Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 precursor

Names and origin

Protein names

Recommended name:
    Ectonucleotide pyrophosphatase/phosphodiesterase family member 7
      Short name=E-NPP7
      Short name=NPP-7
    EC=3.1.4.12
Alternative name(s):
    Alkaline sphingomyelin phosphodiesterase
    Intestinal alkaline sphingomyelinase
      Short name=Alk-SMase

Gene names

Name:	ENPP7
ORF Names:	UNQ3077/PRO9912

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	458 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Converts sphingomyelin to ceramide. Also has phospholipase C activity toward palmitoyl lyso-phosphocholine. Does not appear to have nucleotide pyrophosphatase activity.
Catalytic activity	Sphingomyelin + H(2)O = N-acylsphingosine + choline phosphate.
Enzyme regulation	Inhibited in a dose dependent manner by ATP, imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and EDTA.
Subcellular location	Membrane; Single-pass type I membrane proteinPotential. Note= Localized at the surface of the microvillar membrane in small intestine enterocytes, and in endosome-like structures situated beneath the microvillar membrane, and in Golgi complex.
Tissue specificity	Detected in the colon (at protein level). Expressed in the duodenum, jejunum and liver and at low levels in the ileum. Expression was very low in the esophagus, stomach and colon.
Post-translational modification	N-glycosylated; required for activity and transport to the plasma membrane.
Miscellaneous	Decreased levels of alkaline sphingomyelin phosphodiesterase may be associated with colon cancer.
Sequence similarities	Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of DNA replication Ref.6 Inferred from direct assay. Source: UniProtKB negative regulation of cell proliferation Ref.6 Inferred from direct assay. Source: UniProtKB sphingomyelin metabolic process Ref.1 Ref.6 Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi apparatus Ref.6 Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microvillus Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	sphingomyelin phosphodiesterase activity Ref.1 Ref.6 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Chain

22 – 458

437

Ectonucleotide pyrophosphatase/phosphodiesterase family member 7

PRO_0000036403

Regions

Transmembrane

434 – 454

21

Potential

Region

72 – 78

7

Required for enzyme activity

Sites

Active site

75

1

By similarity

Amino acid modifications

Glycosylation

100

1

N-linked (GlcNAc...)

Glycosylation

121

1

N-linked (GlcNAc...)

Glycosylation

146

1

N-linked (GlcNAc...)

Glycosylation

168

1

N-linked (GlcNAc...)

Glycosylation

267

1

N-linked (GlcNAc...)

Natural variations

Natural variant

4

1

L → P: dbSNP rs8074547.

VAR_021506

Experimental info

Mutagenesis

76

1

S → F: Loss of activity

Mutagenesis

78

1

C → N: Strongly reduces activity

Mutagenesis

100

1

N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267

Mutagenesis

121

1

N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267

Mutagenesis

146

1

N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267

Mutagenesis

168

1

N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267

Mutagenesis

267

1

N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168

Mutagenesis

353

1

H → A: Loss of activity

Sequence conflict

101

1

T → I in AAQ88985. Ref.2

Sequence conflict

388

1

Y → N in BAC86504. Ref.3

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Sequences

Sequence

Length

Mass (Da)

Tools

Q6UWV6-1 [UniParc].

Last modified March 20, 2007. Version 3.
Checksum: F6A06913C33E4398
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FASTA

458

51,494

        10         20         30         40         50         60 
MRGLAVLLTV ALATLLAPGA GAPVQSQGSQ NKLLLVSFDG FRWNYDQDVD TPNLDAMARD 

        70         80         90        100        110        120 
GVKARYMTPA FVTMTSPCHF TLVTGKYIEN HGVVHNMYYN TTSKVKLPYH ATLGIQRWWD 

       130        140        150        160        170        180 
NGSVPIWITA QRQGLRAGSF FYPGGNVTYQ GVAVTRSRKE GIAHNYKNET EWRANIDTVM 

       190        200        210        220        230        240 
AWFTEEDLDL VTLYFGEPDS TGHRYGPESP ERREMVRQVD RTVGYLRESI ARNHLTDRLN 

       250        260        270        280        290        300 
LIITSDHGMT TVDKRAGDLV EFHKFPNFTF RDIEFELLDY GPNGMLLPKE GRLEKVYDAL 

       310        320        330        340        350        360 
KDAHPKLHVY KKEAFPEAFH YANNPRVTPL LMYSDLGYVI HGRINVQFNN GEHGFDNKDM 

       370        380        390        400        410        420 
DMKTIFRAVG PSFRAGLEVE PFESVHVYEL MCRLLGIVPE ANDGHLATLL PMLHTESALP 

       430        440        450 
PDGRPTLLPK GRSALPPSSR PLLVMGLLGT VILLSEVA

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of human intestinal alkaline sphingomyelinase as a novel ecto-enzyme related to the nucleotide phosphodiesterase family." Duan R.-D., Bergman T., Xu N., Wu J., Cheng Y., Duan J., Nelander S., Palmberg C., Nilsson A. J. Biol. Chem. 278:38528-38536(2003) [PubMed: 12885774] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 137-151; 239-248; 256-271 AND 313-326, VARIANT PRO-4, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Colon, Kidney, Small intestine and Stomach.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-4. Tissue: Liver.
[4]	"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], VARIANT PRO-4. Tissue: Colon.
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-36.
[6]	"Purification, localization, and expression of human intestinal alkaline sphingomyelinase." Duan R.-D., Cheng Y., Hansen G., Hertervig E., Liu J.-J., Syk I., Sjostrom H., Nilsson A. J. Lipid Res. 44:1241-1250(2003) [PubMed: 12671034] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Identification of one exon deletion of intestinal alkaline sphingomyelinase in colon cancer HT-29 cells and a differentiation-related expression of the wild-type enzyme in Caco-2 cells." Wu J., Cheng Y., Nilsson A., Duan R.-D. Carcinogenesis 25:1327-1333(2004) [PubMed: 15016655] [Abstract] Cited for: MUTAGENESIS OF HIS-353.
[8]	"Functional studies of human intestinal alkaline sphingomyelinase by deglycosylation and mutagenesis." Wu J., Hansen G.H., Nilsson A., Duan R.-D. Biochem. J. 386:153-160(2005) [PubMed: 15458386] [Abstract] Cited for: GLYCOSYLATION AT ASN-100; ASN-121; ASN-146; ASN-168 AND ASN-267, MUTAGENESIS OF SER-76; CYS-78; ASN-100; ASN-121; ASN-146; ASN-168 AND ASN-267.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AY230663 mRNA. Translation: AAP69661.1. AY358622 mRNA. Translation: AAQ88985.1. AK126250 mRNA. Translation: BAC86504.1. BC041453 mRNA. Translation: AAH41453.2.
RefSeq	NP_848638.2.
UniGene	Hs.114084
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000182156. Homo sapiens. [Contig view]
GeneID	339221.
KEGG	hsa:339221.
Organism-specific databases
H-InvDB	HIX0027161.
HGNC	HGNC:23764. ENPP7.
PharmGKB	PA134986550.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q6UWV6.
HOVERGEN	Q6UWV6.
Gene expression databases
ArrayExpress	Q6UWV6.
CleanEx	HS_ENPP7.
GermOnline	ENSG00000182156. Homo sapiens.
Family and domain databases
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR002591. Phosphodiest/P_Trfase. [Graphical view]
Gene3D	G3DSA:3.40.720.10. Alk_phosphtse. 1 hit.
Pfam	PF01663. Phosphodiest. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	Q6UWV6.
NextBio	97283.

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Entry information

Entry name

ENPP7_HUMAN

Accession

Primary (citable) accession number: Q6UWV6
Secondary accession number(s): Q6ZTS5, Q8IUS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 20, 2007
Last modified:	November 25, 2008
This is version 49 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents