Q924C3 (ENPP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Short name=E-NPP 1

Alternative name(s):
Phosphodiesterase I/nucleotide pyrophosphatase 1
Plasma-cell membrane glycoprotein PC-1

Including the following 2 domains:

1. Alkaline phosphodiesterase I
   EC=3.1.4.1
2. Nucleotide pyrophosphatase
   Short name=NPPase
   EC=3.6.1.9

Gene names

Name:	Enpp1
Synonyms:	Npps, Pc1, Pdnp1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	906 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapatite (HA) crystals, thereby preventing further growth of these crystals. In vitro, has a broad specificity, hydrolyzing other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity By similarity.
Catalytic activity	Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides. A dinucleotide + H2O = 2 mononucleotides.
Cofactor	Binds 2 divalent metal cations per subunit By similarity.
Enzyme regulation	At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.
Subunit structure	Homodimer; disulfide-linked. The secreted form is monomeric. Interacts with INSR By similarity.
Subcellular location	Cell membrane; Single-pass type II membrane protein By similarity. Basolateral cell membrane; Single-pass type II membrane protein By similarity. Secreted By similarity. Note: Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. In bile duct cells and cancer cells, located to the apical cytoplasmic side. The proteolytically processed form is secreted By similarity.
Domain	The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells By similarity.
Post-translational modification	It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both. The interchain disulfide bonding resides in the transmembrane segment By similarity. A secreted form is produced through cleavage at Lys-85 by intracellular processing By similarity.
Sequence similarities	Belongs to the nucleotide pyrophosphatase/phosphodiesterase family. Contains 2 SMB (somatomedin-B) domains.
Caution	It is uncertain whether Met-1 or Met-35 is the initiator.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal-anchor Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	biomineral tissue development Inferred from electronic annotation. Source: UniProtKB-KW immune response Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 19474315. Source: MGI
Molecular_function	NADH pyrophosphatase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid binding Inferred from electronic annotation. Source: InterPro phosphodiesterase I activity Inferred from electronic annotation. Source: EC polysaccharide binding Inferred from electronic annotation. Source: InterPro scavenger receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q924C3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: Q924C3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     630-630: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 906	906	Ectonucleotide pyrophosphatase/phosphodiesterase family member 1		PRO_0000188566
Regions
	Topological domain	1 – 58	58	Cytoplasmic Potential
	Transmembrane	59 – 79	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	80 – 906	827	Extracellular Potential
	Domain	86 – 126	41	SMB 1
	Domain	127 – 170	44	SMB 2
	Calcium binding	781 – 789	9	By similarity
	Region	173 – 573	401	Phosphodiesterase
	Region	635 – 906	272	Nuclease
	Motif	27 – 34	8	Di-leucine motif
Sites
	Active site	238	1	AMP-threonine intermediate By similarity
	Metal binding	200	1	Divalent metal cation 2 Probable
	Metal binding	238	1	Divalent metal cation 2 By similarity
	Metal binding	358	1	Divalent metal cation 1 Probable
	Metal binding	362	1	Divalent metal cation 1 Probable
	Metal binding	405	1	Divalent metal cation 2 Probable
	Metal binding	406	1	Divalent metal cation 2 Probable
	Metal binding	517	1	Divalent metal cation 1 Probable
	Site	84 – 85	2	Cleavage By similarity
	Site	896	1	Essential for catalytic activity By similarity
Amino acid modifications
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	267	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Potential
	Glycosylation	459	1	N-linked (GlcNAc...) Potential
	Glycosylation	567	1	N-linked (GlcNAc...) Potential
	Glycosylation	624	1	N-linked (GlcNAc...) Potential
	Disulfide bond	90 ↔ 104		Alternate By similarity
	Disulfide bond	90 ↔ 94		Alternate By similarity
	Disulfide bond	94 ↔ 122		Alternate By similarity
	Disulfide bond	102 ↔ 115		Alternate By similarity
	Disulfide bond	102 ↔ 104		Alternate By similarity
	Disulfide bond	108 ↔ 114		By similarity
	Disulfide bond	115 ↔ 122		Alternate By similarity
	Disulfide bond	131 ↔ 148		Alternate By similarity
	Disulfide bond	131 ↔ 136		Alternate By similarity
	Disulfide bond	136 ↔ 166		Alternate By similarity
	Disulfide bond	146 ↔ 159		Alternate By similarity
	Disulfide bond	146 ↔ 148		Alternate By similarity
	Disulfide bond	152 ↔ 158		By similarity
	Disulfide bond	159 ↔ 166		Alternate By similarity
	Disulfide bond	177 ↔ 223		By similarity
	Disulfide bond	185 ↔ 397		By similarity
	Disulfide bond	413 ↔ 512		By similarity
	Disulfide bond	462 ↔ 849		By similarity
	Disulfide bond	596 ↔ 653		By similarity
	Disulfide bond	607 ↔ 707		By similarity
	Disulfide bond	609 ↔ 692		By similarity
	Disulfide bond	819 ↔ 829		By similarity
Natural variations
	Alternative sequence	630	1	Missing in isoform 1.		VSP_006749
	Natural variant	440 – 442	3	RPT → NPP in strain: Wistar.
	Natural variant	457	1	A → T in strain: Lewis.
	Natural variant	555	1	M → I in strain: Lewis.
	Natural variant	568	1	E → G in strain: Wistar.
	Natural variant	583	1	T → I in strain: Lewis.
	Natural variant	592	1	F → V in strain: Lewis.
	Natural variant	624	1	N → K in strain: Lewis.
	Natural variant	640	1	N → H in strain: Lewis.
	Natural variant	774	1	V → I in strain: Lewis.
	Natural variant	806	1	N → I in strain: Lewis.
	Natural variant	850	1	T → I in strain: Lewis.
	Natural variant	898	1	H → Q in strain: Lewis.

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 71F56780B279A919	FASTA	906	102,942
	10 20 30 40 50 60 MERDGEQAGQ GPRHGPAGNG RELESPAAAS LLAPMDLGEE PLEKAERART AKDPNTYKVL 70 80 90 100 110 120 SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE 130 140 150 160 170 180 TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKAHNDCCI NYSSVCQEKK SWVEEACETI 190 200 210 220 230 240 DAPQCPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPVYPTKTFP 250 260 270 280 290 300 NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVRSG 310 320 330 340 350 360 TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSYERPHFY TLYLEEPDSS 370 380 390 400 410 420 GHSHGPVSSE VIKALQKVDH IVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN 430 440 450 460 470 480 KYLGDVNNVK VVYGPAARLR PTEVPETYYS FNYEALAKNL SCRETNQHFR PYLKHFLPKR 490 500 510 520 530 540 LHFAKNDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG 550 560 570 580 590 600 AEVDSFENIE VYNLMCDLLG LIPAPNNESH GSLNHLLKKP IYTPSHPKEE SFLSQCPIKS 610 620 630 640 650 660 VSSDLGCTCD PSIVPIMDFE KQFNLTTDAV EDVYSMTVPN GRPRNLQKQH RVCLLHQQQF 670 680 690 700 710 720 LTGYSLDLLM PLWTSYTFLS NDQFSTDDFS NCLYQDLRIP LSPMHKCSYY KSTSKLSYGF 730 740 750 760 770 780 LTPPRLNRVS RQIYSEALLT SNIVPMYQSF QVIWQYLHDT VLRRYAQERN GVNVVSGPVF 790 800 810 820 830 840 DFDYDGRYDS SEILKQNTRV IRSQENLIPT HFFIVLTSCK QLSESPLKCT ALESSAFLLP 850 860 870 880 890 900 HRPDNIESCT HGKQESAWVE ELLALHRARV TDVELITGLS FYQDRQESVS ELLRLKTHLP IFSQED
	Isoform 1 [UniParc]. Checksum: 46EE88917B4BBCD3	FASTA	905	102,843
	10 20 30 40 50 60 MERDGEQAGQ GPRHGPAGNG RELESPAAAS LLAPMDLGEE PLEKAERART AKDPNTYKVL 70 80 90 100 110 120 SLVLSVCVLT TILGCIFGLK PSCAKEVKSC KGRCFERTFS NCRCDAACVS LGNCCLDFQE 130 140 150 160 170 180 TCVEPTHIWT CNKFRCGEKR LSRFVCSCAD DCKAHNDCCI NYSSVCQEKK SWVEEACETI 190 200 210 220 230 240 DAPQCPAEFE SPPTLLFSLD GFRAEYLHTW GGLLPVISKL KNCGTYTKNM RPVYPTKTFP 250 260 270 280 290 300 NHYSIVTGLY PESHGIIDNK MYDPKMNASF SLKSKEKFNP LWYKGQPIWV TANHQEVRSG 310 320 330 340 350 360 TYFWPGSDVE IDGILPDIYK VYNGSVPFEE RILAVLEWLQ LPSYERPHFY TLYLEEPDSS 370 380 390 400 410 420 GHSHGPVSSE VIKALQKVDH IVGMLMDGLK DLGLDKCLNL ILISDHGMEQ GSCKKYVYLN 430 440 450 460 470 480 KYLGDVNNVK VVYGPAARLR PTEVPETYYS FNYEALAKNL SCRETNQHFR PYLKHFLPKR 490 500 510 520 530 540 LHFAKNDRIE PLTFYLDPQW QLALNPSERK YCGSGFHGSD NLFSNMQALF IGYGPAFKHG 550 560 570 580 590 600 AEVDSFENIE VYNLMCDLLG LIPAPNNESH GSLNHLLKKP IYTPSHPKEE SFLSQCPIKS 610 620 630 640 650 660 VSSDLGCTCD PSIVPIMDFE KQFNLTTDAE DVYSMTVPNG RPRNLQKQHR VCLLHQQQFL 670 680 690 700 710 720 TGYSLDLLMP LWTSYTFLSN DQFSTDDFSN CLYQDLRIPL SPMHKCSYYK STSKLSYGFL 730 740 750 760 770 780 TPPRLNRVSR QIYSEALLTS NIVPMYQSFQ VIWQYLHDTV LRRYAQERNG VNVVSGPVFD 790 800 810 820 830 840 FDYDGRYDSS EILKQNTRVI RSQENLIPTH FFIVLTSCKQ LSESPLKCTA LESSAFLLPH 850 860 870 880 890 900 RPDNIESCTH GKQESAWVEE LLALHRARVT DVELITGLSF YQDRQESVSE LLRLKTHLPI FSQED

References

[1]

"Structural basis of allotypes of ecto-nucleotide pyrophosphatase/phosphodiesterase (plasma cell membrane glycoprotein PC-1) in the mouse and rat, and analysis of allele-specific xenogeneic antibodies." Banakh I., Sali A., Dubljevic V., Grobben B., Slegers H., Goding J.W. Eur. J. Immunogenet. 29:307-313(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS. Strain: Lewis, Louvain and Wistar.

+

Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF340185 mRNA. Translation: AAK69653.1. AF340186 mRNA. Translation: AAK69654.1. AF320054 mRNA. Translation: AAL26912.1.
IPI	IPI00339118. IPI00390328.
RefSeq	NP_445987.1. NM_053535.1.
UniGene	Rn.1199.
3D structure databases
ProteinModelPortal	Q924C3.
SMR	Q924C3. Positions 129-171.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4997931.
PTM databases
PhosphoSite	Q924C3.
Proteomic databases
PaxDb	Q924C3.
PRIDE	Q924C3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	85496.
KEGG	rno:85496.
Organism-specific databases
CTD	5167.
RGD	628825. Enpp1.
Phylogenomic databases
eggNOG	COG1524.
HOGENOM	HOG000037439.
HOVERGEN	HBG051484.
InParanoid	Q924C3.
KO	K01513.
OrthoDB	EOG4S7JPJ.
Enzyme and pathway databases
SABIO-RK	Q924C3.
Gene expression databases
Genevestigator	Q924C3.
GermOnline	ENSRNOG00000013994. Rattus norvegicus.
Family and domain databases
Gene3D	3.40.570.10. 1 hit. 3.40.720.10. 1 hit.
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR017850. Alkaline_phosphatase_core. IPR001604. DNA/RNA_non-sp_Endonuclease. IPR024873. E-NPP. IPR020821. Extracellular_endonuc_su_A. IPR002591. Phosphodiest/P_Trfase. IPR020436. Somatomedin_B_chordata. IPR001212. Somatomedin_B_dom. [Graphical view]
PANTHER	PTHR10151. PTHR10151. 1 hit.
Pfam	PF01223. Endonuclease_NS. 1 hit. PF01663. Phosphodiest. 1 hit. PF01033. Somatomedin_B. 2 hits. [Graphical view]
PRINTS	PR00022. SOMATOMEDINB.
SMART	SM00892. Endonuclease_NS. 1 hit. SM00477. NUC. 1 hit. SM00201. SO. 2 hits. [Graphical view]
SUPFAM	SSF53649. Alkaline_phosphatase_core. 1 hit.
PROSITE	PS00524. SMB_1. 2 hits. PS50958. SMB_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	617598.

Entry information

Entry name

ENPP1_RAT

Accession

Primary (citable) accession number: Q924C3
Secondary accession number(s): Q91XQ3, Q920C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	September 19, 2002
Last modified:	May 29, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program