O95340 (PAPS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Sulfate adenylyltransferase
   EC=2.7.7.4
   Alternative name(s):
   ATP-sulfurylase
   Sulfate adenylate transferase
   Short name=SAT
2. 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:	PAPSS2
Synonyms:	ATPSK2

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	614 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. May have a important role in skeletogenesis during postnatal growth By similarity.
Catalytic activity	ATP + sulfate = diphosphate + adenylyl sulfate. ATP + adenylyl sulfate = ADP + 3'-phosphoadenylyl sulfate.
Pathway	Sulfur metabolism; sulfate assimilation.
Tissue specificity	Expressed in cartilage and adrenal gland. Ref.9
Involvement in disease	Defects in PAPSS2 are the cause of spondyloepimetaphyseal dysplasia Pakistani type (SEMD-PA) [MIM:612847]. A bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature. Ref.8 Ref.9
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	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: O95340-1)

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.

Isoform B (identifier: O95340-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 614

614

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2

PRO_0000105961

Regions

Nucleotide binding

49 – 56

8

ATP Potential

Region

1 – ?210

210

Adenylyl-sulfate kinase

Region

?211 – 614

404

Sulfate adenylyltransferase

Motif

511 – 515

5

PP-motif

Sites

Active site

123

1

Phosphoserine intermediate By similarity

Natural variations

Alternative sequence

288

1

D → DGMALP in isoform B.

VSP_001259

Natural variant

10

1

E → K Significant decrease of activity. Ref.11
Corresponds to variant rs17173698 [ dbSNP | Ensembl ].

VAR_029136

Natural variant

48

1

T → R in SEMD-PA; patient with premature pubarche and hyperandrogenism; results in partial loss of activity. Ref.9

VAR_063049

Natural variant

281

1

M → L. Ref.11
Corresponds to variant rs45624631 [ dbSNP | Ensembl ].

VAR_029137

Natural variant

291

1

V → M Significant decrease of activity. Ref.11
Corresponds to variant rs45467596 [ dbSNP | Ensembl ].

VAR_022077

Natural variant

432

1

R → K. Ref.11

VAR_029138

Experimental info

Sequence conflict

166

1

R → K in AAD38423. Ref.2

Sequence conflict

361

1

E → G in AAK00296. Ref.3

Sequence conflict

426

1

R → C in AAC64583. Ref.1

Sequence conflict

567

1

P → L in AAD38423. Ref.2

Secondary structure

1

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614

Helix Strand Turn

Details...

Helix

27 – 33

7

Beta strand

34 – 37

4

Beta strand

43 – 48

6

Helix

55 – 68

14

Beta strand

73 – 76

4

Helix

78 – 81

4

Turn

82 – 88

7

Helix

93 – 112

20

Beta strand

116 – 120

5

Helix

126 – 138

13

Beta strand

143 – 149

7

Helix

152 – 158

7

Beta strand

160 – 162

3

Helix

163 – 168

6

Turn

176 – 178

3

Beta strand

189 – 193

5

Helix

199 – 212

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 52F4B6D972DDA91E	FASTA	614	69,501
	10 20 30 40 50 60 MSGIKKQKTE NQQKSTNVVY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL SGAGKTTISF 70 80 90 100 110 120 ALEEYLVSHA IPCYSLDGDN VRHGLNRNLG FSPGDREENI RRIAEVAKLF ADAGLVCITS 130 140 150 160 170 180 FISPFAKDRE NARKIHESAG LPFFEIFVDA PLNICESRDV KGLYKRARAG EIKGFTGIDS 190 200 210 220 230 240 DYEKPETPER VLKTNLSTVS DCVHQVVELL QEQNIVPYTI IKDIHELFVP ENKLDHVRAE 250 260 270 280 290 300 AETLPSLSIT KLDLQWVQVL SEGWATPLKG FMREKEYLQV MHFDTLLDDG VINMSIPIVL 310 320 330 340 350 360 PVSAEDKTRL EGCSKFVLAH GGRRVAILRD AEFYEHRKEE RCSRVWGTTC TKHPHIKMVM 370 380 390 400 410 420 ESGDWLVGGD LQVLEKIRWN DGLDQYRLTP LELKQKCKEM NADAVFAFQL RNPVHNGHAL 430 440 450 460 470 480 LMQDTRRRLL ERGYKHPVLL LHPLGGWTKD DDVPLDWRMK QHAAVLEEGV LDPKSTIVAI 490 500 510 520 530 540 FPSPMLYAGP TEVQWHCRSR MIAGANFYIV GRDPAGMPHP ETKKDLYEPT HGGKVLSMAP 550 560 570 580 590 600 GLTSVEIIPF RVAAYNKAKK AMDFYDPARH NEFDFISGTR MRKLAREGEN PPDGFMAPKA 610 WKVLTDYYRS LEKN
	Isoform B [UniParc]. Checksum: D4268D03982283E6	FASTA	619	69,970
	10 20 30 40 50 60 MSGIKKQKTE NQQKSTNVVY QAHHVSRNKR GQVVGTRGGF RGCTVWLTGL SGAGKTTISF 70 80 90 100 110 120 ALEEYLVSHA IPCYSLDGDN VRHGLNRNLG FSPGDREENI RRIAEVAKLF ADAGLVCITS 130 140 150 160 170 180 FISPFAKDRE NARKIHESAG LPFFEIFVDA PLNICESRDV KGLYKRARAG EIKGFTGIDS 190 200 210 220 230 240 DYEKPETPER VLKTNLSTVS DCVHQVVELL QEQNIVPYTI IKDIHELFVP ENKLDHVRAE 250 260 270 280 290 300 AETLPSLSIT KLDLQWVQVL SEGWATPLKG FMREKEYLQV MHFDTLLDGM ALPDGVINMS 310 320 330 340 350 360 IPIVLPVSAE DKTRLEGCSK FVLAHGGRRV AILRDAEFYE HRKEERCSRV WGTTCTKHPH 370 380 390 400 410 420 IKMVMESGDW LVGGDLQVLE KIRWNDGLDQ YRLTPLELKQ KCKEMNADAV FAFQLRNPVH 430 440 450 460 470 480 NGHALLMQDT RRRLLERGYK HPVLLLHPLG GWTKDDDVPL DWRMKQHAAV LEEGVLDPKS 490 500 510 520 530 540 TIVAIFPSPM LYAGPTEVQW HCRSRMIAGA NFYIVGRDPA GMPHPETKKD LYEPTHGGKV 550 560 570 580 590 600 LSMAPGLTSV EIIPFRVAAY NKAKKAMDFY DPARHNEFDF ISGTRMRKLA REGENPPDGF 610 MAPKAWKVLT DYYRSLEKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse." ul Haque M.F., King L.M., Krakow D., Cantor R.M., Rusiniak M.E., Swank R.T., Superti-Furga A., Haque S., Abbas H., Ahmad W., Ahmad M., Cohn D.H. Nat. Genet. 20:157-162(1998) [PubMed: 9771708] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Fetal cartilage.
[2]	Franzon V.L., Gibson M.A., Hatzinikolas G., Cleary E.G., Woolatt E., Sutherland G.R. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[3]	"Human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase: differential expression of isoforms and effect of polymorphisms on activity." Fuda H., Shimizu C., Strott C.A. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[4]	"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] (ISOFORM A).
[5]	"Genomic organization of the mouse and human genes encoding the ATP sulfurylase/adenosine 5'-phosphosulfate kinase isoform SK2." Kurima K., Singh B., Schwartz N.B. J. Biol. Chem. 274:33306-33312(1999) [PubMed: 10559207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). Tissue: Liver.
[6]	"3'-phosphoadenosine 5'-phosphosulfate synthase 2b isoform." Venkatachalam K.V., Fuda H., Strott C.A. Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
[7]	"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] (ISOFORM A). Tissue: Colon.
[8]	"Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred." Ahmad M., Haque M.F., Ahmad W., Abbas H., Haque S., Krakow D., Rimoin D.L., Lachman R.S., Cohn D.H. Am. J. Med. Genet. 78:468-473(1998) [PubMed: 9714015] [Abstract] Cited for: INVOLVEMENT IN SEMD-PA.
[9]	"Inactivating PAPSS2 mutations in a patient with premature pubarche." Noordam C., Dhir V., McNelis J.C., Schlereth F., Hanley N.A., Krone N., Smeitink J.A., Smeets R., Sweep F.C., Claahsen-van der Grinten H.L., Arlt W. N. Engl. J. Med. 360:2310-2318(2009) [PubMed: 19474428] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANT SEMD-PA ARG-48, CHARACTERIZATION OF VARIANT SEMD-PA ARG-48.
[10]	"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].
[11]	"Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) pharmacogenetics: gene resequencing, genetic polymorphisms and functional characterization of variant allozymes." Xu Z.-H., Freimuth R.R., Eckloff B., Wieben E., Weinshilboum R.M. Pharmacogenetics 12:11-21(2002) [PubMed: 11773860] [Abstract] Cited for: VARIANTS LYS-10; LEU-281; MET-291 AND LYS-432, CHARACTERIZATION OF VARIANTS LYS-10 AND MET-291.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00030009.
IPI00220873.

RefSeq

NP_001015880.1. NM_001015880.1.
NP_004661.2. NM_004670.3.

UniGene

Hs.524491.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AX4	X-ray	2.50	A/B/C/D	21-218	[»]

ProteinModelPortal

O95340.

SMR

O95340. Positions 21-613.

ModBase

Search...

Protein-protein interaction databases

STRING

O95340.

PTM databases

PhosphoSite

O95340.

Proteomic databases

PRIDE

O95340.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361175; ENSP00000354436; ENSG00000198682.

GeneID

9060.

KEGG

hsa:9060.

UCSC

uc001kew.1. human.
uc001kex.1. human.

Organism-specific databases

CTD

9060.

GeneCards

GC10P089409.

HGNC

HGNC:8604. PAPSS2.

MIM

603005. gene.
612847. phenotype.

neXtProt

NX_O95340.

Orphanet

93282. Spondyloepimetaphyseal dysplasia, Pakistani type.

PharmGKB

PA383.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07483.

HOVERGEN

HBG053503.

OMA

LEGCSEF.

OrthoDB

EOG4VT5WR.

PhylomeDB

O95340.

Enzyme and pathway databases

BRENDA

2.7.1.25. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O95340.

Bgee

O95340.

CleanEx

HS_PAPSS2.

Genevestigator

O95340.

GermOnline

ENSG00000198682. 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.

KO

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

33949.

SOURCE

Search...

Entry information

Entry name

PAPS2_HUMAN

Accession

Primary (citable) accession number: O95340
Secondary accession number(s): Q9BZL2 , Q9P0G6, Q9UHM1, Q9UKD3, Q9UP30

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	April 16, 2002
Last modified:	January 25, 2012
This is version 111 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.