Q9UKK9 (NUDT5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ADP-sugar pyrophosphatase
EC=3.6.1.-
EC=3.6.1.13

Alternative name(s):
Nucleoside diphosphate-linked moiety X motif 5
Short name=Nudix motif 5
YSA1H

Gene names

Name:	NUDT5
ORF Names:	HSPC115

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

General annotation (Comments)

Function	Hydrolyzes with similar activities ADP-ribose, ADP-mannose, and ADP-glucose. Can also hydrolyze other nucleotide sugars with low activity. Ref.12
Catalytic activity	ADP-ribose + H2O = AMP + D-ribose 5-phosphate. Ref.12 ADP-sugar + H2O = AMP + alpha-D-aldose 5-phosphate. Ref.12
Cofactor	Binds 3 magnesium ions per subunit. Ref.12 Ref.13
Subunit structure	Homodimer. Ref.12 Ref.13
Tissue specificity	Widely expressed. Most abundant in liver.
Sequence similarities	Belongs to the Nudix hydrolase family. Contains 1 nudix hydrolase domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	D-ribose catabolic process Non-traceable author statement Ref.1. Source: UniProtKB ribonucleoside diphosphate catabolic process Inferred from direct assay Ref.13. Source: UniProtKB
Cellular component	intracellular Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	ADP-ribose diphosphatase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from direct assay Ref.13. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 219

219

ADP-sugar pyrophosphatase

PRO_0000057048

Regions

Domain

57 – 197

141

Nudix hydrolase

Region

46 – 47

2

Substrate binding; shared with dimeric partner

Motif

97 – 118

22

Nudix box

Sites

Metal binding

96

1

Magnesium 1; via carbonyl oxygen

Metal binding

112

1

Magnesium 2

Metal binding

112

1

Magnesium 3

Metal binding

116

1

Magnesium 1

Metal binding

116

1

Magnesium 3

Metal binding

166

1

Magnesium 3

Binding site

28

1

Substrate

Binding site

51

1

Substrate; shared with dimeric partner

Binding site

84

1

Substrate

Binding site

98

1

Substrate; via amide nitrogen

Binding site

133

1

Substrate

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.10

Modified residue

9

1

Phosphoserine By similarity

Modified residue

10

1

Phosphoserine By similarity

Modified residue

42

1

N6-acetyllysine Ref.9

Modified residue

74

1

Phosphotyrosine Ref.8

Modified residue

210

1

N6-acetyllysine Ref.9

Modified residue

218

1

N6-acetyllysine Ref.9

Natural variations

Natural variant

123

1

I → T.
Corresponds to variant rs34863826 [ dbSNP | Ensembl ].

VAR_034159

Experimental info

Mutagenesis

28

1

W → A: Reduces affinity for substrate about 8-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-46. Ref.13

Mutagenesis

46

1

W → A: Reduces affinity for substrate about 6-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-28. Ref.13

Mutagenesis

51

1

R → Q: Reduces affinity for substrate about 15-fold and reduces catalytic rate about 17-fold. Ref.13

Mutagenesis

84

1

R → Q: Reduces affinity for substrate about 5-fold and reduces catalytic rate 67-fold. Ref.13

Mutagenesis

98

1

L → A: Reduces affinity for substrate about 6-fold. Ref.13

Mutagenesis

112

1

E → Q: Reduces catalytic rate 6300-fold. Ref.13

Mutagenesis

116

1

E → Q: Reduces catalytic rate 2000-fold. Ref.13

Mutagenesis

166

1

E → Q: Reduces catalytic rate 120-fold. Ref.13

Sequence conflict

50 – 52

3

KRT → NVP in AAF25479. Ref.2

Secondary structure

1

.

.

.

.

.

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.

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.

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.

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219

Helix Strand Turn

Details...

Beta strand

16 – 25

10

Beta strand

27 – 37

11

Beta strand

43 – 51

9

Beta strand

60 – 69

10

Beta strand

76 – 84

9

Helix

85 – 87

3

Beta strand

89 – 93

5

Beta strand

96 – 98

3

Helix

105 – 117

13

Beta strand

122 – 126

5

Beta strand

130 – 132

3

Turn

134 – 136

3

Beta strand

140 – 149

10

Helix

153 – 155

3

Beta strand

169 – 174

6

Helix

175 – 177

3

Helix

178 – 189

12

Beta strand

192 – 194

3

Helix

195 – 207

13

Turn

211 – 213

3

Helix

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Q9UKK9 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6574E0BF1EA2BB26	FASTA	219	24,328
	10 20 30 40 50 60 MESQEPTESS QNGKQYIISE ELISEGKWVK LEKTTYMDPT GKTRTWESVK RTTRKEQTAD 70 80 90 100 110 120 GVAVIPVLQR TLHYECIVLV KQFRPPMGGY CIEFPAGLID DGETPEAAAL RELEEETGYK 130 140 150 160 170 180 GDIAECSPAV CMDPGLSNCT IHIVTVTING DDAENARPKP KPGDGEFVEV ISLPKNDLLQ 190 200 210 RLDALVAEEH LTVDARVYSY ALALKHANAK PFEVPFLKF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and characterization of YSA1H, a human adenosine 5'-diphosphosugar pyrophosphatase possessing a MutT motif." Gasmi L., Cartwright J.L., McLennan A.G. Biochem. J. 344:331-337(1999) [PubMed: 10567213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[2]	"Cloning and characterization of a new member of the Nudix hydrolases from human and mouse." Yang H., Slupska M.M., Wei Y.-F., Tai J.H., Luther W.M., Xia Y.-R., Shih D.M., Chiang J.-H., Baikalov C., Fitz-Gibbon S., Phan I.T., Conrad A., Miller J.H. J. Biol. Chem. 275:8844-8853(2000) [PubMed: 10722730] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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].
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]. Tissue: Placenta.
[8]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-74, MASS SPECTROMETRY.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42; LYS-210 AND LYS-218, MASS SPECTROMETRY.
[10]	"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.
[11]	"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].
[12]	"Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity." Zha M., Zhong C., Peng Y., Hu H., Ding J. J. Mol. Biol. 364:1021-1033(2006) [PubMed: 17052728] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMP; MAGNESIUM IONS AND ADP-RIBOSE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR.
[13]	"Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studies." Zha M., Guo Q., Zhang Y., Yu B., Ou Y., Zhong C., Ding J. J. Mol. Biol. 379:568-578(2008) [PubMed: 18462755] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMPCPR AND MAGNESIUM IONS, COFACTOR, MUTAGENESIS OF TRP-28; TRP-46; ARG-51; ARG-84; LEU-98; GLU-112; GLU-116 AND GLU-166, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF155832 mRNA. Translation: AAF06734.1.
AF218818 mRNA. Translation: AAF25479.1.
AF161464 mRNA. Translation: AAF29079.1.
CR457195 mRNA. Translation: CAG33476.1.
AK291131 mRNA. Translation: BAF83820.1.
CH471072 Genomic DNA. Translation: EAW86322.1.
BC000025 mRNA. Translation: AAH00025.1.

IPI

IPI00296913.

RefSeq

NP_054861.2. NM_014142.2.

UniGene

Hs.555956.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DSB	X-ray	2.50	A/B/C/D	1-219	[»]
2DSC	X-ray	2.00	A/B	1-210	[»]
2DSD	X-ray	2.60	A/B	1-210	[»]
3AC9	X-ray	2.10	A/B	14-208	[»]
3ACA	X-ray	2.05	A/B	13-208	[»]
3BM4	X-ray	2.00	A/B	1-210	[»]
3L85	X-ray	2.30	A/B	14-208	[»]

ProteinModelPortal

Q9UKK9.

SMR

Q9UKK9. Positions 13-209.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UKK9. 4 interactions.

MINT

MINT-1370495.

STRING

Q9UKK9.

PTM databases

PhosphoSite

Q9UKK9.

Polymorphism databases

DMDM

20455192.

Proteomic databases

PRIDE

Q9UKK9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000491614; ENSP00000419628; ENSG00000165609.

GeneID

11164.

KEGG

hsa:11164.

UCSC

uc001ilj.1. human.

Organism-specific databases

CTD

11164.

GeneCards

GC10M012207.

H-InvDB

HIX0008645.

HGNC

HGNC:8052. NUDT5.

HPA

HPA019827.

MIM

609230. gene.

neXtProt

NX_Q9UKK9.

PharmGKB

PA31838.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12527.

GeneTree

ENSGT00390000006280.

HOVERGEN

HBG052691.

OrthoDB

EOG46Q6TG.

PhylomeDB

Q9UKK9.

Enzyme and pathway databases

BRENDA

3.6.1.13. 2681.

Gene expression databases

ArrayExpress

Q9UKK9.

Bgee

Q9UKK9.

CleanEx

HS_NUDT5.

Genevestigator

Q9UKK9.

GermOnline

ENSG00000165609. Homo sapiens.

Family and domain databases

InterPro

IPR020476. Nudix_hydrolase.
IPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]

Gene3D

G3DSA:3.90.79.10. NUDIX_hydrolase. 1 hit.

KO

K13987.

Pfam

PF00293. NUDIX. 1 hit.
[Graphical view]

PRINTS

PR00502. NUDIXFAMILY.

SUPFAM

SSF55811. NUDIX_hydrolase. 1 hit.

PROSITE

PS51462. NUDIX. 1 hit.
PS00893. NUDIX_BOX. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

42475.

SOURCE

Search...

Entry information

Entry name

NUDT5_HUMAN

Accession

Primary (citable) accession number: Q9UKK9
Secondary accession number(s): A8K516, Q6IAG0, Q9UH49

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2002
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 101 of the entry and version 1 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.