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Reviewed, UniProtKB/Swiss-Prot Q6UWV6 (ENPP7_HUMAN)

Last modified November 25, 2008. Version 49. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length458 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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.

Ontologies

Keywords

   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termDirect protein sequencing

Gene Ontology (GO)

   Biological processnegative 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 componentGolgi 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 functionsphingomyelin phosphodiesterase activity Ref.1 Ref.6

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 458437Ectonucleotide pyrophosphatase/phosphodiesterase family member 7
PRO_0000036403

Regions

Transmembrane434 – 45421 Potential
Region72 – 787Required for enzyme activity

Sites

Active site751 By similarity

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...)
Glycosylation1211N-linked (GlcNAc...)
Glycosylation1461N-linked (GlcNAc...)
Glycosylation1681N-linked (GlcNAc...)
Glycosylation2671N-linked (GlcNAc...)

Natural variations

Natural variant41L → P: dbSNP rs8074547.
VAR_021506

Experimental info

Mutagenesis761S → F: Loss of activity
Mutagenesis781C → N: Strongly reduces activity
Mutagenesis1001N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267
Mutagenesis1211N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267
Mutagenesis1461N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267
Mutagenesis1681N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267
Mutagenesis2671N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168
Mutagenesis3531H → A: Loss of activity
Sequence conflict1011T → I in AAQ88985. Ref.2
Sequence conflict3881Y → N in BAC86504. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q6UWV6-1 [UniParc].

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

FASTA45851,494
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

AY230663 mRNA. Translation: AAP69661.1.
AY358622 mRNA. Translation: AAQ88985.1.
AK126250 mRNA. Translation: BAC86504.1.
BC041453 mRNA. Translation: AAH41453.2.
RefSeqNP_848638.2.
UniGeneHs.114084

3D structure databases

ModBaseSearch...

Genome annotation databases

EnsemblENSG00000182156. Homo sapiens. [Contig view]
GeneID339221.
KEGGhsa:339221.

Organism-specific databases

H-InvDBHIX0027161.
HGNCHGNC:23764. ENPP7.
PharmGKBPA134986550.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ6UWV6.
HOVERGENQ6UWV6.

Gene expression databases

ArrayExpressQ6UWV6.
CleanExHS_ENPP7.
GermOnlineENSG00000182156. Homo sapiens.

Family and domain databases

InterProIPR017849. Alkaline_Pase-like_a/b/a.
IPR002591. Phosphodiest/P_Trfase.
[Graphical view]
Gene3DG3DSA:3.40.720.10. Alk_phosphtse. 1 hit.
PfamPF01663. Phosphodiest. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

LinkHubQ6UWV6.
NextBio97283.

Entry information

Entry nameENPP7_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

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 · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents