Details for: BCL9

Gene ID: 607

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: BCL9

Ensembl ID: ENSG00000116128

Description: BCL9 transcription coactivator

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 10.94
    rCSI 23.26%
    PRS 82.98
  • melanocyte CL0000148
    CSI 6.03
    rCSI 4.47%
    PRS 84.6
  • type B pancreatic cell CL0000169
    CSI 4.9
    rCSI 10.85%
    PRS 88.71
  • mesothelial cell CL0000077
    CSI 4.2
    rCSI 16.42%
    PRS 70.85
  • cerebellar granule cell CL0001031
    CSI 3.66
    rCSI 5.39%
    PRS 83.17
  • pancreatic A cell CL0000171
    CSI 3.48
    rCSI 3.65%
    PRS 90.88
  • interneuron CL0000099
    CSI 3.32
    rCSI 6.67%
    PRS 82.05
  • neural crest cell CL0011012
    CSI 3.31
    rCSI 2.62%
    PRS 80.93
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.16
    rCSI 5.58%
    PRS 74.13
  • cerebral cortex endothelial cell CL1001602
    CSI 3.02
    rCSI 5.23%
    PRS 82.85
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.97
    rCSI 4.21%
    PRS 86.23
  • melanocyte of skin CL1000458
    CSI 2.83
    rCSI 3.86%
    PRS 58.68
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.63
    rCSI 3.4%
    PRS 75.79
  • rod bipolar cell CL0000751
    CSI 2.56
    rCSI 4.61%
    PRS 83.45
  • lung ciliated cell CL1000271
    CSI 2.45
    rCSI 2.84%
    PRS 82.99
  • forebrain radial glial cell CL0013000
    CSI 2.36
    rCSI 7.59%
    PRS 88.81
  • Bergmann glial cell CL0000644
    CSI 2.35
    rCSI 3.22%
    PRS 80.84
  • radial glial cell CL0000681
    CSI 2.34
    rCSI 3.25%
    PRS 87.29
  • retinal bipolar neuron CL0000748
    CSI 2.19
    rCSI 4.1%
    PRS 79.61
  • ependymal cell CL0000065
    CSI 2.17
    rCSI 4.4%
    PRS 70.34
  • vascular leptomeningeal cell CL4023051
    CSI 2.14
    rCSI 3.76%
    PRS 84.7
  • epithelial cell of proximal tubule CL0002306
    CSI 2.1
    rCSI 5.13%
    PRS 81.74
  • glioblast CL0000030
    CSI 2.09
    rCSI 3.33%
    PRS 81.16
  • inhibitory interneuron CL0000498
    CSI 2.04
    rCSI 4.71%
    PRS 79.16
  • ciliated epithelial cell CL0000067
    CSI 2.02
    rCSI 1.78%
    PRS 79.82
  • renal beta-intercalated cell CL0002201
    CSI 1.98
    rCSI 4.72%
    PRS 88.75
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.91
    rCSI 2.38%
    PRS 72.45
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.89
    rCSI 11.83%
    PRS 82.09
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.87
    rCSI 2.16%
    PRS 81.6
  • amacrine cell CL0000561
    CSI 1.86
    rCSI 5.38%
    PRS 79.93
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.83
    rCSI 2.35%
    PRS 85.36
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.71
    rCSI 2.04%
    PRS 74.72
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.69
    rCSI 4.98%
    PRS 89.17
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.67
    rCSI 4.32%
    PRS 85.47
  • retinal pigment epithelial cell CL0002586
    CSI 1.62
    rCSI 3.23%
    PRS 85.05
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.61
    rCSI 2.7%
    PRS 74.68
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.6
    rCSI 4.05%
    PRS 81.83
  • cardiac neuron CL0010022
    CSI 1.52
    rCSI 4.88%
    PRS 87.01
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.4
    rCSI 2.26%
    PRS 75.83
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.38
    rCSI 1.67%
    PRS 69.42
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.38
    rCSI 3.1%
    PRS 75.27
  • basal cell of epidermis CL0002187
    CSI 1.3
    rCSI 2.3%
    PRS 59.46
  • cardiac muscle cell CL0000746
    CSI 1.26
    rCSI 1.8%
    PRS 80.55
  • helper T cell CL0000912
    CSI 1.25
    rCSI 1.77%
    PRS 85.13
  • retinal ganglion cell CL0000740
    CSI 1.1
    rCSI 2.43%
    PRS 77.44
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.91
    rCSI 2.22%
    PRS 72.36
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.86
    rCSI 5.05%
    PRS 75.14
  • parietal epithelial cell CL1000452
    CSI 0.83
    rCSI 2.21%
    PRS 82.68
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.75
    rCSI 2.35%
    PRS 77.94
  • suprabasal keratinocyte CL4033013
    CSI 0.74
    rCSI 1.21%
    PRS 58.95
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.72
    rCSI 2.25%
    PRS 76.1
  • central nervous system neuron CL2000029
    CSI 0.63
    rCSI 4.62%
    PRS 79.42
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.6
    rCSI 2.25%
    PRS 74.93
  • blood vessel smooth muscle cell CL0019018
    CSI 0.52
    rCSI 4.21%
    PRS 85.24
  • GABAergic interneuron CL0011005
    CSI 0.37
    rCSI 5.78%
    PRS 89.24
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.29
    rCSI 3.05%
    PRS 84.78

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 [BCL9](/details-gene/607) (B-cell CLL/lymphoma 9) is a protein-coding gene located on chromosome 1q21.2 that functions as a critical transcription coactivator within the canonical Wnt signaling pathway. Its protein product binds directly to beta-catenin, a key step in forming a transactivating complex with TCF/LEF transcription factors to drive the expression of Wnt target genes ([Link](https://doi.org/10.1016/s0092-8674(02)00679-7)). This role is fundamental to various developmental processes, including cell differentiation and stem cell maintenance. Expression data reveals that [BCL9](/details-gene/607) has the highest significance in [progenitor cell](/details-cell/CL0011026)s, which is consistent with its established function. Its expression is also notable in diverse differentiated cell types, such as [melanocyte](/details-cell/CL0000148)s and pancreatic islet cells, suggesting its importance extends beyond development into the maintenance of specialized cellular identity. The gene was originally identified due to its involvement in a chromosomal translocation t(1;14)(q21;q32) found in B-cell leukemia ([Link](https://pubmed.ncbi.nlm.nih.gov/9490669/)), linking its dysregulation to oncogenesis. ## Cellular Roles and Expression Landscape The expression profile of [BCL9](/details-gene/607) highlights its central role in cellular development, differentiation, and the maintenance of specific cell lineages. **Overall**, the gene's most significant expression is observed in [progenitor cell](/details-cell/CL0011026)s (CSI: 10.94), which directly aligns with its function in Wnt-mediated [somatic stem cell population maintenance](/details-go/GO:0035019). Beyond its role in undifferentiated cells, [BCL9](/details-gene/607) is also a significant marker in a wide array of specialized cell types, suggesting a continued requirement for Wnt signaling in maintaining their function and identity. These include: * **Pigment Cells:** High significance in [melanocyte](/details-cell/CL0000148) (CSI: 6.03) and [melanocyte of skin](/details-cell/CL1000458) (CSI: 2.83) is consistent with the known role of Wnt signaling in melanocyte development and homeostasis. * **Endocrine and Exocrine Cells:** Notable expression in [type B pancreatic cell](/details-cell/CL0000169) (CSI: 4.90) and [pancreatic A cell](/details-cell/CL0000171) (CSI: 3.48) points to a potential role in islet cell function or maintenance. * **Neuronal and Glial Cells:** Significant expression is found across several neuronal subtypes, including [cerebellar granule cell](/details-cell/CL0001031) (CSI: 3.66), [interneuron](/details-cell/CL0000099) (CSI: 3.32), and [rod bipolar cell](/details-cell/CL0000751) (CSI: 2.56), indicating its involvement in the nervous system. * **Epithelial and Mesothelial Cells:** The gene is also prominent in [mesothelial cell](/details-cell/CL0000077) (CSI: 4.20) and specialized epithelial cells like [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 2.97). This broad but specific expression pattern suggests that [BCL9](/details-gene/607) is a key facilitator of the Wnt pathway in diverse biological contexts, from governing progenitor cell fate to supporting the transcriptional programs of terminally differentiated cells. ## Pathways and Molecular Function Functional annotation data firmly places [BCL9](/details-gene/607) as a core component of the Wnt signaling cascade. Its primary molecular function is to act as a [transcription coactivator](/details-go/GO:0003713) by mediating [beta-catenin binding](/details-go/GO:0008013). This interaction is essential for the assembly of the nuclear [beta-catenin-TCF complex](/details-go/GO:1990907), which activates target gene transcription ([Link](https://doi.org/10.1016/j.molcel.2006.09.001)). The biological processes influenced by [BCL9](/details-gene/607) are direct consequences of its role in Wnt signaling. It is integral to the [canonical Wnt signaling pathway](/details-go/GO:0060070) and the [positive regulation of transcription by RNA polymerase II](/details-go/GO:0045944). These fundamental activities translate into specific developmental and homeostatic programs, including [skeletal muscle cell differentiation](/details-go/GO:0035914) and the previously mentioned maintenance of [somatic stem cell](/details-cell/CL0000034) populations ([GO:0035019](/details-go/GO:0035019)). Reactome pathway analysis corroborates this with high precision, mapping [BCL9](/details-gene/607) to the [formation of the beta-catenin:TCF transactivating complex](/details-reactome/R-HSA-201722) and the broader pathways of [signaling by WNT](/details-reactome/R-HSA-195721) and [TCF dependent signaling in response to WNT](/details-reactome/R-HSA-201681). This molecular machinery is essential for the cellular roles observed in the expression landscape, linking its function as a Wnt coactivator directly to its significance in progenitor and other specialized cells. ## Research Directions The role of [BCL9](/details-gene/607) as a non-redundant coactivator in the Wnt pathway, coupled with its initial discovery in B-cell lymphoma, positions it as a protein of significant interest in both developmental biology and oncology. Based on the available data, several testable hypotheses can be proposed: 1. Since [BCL9](/details-gene/607) is highly expressed in [progenitor cell](/details-cell/CL0011026)s and its dysregulation is linked to lymphoma, it is hypothesized that aberrant overexpression of [BCL9](/details-gene/607) in hematopoietic progenitors drives oncogenesis by constitutively activating Wnt target genes that promote self-renewal and block differentiation, leading to malignant transformation. 2. The high significance of [BCL9](/details-gene/607) in functionally distinct, terminally differentiated cells (e.g., [melanocyte](/details-cell/CL0000148) vs. [type B pancreatic cell](/details-cell/CL0000169)) suggests that its transcriptional output is context-dependent. It is hypothesized that cell-type-specific protein interactors bind to the BCL9/β-catenin complex, directing it to distinct sets of gene promoters and enhancers to regulate specialized cellular functions beyond a core proliferation program. To investigate the second hypothesis regarding context-dependent function, a key experiment would be to map the BCL9 interactome in different cellular environments. One could use CRISPR-Cas9 to endogenously tag [BCL9](/details-gene/607) with an affinity tag (e.g., TurboID) in both a melanoma cell line and a pancreatic beta-cell line. Subsequent proximity-labeling mass spectrometry would identify proteins that interact with [BCL9](/details-gene/607) in each cell type. A comparative analysis of these interactomes would reveal shared and unique binding partners, providing a mechanistic basis for its cell-specific roles. Given its function as an oncogenic driver in certain contexts, [BCL9](/details-gene/607) presents a compelling therapeutic target. As an intracellular protein whose function is mediated by a protein-protein interaction (PPI) with β-catenin, it is challenging to target with traditional approaches. However, this PPI interface is a well-defined molecular surface. Therefore, the development of small molecules or stapled peptides designed to specifically disrupt the BCL9-β-catenin interaction would represent a targeted therapeutic strategy. Such an approach would aim for inhibition and could be particularly effective in Wnt-driven cancers, such as certain colorectal carcinomas and B-cell malignancies.

Genular Protein ID: 3916718572

Symbol: BCL9_HUMAN

Name: B-cell CLL/lymphoma 9 protein

UniProtKB Accession Codes:

O00512 Q5T489

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9490669

Title: Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21.

PubMed ID: 9490669

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 11955446

Title: Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex.

PubMed ID: 11955446

DOI: 10.1016/s0092-8674(02)00679-7

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

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: 17052462

Title: Crystal structure of a beta-catenin/BCL9/Tcf4 complex.

PubMed ID: 17052462

DOI: 10.1016/j.molcel.2006.09.001

PubMed ID: 18498752

Title: Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex.

PubMed ID: 18498752

DOI: 10.1016/j.molcel.2008.03.011

Sequence Information:

  • Length: 1426
  • Mass: 149290
  • Checksum: 51EF3D0DCA2103CB
  • Sequence:
    • MHSSNPKVRS SPSGNTQSSP KSKQEVMVRP PTVMSPSGNP QLDSKFSNQG KQGGSASQSQ 
PSPCDSKSGG HTPKALPGPG GSMGLKNGAG NGAKGKGKRE RSISADSFDQ RDPGTPNDDS 
DIKECNSADH IKSQDSQHTP HSMTPSNATA PRSSTPSHGQ TTATEPTPAQ KTPAKVVYVF 
STEMANKAAE AVLKGQVETI VSFHIQNISN NKTERSTAPL NTQISALRND PKPLPQQPPA 
PANQDQNSSQ NTRLQPTPPI PAPAPKPAAP PRPLDRESPG VENKLIPSVG SPASSTPLPP 
DGTGPNSTPN NRAVTPVSQG SNSSSADPKA PPPPPVSSGE PPTLGENPDG LSQEQLEHRE 
RSLQTLRDIQ RMLFPDEKEF TGAQSGGPQQ NPGVLDGPQK KPEGPIQAMM AQSQSLGKGP 
GPRTDVGAPF GPQGHRDVPF SPDEMVPPSM NSQSGTIGPD HLDHMTPEQI AWLKLQQEFY 
EEKRRKQEQV VVQQCSLQDM MVHQHGPRGV VRGPPPPYQM TPSEGWAPGG TEPFSDGINM 
PHSLPPRGMA PHPNMPGSQM RLPGFAGMIN SEMEGPNVPN PASRPGLSGV SWPDDVPKIP 
DGRNFPPGQG IFSGPGRGER FPNPQGLSEE MFQQQLAEKQ LGLPPGMAME GIRPSMEMNR 
MIPGSQRHME PGNNPIFPRI PVEGPLSPSR GDFPKGIPPQ MGPGRELEFG MVPSGMKGDV 
NLNVNMGSNS QMIPQKMREA GAGPEEMLKL RPGGSDMLPA QQKMVPLPFG EHPQQEYGMG 
PRPFLPMSQG PGSNSGLRNL REPIGPDQRT NSRLSHMPPL PLNPSSNPTS LNTAPPVQRG 
LGRKPLDISV AGSQVHSPGI NPLKSPTMHQ VQSPMLGSPS GNLKSPQTPS QLAGMLAGPA 
AAASIKSPPV LGSAAASPVH LKSPSLPAPS PGWTSSPKPP LQSPGIPPNH KAPLTMASPA 
MLGNVESGGP PPPTASQPAS VNIPGSLPSS TPYTMPPEPT LSQNPLSIMM SRMSKFAMPS 
STPLYHDAIK TVASSDDDSP PARSPNLPSM NNMPGMGINT QNPRISGPNP VVPMPTLSPM 
GMTQPLSHSN QMPSPNAVGP NIPPHGVPMG PGLMSHNPIM GHGSQEPPMV PQGRMGFPQG 
FPPVQSPPQQ VPFPHNGPSG GQGSFPGGMG FPGEGPLGRP SNLPQSSADA ALCKPGGPGG 
PDSFTVLGNS MPSVFTDPDL QEVIRPGATG IPEFDLSRII PSEKPSQTLQ YFPRGEVPGR 
KQPQGPGPGF SHMQGMMGEQ APRMGLALPG MGGPGPVGTP DIPLGTAPSM PGHNPMRPPA 
FLQQGMMGPH HRMMSPAQST MPGQPTLMSN PAAAVGMIPG KDRGPAGLYT HPGPVGSPGM 
MMSMQGMMGP QQNIMIPPQM RPRGMAADVG MGGFSQGPGN PGNMMF

Genular Protein ID: 3692688952

Symbol: Q1JQ81_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q1JQ81

Database IDs:

ARBA 3 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 RefSeq 1 SAM 1

Citations:

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

Sequence Information:

  • Length: 1426
  • Mass: 149302
  • Checksum: E8F7AC81730A02C2
  • Sequence:
    • MHSSNPKVRS SPSGNTQSSP KSKQEVMVRP PTVMSPSGNP QLDSKFSNQG KQGGSASQSQ 
PSPCDSKSGG HTPKALPGPG GSMGLKNGAG NGAKGKGKRE RSISADSFDQ RDPGTPNDDS 
DIKECNSADH IKSQDSQHTP HSMTPSNATA PRSSTPSHGQ TTATEPTPAQ KTPAKVVYVF 
STEMANKAAE AVLKGQVETI VSFHIQNISN NKTERSTAPL NTQISALRND PKPLPQQPPA 
PANQDQNSSQ NTRLQPTPPI PAPAPKPAAP PRPLDRESPG VENKLIPSVG SPASSTPLPP 
DGTGPNSTPN NRAVTPVSQG SNSSSADPKA PPPPPVSSGE PPTLGENPDG LSQEQLEHRE 
RSLQTLRDIQ RMLFPDEKEF TGAQSGGPQQ NPGVLDGPQK KPEGPIQAMM AQSQSLGKGP 
GPRTDVGAPF GPQGHRDVPF SPDEMVPPSM NSQSGTIGPD HLDHMTPEQI AWLKLQQEFY 
EEKRRKQEQV VVQQCSLQDM MVHQHGPRGV VRGPPPPYQM TPSEGWAPGG TEPFSDGINM 
PHSLPPRGMA PHPNMPGSQM RLPGFAGMIN SEMEGPNVPN PASRPGLSGV SWPDDVPKIP 
DGRNFPPGQG IFSGPGRGER FPNPQGLSEE MFQQQLAEKQ LGLPPGMAME GIRPSMEMNR 
MIPGSQRHME PGNNPIFPRI PVEGPLSPSR GDFPKGIPPQ MGPGRELEFG MVPSGMKGDV 
NLNVNMGSNS QMIPQKMREA GAGPEEMLKL RPGGSDMLPA QQKMVPLPFG EHPQQEYGMG 
PRPFLPMSQG PGSNSGLRNL REPIGPDQRT NSRLSHMPPL PLNPSSNPIS LNTAPPVQRG 
LGRKPLDISV AGSQVHSPGI NPLKSPTMHQ VQSPMLGSPS GNLKSPQTPS QLAGMLAGPA 
AAASIKSPPV LGSAAASPVH LKSPSLPAPS PGWTSSPKPP LQSPGIPPNH KAPLTMASPA 
MLGNVESGGP PPPTASQPAS VNIPGSLPSS TPYTMPPEPT LSQNPLSIMM SRMSKFAMPS 
STPLYHDAIK TVASSDDDSP PARSPNLPSM NNMPGMGINT QNPRISGPNP VVPMPTLSPM 
GMTQPLSHSN QMPSPNAVGP NIPPHGVPMG PGLMSHNPIM GHGSQEPPMV PQGRMGFPQG 
FPPVQSPPQQ VPFPHNGPSG GQGSFPGGMG FPGEGPLGRP SNLPQSSADA ALCKPGGPGG 
PDSFTVLGNS MPSVFTDPDL QEVIRPGATG IPEFDLSRII PSEKPSQTLQ YFPRGEVPGR 
KQPQGPGPGF SHMQGMMGEQ APRMGLALPG MGGPGPVGTP DIPLGTAPSM PGHNPMRPPA 
FLQQGMMGPH HRMMSPAQST MPGQPTLMSN PAAAVGMIPG KDRGPAGLYT HPGPVGSPGM 
MMSMQGMMGP QQNIMIPPQM RPRGMAADVG MGGFSQGPGN PGNMMF