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Protein

Ectonucleotide pyrophosphatase/phosphodiesterase family member 6

Gene

ENPP6

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

Functioni

Choline-specific glycerophosphodiester phosphodiesterase. The preferred substrate may be lysosphingomyelin (By similarity). Hydrolyzes lysophosphatidylcholine (LPC) to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. Also hydrolyzes glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. Hydrolyzes the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine in vitro, while it does not hydrolyze the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. Does not hydrolyze diacyl phospholipids such as phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol and phosphatidic acid.By similarity1 Publication

Catalytic activityi

A lysophosphatidylcholine + H2O = a monoacylglycerol + phosphocholine.1 Publication
sn-glycero-3-phosphocholine + H2O = glycerol + phosphocholine.1 Publication

Cofactori

a divalent metal cation1 Publication

Enzyme regulationi

Inhibited by EDTA and EGTA in vitro.1 Publication

Kineticsi

  1. KM=344 µM for GPC1 Publication
  2. KM=296 µM for 12:0-LPC1 Publication
  3. KM=440 µM for 14:0-LPC1 Publication
  4. KM=165 µM for 16:0-LPC1 Publication
  5. KM=434 µM for 18:2-LPC1 Publication
  6. KM=563 µM for 20:4-LPC1 Publication
  1. Vmax=484 nmol/min/mg enzyme with GPC as substrate1 Publication
  2. Vmax=463 nmol/min/mg enzyme with 12:0-LPC as substrate1 Publication
  3. Vmax=367 nmol/min/mg enzyme with 14:0-LPC as substrate1 Publication
  4. Vmax=89 nmol/min/mg enzyme with 16:0-LPC as substrate1 Publication
  5. Vmax=285 nmol/min/mg enzyme with 18:2-LPC as substrate1 Publication
  6. Vmax=470 nmol/min/mg enzyme with 20:4-LPC as substrate1 Publication

pH dependencei

Optimum pH is 8.5-7.5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei71 – 711NucleophileSequence analysis

GO - Molecular functioni

  • glycerophosphocholine cholinephosphodiesterase activity Source: UniProtKB
  • glycerophosphodiester phosphodiesterase activity Source: Ensembl
  • phosphoric diester hydrolase activity Source: UniProtKB

GO - Biological processi

  • choline metabolic process Source: UniProtKB
  • glycerophospholipid catabolic process Source: Reactome
  • lipid metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Enzyme and pathway databases

BRENDAi3.1.4.3. 2681.
ReactomeiR-HSA-6814848. Glycerophospholipid catabolism.

Names & Taxonomyi

Protein namesi
Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 6 (EC:3.1.4.-, EC:3.1.4.38)
Short name:
E-NPP 6
Short name:
NPP-6
Alternative name(s):
Choline-specific glycerophosphodiester phosphodiesterase
Glycerophosphocholine cholinephosphodiesterase
Short name:
GPC-Cpde
Gene namesi
Name:ENPP6
ORF Names:UNQ1889/PRO4334
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:23409. ENPP6.

Subcellular locationi

  • Cell membrane 1 Publication; Lipid-anchorGPI-anchor 1 Publication

  • Note: A small amount of the protein may be found in the extracellular milieu.

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134945118.

Chemistry

ChEMBLiCHEMBL6033.

Polymorphism and mutation databases

BioMutaiENPP6.
DMDMi108935979.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222By similarityAdd
BLAST
Chaini23 – 419397Ectonucleotide pyrophosphatase/phosphodiesterase family member 6PRO_0000239361Add
BLAST
Propeptidei420 – 44021Removed in mature formSequence analysisPRO_0000420890Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei71 – 711PhosphoserineBy similarity
Glycosylationi100 – 1001N-linked (GlcNAc...)By similarity
Glycosylationi118 – 1181N-linked (GlcNAc...)By similarity
Disulfide bondi142 ↔ 154By similarity
Glycosylationi341 – 3411N-linked (GlcNAc...)By similarity
Glycosylationi404 – 4041N-linked (GlcNAc...)By similarity
Disulfide bondi412 – 412InterchainBy similarity
Lipidationi419 – 4191GPI-anchor amidated serineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Phosphoprotein

Proteomic databases

EPDiQ6UWR7.
PaxDbiQ6UWR7.
PeptideAtlasiQ6UWR7.
PRIDEiQ6UWR7.

PTM databases

iPTMnetiQ6UWR7.
PhosphoSiteiQ6UWR7.

Expressioni

Tissue specificityi

Predominantly expressed in kidney and brain. In the kidney, expressed specifically in the proximal tubules and thin descending limbs of Henle (at protein level).1 Publication

Gene expression databases

BgeeiQ6UWR7.
CleanExiHS_ENPP6.
ExpressionAtlasiQ6UWR7. baseline and differential.
GenevisibleiQ6UWR7. HS.

Organism-specific databases

HPAiHPA042740.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.

Protein-protein interaction databases

BioGridi126350. 40 interactions.
STRINGi9606.ENSP00000296741.

Structurei

3D structure databases

ProteinModelPortaliQ6UWR7.
SMRiQ6UWR7. Positions 25-414.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000112376.
HOVERGENiHBG107851.
InParanoidiQ6UWR7.
KOiK08743.
OMAiCNVVGIT.
OrthoDBiEOG7DC246.
PhylomeDBiQ6UWR7.
TreeFamiTF330032.

Family and domain databases

Gene3Di3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR024873. E-NPP.
IPR029889. ENPP6.
IPR002591. Phosphodiest/P_Trfase.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF66. PTHR10151:SF66. 1 hit.
PfamiPF01663. Phosphodiest. 1 hit.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q6UWR7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVKLGTLLL ALALGLAQPA SARRKLLVFL LDGFRSDYIS DEALESLPGF
60 70 80 90 100
KEIVSRGVKV DYLTPDFPSL SYPNYYTLMT GRHCEVHQMI GNYMWDPTTN
110 120 130 140 150
KSFDIGVNKD SLMPLWWNGS EPLWVTLTKA KRKVYMYYWP GCEVEILGVR
160 170 180 190 200
PTYCLEYKNV PTDINFANAV SDALDSFKSG RADLAAIYHE RIDVEGHHYG
210 220 230 240 250
PASPQRKDAL KAVDTVLKYM TKWIQERGLQ DRLNVIIFSD HGMTDIFWMD
260 270 280 290 300
KVIELNKYIS LNDLQQVKDR GPVVSLWPAP GKHSEIYNKL STVEHMTVYE
310 320 330 340 350
KEAIPSRFYY KKGKFVSPLT LVADEGWFIT ENREMLPFWM NSTGRREGWQ
360 370 380 390 400
RGWHGYDNEL MDMRGIFLAF GPDFKSNFRA APIRSVDVYN VMCNVVGITP
410 420 430 440
LPNNGSWSRV MCMLKGRAST APPVWPSHCA LALILLFLLA
Length:440
Mass (Da):50,241
Last modified:June 13, 2006 - v2
Checksum:i5F4F930D26EFB6B6
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti357 – 3571D → N.
Corresponds to variant rs4488969 [ dbSNP | Ensembl ].
VAR_052942
Natural varianti419 – 4191S → G.1 Publication
Corresponds to variant rs4479748 [ dbSNP | Ensembl ].
VAR_026644

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358676 mRNA. Translation: AAQ89039.1.
AK057370 mRNA. Translation: BAB71455.1.
AC079080 Genomic DNA. Translation: AAY40908.1.
AC107222 Genomic DNA. No translation available.
BC035035 mRNA. Translation: AAH35035.1.
CCDSiCCDS3834.1.
RefSeqiNP_699174.1. NM_153343.3.
UniGeneiHs.297814.

Genome annotation databases

EnsembliENST00000296741; ENSP00000296741; ENSG00000164303.
GeneIDi133121.
KEGGihsa:133121.
UCSCiuc003iwc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358676 mRNA. Translation: AAQ89039.1.
AK057370 mRNA. Translation: BAB71455.1.
AC079080 Genomic DNA. Translation: AAY40908.1.
AC107222 Genomic DNA. No translation available.
BC035035 mRNA. Translation: AAH35035.1.
CCDSiCCDS3834.1.
RefSeqiNP_699174.1. NM_153343.3.
UniGeneiHs.297814.

3D structure databases

ProteinModelPortaliQ6UWR7.
SMRiQ6UWR7. Positions 25-414.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126350. 40 interactions.
STRINGi9606.ENSP00000296741.

Chemistry

ChEMBLiCHEMBL6033.

PTM databases

iPTMnetiQ6UWR7.
PhosphoSiteiQ6UWR7.

Polymorphism and mutation databases

BioMutaiENPP6.
DMDMi108935979.

Proteomic databases

EPDiQ6UWR7.
PaxDbiQ6UWR7.
PeptideAtlasiQ6UWR7.
PRIDEiQ6UWR7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296741; ENSP00000296741; ENSG00000164303.
GeneIDi133121.
KEGGihsa:133121.
UCSCiuc003iwc.3. human.

Organism-specific databases

CTDi133121.
GeneCardsiENPP6.
HGNCiHGNC:23409. ENPP6.
HPAiHPA042740.
neXtProtiNX_Q6UWR7.
PharmGKBiPA134945118.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2645. Eukaryota.
COG1524. LUCA.
GeneTreeiENSGT00760000119157.
HOGENOMiHOG000112376.
HOVERGENiHBG107851.
InParanoidiQ6UWR7.
KOiK08743.
OMAiCNVVGIT.
OrthoDBiEOG7DC246.
PhylomeDBiQ6UWR7.
TreeFamiTF330032.

Enzyme and pathway databases

BRENDAi3.1.4.3. 2681.
ReactomeiR-HSA-6814848. Glycerophospholipid catabolism.

Miscellaneous databases

GenomeRNAii133121.
PROiQ6UWR7.

Gene expression databases

BgeeiQ6UWR7.
CleanExiHS_ENPP6.
ExpressionAtlasiQ6UWR7. baseline and differential.
GenevisibleiQ6UWR7. HS.

Family and domain databases

Gene3Di3.40.720.10. 1 hit.
InterProiIPR017849. Alkaline_Pase-like_a/b/a.
IPR017850. Alkaline_phosphatase_core.
IPR024873. E-NPP.
IPR029889. ENPP6.
IPR002591. Phosphodiest/P_Trfase.
[Graphical view]
PANTHERiPTHR10151. PTHR10151. 1 hit.
PTHR10151:SF66. PTHR10151:SF66. 1 hit.
PfamiPF01663. Phosphodiest. 1 hit.
[Graphical view]
SUPFAMiSSF53649. SSF53649. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-419.
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "Biochemical and molecular characterization of a novel choline-specific glycerophosphodiester phosphodiesterase belonging to the nucleotide pyrophosphatase/phosphodiesterase family."
    Sakagami H., Aoki J., Natori Y., Nishikawa K., Kakehi Y., Natori Y., Arai H.
    J. Biol. Chem. 280:23084-23093(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBSTRATE SPECIFICITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
  6. "Bovine brain myelin glycerophosphocholine choline phosphodiesterase is an alkaline lysosphingomyelinase of the eNPP-family, regulated by lysosomal sorting."
    Greiner-Tollersrud L., Berg T., Stensland H.M., Evjen G., Greiner-Tollersrud O.K.
    Neurochem. Res. 38:300-310(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: HOMODIMERIZATION, GPI-ANCHOR.
    Tissue: Brain.

Entry informationi

Entry nameiENPP6_HUMAN
AccessioniPrimary (citable) accession number: Q6UWR7
Secondary accession number(s): Q4W5Q1, Q96M57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: June 13, 2006
Last modified: July 6, 2016
This is version 106 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. 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.