Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

UniProt data

UniProt name: ENPP1_HUMAN (P22413)

Gene name: ENPP1; Synonyms=M6S1, NPPS, PC1, PDNP1

Organism: Homo sapiens (Human).

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. Preferentially hydrolyzes ATP, but can also hydrolyze 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 and function. {ECO:0000269|PubMed:10615944, ECO:0000269|PubMed:8001561}.

Subcellular location: Cell membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Secreted {ECO:0000250}. Note=The proteolytically processed form is secreted (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:11598187, ECO:0000269|PubMed:15072822, ECO:0000269|PubMed:8001561}.

Transmembrane domains:

  1. 77-97, 21 AA, Helical; Signal-anchor for type II membrane protein. {ECO:0000255}.

Sequence: 925 AA

10 20 30 40 50 60 MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL APMDVGEEPL 70 80 90 100 110 120 EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS CAKEVKSCKG RCFERTFGNC 130 140 150 160 170 180 RCDAACVELG NCCLDYQETC IEPEHIWTCN KFRCGEKRLT RSLCACSDDC KDKGDCCINY 190 200 210 220 230 240 SSVCQGEKSW VEEPCESINE PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK 250 260 270 280 290 300 CGTYTKNMRP VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW 310 320 330 340 350 360 YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI LAVLQWLQLP 370 380 390 400 410 420 KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV GMLMDGLKEL NLHRCLNLIL 430 440 450 460 470 480 ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI YGPAARLRPS DVPDKYYSFN YEGIARNLSC 490 500 510 520 530 540 REPNQHFKPY LKHFLPKRLH FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV 550 560 570 580 590 600 FSNMQALFVG YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY 610 620 630 640 650 660 TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK IIKHETLPYG 670 680 690 700 710 720 RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN DSFSTEDFSN CLYQDFRIPL 730 740 750 760 770 780 SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL 790 800 810 820 830 840 LRKYAEERNG VNVVSGPVFD FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD 850 860 870 880 890 900 TSQTPLHCEN LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF 910 920 YQQRKEPVSD ILKLKTHLPT FSQED

CATM prediction

The sequence of ENPP1_HUMAN returned 2 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
        80        90        1
 +    |    +    |    +    |		 (Å) (°) (Å) (°)  
Model 1 TYKVLSLVLSVCVLTTILGCIFGLKAS 6.6 -41.0° 0.0 45.1 -26.9
Model 2 TYKVLSLVLSVCVLTTILGCIFGLKAS 7.1 -54.8° 0.3 45.2 -2.5
Prolines* TYKVLSLVLSVCVLTTILGCIFGLKPS          

* Note: this sequence contains Pro residues. CATM substituted them with Ala during the modeling. The positions are marked.

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


Click on the image to enlarge

Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 89, THR, HA A, 88, THR, O 3.24Å
B, 92, GLY, HA1 A, 89, THR, O 2.74Å
B, 93, CYS, HA A, 92, GLY, O 2.48Å
B, 96, GLY, HA1 A, 93, CYS, O 3.18Å
A, 89, THR, HA B, 88, THR, O 3.24Å
A, 92, GLY, HA1 B, 89, THR, O 2.74Å
A, 93, CYS, HA B, 92, GLY, O 2.48Å
A, 96, GLY, HA1 B, 93, CYS, O 3.18Å