STRINGi9606.ENSP00000406157

PTM databases

iPTMnetiO95340
PhosphoSitePlusiO95340
SwissPalmiO95340

Polymorphism and mutation databases

BioMutaiPAPSS2

Proteomic databases

EPDiO95340
PaxDbiO95340
PeptideAtlasiO95340
PRIDEiO95340
ProteomicsDBi50808
50809 [O95340-2]
TopDownProteomicsiO95340-1 [O95340-1]

Protocols and materials databases

DNASUi9060
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361175; ENSP00000354436; ENSG00000198682 [O95340-1]
ENST00000456849; ENSP00000406157; ENSG00000198682 [O95340-2]
GeneIDi9060
KEGGihsa:9060
UCSCiuc001kew.4 human [O95340-1]

Organism-specific databases

CTDi9060
DisGeNETi9060
EuPathDBiHostDB:ENSG00000198682.12
GeneCardsiPAPSS2
HGNCiHGNC:8604 PAPSS2
HPAiHPA071224
MalaCardsiPAPSS2
MIMi603005 gene
612847 phenotype
neXtProtiNX_O95340
OpenTargetsiENSG00000198682
Orphaneti448242 Autosomal recessive brachyolmia
93282 Spondyloepimetaphyseal dysplasia, PAPSS2 type
PharmGKBiPA383
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0635 Eukaryota
KOG4238 Eukaryota
COG0529 LUCA
COG2046 LUCA
GeneTreeiENSGT00390000009613
HOVERGENiHBG053503
KOiK13811
OMAiQHPYIKM
OrthoDBiEOG091G07ZR
PhylomeDBiO95340
TreeFamiTF313143

Enzyme and pathway databases

UniPathwayi
UPA00097

BioCyciMetaCyc:HS07544-MONOMER
BRENDAi2.7.1.25 2681
ReactomeiR-HSA-174362 Transport and synthesis of PAPS
R-HSA-2408550 Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3560796 Defective PAPSS2 causes SEMD-PA
SABIO-RKiO95340

Miscellaneous databases

ChiTaRSiPAPSS2 human
EvolutionaryTraceiO95340
GeneWikiiPAPSS2
GenomeRNAii9060
PROiPR:O95340
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198682 Expressed in 215 organ(s), highest expression level in metanephros
CleanExiHS_PAPSS2
ExpressionAtlasiO95340 baseline and differential
GenevisibleiO95340 HS

Family and domain databases

CDDicd02027 APSK, 1 hit
cd00517 ATPS, 1 hit
Gene3Di3.40.50.620, 1 hit
HAMAPiMF_00065 Adenylyl_sulf_kinase, 1 hit
InterProiView protein in InterPro
IPR002891 APS_kinase
IPR025980 ATP-Sase_PUA-like_dom
IPR027417 P-loop_NTPase
IPR015947 PUA-like_sf
IPR014729 Rossmann-like_a/b/a_fold
IPR024951 Sulfurylase_cat_dom
IPR002650 Sulphate_adenylyltransferase
PfamiView protein in Pfam
PF01747 ATP-sulfurylase, 1 hit
PF14306 PUA_2, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
SSF88697 SSF88697, 1 hit
TIGRFAMsiTIGR00455 apsK, 1 hit
TIGR00339 sopT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPAPS2_HUMAN
AccessioniPrimary (citable) accession number: O95340
Secondary accession number(s): Q9BZL2
, Q9P0G6, Q9UHM1, Q9UKD3, Q9UP30
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 16, 2002
Last modified: November 7, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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