Q9NZJ9 (NUDT4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Diphosphoinositol polyphosphate phosphohydrolase 2
Short name=DIPP-2
EC=3.6.1.52

Alternative name(s):
Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2
EC=3.6.1.-
Nucleoside diphosphate-linked moiety X motif 4
Short name=Nudix motif 4

Gene names

Name:	NUDT4
Synonyms:	DIPP2, KIAA0487
ORF Names:	HDCMB47P

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	180 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA. Ref.1
Catalytic activity	Diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate. Ref.1 Ref.10
Cofactor	Binds 3 magnesium or manganese ions per subunit By similarity.
Subcellular location	Cytoplasm Ref.9.
Tissue specificity	Expressed in heart and, at lower level in skeletal muscle, pancreas and kidney. Ref.1
Sequence similarities	Belongs to the Nudix hydrolase family. DIPP subfamily. Contains 1 nudix hydrolase domain.
Biophysicochemical properties	Kinetic parameters: KM=4.2 nM for PP-InsP5 Ref.1
Sequence caution	The sequence AAF75563.1 differs from that shown. Reason: Erroneous termination at position 181. Translated as stop. The sequence BAE16985.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Manganese Metal-binding RNA-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-mediated signaling Traceable author statement Ref.1. Source: UniProtKB cyclic nucleotide metabolic process Traceable author statement Ref.1. Source: ProtInc cyclic-nucleotide-mediated signaling Traceable author statement Ref.1. Source: UniProtKB intracellular transport Traceable author statement Ref.1. Source: UniProtKB regulation of RNA export from nucleus Traceable author statement Ref.1. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular Traceable author statement Ref.1. Source: UniProtKB
Molecular_function	diphosphoinositol-polyphosphate diphosphatase activity Inferred from direct assay Ref.1. Source: UniProtKB inositol diphosphate tetrakisphosphate diphosphatase activity Inferred from electronic annotation. Source: EC inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity Inferred from electronic annotation. Source: EC inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity Inferred from electronic annotation. Source: EC inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity Inferred from electronic annotation. Source: EC inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity Inferred from electronic annotation. Source: EC inositol-3-diphosphate-1,2,4,5,6-pentakisphosphate diphosphatase activity Inferred from electronic annotation. Source: EC inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW snoRNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NZJ9-1)

Also known as: Alpha; DIPP2alpha;

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 2 (identifier: Q9NZJ9-2)

Also known as: Beta; DIPP2beta;

The sequence of this isoform differs from the canonical sequence as follows:
     85-85: E → EQ

Isoform 3 (identifier: Q9NZJ9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
     85-85: E → EQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 180	180	Diphosphoinositol polyphosphate phosphohydrolase 2		PRO_0000057058
Regions
	Domain	18 – 144	127	Nudix hydrolase
	Region	18 – 20	3	Substrate binding By similarity
	Region	89 – 91	3	Substrate binding By similarity
	Motif	51 – 72	22	Nudix box
Sites
	Active site	69	1	Proton acceptor By similarity
	Metal binding	50	1	Magnesium 1; via carbonyl oxygen By similarity
	Metal binding	66	1	Magnesium 2 By similarity
	Metal binding	66	1	Magnesium 3 By similarity
	Metal binding	70	1	Magnesium 1 By similarity
	Binding site	10	1	Substrate By similarity
	Binding site	41	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 52	52	Missing in isoform 3.		VSP_014269
	Alternative sequence	85	1	E → EQ in isoform 2 and isoform 3.		VSP_014270
Experimental info
	Sequence conflict	16	1	G → D in AAF68857. Ref.1
	Sequence conflict	41	1	R → Q in BAD97217. Ref.7
	Sequence conflict	73	1	V → D in AAF75563. Ref.3
	Sequence conflict	164	1	A → V in AAF68857. Ref.1
	Sequence conflict	177	1	S → P in AAF68858. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) (DIPP2alpha) [UniParc]. Last modified July 5, 2005. Version 2. Checksum: 86D766F8F5B22D13	FASTA	180	20,306
	10 20 30 40 50 60 MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG GGMEPEEEPG 70 80 90 100 110 120 GAAVREVYEE AGVKGKLGRL LGIFENQDRK HRTYVYVLTV TEILEDWEDS VNIGRKREWF 130 140 150 160 170 180 KVEDAIKVLQ CHKPVHAEYL EKLKLGCSPA NGNSTVPSLP DNNALFVTAA QTSGLPSSVR
	Isoform 2 (Beta) (DIPP2beta) [UniParc]. Checksum: CB3C131FAD21A4AA	FASTA	181	20,434
	10 20 30 40 50 60 MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG GGMEPEEEPG 70 80 90 100 110 120 GAAVREVYEE AGVKGKLGRL LGIFEQNQDR KHRTYVYVLT VTEILEDWED SVNIGRKREW 130 140 150 160 170 180 FKVEDAIKVL QCHKPVHAEY LEKLKLGCSP ANGNSTVPSL PDNNALFVTA AQTSGLPSSV R
	Isoform 3 [UniParc]. Checksum: 2A8C483085B2D4D3	FASTA	129	14,395
	10 20 30 40 50 60 MEPEEEPGGA AVREVYEEAG VKGKLGRLLG IFEQNQDRKH RTYVYVLTVT EILEDWEDSV 70 80 90 100 110 120 NIGRKREWFK VEDAIKVLQC HKPVHAEYLE KLKLGCSPAN GNSTVPSLPD NNALFVTAAQ TSGLPSSVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases. The expanding NUDT family." Caffrey J.J., Safrany S.T., Yang X., Shears S.B. J. Biol. Chem. 275:12730-12736(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Cerebellum.
[2]	"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain." Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O. DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Novel gene identified from dendritic cells." Zhao Z., Huang X., Li N., Zhu X., Cao X. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Retina.
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Trachea.
[7]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Lymph and Placenta.
[9]	"Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases." Leslie N.R., McLennan A.G., Safrany S.T. BMC Biochem. 3:20-20(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate." Fisher D.I., Safrany S.T., Strike P., McLennan A.G., Cartwright J.L. J. Biol. Chem. 277:47313-47317(2002) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY.
[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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF191649 mRNA. Translation: AAF68855.1. AF191650 mRNA. Translation: AAF68856.1. AF191651 mRNA. Translation: AAF68857.1. AF191652 mRNA. Translation: AAF68858.2. AF191653 mRNA. Translation: AAF68859.1. AB007956 mRNA. Translation: BAE16985.1. Different initiation. AF067803 mRNA. Translation: AAF75563.1. Sequence problems. CR749445 mRNA. Translation: CAH18283.1. BT020109 mRNA. Translation: AAV38912.1. BT020110 mRNA. Translation: AAV38913.1. AK304296 mRNA. Translation: BAH14152.1. AK223497 mRNA. Translation: BAD97217.1. BC012069 mRNA. Translation: AAH12069.1. BC051310 mRNA. Translation: AAH51310.1.
IPI	IPI00021408. IPI00396090. IPI00607685.
RefSeq	NP_061967.3. NM_019094.4. NP_950241.1. NM_199040.2.
UniGene	Hs.506325.
3D structure databases
ProteinModelPortal	Q9NZJ9.
ModBase	Search...
PTM databases
PhosphoSite	Q9NZJ9.
Polymorphism databases
DMDM	68565946.
Proteomic databases
PRIDE	Q9NZJ9.
Protocols and materials databases
DNASU	11163.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000337179; ENSP00000338352; ENSG00000173598. ENST00000415493; ENSP00000406612; ENSG00000173598. ENST00000547014; ENSP00000448032; ENSG00000173598. ENST00000548662; ENSP00000449724; ENSG00000173598. ENST00000549992; ENSP00000449552; ENSG00000173598.
GeneID	11163.
KEGG	hsa:100996752. hsa:11163.
UCSC	uc001tcm.3. human. uc010sup.2. human. uc010suq.2. human.
Organism-specific databases
CTD	11163.
GeneCards	GC12P093771.
HGNC	HGNC:8051. NUDT4.
HPA	HPA017593.
MIM	609229. gene.
neXtProt	NX_Q9NZJ9.
PharmGKB	PA31835.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG053341.
InParanoid	Q9NZJ9.
KO	K07766.
OMA	IGMFQDD.
OrthoDB	EOG479F89.
Enzyme and pathway databases
BioCyc	MetaCyc:HS10696-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9NZJ9.
Bgee	Q9NZJ9.
CleanEx	HS_NUDT4.
Genevestigator	Q9NZJ9.
GermOnline	ENSG00000173598. Homo sapiens.
Family and domain databases
Gene3D	3.90.79.10. 1 hit.
InterPro	IPR020084. NUDIX_hydrolase_CS. IPR000086. NUDIX_hydrolase_dom. IPR015797. NUDIX_hydrolase_dom-like. [Graphical view]
Pfam	PF00293. NUDIX. 1 hit. [Graphical view]
SUPFAM	SSF55811. NUDIX_hydrolase. 1 hit.
PROSITE	PS51462. NUDIX. 1 hit. PS00893. NUDIX_BOX. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NUDT4. human.
NextBio	42469.
SOURCE	Search...

Entry information

Entry name

NUDT4_HUMAN

Accession

Primary (citable) accession number: Q9NZJ9
Secondary accession number(s): B7Z916 , Q4AEJ6, Q53EZ2, Q68DD7, Q9NPC5, Q9NS30, Q9NZK0, Q9NZK1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	July 5, 2005
Last modified:	May 1, 2013
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.