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Protein

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

Gene

PAPSS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei123 – 1231Phosphoserine intermediateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi49 – 568ATPSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Nucleotidyltransferase, Transferase

Keywords - Ligandi

ATP-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-RKO95340.
UniPathwayiUPA00097.

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

HGNCiHGNC:8604. PAPSS2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti43 – 431C → Y in BCYM4; reduces strongly PAPS synthase activity. 1 Publication
VAR_073026
Natural varianti48 – 481T → R in BCYM4; patient with premature pubarche and hyperandrogenism; results in partial loss of activity; increases ubiquitin-dependent protein instability. 2 Publications
Corresponds to variant rs121908951 [ dbSNP | Ensembl ].
VAR_063049
Natural varianti76 – 761L → Q in BCYM4; reduces strongly PAPS synthase activity. 1 Publication
VAR_073027
Natural varianti270 – 2701G → D in BCYM4; increases ubiquitin-dependent protein instability. 1 Publication
Corresponds to variant rs138943074 [ dbSNP | Ensembl ].
VAR_073029

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MalaCardsiPAPSS2.
MIMi612847. phenotype.
Orphaneti93303. Brachyolmia type 1, Toledo type.
93282. Spondyloepimetaphyseal dysplasia, Pakistani type.
PharmGKBiPA383.

Polymorphism and mutation databases

BioMutaiPAPSS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 614614Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2PRO_0000105961Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO95340.
PaxDbiO95340.
PeptideAtlasiO95340.
PRIDEiO95340.
TopDownProteomicsiO95340-1. [O95340-1]

PTM databases

iPTMnetiO95340.
PhosphoSiteiO95340.
SwissPalmiO95340.

Expressioni

Tissue specificityi

Expressed in cartilage and adrenal gland.1 Publication

Gene expression databases

BgeeiENSG00000198682.
CleanExiHS_PAPSS2.
ExpressionAtlasiO95340. baseline and differential.
GenevisibleiO95340. HS.

Organism-specific databases

HPAiHPA071224.

Interactioni

Protein-protein interaction databases

BioGridi114521. 14 interactions.
IntActiO95340. 1 interaction.
MINTiMINT-5000453.
STRINGi9606.ENSP00000406157.

Structurei

Secondary structure

1
614
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi27 – 337Combined sources
Beta strandi34 – 374Combined sources
Beta strandi43 – 486Combined sources
Helixi55 – 6814Combined sources
Beta strandi73 – 764Combined sources
Helixi78 – 814Combined sources
Turni82 – 887Combined sources
Helixi93 – 11220Combined sources
Beta strandi116 – 1205Combined sources
Helixi126 – 13813Combined sources
Beta strandi143 – 1497Combined sources
Helixi152 – 1587Combined sources
Beta strandi160 – 1623Combined sources
Helixi163 – 1686Combined sources
Turni176 – 1783Combined sources
Beta strandi189 – 1935Combined sources
Helixi199 – 21214Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AX4X-ray2.50A/B/C/D21-218[»]
ProteinModelPortaliO95340.
SMRiO95340. Positions 21-613.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95340.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – ?210210Adenylyl-sulfate kinaseAdd
BLAST
Regioni?211 – 614404Sulfate adenylyltransferaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi511 – 5155PP-motif

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

CDDicd00517. ATPS. 1 hit.
Gene3Di3.40.50.300. 1 hit.
3.40.50.620. 1 hit.
HAMAPiMF_00065. Adenylyl_sulf_kinase. 1 hit.
InterProiIPR002891. APS_kinase.
IPR025980. ATP-Sase_PUA-like_dom.
IPR027417. P-loop_NTPase.
IPR015947. PUA-like_domain.
IPR014729. Rossmann-like_a/b/a_fold.
IPR024951. Sulfurylase_cat_dom.
IPR002650. Sulphate_adenylyltransferase.
[Graphical view]
PfamiPF01747. ATP-sulfurylase. 1 hit.
PF14306. PUA_2. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti166 – 1661R → K in AAD38423 (Ref. 2) Curated
Sequence conflicti361 – 3611E → G in AAK00296 (Ref. 3) Curated
Sequence conflicti426 – 4261R → C in AAC64583 (PubMed:9771708).Curated
Sequence conflicti567 – 5671P → L in AAD38423 (Ref. 2) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101E → K Significant decrease of activity. 1 Publication
Corresponds to variant rs17173698 [ dbSNP | Ensembl ].
VAR_029136
Natural varianti43 – 431C → Y in BCYM4; reduces strongly PAPS synthase activity. 1 Publication
VAR_073026
Natural varianti48 – 481T → R in BCYM4; patient with premature pubarche and hyperandrogenism; results in partial loss of activity; increases ubiquitin-dependent protein instability. 2 Publications
Corresponds to variant rs121908951 [ dbSNP | Ensembl ].
VAR_063049
Natural varianti76 – 761L → Q in BCYM4; reduces strongly PAPS synthase activity. 1 Publication
VAR_073027
Natural varianti183 – 1831E → K Polymorphism; similar PAPS synthase activity as the wild-type. 1 Publication
Corresponds to variant rs774709274 [ dbSNP | Ensembl ].
VAR_073028
Natural varianti270 – 2701G → D in BCYM4; increases ubiquitin-dependent protein instability. 1 Publication
Corresponds to variant rs138943074 [ dbSNP | Ensembl ].
VAR_073029
Natural varianti281 – 2811M → L.1 Publication
Corresponds to variant rs45624631 [ dbSNP | Ensembl ].
VAR_029137
Natural varianti291 – 2911V → M Significant decrease of activity. 1 Publication
Corresponds to variant rs45467596 [ dbSNP | Ensembl ].
VAR_022077
Natural varianti432 – 4321R → K.1 Publication
VAR_029138

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei288 – 2881D → DGMALP in isoform B. 2 PublicationsVSP_001259

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

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2AX4X-ray2.50A/B/C/D21-218[»]
ProteinModelPortaliO95340.
SMRiO95340. Positions 21-613.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114521. 14 interactions.
IntActiO95340. 1 interaction.
MINTiMINT-5000453.
STRINGi9606.ENSP00000406157.

PTM databases

iPTMnetiO95340.
PhosphoSiteiO95340.
SwissPalmiO95340.

Polymorphism and mutation databases

BioMutaiPAPSS2.

Proteomic databases

EPDiO95340.
PaxDbiO95340.
PeptideAtlasiO95340.
PRIDEiO95340.
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.
GeneCardsiPAPSS2.
HGNCiHGNC:8604. PAPSS2.
HPAiHPA071224.
MalaCardsiPAPSS2.
MIMi603005. gene.
612847. phenotype.
neXtProtiNX_O95340.
Orphaneti93303. Brachyolmia type 1, Toledo type.
93282. Spondyloepimetaphyseal dysplasia, Pakistani type.
PharmGKBiPA383.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00097.
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-RKO95340.

Miscellaneous databases

ChiTaRSiPAPSS2. human.
EvolutionaryTraceiO95340.
GeneWikiiPAPSS2.
GenomeRNAii9060.
PROiO95340.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198682.
CleanExiHS_PAPSS2.
ExpressionAtlasiO95340. baseline and differential.
GenevisibleiO95340. HS.

Family and domain databases

CDDicd00517. ATPS. 1 hit.
Gene3Di3.40.50.300. 1 hit.
3.40.50.620. 1 hit.
HAMAPiMF_00065. Adenylyl_sulf_kinase. 1 hit.
InterProiIPR002891. APS_kinase.
IPR025980. ATP-Sase_PUA-like_dom.
IPR027417. P-loop_NTPase.
IPR015947. PUA-like_domain.
IPR014729. Rossmann-like_a/b/a_fold.
IPR024951. Sulfurylase_cat_dom.
IPR002650. Sulphate_adenylyltransferase.
[Graphical view]
PfamiPF01747. ATP-sulfurylase. 1 hit.
PF14306. PUA_2. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 16, 2002
Last modified: September 7, 2016
This is version 162 of the entry and version 2 of the sequence. [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, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.