UniProtKB - Q6UWV6 (ENPP7_HUMAN)
Ectonucleotide pyrophosphatase/phosphodiesterase family member 7
ENPP7
Functioni
Choline-specific phosphodiesterase that hydrolyzes sphingomyelin releasing the ceramide and phosphocholine and therefore is involved in sphingomyelin digestion, ceramide formation, and fatty acid (FA) absorption in the gastrointestinal tract (PubMed:12885774, PubMed:12671034, PubMed:15205117, PubMed:16255717, PubMed:28292932).
Has also phospholipase C activity and can also cleave phosphocholine from palmitoyl lyso-phosphatidylcholine and platelet-activating factor (PAF) leading to its inactivation (PubMed:16255717, PubMed:12885774).
Does not have nucleotide pyrophosphatase activity (PubMed:12885774).
May promote cholesterol absorption by affecting the levels of sphingomyelin derived from either diet or endogenous sources, in the intestinal lumen (By similarity).
By similarity5 PublicationsMiscellaneous
Catalytic activityi
- EC:3.1.4.125 PublicationsThis reaction proceeds in the forward1 Publication direction.
- 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycerol + H+ + phosphocholine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = a 1-O-alkyl-2-acetyl-sn-glycerol + H+ + phosphocholine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-octadecyl-2-acetyl-sn-glycerol + H+ + phosphocholineBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 39 | Zinc 1Combined sources1 Publication | 1 | |
Active sitei | 75 | Nucleophile1 Publication | 1 | |
Metal bindingi | 75 | Zinc 1Combined sources1 Publication | 1 | |
Binding sitei | 96 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 199 | Zinc 2Combined sources1 Publication | 1 | |
Metal bindingi | 203 | Zinc 2; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 246 | Zinc 1Combined sources1 Publication | 1 | |
Metal bindingi | 247 | Zinc 1; via tele nitrogenCombined sources1 Publication | 1 | |
Metal bindingi | 353 | Zinc 2; via tele nitrogenCombined sources1 Publication | 1 |
GO - Molecular functioni
- phosphoric diester hydrolase activity Source: UniProtKB
- sphingomyelin phosphodiesterase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- fatty acid homeostasis Source: UniProtKB
- glycosphingolipid metabolic process Source: Reactome
- lipid digestion Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of DNA replication Source: UniProtKB
- positive regulation of ceramide biosynthetic process Source: UniProtKB
- positive regulation of intestinal cholesterol absorption Source: UniProtKB
- positive regulation of sphingomyelin catabolic process Source: UniProtKB
- regulation of intestinal lipid absorption Source: UniProtKB
- sphingomyelin catabolic process Source: InterPro
- sphingomyelin metabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid metabolism |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.1.4.12, 2681 |
PathwayCommonsi | Q6UWV6 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism |
SignaLinki | Q6UWV6 |
Chemistry databases
SwissLipidsi | SLP: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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23764, ENPP7 |
MIMi | 616997, gene |
neXtProti | NX_Q6UWV6 |
VEuPathDBi | HostDB:ENSG00000182156 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Single-pass type I membrane protein 2 Publications
Note: The catalytic domain is released into the extracellular medium when cells are treated with trypsin (PubMed:15205117). 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 (PubMed:12671034, PubMed:12885774).3 Publications
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
Other locations
- membrane Source: UniProtKB
- microvillus Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 22 – 433 | ExtracellularCuratedAdd BLAST | 412 | |
Transmembranei | 434 – 454 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 455 – 458 | CytoplasmicCurated | 4 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 76 | S → F: Loss of activity. 1 Publication | 1 | |
Mutagenesisi | 78 | C → N: Strongly reduces activity. 1 Publication | 1 | |
Mutagenesisi | 100 | N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267. 1 Publication | 1 | |
Mutagenesisi | 109 | Y → L: Decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine. 1 Publication | 1 | |
Mutagenesisi | 121 | N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 1 Publication | 1 | |
Mutagenesisi | 146 | N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 1 Publication | 1 | |
Mutagenesisi | 166 | Y → L: Decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine. 1 Publication | 1 | |
Mutagenesisi | 168 | N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267. 1 Publication | 1 | |
Mutagenesisi | 267 | N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168. 1 Publication | 1 | |
Mutagenesisi | 271 | R → E: Decreased enzyme activity; when associated with E-343. 1 Publication | 1 | |
Mutagenesisi | 343 | R → E: Decreased enzyme activity; when associated with E-271. 1 Publication | 1 | |
Mutagenesisi | 344 – 348 | INVQF → ENEQE: Loss of enzyme activity with sphingomyelin. 1 Publication | 5 | |
Mutagenesisi | 344 – 348 | INVQF → NNNQN: Loss of enzyme activity with sphingomyelin. 1 Publication | 5 | |
Mutagenesisi | 353 | H → A: Loss of activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 339221 |
PharmGKBi | PA134986550 |
Miscellaneous databases
Pharosi | Q6UWV6, Tbio |
Chemistry databases
ChEMBLi | CHEMBL6058 |
Genetic variation databases
BioMutai | ENPP7 |
DMDMi | 134047772 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysis1 PublicationAdd BLAST | 21 | |
ChainiPRO_0000036403 | 22 – 458 | Ectonucleotide pyrophosphatase/phosphodiesterase family member 7Add BLAST | 437 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 100 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Glycosylationi | 121 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Glycosylationi | 146 | N-linked (GlcNAc...) asparagineCombined sources3 Publications | 1 | |
Glycosylationi | 168 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Glycosylationi | 267 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | Q6UWV6 |
MassIVEi | Q6UWV6 |
PaxDbi | Q6UWV6 |
PeptideAtlasi | Q6UWV6 |
PRIDEi | Q6UWV6 |
ProteomicsDBi | 67528 |
PTM databases
GlyGeni | Q6UWV6, 5 sites |
iPTMneti | Q6UWV6 |
PhosphoSitePlusi | Q6UWV6 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000182156, Expressed in jejunal mucosa and 139 other tissues |
ExpressionAtlasi | Q6UWV6, baseline and differential |
Genevisiblei | Q6UWV6, HS |
Organism-specific databases
HPAi | ENSG00000182156, Tissue enriched (intestine) |
Interactioni
Binary interactionsi
Q6UWV6
Protein-protein interaction databases
BioGRIDi | 130844, 30 interactors |
IntActi | Q6UWV6, 14 interactors |
STRINGi | 9606.ENSP00000332656 |
Miscellaneous databases
RNActi | Q6UWV6, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q6UWV6 |
SMRi | Q6UWV6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 72 – 78 | Required for enzyme activity1 Publication | 7 |
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2645, Eukaryota |
HOGENOMi | CLU_017594_1_0_1 |
InParanoidi | Q6UWV6 |
OrthoDBi | 999163at2759 |
PhylomeDBi | Q6UWV6 |
TreeFami | TF330032 |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017850, Alkaline_phosphatase_core_sf IPR029895, ENPP7 IPR002591, Phosphodiest/P_Trfase |
PANTHERi | PTHR10151:SF63, PTHR10151:SF63, 1 hit |
Pfami | View protein in Pfam PF01663, Phosphodiest, 1 hit |
SUPFAMi | SSF53649, SSF53649, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MRGPAVLLTV 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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketI3L3G5 | I3L3G5_HUMAN | Ectonucleotide pyrophosphatase/phos... | ENPP7 | 159 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 101 | T → I in AAQ88985 (PubMed:12975309).Curated | 1 | |
Sequence conflicti | 388 | Y → N in BAC86504 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021506 | 4 | P → L. Corresponds 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 |
CCDSi | CCDS11763.1 |
RefSeqi | NP_848638.3, NM_178543.4 |
Genome annotation databases
Ensembli | ENST00000328313.10; ENSP00000332656.5; ENSG00000182156.10 |
GeneIDi | 339221 |
KEGGi | hsa:339221 |
MANE-Selecti | ENST00000328313.10; ENSP00000332656.5; NM_178543.5; NP_848638.3 |
UCSCi | uc002jxa.5, human |
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 |
CCDSi | CCDS11763.1 |
RefSeqi | NP_848638.3, NM_178543.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5TCD | X-ray | 2.40 | A | 22-433 | [»] | |
5UDY | X-ray | 2.60 | A | 22-433 | [»] | |
AlphaFoldDBi | Q6UWV6 | |||||
SMRi | Q6UWV6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 130844, 30 interactors |
IntActi | Q6UWV6, 14 interactors |
STRINGi | 9606.ENSP00000332656 |
Chemistry databases
ChEMBLi | CHEMBL6058 |
SwissLipidsi | SLP:000000173 |
PTM databases
GlyGeni | Q6UWV6, 5 sites |
iPTMneti | Q6UWV6 |
PhosphoSitePlusi | Q6UWV6 |
Genetic variation databases
BioMutai | ENPP7 |
DMDMi | 134047772 |
Proteomic databases
jPOSTi | Q6UWV6 |
MassIVEi | Q6UWV6 |
PaxDbi | Q6UWV6 |
PeptideAtlasi | Q6UWV6 |
PRIDEi | Q6UWV6 |
ProteomicsDBi | 67528 |
Protocols and materials databases
Antibodypediai | 19751, 252 antibodies from 27 providers |
DNASUi | 339221 |
Genome annotation databases
Ensembli | ENST00000328313.10; ENSP00000332656.5; ENSG00000182156.10 |
GeneIDi | 339221 |
KEGGi | hsa:339221 |
MANE-Selecti | ENST00000328313.10; ENSP00000332656.5; NM_178543.5; NP_848638.3 |
UCSCi | uc002jxa.5, human |
Organism-specific databases
CTDi | 339221 |
DisGeNETi | 339221 |
GeneCardsi | ENPP7 |
HGNCi | HGNC:23764, ENPP7 |
HPAi | ENSG00000182156, Tissue enriched (intestine) |
MIMi | 616997, gene |
neXtProti | NX_Q6UWV6 |
PharmGKBi | PA134986550 |
VEuPathDBi | HostDB:ENSG00000182156 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2645, Eukaryota |
HOGENOMi | CLU_017594_1_0_1 |
InParanoidi | Q6UWV6 |
OrthoDBi | 999163at2759 |
PhylomeDBi | Q6UWV6 |
TreeFami | TF330032 |
Enzyme and pathway databases
BRENDAi | 3.1.4.12, 2681 |
PathwayCommonsi | Q6UWV6 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism |
SignaLinki | Q6UWV6 |
Miscellaneous databases
BioGRID-ORCSi | 339221, 16 hits in 1070 CRISPR screens |
GeneWikii | ENPP7 |
GenomeRNAii | 339221 |
Pharosi | Q6UWV6, Tbio |
PROi | PR:Q6UWV6 |
RNActi | Q6UWV6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000182156, Expressed in jejunal mucosa and 139 other tissues |
ExpressionAtlasi | Q6UWV6, baseline and differential |
Genevisiblei | Q6UWV6, HS |
Family and domain databases
Gene3Di | 3.40.720.10, 1 hit |
InterProi | View protein in InterPro IPR017850, Alkaline_phosphatase_core_sf IPR029895, ENPP7 IPR002591, Phosphodiest/P_Trfase |
PANTHERi | PTHR10151:SF63, PTHR10151:SF63, 1 hit |
Pfami | View protein in Pfam PF01663, Phosphodiest, 1 hit |
SUPFAMi | SSF53649, SSF53649, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ENPP7_HUMAN | |
Accessioni | Q6UWV6Primary (citable) accession number: Q6UWV6 Secondary accession number(s): Q6ZTS5, Q8IUS8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2005 |
Last sequence update: | May 25, 2022 | |
Last modified: | May 25, 2022 | |
This is version 152 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families