Details for: ANGPT2

Gene ID: 285

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: ANGPT2

Ensembl ID: ENSG00000091879

Description: angiopoietin 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • granulocyte CL0000094
    CSI 12.12
    rCSI 18.52%
    PRS 73.25
  • retinal blood vessel endothelial cell CL0002585
    CSI 11.63
    rCSI 18.57%
    PRS 68.26
  • lung endothelial cell CL1001567
    CSI 10.98
    rCSI 25.6%
    PRS 81.18
  • endothelial cell of lymphatic vessel CL0002138
    CSI 10.94
    rCSI 21.69%
    PRS 77.18
  • microcirculation associated smooth muscle cell CL0008035
    CSI 10.25
    rCSI 29.67%
    PRS 65.28
  • endothelial cell of placenta CL0009092
    CSI 10.15
    rCSI 50.02%
    PRS 74.98
  • syncytiotrophoblast cell CL0000525
    CSI 9.45
    rCSI 27.23%
    PRS 76.63
  • cerebral cortex endothelial cell CL1001602
    CSI 8.42
    rCSI 14.57%
    PRS 54.05
  • rod bipolar cell CL0000751
    CSI 7.56
    rCSI 13.59%
    PRS 57.25
  • tracheobronchial smooth muscle cell CL0019019
    CSI 7.33
    rCSI 12.93%
    PRS 72.14
  • melanocyte CL0000148
    CSI 6.96
    rCSI 5.15%
    PRS 56.55
  • ependymal cell CL0000065
    CSI 6.34
    rCSI 12.87%
    PRS 43.05
  • endothelial cell of uterus CL0009095
    CSI 6.09
    rCSI 44.51%
    PRS 79.51
  • vein endothelial cell of respiratory system CL4033008
    CSI 6.01
    rCSI 41.28%
    PRS 76.33
  • perivascular cell CL4033054
    CSI 5.96
    rCSI 8.15%
    PRS 69.97
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 5.44
    rCSI 6.76%
    PRS 43.64
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 5.19
    rCSI 5.99%
    PRS 56.99
  • hepatic stellate cell CL0000632
    CSI 5.17
    rCSI 19.36%
    PRS 55.97
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.75
    rCSI 10.64%
    PRS 46.16
  • blood vessel endothelial cell CL0000071
    CSI 4.62
    rCSI 9.59%
    PRS 61.19
  • brush cell of tracheobronchial tree CL0002075
    CSI 4.57
    rCSI 13.57%
    PRS 73.74
  • renal interstitial pericyte CL1001318
    CSI 4.35
    rCSI 11.99%
    PRS 59.36
  • vascular leptomeningeal cell CL4023051
    CSI 4.24
    rCSI 7.43%
    PRS 55.93
  • cardiac muscle cell CL0000746
    CSI 4.2
    rCSI 6.03%
    PRS 53.56
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 4.2
    rCSI 3.79%
    PRS 61.07
  • lung ciliated cell CL1000271
    CSI 4.07
    rCSI 4.7%
    PRS 54.37
  • peripheral nervous system neuron CL2000032
    CSI 3.98
    rCSI 5.42%
    PRS 55.68
  • capillary endothelial cell CL0002144
    CSI 3.97
    rCSI 7.27%
    PRS 74.56
  • endothelial cell of vascular tree CL0002139
    CSI 3.87
    rCSI 21.14%
    PRS 62.41
  • mesothelial cell CL0000077
    CSI 3.75
    rCSI 14.68%
    PRS 40.84
  • myofibroblast cell CL0000186
    CSI 3.69
    rCSI 5.11%
    PRS 64.65
  • cardiac endothelial cell CL0010008
    CSI 3.62
    rCSI 14.6%
    PRS 62.8
  • vascular associated smooth muscle cell CL0000359
    CSI 3.4
    rCSI 11.03%
    PRS 63.92
  • interneuron CL0000099
    CSI 3.36
    rCSI 6.74%
    PRS 53.04
  • retinal bipolar neuron CL0000748
    CSI 3.18
    rCSI 5.96%
    PRS 52.19
  • extravillous trophoblast CL0008036
    CSI 3.12
    rCSI 3.86%
    PRS 60.79
  • vein endothelial cell CL0002543
    CSI 2.98
    rCSI 8.13%
    PRS 80.6
  • pro-B cell CL0000826
    CSI 2.97
    rCSI 2.46%
    PRS 66.47
  • stromal cell CL0000499
    CSI 2.97
    rCSI 8.35%
    PRS 60.65
  • adipocyte CL0000136
    CSI 2.93
    rCSI 3.76%
    PRS 56.3
  • neural cell CL0002319
    CSI 2.83
    rCSI 10.68%
    PRS 49.78
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.67
    rCSI 3.79%
    PRS 60.34
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.61
    rCSI 3.37%
    PRS 46.74
  • lung secretory cell CL1000272
    CSI 2.59
    rCSI 6.41%
    PRS 62.55
  • cardiac blood vessel endothelial cell CL0010006
    CSI 2.56
    rCSI 18.1%
    PRS 56.03
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.49
    rCSI 4.52%
    PRS 55.63
  • Mueller cell CL0000636
    CSI 2.44
    rCSI 5.57%
    PRS 55.53
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 2.39
    rCSI 10.97%
    PRS 74.38
  • lung pericyte CL0009089
    CSI 2.38
    rCSI 6.29%
    PRS 72.71
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.3
    rCSI 7.1%
    PRS 72.04
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.26
    rCSI 2.7%
    PRS 45.24
  • mesenchymal cell CL0008019
    CSI 2.19
    rCSI 5.55%
    PRS 58.12
  • retina horizontal cell CL0000745
    CSI 2.17
    rCSI 3.3%
    PRS 60.54
  • chondrocyte CL0000138
    CSI 2.14
    rCSI 3.41%
    PRS 56.4
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.07
    rCSI 5.02%
    PRS 44
  • smooth muscle cell of prostate CL1000487
    CSI 2.06
    rCSI 12.13%
    PRS 77.47
  • Bergmann glial cell CL0000644
    CSI 2
    rCSI 2.73%
    PRS 57.14
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.96
    rCSI 3.46%
    PRS 44.56
  • contractile cell CL0000183
    CSI 1.94
    rCSI 5.73%
    PRS 62.62
  • fibroblast of cardiac tissue CL0002548
    CSI 1.94
    rCSI 9.3%
    PRS 63.89
  • prostate gland microvascular endothelial cell CL2000059
    CSI 1.93
    rCSI 46.24%
    PRS 80.68
  • S cone cell CL0003050
    CSI 1.75
    rCSI 7.71%
    PRS 60.48
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.68
    rCSI 2.82%
    PRS 45.45
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.66
    rCSI 10.34%
    PRS 55.7
  • amacrine cell CL0000561
    CSI 1.62
    rCSI 4.69%
    PRS 53.53
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.61
    rCSI 5.04%
    PRS 47.17
  • ON midget ganglion cell CL4033046
    CSI 1.56
    rCSI 31.79%
    PRS 54.67
  • retinal cone cell CL0000573
    CSI 1.47
    rCSI 2.37%
    PRS 53.55
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.35
    rCSI 2.17%
    PRS 47.43
  • retinal ganglion cell CL0000740
    CSI 1.29
    rCSI 2.86%
    PRS 50.02
  • OFF midget ganglion cell CL4033047
    CSI 1.26
    rCSI 25.74%
    PRS 56.11
  • blood vessel smooth muscle cell CL0019018
    CSI 1.23
    rCSI 10%
    PRS 57.35
  • cerebellar granule cell CL0001031
    CSI 1.19
    rCSI 1.75%
    PRS 57.3
  • pancreatic stellate cell CL0002410
    CSI 1.17
    rCSI 6.79%
    PRS 72.6
  • diffuse bipolar 6 cell CL4033032
    CSI 1.14
    rCSI 5.98%
    PRS 58.08
  • smooth muscle cell of the pulmonary artery CL0002591
    CSI 1.09
    rCSI 8.34%
    PRS 69.94
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.08
    rCSI 3.89%
    PRS 43.79
  • central nervous system neuron CL2000029
    CSI 1.01
    rCSI 7.43%
    PRS 50.42
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.98
    rCSI 3.69%
    PRS 46.16
  • invaginating midget bipolar cell CL4033034
    CSI 0.92
    rCSI 5.46%
    PRS 58.41
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.85
    rCSI 2.67%
    PRS 49.6
  • GABAergic amacrine cell CL4030027
    CSI 0.82
    rCSI 2.79%
    PRS 52.62
  • ON parasol ganglion cell CL4033052
    CSI 0.81
    rCSI 11.51%
    PRS 54.92
  • diffuse bipolar 3a cell CL4033029
    CSI 0.72
    rCSI 4.9%
    PRS 59.16
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.63
    rCSI 3.73%
    PRS 46.63
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.54
    rCSI 13.14%
    PRS 45.32
  • direct pathway medium spiny neuron CL4023026
    CSI 0.46
    rCSI 11.04%
    PRS 44.5
  • kidney interstitial cell CL1000500
    CSI 0.42
    rCSI 6.81%
    PRS 75.74

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.

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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)

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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 [ANGPT2](/details-gene/285) (angiopoietin 2) is a protein-coding gene located on chromosome 8p23.1 that encodes a secreted glycoprotein crucial for vascular development and remodeling. As a key ligand in the angiopoietin-Tie signaling system, [ANGPT2](/details-gene/285) functions primarily as a context-dependent antagonist of the TIE2 receptor tyrosine kinase. This function plays a critical role in destabilizing blood vessels, promoting both physiological and pathological '[Angiogenesis](/details-go/GO:0001525)'. Expression data highlights its profound significance in various endothelial cell populations, including those of the retina, lung, and placenta, as well as in [granulocyte](/details-cell/CL0000094), suggesting a dual role in vascular homeostasis and inflammation. Mutations in [ANGPT2](/details-gene/285) are associated with conditions such as primary lymphedema ([153245](https://omim.org/entry/601922)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ANGPT2](/details-gene/285) firmly establishes its identity as a central regulator of the vascular endothelium. The gene demonstrates high significance across a diverse array of endothelial cell types, underscoring its widespread importance in vascular beds. It is a top marker in [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 11.63), [lung endothelial cell](/details-cell/CL1001567) (CSI: 10.98), [endothelial cell of lymphatic vessel](/details-cell/CL0002138) (CSI: 10.94), and [endothelial cell of placenta](/details-cell/CL0009092) (CSI: 10.15). This broad endothelial expression is consistent with its fundamental role in regulating vascular permeability, maturation, and remodeling throughout the body. Beyond the endothelium, [ANGPT2](/details-gene/285) shows the highest significance in [granulocyte](/details-cell/CL0000094) (CSI: 12.12), suggesting a key function in the interplay between the innate immune system and the vasculature, possibly by promoting vascular leakage to facilitate immune cell extravasation during inflammation. Its expression in perivascular support cells like [microcirculation associated smooth muscle cell](/details-cell/CL0008035) and [perivascular cell](/details-cell/CL4033054) further supports its role in the broader vascular niche. Additionally, high significance in specialized cells such as [syncytiotrophoblast cell](/details-cell/CL0000525) points to a critical function in the extensive vascular remodeling required for placental development during pregnancy. ## Pathways and Molecular Function The molecular functions of [ANGPT2](/details-gene/285) are intrinsically linked to the '[Tie2 signaling](/details-reactome/R-HSA-210993)' pathway. It primarily acts as a '[Receptor ligand activity](/details-go/GO:0048018)' that binds to the TIE2 receptor on endothelial cells. In most contexts, it functions as an antagonist to the primary agonist, ANGPT1, thereby disrupting vessel stability and making the endothelium more responsive to pro-angiogenic signals like VEGF. This dual regulatory capacity is reflected in its annotation for both '[Positive regulation of angiogenesis](/details-go/GO:0045766)' and '[Negative regulation of angiogenesis](/details-go/GO:0016525)'. Seminal research established [ANGPT2](/details-gene/285) as a natural antagonist that disrupts angiogenesis *in vivo* ([Link](https://doi.org/10.1126/science.277.5322.55)), although more recent studies suggest it can also act as a partial agonist ([Link](https://doi.org/10.1128/mcb.01472-08)). As a secreted protein found in the '[Extracellular space](/details-go/GO:0005615)', its functions extend to broader processes involving the vascular system, including '[Hemostasis](/details-reactome/R-HSA-109582)' and '[Cell surface interactions at the vascular wall](/details-reactome/R-HSA-202733)'. The gene's involvement in the '[Response to hypoxia](/details-go/GO:0001666)' is particularly relevant in pathological settings like cancer, where hypoxic tumor microenvironments induce [ANGPT2](/details-gene/285) expression to drive neovascularization ([Link](https://doi.org/10.1172/jci4891)). ## Research Directions The widespread yet specific expression of [ANGPT2](/details-gene/285) in endothelial and immune cells, coupled with its critical role in vascular stability, presents several avenues for future investigation. Its dysregulation is implicated in numerous diseases, from cancer to lymphatic disorders ([Link](https://doi.org/10.1126/scitranslmed.aax8013)), making it a high-value target for both basic and translational research. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its top significance score in [granulocyte](/details-cell/CL0000094), [ANGPT2](/details-gene/285) released by these immune cells at sites of inflammation acts as a primary signal to locally increase vascular permeability, creating a permissive environment for immune cell infiltration into tissues. 2. **Hypothesis 2:** The context-dependent agonistic versus antagonistic activity of [ANGPT2](/details-gene/285) on the TIE2 receptor is determined by the specific composition of the extracellular matrix in different vascular beds (e.g., retina vs. lung), which modulates its conformation and binding affinity. ### Experimental Approach: To test the first hypothesis regarding the role of granulocyte-derived [ANGPT2](/details-gene/285), a conditional knockout mouse model could be employed. Specifically, crossing mice with a floxed *Angpt2* allele to mice expressing Cre recombinase under a granulocyte-specific promoter (e.g., *Mrp8*-Cre or *Lyz2*-Cre) would generate animals lacking [ANGPT2](/details-gene/285) only in that lineage. These mice, alongside control littermates, could be subjected to an inflammatory challenge, such as intraperitoneal LPS injection or a thioglycollate-induced peritonitis model. The key readouts would be quantifying the extent of vascular leakage using an Evans blue dye assay and measuring the number and type of immune cells that successfully extravasate into the peritoneal cavity via flow cytometry. A significant reduction in both vascular permeability and immune cell infiltration in the knockout mice would confirm that granulocyte-derived [ANGPT2](/details-gene/285) is a critical mediator of inflammatory responses. ### Therapeutic Potential: [ANGPT2](/details-gene/285) is a highly attractive therapeutic target. Its role in promoting pathological angiogenesis and vascular leakage in diseases like cancer and diabetic retinopathy makes **inhibition** a primary therapeutic strategy. As a secreted, extracellular ligand, it is readily accessible to biologic drugs. Monoclonal antibodies that neutralize [ANGPT2](/details-gene/285) (e.g., Nesvacumab) or bispecific antibodies that simultaneously block [ANGPT2](/details-gene/285) and VEGF-A (e.g., Faricimab) have shown promise in clinical trials, particularly for ocular diseases. Targeting [ANGPT2](/details-gene/285) represents a strategy to "normalize" vasculature, making it less leaky and more stable, which can inhibit tumor growth and reduce edema.

Genular Protein ID: 2732424518

Symbol: ANGP2_HUMAN

Name: Angiopoietin-2

UniProtKB Accession Codes:

O15123 A0AV38 A8K205 B7ZLM7 Q9NRR7 Q9P2Y7

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EMBL 9 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 26 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9204896

Title: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.

PubMed ID: 9204896

DOI: 10.1126/science.277.5322.55

PubMed ID: 9927494

Title: Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma.

PubMed ID: 9927494

DOI: 10.1172/jci4891

PubMed ID: 10766762

Title: Characterization and expression of a novel alternatively spliced human angiopoietin-2.

PubMed ID: 10766762

DOI: 10.1074/jbc.m910084199

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

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: 12427764

Title: Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats.

PubMed ID: 12427764

DOI: 10.1074/jbc.m208550200

PubMed ID: 15284220

Title: Biological characterization of angiopoietin-3 and angiopoietin-4.

PubMed ID: 15284220

DOI: 10.1096/fj.03-1466com

PubMed ID: 19116766

Title: Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells.

PubMed ID: 19116766

DOI: 10.1007/s10456-008-9126-0

PubMed ID: 19223473

Title: Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium.

PubMed ID: 19223473

DOI: 10.1128/mcb.01472-08

PubMed ID: 19234476

Title: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system.

PubMed ID: 19234476

DOI: 10.1038/nrm2639

PubMed ID: 29323190

Title: Angiopoietins bind thrombomodulin and inhibit its function as a thrombin cofactor.

PubMed ID: 29323190

DOI: 10.1038/s41598-017-18912-8

PubMed ID: 15893672

Title: Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.

PubMed ID: 15893672

DOI: 10.1016/j.str.2005.03.009

PubMed ID: 16732286

Title: Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.

PubMed ID: 16732286

DOI: 10.1038/nsmb1101

PubMed ID: 32908006

Title: Characterization of ANGPT2 mutations associated with primary lymphedema.

PubMed ID: 32908006

DOI: 10.1126/scitranslmed.aax8013

Sequence Information:

  • Length: 496
  • Mass: 56919
  • Checksum: 5642A58847A7385C
  • Sequence:
    • MWQIVFFTLS CDLVLAAAYN NFRKSMDSIG KKQYQVQHGS CSYTFLLPEM DNCRSSSSPY 
VSNAVQRDAP LEYDDSVQRL QVLENIMENN TQWLMKLENY IQDNMKKEMV EIQQNAVQNQ 
TAVMIEIGTN LLNQTAEQTR KLTDVEAQVL NQTTRLELQL LEHSLSTNKL EKQILDQTSE 
INKLQDKNSF LEKKVLAMED KHIIQLQSIK EEKDQLQVLV SKQNSIIEEL EKKIVTATVN 
NSVLQKQQHD LMETVNNLLT MMSTSNSAKD PTVAKEEQIS FRDCAEVFKS GHTTNGIYTL 
TFPNSTEEIK AYCDMEAGGG GWTIIQRRED GSVDFQRTWK EYKVGFGNPS GEYWLGNEFV 
SQLTNQQRYV LKIHLKDWEG NEAYSLYEHF YLSSEELNYR IHLKGLTGTA GKISSISQPG 
NDFSTKDGDN DKCICKCSQM LTGGWWFDAC GPSNLNGMYY PQRQNTNKFN GIKWYYWKGS 
GYSLKATTMM IRPADF