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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 7

Gene

ENPP7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts sphingomyelin to ceramide. Also has phospholipase C activity toward palmitoyl lyso-phosphocholine. Does not appear to have nucleotide pyrophosphatase activity.1 Publication

Miscellaneous

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

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.1 Publication

Enzyme 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
Active sitei75NucleophileBy similarity1

GO - Molecular functioni

  • sphingomyelin phosphodiesterase activity Source: UniProtKB

GO - Biological processi

  • glycosphingolipid metabolic process Source: Reactome
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of DNA replication Source: UniProtKB
  • sphingomyelin catabolic process Source: InterPro
  • sphingomyelin metabolic process Source: UniProtKB

Keywordsi

Molecular functionHydrolase

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:3.1.4.12)
Short name:
E-NPP 7
Short name:
NPP-7
Alternative name(s):
Alkaline sphingomyelin phosphodiesterase
Intestinal alkaline sphingomyelinase
Short name:
Alk-SMase
Gene namesi
Name:ENPP7Imported
ORF Names:UNQ3077/PRO9912
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:23764. ENPP7.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei434 – 454HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • microvillus Source: UniProtKB
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi76S → F: Loss of activity. 2 Publications1
Mutagenesisi78C → N: Strongly reduces activity. 2 Publications1
Mutagenesisi100N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267. 2 Publications1
Mutagenesisi121N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 2 Publications1
Mutagenesisi146N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267. 2 Publications1
Mutagenesisi168N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267. 2 Publications1
Mutagenesisi267N → Q: Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168. 2 Publications1
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...) asparagine1 Publication1
Glycosylationi121N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi146N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi168N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi267N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ6UWV6.
PeptideAtlasiQ6UWV6.
PRIDEiQ6UWV6.

PTM databases

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.
CleanExiHS_ENPP7.
ExpressionAtlasiQ6UWV6. baseline and differential.
GenevisibleiQ6UWV6. HS.

Organism-specific databases

HPAiHPA024603.

Interactioni

Protein-protein interaction databases

BioGridi130844. 9 interactors.
IntActiQ6UWV6. 8 interactors.
STRINGi9606.ENSP00000332656.

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi32 – 38Combined sources7
Turni43 – 48Combined sources6
Helixi52 – 60Combined sources9
Beta strandi61 – 65Combined sources5
Helixi75 – 84Combined sources10
Helixi88 – 91Combined sources4
Beta strandi96 – 100Combined sources5
Turni101 – 104Combined sources4
Beta strandi105 – 107Combined sources3
Helixi109 – 112Combined sources4
Helixi116 – 119Combined sources4
Helixi126 – 131Combined sources6
Turni132 – 134Combined sources3
Beta strandi137 – 141Combined sources5
Turni143 – 146Combined sources4
Beta strandi155 – 158Combined sources4
Helixi169 – 185Combined sources17
Beta strandi189 – 195Combined sources7
Helixi199 – 205Combined sources7
Helixi210 – 232Combined sources23
Turni236 – 238Combined sources3
Beta strandi239 – 244Combined sources6
Helixi262 – 264Combined sources3
Helixi270 – 272Combined sources3
Beta strandi273 – 277Combined sources5
Beta strandi283 – 288Combined sources6
Helixi293 – 300Combined sources8
Beta strandi307 – 311Combined sources5
Helixi312 – 314Combined sources3
Helixi317 – 319Combined sources3
Beta strandi329 – 334Combined sources6
Beta strandi350 – 352Combined sources3
Helixi360 – 362Combined sources3
Beta strandi366 – 370Combined sources5
Beta strandi375 – 379Combined sources5
Helixi384 – 386Combined sources3
Helixi387 – 395Combined sources9
Helixi406 – 408Combined sources3
Helixi410 – 412Combined sources3

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...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni72 – 78Required for enzyme activity7

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.
IPR029895. ENPP7.
IPR002591. Phosphodiest/P_Trfase.
PANTHERiPTHR10151:SF87. PTHR10151:SF87. 1 hit.
PfamiView protein in Pfam
PF01663. Phosphodiest. 1 hit.
SUPFAMiSSF53649. SSF53649. 1 hit.

Sequencei

Sequence statusi: Complete.

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

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

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

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. 9 interactors.
IntActiQ6UWV6. 8 interactors.
STRINGi9606.ENSP00000332656.

Chemistry databases

ChEMBLiCHEMBL6058.
SwissLipidsiSLP:000000173.

PTM databases

PhosphoSitePlusiQ6UWV6.

Polymorphism and mutation databases

DMDMi134047772.

Proteomic databases

PaxDbiQ6UWV6.
PeptideAtlasiQ6UWV6.
PRIDEiQ6UWV6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi339221.
DisGeNETi339221.
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.
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.
IPR029895. ENPP7.
IPR002591. Phosphodiest/P_Trfase.
PANTHERiPTHR10151:SF87. PTHR10151:SF87. 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: June 7, 2017
This is version 124 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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.