Details for: BBS4

Gene ID: 585

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: BBS4

Ensembl ID: ENSG00000140463

Description: Bardet-Biedl syndrome 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 4.41
    rCSI 7.41%
    PRS 71.66
  • mesodermal cell CL0000222
    CSI 3.93
    rCSI 4.71%
    PRS 85.24
  • type B pancreatic cell CL0000169
    CSI 3.86
    rCSI 8.54%
    PRS 86.71
  • pancreatic D cell CL0000173
    CSI 3.51
    rCSI 3.46%
    PRS 88.57
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.21
    rCSI 20.07%
    PRS 79.75
  • pancreatic A cell CL0000171
    CSI 3.13
    rCSI 3.28%
    PRS 89.33
  • interstitial cell of Cajal CL0002088
    CSI 3.09
    rCSI 3.94%
    PRS 90.93
  • bronchus fibroblast of lung CL2000093
    CSI 3.06
    rCSI 2.49%
    PRS 86.39
  • melanocyte CL0000148
    CSI 2.88
    rCSI 2.13%
    PRS 82.1
  • neural crest cell CL0011012
    CSI 2.88
    rCSI 2.27%
    PRS 78.15
  • fibroblast of lung CL0002553
    CSI 2.87
    rCSI 2.67%
    PRS 87.91
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.7
    rCSI 3.36%
    PRS 69.51
  • multi-ciliated epithelial cell CL0005012
    CSI 2.69
    rCSI 2.69%
    PRS 81.16
  • interneuron CL0000099
    CSI 2.69
    rCSI 5.4%
    PRS 79.38
  • choroid plexus epithelial cell CL0000706
    CSI 2.68
    rCSI 4.38%
    PRS 78.35
  • lung neuroendocrine cell CL1000223
    CSI 2.59
    rCSI 3.83%
    PRS 89.25
  • ON-bipolar cell CL0000749
    CSI 2.59
    rCSI 3.85%
    PRS 86.25
  • hepatic stellate cell CL0000632
    CSI 2.45
    rCSI 9.17%
    PRS 81.05
  • cerebral cortex endothelial cell CL1001602
    CSI 2.35
    rCSI 4.07%
    PRS 80.25
  • vascular leptomeningeal cell CL4023051
    CSI 2.32
    rCSI 4.07%
    PRS 82.24
  • Mueller cell CL0000636
    CSI 2.29
    rCSI 5.23%
    PRS 79.57
  • ciliated cell CL0000064
    CSI 2.29
    rCSI 3.71%
    PRS 81.49
  • retinal pigment epithelial cell CL0002586
    CSI 2.29
    rCSI 4.54%
    PRS 83.02
  • ionocyte CL0005006
    CSI 2.24
    rCSI 2.4%
    PRS 88.81
  • ciliated epithelial cell CL0000067
    CSI 2.19
    rCSI 1.93%
    PRS 77.5
  • cardiac neuron CL0010022
    CSI 2.19
    rCSI 6.99%
    PRS 85.04
  • retinal rod cell CL0000604
    CSI 2.1
    rCSI 3.7%
    PRS 82.35
  • rod bipolar cell CL0000751
    CSI 2.08
    rCSI 3.73%
    PRS 81.23
  • lung secretory cell CL1000272
    CSI 2.07
    rCSI 5.12%
    PRS 87.2
  • retinal cone cell CL0000573
    CSI 2.06
    rCSI 3.31%
    PRS 78.23
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.05
    rCSI 2.9%
    PRS 84.05
  • lung ciliated cell CL1000271
    CSI 2.04
    rCSI 2.35%
    PRS 80.6
  • chondrocyte CL0000138
    CSI 1.99
    rCSI 3.16%
    PRS 81.36
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.99
    rCSI 5.75%
    PRS 86.13
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.98
    rCSI 5.13%
    PRS 83.3
  • ependymal cell CL0000065
    CSI 1.93
    rCSI 3.92%
    PRS 67.64
  • glioblast CL0000030
    CSI 1.92
    rCSI 3.07%
    PRS 78.9
  • retinal bipolar neuron CL0000748
    CSI 1.91
    rCSI 3.58%
    PRS 77.16
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.9
    rCSI 2.45%
    PRS 72.82
  • radial glial cell CL0000681
    CSI 1.88
    rCSI 2.61%
    PRS 85.19
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.84
    rCSI 2.36%
    PRS 83.27
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.83
    rCSI 4.11%
    PRS 72.39
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.83
    rCSI 3.32%
    PRS 79.57
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.73
    rCSI 2%
    PRS 79.38
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.69
    rCSI 2.02%
    PRS 71.82
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.62
    rCSI 4.12%
    PRS 79.11
  • peripheral nervous system neuron CL2000032
    CSI 1.61
    rCSI 2.2%
    PRS 79.73
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.49
    rCSI 2.4%
    PRS 72.89
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.46
    rCSI 2.57%
    PRS 71.15
  • cardiac muscle cell CL0000746
    CSI 1.39
    rCSI 2%
    PRS 78.03
  • amacrine cell CL0000561
    CSI 1.39
    rCSI 4.02%
    PRS 77.55
  • S cone cell CL0003050
    CSI 1.18
    rCSI 5.2%
    PRS 81.48
  • retinal ganglion cell CL0000740
    CSI 1.13
    rCSI 2.5%
    PRS 74.69
  • parietal epithelial cell CL1000452
    CSI 1.06
    rCSI 2.84%
    PRS 80.18
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.06
    rCSI 6.22%
    PRS 72.07
  • central nervous system neuron CL2000029
    CSI 1.02
    rCSI 7.5%
    PRS 76.42
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.99
    rCSI 2.41%
    PRS 69.43
  • glial cell CL0000125
    CSI 0.96
    rCSI 3.64%
    PRS 79.31
  • podocyte CL0000653
    CSI 0.94
    rCSI 4.17%
    PRS 87.49
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.92
    rCSI 2.11%
    PRS 80.05
  • neural progenitor cell CL0011020
    CSI 0.92
    rCSI 4.06%
    PRS 75.56
  • dopaminergic neuron CL0000700
    CSI 0.74
    rCSI 4.2%
    PRS 74.64
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.62
    rCSI 2.36%
    PRS 71.95
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.62
    rCSI 1.95%
    PRS 75.15
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.56
    rCSI 1.76%
    PRS 72.99
  • blood vessel smooth muscle cell CL0019018
    CSI 0.48
    rCSI 3.9%
    PRS 82.84
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.43
    rCSI 1.54%
    PRS 69.63
  • medium spiny neuron CL1001474
    CSI 0.23
    rCSI 2.02%
    PRS 77.02

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)

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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 [BBS4](/details-gene/585), or Bardet-Biedl syndrome 4, encodes a crucial protein component of the BBSome complex. This complex functions as a key adaptor in intracellular protein trafficking, particularly in the transport of cargo to the primary cilium [Link](https://doi.org/10.1016/j.cell.2007.03.053). Its central role in ciliary biology is highlighted by its involvement in pathways such as '[Bbsome-mediated cargo-targeting to cilium](https://reactome.org/content/detail/R-HSA-5620922)' and '[Cilium assembly](https://reactome.org/content/detail/R-HSA-5617833)'. Mutations in [BBS4](/details-gene/585) are a cause of Bardet-Biedl syndrome, a pleiotropic genetic disorder characterized by obesity, retinal degeneration, and polydactyly ([OMIM: 600374](https://omim.org/entry/600374)) [Link](https://doi.org/10.1038/88925). **Overall**, expression data reveals significant enrichment of [BBS4](/details-gene/585) in a diverse range of cell types, including specific neuronal populations, pancreatic endocrine cells, and mesenchymal lineages, underscoring the widespread importance of ciliary function across multiple physiological systems. ## Cellular Roles and Expression Landscape The expression profile of [BBS4](/details-gene/585) suggests a fundamental role in specialized cell types where ciliary function is paramount. **Overall**, the gene shows high significance in the nervous system, particularly in specific inhibitory neuron subtypes such as the '[lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)' (CSI: 4.41) and '[pvalb GABAergic cortical interneuron](/details-cell/CL4023018)' (CSI: 2.70). This is consistent with its established role in neuronal development, migration, and the maintenance of photoreceptors, as annotated by Gene Ontology terms like '[Brain morphogenesis](/details-ontology/GO:0048854)' and '[Photoreceptor cell maintenance](/details-ontology/GO:0045494)'. A second major site of significant [BBS4](/details-gene/585) expression is the pancreas, with high CSI values in '[type B pancreatic cell](/details-cell/CL0000169)' (CSI: 3.86), '[pancreatic D cell](/details-cell/CL0000173)' (CSI: 3.51), and '[pancreatic A cell](/details-cell/CL0000171)' (CSI: 3.13). The primary cilia on these endocrine cells act as critical sensory and signaling hubs, and the high expression of [BBS4](/details-gene/585) likely reflects its importance in mediating these processes, which is relevant to the metabolic phenotypes, including obesity, seen in Bardet-Biedl syndrome. Furthermore, [BBS4](/details-gene/585) is significantly expressed in various developmental and structural cell types, including '[mesodermal cell](/details-cell/CL0000222)' (CSI: 3.93), '[bronchus fibroblast of lung](/details-cell/CL2000093)' (CSI: 3.06), and '[neural crest cell](/details-cell/CL0011012)' (CSI: 2.88). Its enrichment in '[multi-ciliated epithelial cell](/details-cell/CL0005012)' (CSI: 2.69) and '[regular ventricular cardiac myocyte](/details-cell/CL0002131)' (CSI: 3.21) further highlights its broad involvement in maintaining cellular architecture and function in tissues reliant on microtubule organization and ciliary activity. ## Pathways and Molecular Function [BBS4](/details-gene/585) functions as a core subunit of the '[Bbsome](/details-ontology/GO:0034464)', a stable octameric protein complex that acts as a coat or adaptor for membrane proteins destined for the ciliary membrane. This function is captured by its molecular annotation as having '[Protein-macromolecule adaptor activity](/details-ontology/GO:0030674)'. The primary role of the BBSome, and therefore [BBS4](/details-gene/585), is to recognize and sort cargo for transport along microtubules to the base of the cilium and into the ciliary compartment, a process detailed in the Reactome pathway '[Bbsome-mediated cargo-targeting to cilium](https://reactome.org/content/detail/R-HSA-5620922)'. The protein's function is intimately linked to the cytoskeleton, as evidenced by its binding to tubulin ('[Alpha-tubulin binding](/details-ontology/GO:0043014)', '[Beta-tubulin binding](/details-ontology/GO:0048487)') and its requirement for '[Microtubule anchoring at centrosome](/details-ontology/GO:0034454)' [Link](https://doi.org/10.1038/ng1352). This interaction is fundamental to the process of '[Cilium assembly](/details-ontology/GO:0060271)' and the proper localization of proteins to the '[Ciliary basal body](/details-ontology/GO:0036064)' and '[Centrosome](/details-ontology/GO:0005813)'. The vast array of biological processes associated with [BBS4](/details-gene/585), including '[Visual perception](/details-ontology/GO:0007601)', '[Sensory perception of smell](/details-ontology/GO:0007608)', '[Spermatid development](/details-ontology/GO:0007286)', and '[Regulation of lipid metabolic process](/details-ontology/GO:0019216)', are all direct consequences of its central role in maintaining the structural and functional integrity of primary cilia in diverse tissues. ## Research Directions The widespread yet specific expression pattern of [BBS4](/details-gene/585) suggests that its function may be subtly tailored to meet the unique ciliary cargo demands of different cell types. Understanding this cell-specific functionality is key to dissecting the complex pleiotropy of Bardet-Biedl syndrome. ### Proposed Hypotheses 1. **Neuronal Circuit Specificity:** The high significance of [BBS4](/details-gene/585) in specific interneuron subtypes ([lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)) suggests that it regulates the ciliary trafficking of receptors or channels that are critical for the synaptic integration and function of these particular circuits. Disruption of this specific trafficking may underlie some of the neurological and behavioral phenotypes associated with the syndrome. 2. **Pancreatic Endocrine Regulation:** Based on its high expression across all major islet cell types, we hypothesize that [BBS4](/details-gene/585) is essential for the cell-intrinsic regulation of hormone secretion in the pancreas. It likely mediates the ciliary trafficking of key GPCRs and ion channels that sense metabolic state, and its loss directly impairs the coordinated hormonal response to glucose fluctuations. 3. **Cardiac Myocyte Homeostasis:** The significant expression in '[regular ventricular cardiac myocyte](/details-cell/CL0002131)' is notable, as the role of primary cilia in terminally differentiated cardiomyocytes is not well-defined. We hypothesize that [BBS4](/details-gene/585) may have a cilium-independent role in these cells, potentially organizing microtubule-dependent trafficking of proteins and organelles around the sarcomere, and that its dysfunction could contribute to the cardiac abnormalities seen in some ciliopathies. ### Experimental Approach To test the hypothesis regarding pancreatic endocrine regulation (Hypothesis 2), a targeted experimental approach could be employed. A conditional knockout mouse model, using a Pdx1-Cre driver to delete [BBS4](/details-gene/585) specifically in the pancreas, would be generated. These mice would undergo rigorous metabolic profiling, including glucose and insulin tolerance tests, to assess systemic metabolic function. Islets isolated from these animals could then be used for *ex vivo* glucose-stimulated hormone secretion assays to directly measure defects in insulin, glucagon, and somatostatin release. Furthermore, advanced imaging techniques like super-resolution microscopy on islet cryosections would be used to determine if the ciliary localization of key signaling receptors (e.g., SSTR3, GLP1R) is disrupted in the absence of [BBS4](/details-gene/585). ### Therapeutic Potential As Bardet-Biedl syndrome is a loss-of-function disorder, [BBS4](/details-gene/585) itself is not a target for inhibition. The therapeutic potential lies in strategies for **functional restoration**. Gene therapy, aiming to deliver a correct copy of the [BBS4](/details-gene/585) gene via AAV vectors, represents the most promising long-term strategy, particularly for localized and accessible tissues like the retina to combat vision loss. However, the systemic nature of the disease presents a major challenge for broad therapeutic correction. Small molecules that could potentially stabilize the BBSome complex or enhance the function of a partially active mutant protein could also be explored, though this remains a speculative and challenging avenue.

Genular Protein ID: 3787677986

Symbol: BBS4_HUMAN

Name: Bardet-Biedl syndrome 4 protein

UniProtKB Accession Codes:

Q96RK4 B4E178 Q53DZ5 Q8NHU9 Q96H45

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 EMDB 1 Ensembl 2 ExpressionAtlas 1 GO 69 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 9 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11381270

Title: Identification of the gene that, when mutated, causes the human obesity syndrome BBS4.

PubMed ID: 11381270

DOI: 10.1038/88925

PubMed ID: 15497446

Title: Cloning and characterization of a splice variant of human Bardet-Biedl syndrome 4 gene (BBS4).

PubMed ID: 15497446

DOI: 10.1080/10425170410001679165

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 16327777

Title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.

PubMed ID: 16327777

DOI: 10.1038/nature04370

PubMed ID: 17574030

Title: A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.

PubMed ID: 17574030

DOI: 10.1016/j.cell.2007.03.053

PubMed ID: 18000879

Title: Novel interaction partners of Bardet-Biedl syndrome proteins.

PubMed ID: 18000879

DOI: 10.1002/cm.20250

PubMed ID: 23943788

Title: BBS mutations modify phenotypic expression of CEP290-related ciliopathies.

PubMed ID: 23943788

DOI: 10.1093/hmg/ddt394

PubMed ID: 24939912

Title: Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein.

PubMed ID: 24939912

DOI: 10.1093/hmg/ddu267

PubMed ID: 15107855

Title: The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression.

PubMed ID: 15107855

DOI: 10.1038/ng1352

PubMed ID: 22072986

Title: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

PubMed ID: 22072986

DOI: 10.1371/journal.pgen.1002358

PubMed ID: 33144677

Title: Dlec1 is required for spermatogenesis and male fertility in mice.

PubMed ID: 33144677

DOI: 10.1038/s41598-020-75957-y

PubMed ID: 12016587

Title: BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance.

PubMed ID: 12016587

DOI: 10.1086/341031

PubMed ID: 12677556

Title: Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome.

PubMed ID: 12677556

DOI: 10.1086/375178

PubMed ID: 12872256

Title: Evaluation of multiplex capillary heteroduplex analysis: a rapid and sensitive mutation screening technique.

PubMed ID: 12872256

DOI: 10.1002/humu.10241

PubMed ID: 12920096

Title: Further support for digenic inheritance in Bardet-Biedl syndrome.

PubMed ID: 12920096

DOI: 10.1136/jmg.40.8.e104

PubMed ID: 15666242

Title: Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome.

PubMed ID: 15666242

DOI: 10.1086/428679

PubMed ID: 15770229

Title: Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome family cohort.

PubMed ID: 15770229

DOI: 10.1038/sj.ejhg.5201372

PubMed ID: 21344540

Title: BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition.

PubMed ID: 21344540

DOI: 10.1002/humu.21480

Sequence Information:

  • Length: 519
  • Mass: 58282
  • Checksum: 59BC9B29355C8E3C
  • Sequence:
    • MAEERVATRT QFPVSTESQK PRQKKAPEFP ILEKQNWLIH LHYIRKDYEA CKAVIKEQLQ 
ETQGLCEYAI YVQALIFRLE GNIQESLELF QTCAVLSPQS ADNLKQVARS LFLLGKHKAA 
IEVYNEAAKL NQKDWEISHN LGVCYIYLKQ FNKAQDQLHN ALNLNRHDLT YIMLGKIHLL 
EGDLDKAIEV YKKAVEFSPE NTELLTTLGL LYLQLGIYQK AFEHLGNALT YDPTNYKAIL 
AAGSMMQTHG DFDVALTKYR VVACAVPESP PLWNNIGMCF FGKKKYVAAI SCLKRANYLA 
PFDWKILYNL GLVHLTMQQY ASAFHFLSAA INFQPKMGEL YMLLAVALTN LEDIENAKRA 
YAEAVHLDKC NPLVNLNYAV LLYNQGEKKN ALAQYQEMEK KVSLLKDNSS LEFDSEMVEM 
AQKLGAALQV GEALVWTKPV KDPKSKHQTT STSKPASFQQ PLGSNQALGQ AMSSAAAYRT 
LPSGAGGTSQ FTKPPSLPLE PEPAVESSPT ETSEQIREK