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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 7

Gene

ENPP7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Converts sphingomyelin to ceramide and phosphocholine (PubMed:12885774, PubMed:12671034, PubMed:15205117, PubMed:28292932). Has also phospholipase C activity and can cleave phosphocholine from palmitoyl lyso-phosphatidylcholine (PubMed:12885774). Does not have nucleotide pyrophosphatase activity (PubMed:12885774).4 Publications

Miscellaneous

Decreased levels of alkaline sphingomyelin phosphodiesterase may be associated with colon cancer.2 Publications

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.4 Publications

Cofactori

Zn2+1 Publication

Activity regulationi

Inhibited in a dose dependent manner by ATP, imidazole, orthovanadate and zinc ion. Not inhibited by ADP, AMP and EDTA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi39Zinc 1Combined sources1 Publication1
Active sitei75Nucleophile1 Publication1
Metal bindingi75Zinc 1Combined sources1 Publication1
Binding sitei96SubstrateCombined sources1 Publication1
Metal bindingi199Zinc 2Combined sources1 Publication1
Metal bindingi203Zinc 2; via tele nitrogenCombined sources1 Publication1
Metal bindingi246Zinc 1Combined sources1 Publication1
Metal bindingi247Zinc 1; via tele nitrogenCombined sources1 Publication1
Metal bindingi353Zinc 2; via tele nitrogenCombined sources1 Publication1

GO - Molecular functioni

  • sphingomyelin phosphodiesterase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid metabolism
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.1.4.12 2681
ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Chemistry databases

SwissLipidsiSLP:000000173

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 (EC:3.1.4.124 Publications)
Short name:
E-NPP 7
Short name:
NPP-7
Alternative name(s):
Alkaline sphingomyelin phosphodiesterase
Intestinal alkaline sphingomyelinase2 Publications
Short name:
Alk-SMase2 Publications
Gene namesi
Name:ENPP7Imported
ORF Names:UNQ3077/PRO9912
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000182156.9
HGNCiHGNC:23764 ENPP7
MIMi616997 gene
neXtProtiNX_Q6UWV6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 433ExtracellularCuratedAdd BLAST412
Transmembranei434 – 454HelicalSequence analysisAdd BLAST21
Topological domaini455 – 458CytoplasmicCurated4

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi76S → F: Loss of activity. 1 Publication1
Mutagenesisi78C → N: Strongly reduces activity. 1 Publication1
Mutagenesisi100N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267. 1 Publication1
Mutagenesisi109Y → L: Decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine. 1 Publication1
Mutagenesisi121N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 1 Publication1
Mutagenesisi146N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 1 Publication1
Mutagenesisi166Y → L: Decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine. 1 Publication1
Mutagenesisi168N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267. 1 Publication1
Mutagenesisi267N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168. 1 Publication1
Mutagenesisi271R → E: Decreased enzyme activity; when associated with E-343. 1 Publication1
Mutagenesisi343R → E: Decreased enzyme activity; when associated with E-271. 1 Publication1
Mutagenesisi344 – 348INVQF → ENEQE: Loss of enzyme activity with sphingomyelin. 1 Publication5
Mutagenesisi344 – 348INVQF → NNNQN: Loss of enzyme activity with sphingomyelin. 1 Publication5
Mutagenesisi353H → A: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi339221
PharmGKBiPA134986550

Chemistry databases

ChEMBLiCHEMBL6058

Polymorphism and mutation databases

DMDMi134047772

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysis1 PublicationAdd BLAST21
ChainiPRO_000003640322 – 458Ectonucleotide pyrophosphatase/phosphodiesterase family member 7Add BLAST437

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi100N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Glycosylationi121N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Glycosylationi146N-linked (GlcNAc...) asparagineCombined sources3 Publications1
Glycosylationi168N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Glycosylationi267N-linked (GlcNAc...) asparagineCombined sources2 Publications1

Post-translational modificationi

N-glycosylated; required for activity and transport to the plasma membrane.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ6UWV6
PeptideAtlasiQ6UWV6
PRIDEiQ6UWV6
ProteomicsDBi67528

PTM databases

iPTMnetiQ6UWV6
PhosphoSitePlusiQ6UWV6

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000182156 Expressed in 138 organ(s), highest expression level in jejunal mucosa
CleanExiHS_ENPP7
ExpressionAtlasiQ6UWV6 baseline and differential
GenevisibleiQ6UWV6 HS

Organism-specific databases

HPAiHPA024603

Interactioni

Protein-protein interaction databases

BioGridi130844, 12 interactors
IntActiQ6UWV6, 8 interactors
STRINGi9606.ENSP00000332656

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6UWV6
SMRiQ6UWV6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni72 – 78Required for enzyme activity1 Publication7

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2645 Eukaryota
COG1524 LUCA
HOGENOMiHOG000231018
HOVERGENiHBG106748
InParanoidiQ6UWV6
KOiK12354
OrthoDBiEOG091G06NA
PhylomeDBiQ6UWV6
TreeFamiTF330032

Family and domain databases

Gene3Di3.40.720.10, 1 hit
InterProiView protein in InterPro
IPR017849 Alkaline_Pase-like_a/b/a
IPR017850 Alkaline_phosphatase_core_sf
IPR029895 ENPP7
IPR002591 Phosphodiest/P_Trfase
PANTHERiPTHR10151:SF63 PTHR10151:SF63, 1 hit
PfamiView protein in Pfam
PF01663 Phosphodiest, 1 hit
SUPFAMiSSF53649 SSF53649, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q6UWV6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MRGLAVLLTV ALATLLAPGA GAPVQSQGSQ NKLLLVSFDG FRWNYDQDVD
60 70 80 90 100
TPNLDAMARD GVKARYMTPA FVTMTSPCHF TLVTGKYIEN HGVVHNMYYN
110 120 130 140 150
TTSKVKLPYH ATLGIQRWWD NGSVPIWITA QRQGLRAGSF FYPGGNVTYQ
160 170 180 190 200
GVAVTRSRKE GIAHNYKNET EWRANIDTVM AWFTEEDLDL VTLYFGEPDS
210 220 230 240 250
TGHRYGPESP ERREMVRQVD RTVGYLRESI ARNHLTDRLN LIITSDHGMT
260 270 280 290 300
TVDKRAGDLV EFHKFPNFTF RDIEFELLDY GPNGMLLPKE GRLEKVYDAL
310 320 330 340 350
KDAHPKLHVY KKEAFPEAFH YANNPRVTPL LMYSDLGYVI HGRINVQFNN
360 370 380 390 400
GEHGFDNKDM DMKTIFRAVG PSFRAGLEVE PFESVHVYEL MCRLLGIVPE
410 420 430 440 450
ANDGHLATLL PMLHTESALP PDGRPTLLPK GRSALPPSSR PLLVMGLLGT

VILLSEVA
Length:458
Mass (Da):51,494
Last modified:March 20, 2007 - v3
Checksum:iF6A06913C33E4398
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L3G5I3L3G5_HUMAN
Ectonucleotide pyrophosphatase/phos...
ENPP7
159Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti101T → I in AAQ88985 (PubMed:12975309).Curated1
Sequence conflicti388Y → N in BAC86504 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0215064L → P3 PublicationsCorresponds to variant dbSNP:rs8074547Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY230663 mRNA Translation: AAP69661.1
AY358622 mRNA Translation: AAQ88985.1
AK126250 mRNA Translation: BAC86504.1
BC041453 mRNA Translation: AAH41453.2
CCDSiCCDS11763.1
RefSeqiNP_848638.3, NM_178543.4
UniGeneiHs.114084

Genome annotation databases

EnsembliENST00000328313; ENSP00000332656; ENSG00000182156
GeneIDi339221
KEGGihsa:339221
UCSCiuc002jxa.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY230663 mRNA Translation: AAP69661.1
AY358622 mRNA Translation: AAQ88985.1
AK126250 mRNA Translation: BAC86504.1
BC041453 mRNA Translation: AAH41453.2
CCDSiCCDS11763.1
RefSeqiNP_848638.3, NM_178543.4
UniGeneiHs.114084

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5TCDX-ray2.40A22-433[»]
5UDYX-ray2.60A22-433[»]
ProteinModelPortaliQ6UWV6
SMRiQ6UWV6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi130844, 12 interactors
IntActiQ6UWV6, 8 interactors
STRINGi9606.ENSP00000332656

Chemistry databases

ChEMBLiCHEMBL6058
SwissLipidsiSLP:000000173

PTM databases

iPTMnetiQ6UWV6
PhosphoSitePlusiQ6UWV6

Polymorphism and mutation databases

DMDMi134047772

Proteomic databases

PaxDbiQ6UWV6
PeptideAtlasiQ6UWV6
PRIDEiQ6UWV6
ProteomicsDBi67528

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328313; ENSP00000332656; ENSG00000182156
GeneIDi339221
KEGGihsa:339221
UCSCiuc002jxa.5 human

Organism-specific databases

CTDi339221
DisGeNETi339221
EuPathDBiHostDB:ENSG00000182156.9
GeneCardsiENPP7
H-InvDBiHIX0027161
HGNCiHGNC:23764 ENPP7
HPAiHPA024603
MIMi616997 gene
neXtProtiNX_Q6UWV6
PharmGKBiPA134986550
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2645 Eukaryota
COG1524 LUCA
HOGENOMiHOG000231018
HOVERGENiHBG106748
InParanoidiQ6UWV6
KOiK12354
OrthoDBiEOG091G06NA
PhylomeDBiQ6UWV6
TreeFamiTF330032

Enzyme and pathway databases

BRENDAi3.1.4.12 2681
ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Miscellaneous databases

GeneWikiiENPP7
GenomeRNAii339221
PROiPR:Q6UWV6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182156 Expressed in 138 organ(s), highest expression level in jejunal mucosa
CleanExiHS_ENPP7
ExpressionAtlasiQ6UWV6 baseline and differential
GenevisibleiQ6UWV6 HS

Family and domain databases

Gene3Di3.40.720.10, 1 hit
InterProiView protein in InterPro
IPR017849 Alkaline_Pase-like_a/b/a
IPR017850 Alkaline_phosphatase_core_sf
IPR029895 ENPP7
IPR002591 Phosphodiest/P_Trfase
PANTHERiPTHR10151:SF63 PTHR10151:SF63, 1 hit
PfamiView protein in Pfam
PF01663 Phosphodiest, 1 hit
SUPFAMiSSF53649 SSF53649, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiENPP7_HUMAN
AccessioniPrimary (citable) accession number: Q6UWV6
Secondary accession number(s): Q6ZTS5, Q8IUS8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 20, 2007
Last modified: November 7, 2018
This is version 133 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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