Reviewed, UniProtKB/Swiss-Prot Q6UWV6 (ENPP7_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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.

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. Ref.1
Catalytic activity	Sphingomyelin + H2O = N-acylsphingosine + choline phosphate. Ref.1
Enzyme regulation	Inhibited in a dose dependent manner by ATP, imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and EDTA. Ref.1
Subcellular location	Membrane; Single-pass type I membrane protein Potential. 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. Ref.1 Ref.6 Ref.8
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. Ref.1 Ref.6 Ref.8
Post-translational modification	N-glycosylated; required for activity and transport to the plasma membrane. Ref.8 Ref.9
Miscellaneous	Decreased levels of alkaline sphingomyelin phosphodiesterase may be associated with colon cancer. Ref.8 Ref.5
Sequence similarities	Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome 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-SubCell 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.5
	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...) Ref.8
	Glycosylation	121	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	146	1	N-linked (GlcNAc...) Ref.8 Ref.9
	Glycosylation	168	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	267	1	N-linked (GlcNAc...) Ref.8
Natural variations
	Natural variant	4	1	L → P: dbSNP rs8074547. Ref.1 Ref.3 Ref.4		VAR_021506
Experimental info
	Mutagenesis	76	1	S → F: Loss of activity. Ref.8 Ref.5
	Mutagenesis	78	1	C → N: Strongly reduces activity. Ref.8 Ref.5
	Mutagenesis	100	1	N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267. Ref.8 Ref.5
	Mutagenesis	121	1	N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. Ref.8 Ref.5
	Mutagenesis	146	1	N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. Ref.8 Ref.5
	Mutagenesis	168	1	N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267. Ref.8 Ref.5
	Mutagenesis	267	1	N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168. Ref.8 Ref.5
	Mutagenesis	353	1	H → A: Loss of activity. Ref.5 Ref.7
	Sequence conflict	101	1	T → I in AAQ88985. Ref.2
	Sequence conflict	388	1	Y → N in BAC86504. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q6UWV6-1 [UniParc]. Last modified March 20, 2007. Version 3. Checksum: F6A06913C33E4398	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

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. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., 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. , 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], 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.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-146, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY230663 mRNA. Translation: AAP69661.1. AY358622 mRNA. Translation: AAQ88985.1. AK126250 mRNA. Translation: BAC86504.1. BC041453 mRNA. Translation: AAH41453.2.
IPI	IPI00419668.
RefSeq	NP_848638.2.
UniGene	Hs.114084
3D structure databases
SMR	Q6UWV6. Positions 30-414.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6UWV6.
Proteomic databases
PRIDE	Q6UWV6.
Genome annotation databases
Ensembl	ENST00000328313; ENSP00000332656; ENSG00000182156; Homo sapiens. [Genome view]
GeneID	339221.
KEGG	hsa:339221.
UCSC	uc002jxa.1. human.
Organism-specific databases
CTD	339221.
GeneCards	GC17P075319.
H-InvDB	HIX0027161.
HGNC	HGNC:23764. ENPP7.
HPA	HPA024603.
PharmGKB	PA134986550.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04236.
HOGENOM	HBG753124.
HOVERGEN	Q6UWV6.
InParanoid	Q6UWV6.
OMA	LGYVIHG.
OrthoDB	EOG9VX4R2.
PhylomeDB	Q6UWV6.
Enzyme and pathway databases
BRENDA	3.1.4.12. 247.
Gene expression databases
ArrayExpress	Q6UWV6.
Bgee	Q6UWV6.
CleanEx	HS_ENPP7.
Genevestigator	Q6UWV6.
GermOnline	ENSG00000182156. Homo sapiens.
Family and domain databases
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR017850. Alkaline_phosphatase_core. 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
NextBio	97283.

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:	January 19, 2010
This is version 63 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.