Details for: ENPP1

Gene ID: 5167

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ENPP1

Ensembl ID: ENSG00000197594

Description: ectonucleotide pyrophosphatase/phosphodiesterase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatocyte CL0000182
    CSI 14.63
    rCSI 26.18%
    PRS 87.8
  • centrilobular region hepatocyte CL0019029
    CSI 5.86
    rCSI 15.28%
    PRS 85.22
  • enteroendocrine cell CL0000164
    CSI 5.49
    rCSI 7.51%
    PRS 87.65
  • pancreatic D cell CL0000173
    CSI 3.93
    rCSI 3.87%
    PRS 90.65
  • midzonal region hepatocyte CL0019028
    CSI 3.65
    rCSI 8.56%
    PRS 86.94
  • group 3 innate lymphoid cell CL0001071
    CSI 3.24
    rCSI 2.43%
    PRS 92.42
  • subcutaneous adipocyte CL0002521
    CSI 3.22
    rCSI 16.47%
    PRS 91.01
  • pericyte CL0000669
    CSI 3.16
    rCSI 8.4%
    PRS 65.43
  • P/D1 enteroendocrine cell CL0002268
    CSI 3.1
    rCSI 16.85%
    PRS 91.76
  • goblet cell CL0000160
    CSI 3.07
    rCSI 2.9%
    PRS 86.7
  • Kupffer cell CL0000091
    CSI 2.96
    rCSI 6.76%
    PRS 89.77
  • hepatic stellate cell CL0000632
    CSI 2.7
    rCSI 10.1%
    PRS 83.76
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.67
    rCSI 3.78%
    PRS 86.42
  • adipocyte CL0000136
    CSI 2.67
    rCSI 3.43%
    PRS 80.31
  • myoepithelial cell CL0000185
    CSI 2.59
    rCSI 6.55%
    PRS 91.76
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.49
    rCSI 3.2%
    PRS 76.05
  • pancreatic A cell CL0000171
    CSI 2.3
    rCSI 2.41%
    PRS 90.99
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.19
    rCSI 3.99%
    PRS 94.29
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.17
    rCSI 2.6%
    PRS 74.98
  • chondrocyte CL0000138
    CSI 2.16
    rCSI 3.44%
    PRS 83.87
  • periportal region hepatocyte CL0019026
    CSI 2.16
    rCSI 8.41%
    PRS 86.27
  • pancreatic acinar cell CL0002064
    CSI 2.07
    rCSI 2.75%
    PRS 92.05
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.98
    rCSI 2.46%
    PRS 72.68
  • endocardial cell CL0002350
    CSI 1.93
    rCSI 9.22%
    PRS 84.94
  • epithelial cell of proximal tubule CL0002306
    CSI 1.88
    rCSI 4.6%
    PRS 81.93
  • stromal cell CL0000499
    CSI 1.8
    rCSI 5.07%
    PRS 84.8
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.64
    rCSI 3.6%
    PRS 92.38
  • type B pancreatic cell CL0000169
    CSI 1.48
    rCSI 3.28%
    PRS 88.82
  • basal cell CL0000646
    CSI 1.47
    rCSI 1.97%
    PRS 86.32
  • parietal epithelial cell CL1000452
    CSI 1.43
    rCSI 3.81%
    PRS 82.87
  • stromal cell of ovary CL0002132
    CSI 1.42
    rCSI 3.89%
    PRS 92.45
  • retinal ganglion cell CL0000740
    CSI 1.01
    rCSI 2.23%
    PRS 77.64
  • pancreatic PP cell CL0002275
    CSI 0.99
    rCSI 3.92%
    PRS 92.67
  • pancreatic epsilon cell CL0005019
    CSI 0.84
    rCSI 3.92%
    PRS 92.92
  • endothelial cell of placenta CL0009092
    CSI 0.77
    rCSI 3.8%
    PRS 93.11
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.67
    rCSI 1.95%
    PRS 88.05
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.63
    rCSI 1.98%
    PRS 78.18
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.41
    rCSI 2.42%
    PRS 75.41
  • ON midget ganglion cell CL4033046
    CSI 0.29
    rCSI 5.83%
    PRS 79.93
  • mesenchymal stem cell CL0000134
    CSI 0.16
    rCSI 1.75%
    PRS 91.22

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ENPP1](/details-gene/5167), or Ectonucleotide Pyrophosphatase/Phosphodiesterase 1, is a type II transmembrane glycoprotein that plays a crucial role in nucleotide metabolism and cellular signaling. The enzyme functions by hydrolyzing pyrophosphate and phosphodiester bonds in various extracellular nucleotides, most notably ATP, to generate adenosine monophosphate (AMP) and inorganic pyrophosphate (PPi). This activity is central to its diverse physiological roles, which include the negative regulation of [bone mineralization](/details-go/GO:0030502), involvement in the [cellular response to insulin stimulus](/details-go/GO:0032869), and participation in the [immune response](/details-go/GO:0006955). **Overall**, expression data reveals that [ENPP1](/details-gene/5167) is most significantly expressed in [hepatocytes](/details-cell/CL0000182), suggesting a primary function in liver metabolism. Clinically, mutations and polymorphisms in [ENPP1](/details-gene/5167) are associated with conditions such as insulin resistance ([OMIM:173335](https://omim.org/entry/173335)) and arterial calcification ([OMIM:208000](https://omim.org/entry/208000)), highlighting its importance in both metabolic and structural homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [ENPP1](/details-gene/5167) points to a prominent role in metabolic and endocrine tissues, with a secondary involvement in specialized immune and structural cells. **Overall**, the gene's significance is overwhelmingly highest in [hepatocytes](/details-cell/CL0000182) (CSI: 14.63), including specific populations like [centrilobular region hepatocytes](/details-cell/CL0019029) and [midzonal region hepatocytes](/details-cell/CL0019028). This strong and specific expression pattern suggests that [ENPP1](/details-gene/5167) is a key functional component of liver biology. Beyond the liver, [ENPP1](/details-gene/5167) shows significant expression in various endocrine and secretory cells, including [enteroendocrine cells](/details-cell/CL0000164), [pancreatic D cells](/details-cell/CL0000173), and [goblet cells](/details-cell/CL0000160). Its high significance in [adipocytes](/details-cell/CL0000136) is consistent with its established role in metabolism and insulin signaling. A notable pattern also emerges in cells involved in tissue structure and immune surveillance within metabolic organs. For instance, [ENPP1](/details-gene/5167) is significantly expressed in [pericytes](/details-cell/CL0000669), [hepatic stellate cells](/details-cell/CL0000632), and [myoepithelial cells](/details-cell/CL0000185). In the immune context, its expression in [Kupffer cells](/details-cell/CL0000091) (liver-resident macrophages) and [group 3 innate lymphoid cells](/details-cell/CL0001071) suggests a potential role in modulating local immune responses within these tissues. ## Pathways and Molecular Function Functionally, [ENPP1](/details-gene/5167) is a multifaceted enzyme with broad substrate specificity, acting as a phosphodiesterase and nucleotide pyrophosphatase. Its molecular functions include [ATP diphosphatase activity](/details-go/GO:0047693) and [phosphodiesterase I activity](/details-go/GO:0004528). As a cell surface protein located on the [plasma membrane](/details-go/GO:0005886), it is positioned to regulate extracellular signaling cues. The biological processes governed by [ENPP1](/details-gene/5167) are diverse. A critical role is its [negative regulation of bone mineralization](/details-go/GO:0030502), where the production of inorganic pyrophosphate (PPi), a potent inhibitor of hydroxyapatite crystal formation, is key. This function is further supported by its interaction with alkaline phosphatase ([Link](https://doi.org/10.1152/ajpregu.2000.279.4.r1365)). In metabolic regulation, [ENPP1](/details-gene/5167) is a well-documented inhibitor of insulin signaling. This occurs through its direct physical interaction with the alpha-subunit of the insulin receptor, which impairs receptor autophosphorylation and downstream signaling cascades ([Link](https://doi.org/10.2337/diabetes.49.1.13)). This mechanism is consistent with its annotation in the [negative regulation of insulin receptor signaling pathway](/details-go/GO:0046627) and its strong clinical association with insulin resistance ([Link](https://doi.org/10.2337/diabetes.48.9.1881)). The gene's involvement in broader metabolic pathways is also indicated by its annotation in Reactome pathways such as [Metabolism](/details-reactome/R-HSA-1430728) and the metabolism of B vitamins like [riboflavin](/details-reactome/R-HSA-196843) and [pantothenate](/details-reactome/R-HSA-199220). ## Research Directions The established roles of [ENPP1](/details-gene/5167) in both metabolic disease and tissue calcification, combined with its distinct expression pattern, provide fertile ground for further investigation. **Proposed Hypotheses:** 1. Given its extremely high expression in [hepatocytes](/details-cell/CL0000182) and its function as an inhibitor of insulin signaling, it is hypothesized that the upregulation of [ENPP1](/details-gene/5167) expression or activity in the liver is a primary driver of hepatic insulin resistance, a key feature of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. 2. Based on its function in generating pyrophosphate and its expression in liver cells, we hypothesize that [hepatocyte](/details-cell/CL0000182)-derived extracellular vesicles are enriched with functional [ENPP1](/details-gene/5167) and serve as systemic carriers of its anti-calcification activity, and that disruption of this process contributes to vascular calcification in patients with chronic liver disease. **Experimental Approach:** To test the first hypothesis regarding hepatic insulin resistance, a targeted *in vivo* study could be conducted. This would involve using an adeno-associated virus (AAV) vector with a liver-specific promoter to overexpress [ENPP1](/details-gene/5167) specifically in the [hepatocytes](/details-cell/CL0000182) of healthy mice. The metabolic consequences would be assessed through glucose and insulin tolerance tests, followed by hyperinsulinemic-euglycemic clamps to quantify insulin sensitivity. At the molecular level, liver tissue would be analyzed for phosphorylation status of key insulin signaling proteins (e.g., IR, AKT, GSK3B) to confirm the impairment of the pathway. **Therapeutic Potential:** [ENPP1](/details-gene/5167) represents a promising therapeutic target, primarily for **inhibition**. Its role as an ecto-enzyme that negatively regulates insulin signaling makes it an attractive candidate for the treatment of type 2 diabetes and metabolic syndrome. Development of highly specific small molecule inhibitors or therapeutic antibodies that block the enzymatic active site or disrupt the [ENPP1](/details-gene/5167)-insulin receptor interaction could restore insulin sensitivity in tissues where the gene is overexpressed, such as the liver and adipose tissue. Such an approach would need to carefully consider potential off-target effects on bone mineralization.

Genular Protein ID: 1656748289

Symbol: ENPP1_HUMAN

Name: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1

UniProtKB Accession Codes:

P22413 Q5T9R6 Q9NPZ3 Q9P1P6 Q9UP61 Q9Y6K3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 83 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 6 EMBL 56 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 50 Gene3D 3 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 11 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 4 OrthoDB 1 PANTHER 2 PDB 7 PDBsum 7 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 Rhea 16 SABIO-RK 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2211644

Title: Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location.

PubMed ID: 2211644

DOI: 10.1016/s0021-9258(18)38193-6

PubMed ID: 1315502

Title: Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase.

PubMed ID: 1315502

DOI: 10.1016/0003-9861(92)90504-p

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10480624

Title: A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.

PubMed ID: 10480624

DOI: 10.2337/diabetes.48.9.1881

PubMed ID: 8001561

Title: Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities.

PubMed ID: 8001561

DOI: 10.1111/j.1432-1033.1994.tb20068.x

PubMed ID: 7737162

Title: Autophosphorylation of PC-1 (alkaline phosphodiesterase I/nucleotide pyrophosphatase) and analysis of the active site.

PubMed ID: 7737162

DOI: 10.1111/j.1432-1033.1995.tb20308.x

PubMed ID: 9344668

Title: Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new member of the human phosphodiesterase I genes.

PubMed ID: 9344668

DOI: 10.1006/geno.1997.4949

PubMed ID: 11004006

Title: Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC-1.

PubMed ID: 11004006

DOI: 10.1152/ajpregu.2000.279.4.r1365

PubMed ID: 10615944

Title: Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit.

PubMed ID: 10615944

DOI: 10.2337/diabetes.49.1.13

PubMed ID: 11598187

Title: Characterization of a di-leucine-based signal in the cytoplasmic tail of the nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not endocytosis.

PubMed ID: 11598187

DOI: 10.1091/mbc.12.10.3004

PubMed ID: 15072822

Title: Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases.

PubMed ID: 15072822

DOI: 10.1016/j.canlet.2003.11.002

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 19349973

Title: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.

PubMed ID: 19349973

DOI: 10.1038/nbt.1532

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25344812

Title: Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs.

PubMed ID: 25344812

DOI: 10.1038/nchembio.1661

PubMed ID: 28011303

Title: The promiscuous ectonucleotidase NPP1: molecular insights into substrate binding and hydrolysis.

PubMed ID: 28011303

DOI: 10.1016/j.bbagen.2016.12.019

PubMed ID: 35147247

Title: The Mineralization Regulator ANKH Mediates Cellular Efflux of ATP, Not Pyrophosphate.

PubMed ID: 35147247

DOI: 10.1002/jbmr.4528

PubMed ID: 10453738

Title: Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL).

PubMed ID: 10453738

DOI: 10.1007/s004390050993

PubMed ID: 12881724

Title: Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification.

PubMed ID: 12881724

DOI: 10.1038/ng1221

PubMed ID: 15940697

Title: Generalized arterial calcification of infancy: different clinical courses in two affected siblings.

PubMed ID: 15940697

DOI: 10.1002/ajmg.a.30800

PubMed ID: 16186408

Title: The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction.

PubMed ID: 16186408

DOI: 10.2337/diabetes.54.10.3021

PubMed ID: 15605415

Title: The mutational spectrum of ENPP1 as arising after the analysis of 23 unrelated patients with generalized arterial calcification of infancy (GACI).

PubMed ID: 15605415

DOI: 10.1002/humu.9297

PubMed ID: 20016754

Title: Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy.

PubMed ID: 20016754

DOI: 10.1161/circgenetics.108.797704

PubMed ID: 20137773

Title: Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets.

PubMed ID: 20137773

DOI: 10.1016/j.ajhg.2010.01.006

PubMed ID: 20137772

Title: Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

PubMed ID: 20137772

DOI: 10.1016/j.ajhg.2010.01.010

PubMed ID: 20034067

Title: An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy.

PubMed ID: 20034067

DOI: 10.1002/ajmg.a.33162

PubMed ID: 23430823

Title: Generalized arterial calcification of infancy: fatal clinical course associated with a novel mutation in ENPP1.

PubMed ID: 23430823

DOI: 10.1007/8904_2011_11

PubMed ID: 22209248

Title: Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6.

PubMed ID: 22209248

DOI: 10.1016/j.ajhg.2011.11.020

PubMed ID: 24075184

Title: Cole disease results from mutations in ENPP1.

PubMed ID: 24075184

DOI: 10.1016/j.ajhg.2013.08.007

PubMed ID: 25741938

Title: Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1.

PubMed ID: 25741938

DOI: 10.1515/jpem-2014-0531

PubMed ID: 26617416

Title: Association of Cole disease with novel heterozygous mutations in the somatomedin-B domains of the ENPP1 gene: necessary, but not always sufficient.

PubMed ID: 26617416

DOI: 10.1111/bjd.14328

PubMed ID: 27467858

Title: Effects of Different Variants in the ENPP1 Gene on the Functional Properties of Ectonucleotide Pyrophosphatase/Phosphodiesterase Family Member 1.

PubMed ID: 27467858

DOI: 10.1002/humu.23057

PubMed ID: 28964717

Title: ENPP1 mutation causes recessive cole disease by altering melanogenesis.

PubMed ID: 28964717

DOI: 10.1016/j.jid.2017.08.045

PubMed ID: 29958952

Title: Association and in silico studies of ENPP1 gene variants with type 2 diabetes mellitus in a Northern Iranian population.

PubMed ID: 29958952

DOI: 10.1016/j.gene.2018.06.006

Sequence Information:

  • Length: 925
  • Mass: 104924
  • Checksum: 0ECAA063801CAFEB
  • Sequence:
    • MERDGCAGGG SRGGEGGRAP REGPAGNGRD RGRSHAAEAP GDPQAAASLL APMDVGEEPL 
EKAARARTAK DPNTYKVLSL VLSVCVLTTI LGCIFGLKPS CAKEVKSCKG RCFERTFGNC 
RCDAACVELG NCCLDYQETC IEPEHIWTCN KFRCGEKRLT RSLCACSDDC KDKGDCCINY 
SSVCQGEKSW VEEPCESINE PQCPAGFETP PTLLFSLDGF RAEYLHTWGG LLPVISKLKK 
CGTYTKNMRP VYPTKTFPNH YSIVTGLYPE SHGIIDNKMY DPKMNASFSL KSKEKFNPEW 
YKGEPIWVTA KYQGLKSGTF FWPGSDVEIN GIFPDIYKMY NGSVPFEERI LAVLQWLQLP 
KDERPHFYTL YLEEPDSSGH SYGPVSSEVI KALQRVDGMV GMLMDGLKEL NLHRCLNLIL 
ISDHGMEQGS CKKYIYLNKY LGDVKNIKVI YGPAARLRPS DVPDKYYSFN YEGIARNLSC 
REPNQHFKPY LKHFLPKRLH FAKSDRIEPL TFYLDPQWQL ALNPSERKYC GSGFHGSDNV 
FSNMQALFVG YGPGFKHGIE ADTFENIEVY NLMCDLLNLT PAPNNGTHGS LNHLLKNPVY 
TPKHPKEVHP LVQCPFTRNP RDNLGCSCNP SILPIEDFQT QFNLTVAEEK IIKHETLPYG 
RPRVLQKENT ICLLSQHQFM SGYSQDILMP LWTSYTVDRN DSFSTEDFSN CLYQDFRIPL 
SPVHKCSFYK NNTKVSYGFL SPPQLNKNSS GIYSEALLTT NIVPMYQSFQ VIWRYFHDTL 
LRKYAEERNG VNVVSGPVFD FDYDGRCDSL ENLRQKRRVI RNQEILIPTH FFIVLTSCKD 
TSQTPLHCEN LDTLAFILPH RTDNSESCVH GKHDSSWVEE LLMLHRARIT DVEHITGLSF 
YQQRKEPVSD ILKLKTHLPT FSQED