P78330 (SERB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphoserine phosphatase
Short name=PSP
Short name=PSPase
EC=3.1.3.3

Alternative name(s):
L-3-phosphoserine phosphatase
O-phosphoserine phosphohydrolase

Gene names

Name:

PSPH

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	225 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the last step in the biosynthesis of serine from carbohydrates. The reaction mechanism proceeds via the formation of a phosphoryl-enzyme intermediates. Ref.9
Catalytic activity	O-phospho-L(or D)-serine + H2O = L(or D)-serine + phosphate. Ref.8 Ref.9 Ref.10
Cofactor	Binds 1 magnesium ion per subunit. Ref.10
Enzyme regulation	Inhibited by calcium ions. Ref.10
Pathway	Amino-acid biosynthesis; L-serine biosynthesis; L-serine from 3-phospho-D-glycerate: step 3/3.
Subunit structure	Homodimer. Ref.8 Ref.9
Involvement in disease	Defects in PSPH are the cause of phosphoserine phosphatase deficiency (PSPHD)[MIM:614023]. A disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome. Ref.11
Sequence similarities	Belongs to the serB family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Serine biosynthesis
Disease	Disease mutation
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-serine biosynthetic process Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	calcium ion binding Inferred from direct assay Ref.9Ref.10. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.10. Source: UniProtKB phosphoserine phosphatase activity Inferred from direct assay Ref.11Ref.10. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASF1B	Q9NVP2	1	EBI-1042956,EBI-1055650
PRPSAP1	Q14558	1	EBI-1042956,EBI-724449
STYXL1	Q9Y6J8	1	EBI-1042956,EBI-1044511

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 225

225

Phosphoserine phosphatase

PRO_0000156879

Regions

Region

109 – 110

2

Substrate binding

Sites

Active site

20

1

Nucleophile Ref.8 Ref.9

Active site

22

1

Proton donor Ref.8 Ref.9

Metal binding

20

1

Magnesium

Metal binding

22

1

Magnesium; via carbonyl oxygen

Metal binding

179

1

Magnesium

Binding site

29

1

Substrate

Binding site

65

1

Substrate

Binding site

158

1

Substrate

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.6

Natural variations

Natural variant

32

1

D → N in PSPHD. Ref.11
Corresponds to variant rs28933976 [ dbSNP | Ensembl ].

VAR_022378

Natural variant

52

1

M → T in PSPHD. Ref.11

VAR_022379

Experimental info

Mutagenesis

23

1

S → A: Reduces activity by about 50%. Ref.8

Mutagenesis

23

1

S → T: Reduces activity by about 80%. Ref.8

Mutagenesis

29

1

E → D: Reduces activity by about 95%. Ref.8

Mutagenesis

29

1

E → Q: Loss of activity. Ref.8

Mutagenesis

65

1

R → A or K: Loss of activity. Ref.8

Mutagenesis

133

1

N → A: Reduces activity by about 75%. Ref.8

Mutagenesis

182

1

T → S: Reduces activity by about 99%. Ref.8

Mutagenesis

182

1

T → V: Reduces activity by about 25%. Ref.8

Mutagenesis

202

1

R → A: Reduces activity by about 99%. Ref.8

Mutagenesis

202

1

R → K: Reduces activity by about 95%. Ref.8

Sequence conflict

2

1

V → I in CAA71318. Ref.1

Secondary structure

1

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225

Helix Strand Turn

Details...

Helix

6 – 13

8

Beta strand

15 – 20

6

Turn

23 – 25

3

Beta strand

26 – 28

3

Helix

30 – 37

8

Turn

41 – 43

3

Helix

58 – 69

12

Helix

73 – 82

10

Helix

91 – 100

10

Beta strand

104 – 112

9

Helix

113 – 122

10

Helix

127 – 129

3

Beta strand

130 – 133

4

Beta strand

135 – 138

4

Beta strand

143 – 146

4

Helix

151 – 153

3

Helix

157 – 169

13

Beta strand

174 – 180

7

Helix

181 – 184

4

Turn

185 – 189

5

Beta strand

190 – 196

7

Helix

203 – 208

6

Beta strand

210 – 214

5

Helix

216 – 219

4

Sequences

	Sequence		Length	Mass (Da)
	P78330 [UniParc]. Last modified April 26, 2005. Version 2. Checksum: BD5D72697747FA30	FASTA	225	25,008
	10 20 30 40 50 60 MVSHSELRKL FYSADAVCFD VDSTVIREEG IDELAKICGV EDAVSEMTRR AMGGAVPFKA 70 80 90 100 110 120 ALTERLALIQ PSREQVQRLI AEQPPHLTPG IRELVSRLQE RNVQVFLISG GFRSIVEHVA 130 140 150 160 170 180 SKLNIPATNV FANRLKFYFN GEYAGFDETQ PTAESGGKGK VIKLLKEKFH FKKIIMIGDG 190 200 210 220 ATDMEACPPA DAFIGFGGNV IRQQVKDNAK WYITDFVELL GELEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human L-3-phosphoserine phosphatase: sequence, expression and evidence for a phosphoenzyme intermediate." Collet J.-F., Gerin I., Rider M.H., Veiga-Da-Cunha M., Van Schaftingen E. FEBS Lett. 408:281-284(1997) [PubMed: 9188776] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Endometrial tumor.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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].
[6]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"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].
[8]	"Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase." Kim H.Y., Heo Y.S., Kim J.H., Park M.H., Moon J., Kim E., Kwon D., Yoon J., Shin D., Jeong E.J., Park S.Y., Lee T.G., Jeon Y.H., Ro S., Cho J.M., Hwang K.Y. J. Biol. Chem. 277:46651-46658(2002) [PubMed: 12213811] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 3-225 IN COMPLEXES WITH INHIBITOR 2-AMINO-3-PHOSPHONOPROPIONIC ACID; SERINE AND PHOSPHATE ION, SUBUNIT, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF SER-23; GLU-29; ARG-65; ASN-133; THR-182 AND ARG-202.
[9]	"High-resolution structure of human phosphoserine phosphatase in open conformation." Peeraer Y., Rabijns A., Verboven C., Collet J.F., Van Schaftingen E., De Ranter C. Acta Crystallogr. D 59:971-977(2003) [PubMed: 12777757] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 3-225 IN COMPLEX WITH CALCIUM IONS, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBUNIT.
[10]	"How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase." Peeraer Y., Rabijns A., Collet J.F., Van Schaftingen E., De Ranter C. Eur. J. Biochem. 271:3421-3427(2004) [PubMed: 15291819] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 3-225 IN COMPLEX WITH CALCIUM IONS, COFACTOR, CATALYTIC ACTIVITY, ENZYME REGULATION.
[11]	"Mutations responsible for 3-phosphoserine phosphatase deficiency." Veiga-da-Cunha M., Collet J.F., Prieur B., Jaeken J., Peeraer Y., Rabbijns A., Van Schaftingen E. Eur. J. Hum. Genet. 12:163-166(2004) [PubMed: 14673469] [Abstract] Cited for: VARIANTS PSPHD ASN-32 AND THR-52.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y10275 mRNA. Translation: CAA71318.1.
AK315235 mRNA. Translation: BAG37662.1.
BX537439 mRNA. Translation: CAD97681.1.
CH471140 Genomic DNA. Translation: EAX07968.1.
BC063614 mRNA. Translation: AAH63614.1.

IPI

IPI00019178.

RefSeq

NP_004568.2. NM_004577.3.

UniGene

Hs.512656.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L8L	X-ray	2.51	A/B	3-225	[»]
1L8O	X-ray	2.80	A/B	3-225	[»]
1NNL	X-ray	1.53	A/B	3-225	[»]

ProteinModelPortal

P78330.

SMR

P78330. Positions 4-225.

ModBase

Search...

Protein-protein interaction databases

STRING

P78330.

PTM databases

PhosphoSite

P78330.

Polymorphism databases

DMDM

62906870.

Proteomic databases

PeptideAtlas

P78330.

PRIDE

P78330.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000275605; ENSP00000275605; ENSG00000146733.
ENST00000395471; ENSP00000378854; ENSG00000146733.
ENST00000437355; ENSP00000401639; ENSG00000146733.

GeneID

5723.

KEGG

hsa:5723.

UCSC

uc003trg.1. human.

Organism-specific databases

CTD

5723.

GeneCards

GC07M056046.

H-InvDB

HIX0021579.

HGNC

HGNC:9577. PSPH.

HPA

HPA020376.
HPA029515.

MIM

172480. gene.
614023. phenotype.

neXtProt

NX_P78330.

Orphanet

79350. 3-Phosphoserine phosphatase deficiency.
35705. Neurometabolic disorder due to serine deficiency.

PharmGKB

PA33928.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17027.

HOGENOM

HBG482410.

HOVERGEN

HBG057486.

InParanoid

P78330.

OMA

YAGFDES.

OrthoDB

EOG4NVZM5.

PhylomeDB

P78330.

Gene expression databases

ArrayExpress

P78330.

Bgee

P78330.

CleanEx

HS_PSPH.

Genevestigator

P78330.

GermOnline

ENSG00000146733. Homo sapiens.

Family and domain databases

InterPro

IPR005834. Dehalogen-like_hydro.
IPR023214. HAD-like_dom.
IPR006383. HAD-SF_hydro_IB_PSP-like.
IPR023190. Pser_Pase_dom_2.
IPR004469. SerB.
[Graphical view]

Gene3D

G3DSA:3.40.50.1000. HAD-like_dom. 2 hits.
G3DSA:1.10.150.210. Pser_Pase_dom_2. 1 hit.

KO

K01079.

Pfam

PF00702. Hydrolase. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

TIGRFAMs

TIGR01488. HAD-SF-IB. 1 hit.
TIGR00338. SerB. 1 hit.

ProtoNet

Search...

Other

NextBio

22244.

SOURCE

Search...

Entry information

Entry name

SERB_HUMAN

Accession

Primary (citable) accession number: P78330
Secondary accession number(s): B2RCR5, Q7Z3S5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	April 26, 2005
Last modified:	January 25, 2012
This is version 112 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.