Details for: CACNA1E

Gene ID: 777

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: CACNA1E

Ensembl ID: ENSG00000198216

Description: calcium voltage-gated channel subunit alpha1 E

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 39.72
    rCSI 47.45%
    PRS 98.78
  • sst GABAergic cortical interneuron CL4023017
    CSI 35.83
    rCSI 46.19%
    PRS 99.06
  • sncg GABAergic cortical interneuron CL4023015
    CSI 32.36
    rCSI 52.04%
    PRS 98.64
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 29.69
    rCSI 49.83%
    PRS 98.84
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 24.62
    rCSI 43.48%
    PRS 98.77
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 22.13
    rCSI 53.79%
    PRS 98.25
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 21.66
    rCSI 46.99%
    PRS 98.19
  • glioblast CL0000030
    CSI 19.86
    rCSI 31.69%
    PRS 99.09
  • L6b glutamatergic cortical neuron CL4023038
    CSI 18.53
    rCSI 57.92%
    PRS 98.75
  • neuron CL0000540
    CSI 17.24
    rCSI 45.92%
    PRS 97.97
  • inhibitory interneuron CL0000498
    CSI 16.15
    rCSI 37.29%
    PRS 98.95
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 15.53
    rCSI 19.93%
    PRS 99.43
  • interneuron CL0000099
    CSI 15.33
    rCSI 30.77%
    PRS 99.27
  • glutamatergic neuron CL0000679
    CSI 14.76
    rCSI 30.34%
    PRS 97.53
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 14.73
    rCSI 48.42%
    PRS 98.21
  • Bergmann glial cell CL0000644
    CSI 14.09
    rCSI 19.28%
    PRS 99.08
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 12.76
    rCSI 45.91%
    PRS 98.51
  • neural cell CL0002319
    CSI 12.74
    rCSI 48.08%
    PRS 98.02
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 12.5
    rCSI 15.55%
    PRS 98.59
  • cerebral cortex neuron CL0010012
    CSI 11.84
    rCSI 48.25%
    PRS 98.83
  • cerebral cortex endothelial cell CL1001602
    CSI 11.39
    rCSI 19.7%
    PRS 99.21
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 9.85
    rCSI 58.02%
    PRS 98.6
  • epithelial cell of proximal tubule CL0002306
    CSI 9.5
    rCSI 23.21%
    PRS 98.71
  • cerebellar granule cell CL0001031
    CSI 9
    rCSI 13.23%
    PRS 99.06
  • amacrine cell CL0000561
    CSI 8.97
    rCSI 25.99%
    PRS 98.96
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 8.84
    rCSI 21.15%
    PRS 98.47
  • ependymal cell CL0000065
    CSI 8.7
    rCSI 17.65%
    PRS 97.17
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 8.62
    rCSI 32.58%
    PRS 98.48
  • glial cell CL0000125
    CSI 7.99
    rCSI 30.42%
    PRS 98.67
  • GABAergic amacrine cell CL4030027
    CSI 7.67
    rCSI 26.27%
    PRS 98.26
  • central nervous system neuron CL2000029
    CSI 7.34
    rCSI 53.97%
    PRS 98.96
  • astrocyte of the cerebral cortex CL0002605
    CSI 7.21
    rCSI 16.17%
    PRS 98.86
  • serotonergic neuron CL0000850
    CSI 6.93
    rCSI 30.96%
    PRS 97.57
  • medium spiny neuron CL1001474
    CSI 6.57
    rCSI 56.65%
    PRS 98.88
  • GABAergic neuron CL0000617
    CSI 6.57
    rCSI 22.02%
    PRS 97.33
  • dopaminergic neuron CL0000700
    CSI 6.37
    rCSI 35.97%
    PRS 98.49
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 6.16
    rCSI 11.19%
    PRS 99.16
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.57
    rCSI 14.28%
    PRS 98.91
  • vascular leptomeningeal cell CL4023051
    CSI 4.33
    rCSI 7.59%
    PRS 99.39
  • cerebellar neuron CL1001611
    CSI 3.89
    rCSI 34.21%
    PRS 97.97
  • regular atrial cardiac myocyte CL0002129
    CSI 3.73
    rCSI 12%
    PRS 99.19
  • retinal ganglion cell CL0000740
    CSI 3.44
    rCSI 7.61%
    PRS 98.78
  • direct pathway medium spiny neuron CL4023026
    CSI 2.18
    rCSI 52.08%
    PRS 97.83
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.15
    rCSI 51.91%
    PRS 97.81
  • midbrain dopaminergic neuron CL2000097
    CSI 1.84
    rCSI 11.82%
    PRS 98.96

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 [CACNA1E](/details-gene/777) encodes the pore-forming alpha-1E subunit of a voltage-gated R-type calcium channel, a key component in regulating calcium influx into electrically excitable cells. The gene's primary function is associated with [high voltage-gated calcium channel activity](/details-go/GO:0008331) and is integral to processes such as [chemical synaptic transmission](/details-go/GO:0007268). Expression data highlights its profound importance within the central nervous system, where it shows exceptionally high significance in numerous neuronal subtypes, including various GABAergic cortical interneurons and glutamatergic neurons. Clinically, mutations in [CACNA1E](/details-gene/777) are linked to severe neurological disorders, such as developmental and epileptic encephalopathy ([OMIM: 601013](https://omim.org/entry/601013)), underscoring its critical role in maintaining proper neuronal excitability and function [Link](https://doi.org/10.1016/j.ajhg.2018.09.006). ## Cellular Roles and Expression Landscape The expression profile of [CACNA1E](/details-gene/777) firmly establishes its identity as a gene specialized for the nervous system. **Overall**, the gene exhibits its highest significance in a diverse array of cortical [neurons](/details-cell/CL0000540). It is a particularly prominent marker for inhibitory interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 39.72), [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 35.83), and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 32.36). Its high significance extends to excitatory neurons as well, such as [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 22.13) and [L6b glutamatergic cortical neuron](/details-cell/CL4023038) (CSI: 18.53). This broad expression across both inhibitory and excitatory neuronal populations suggests a fundamental role in modulating overall cortical circuit activity and synaptic plasticity. Interestingly, [CACNA1E](/details-gene/777) also shows significant expression in [glioblast](/details-cell/CL0000030) (CSI: 19.86), a cell type associated with brain tumors, indicating a potential role in glioma pathology. The conspicuous absence of non-neuronal cell types such as immune, epithelial, or muscle cells from the top-expressed list further underscores the gene's highly specialized function within the central nervous system. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [CACNA1E](/details-gene/777) are highly consistent with its expression pattern. As a core component of the [voltage-gated calcium channel complex](/details-go/GO:0005891) located in the [plasma membrane](/details-go/GO:0005886), its primary molecular function is [voltage-gated calcium channel activity](/details-go/GO:0005245). This activity is essential for mediating [calcium ion import across the plasma membrane](/details-go/GO:0098703) in response to changes in membrane potential. Functionally, these activities are integrated into higher-order biological processes critical for neuronal communication. Reactome pathway analysis places [CACNA1E](/details-gene/777) centrally in '[Transmission across chemical synapses](/details-reactome/R-HSA-112315)' and specifically in '[Presynaptic depolarization and calcium channel opening](/details-reactome/R-HSA-112308)'. This confirms its role at the [synapse](/details-go/GO:0045202), where calcium influx through the channel is a critical trigger for neurotransmitter release. Additionally, its annotation in the '[Regulation of insulin secretion](/details-reactome/R-HSA-422356)' pathway suggests a potential role in other excitable cells, such as pancreatic beta cells, although this is not captured in the provided top-expressed cell data. ## Research Directions The data strongly implicates [CACNA1E](/details-gene/777) in both normal neuronal function and neuropathology. Its high expression across functionally distinct neuronal subtypes and its linkage to severe epileptic disorders present clear avenues for future research. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in both GABAergic (inhibitory) and glutamatergic (excitatory) neurons, pathogenic variants in [CACNA1E](/details-gene/777) likely disrupt the critical excitation-inhibition balance within cortical circuits, leading to the hyperexcitability characteristic of the epileptic encephalopathies with which it is associated [Link](https://doi.org/10.1016/j.ajhg.2018.09.006). 2. The significant expression of [CACNA1E](/details-gene/777) in [glioblast](/details-cell/CL0000030) suggests that it may contribute to glioblastoma pathogenesis by mediating calcium-dependent signaling pathways that control tumor cell proliferation, invasion, or resistance to therapy. To investigate the second hypothesis, a key experiment would be to use CRISPR-Cas9 to knock out [CACNA1E](/details-gene/777) in multiple patient-derived glioblastoma cell lines. The functional consequences could be assessed by measuring changes in cell proliferation rates (via BrdU incorporation assays), migratory capacity (via transwell migration assays), and intracellular calcium signaling dynamics in response to stimuli (via calcium imaging with indicators like GCaMP). These in vitro findings could then be validated using an in vivo orthotopic xenograft mouse model to determine the effect of [CACNA1E](/details-gene/777) loss on tumor growth and animal survival. From a therapeutic standpoint, [CACNA1E](/details-gene/777) presents a complex but potentially valuable target. For channelopathies like epilepsy caused by specific mutations, developing highly selective small-molecule modulators that can either inhibit (for gain-of-function variants) or potentiate (for loss-of-function variants) channel activity is a promising strategy. Its expression in glioblastoma may also offer a therapeutic window, but targeting a channel so critical for normal neuronal function would require strategies with high tumor specificity, such as antibody-drug conjugates or localized delivery systems, to avoid severe neurological side effects.

Genular Protein ID: 1597205708

Symbol: CAC1E_HUMAN

Name: Voltage-dependent R-type calcium channel subunit alpha-1E

UniProtKB Accession Codes:

Q15878 B1AM12 B1AM13 B1AM14 Q14580 Q14581

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 12 EMBL 7 EMDB 4 Ensembl 3 ExpressionAtlas 1 GO 10 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PIR 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 2 RefSeq 3 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7536609

Title: Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit.

PubMed ID: 7536609

PubMed ID: 8071363

Title: Structure and functional characterization of neuronal alpha 1E calcium channel subtypes.

PubMed ID: 8071363

DOI: 10.1016/s0021-9258(17)31796-9

PubMed ID: 16710414

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

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15258581

Title: Mutations in EFHC1 cause juvenile myoclonic epilepsy.

PubMed ID: 15258581

DOI: 10.1038/ng1393

PubMed ID: 30343943

Title: De novo pathogenic variants in CACNA1E cause developmental and epileptic encephalopathy with contractures, macrocephaly, and dyskinesias.

PubMed ID: 30343943

DOI: 10.1016/j.ajhg.2018.09.006

PubMed ID: 18400181

Title: Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+.

PubMed ID: 18400181

DOI: 10.1016/j.str.2008.01.011

Sequence Information:

  • Length: 2313
  • Mass: 261731
  • Checksum: CCC7F309C27C42F1
  • Sequence:
    • MARFGEAVVA RPGSGDGDSD QSRNRQGTPV PASGQAAAYK QTKAQRARTM ALYNPIPVRQ 
NCFTVNRSLF IFGEDNIVRK YAKKLIDWPP FEYMILATII ANCIVLALEQ HLPEDDKTPM 
SRRLEKTEPY FIGIFCFEAG IKIVALGFIF HKGSYLRNGW NVMDFIVVLS GILATAGTHF 
NTHVDLRTLR AVRVLRPLKL VSGIPSLQIV LKSIMKAMVP LLQIGLLLFF AILMFAIIGL 
EFYSGKLHRA CFMNNSGILE GFDPPHPCGV QGCPAGYECK DWIGPNDGIT QFDNILFAVL 
TVFQCITMEG WTTVLYNTND ALGATWNWLY FIPLIIIGSF FVLNLVLGVL SGEFAKERER 
VENRRAFMKL RRQQQIEREL NGYRAWIDKA EEVMLAEENK NAGTSALEVL RRATIKRSRT 
EAMTRDSSDE HCVDISSVGT PLARASIKSA KVDGVSYFRH KERLLRISIR HMVKSQVFYW 
IVLSLVALNT ACVAIVHHNQ PQWLTHLLYY AEFLFLGLFL LEMSLKMYGM GPRLYFHSSF 
NCFDFGVTVG SIFEVVWAIF RPGTSFGISV LRALRLLRIF KITKYWASLR NLVVSLMSSM 
KSIISLLFLL FLFIVVFALL GMQLFGGRFN FNDGTPSANF DTFPAAIMTV FQILTGEDWN 
EVMYNGIRSQ GGVSSGMWSA IYFIVLTLFG NYTLLNVFLA IAVDNLANAQ ELTKDEQEEE 
EAFNQKHALQ KAKEVSPMSA PNMPSIERDR RRRHHMSMWE PRSSHLRERR RRHHMSVWEQ 
RTSQLRKHMQ MSSQEALNRE EAPTMNPLNP LNPLSSLNPL NAHPSLYRRP RAIEGLALGL 
ALEKFEEERI SRGGSLKGDG GDRSSALDNQ RTPLSLGQRE PPWLARPCHG NCDPTQQEAG 
GGEAVVTFED RARHRQSQRR SRHRRVRTEG KESSSASRSR SASQERSLDE AMPTEGEKDH 
ELRGNHGAKE PTIQEERAQD LRRTNSLMVS RGSGLAGGLD EADTPLVLPH PELEVGKHVV 
LTEQEPEGSS EQALLGNVQL DMGRVISQSE PDLSCITANT DKATTESTSV TVAIPDVDPL 
VDSTVVHISN KTDGEASPLK EAEIREDEEE VEKKKQKKEK RETGKAMVPH SSMFIFSTTN 
PIRRACHYIV NLRYFEMCIL LVIAASSIAL AAEDPVLTNS ERNKVLRYFD YVFTGVFTFE 
MVIKMIDQGL ILQDGSYFRD LWNILDFVVV VGALVAFALA NALGTNKGRD IKTIKSLRVL 
RVLRPLKTIK RLPKLKAVFD CVVTSLKNVF NILIVYKLFM FIFAVIAVQL FKGKFFYCTD 
SSKDTEKECI GNYVDHEKNK MEVKGREWKR HEFHYDNIIW ALLTLFTVST GEGWPQVLQH 
SVDVTEEDRG PSRSNRMEMS IFYVVYFVVF PFFFVNIFVA LIIITFQEQG DKMMEECSLE 
KNERACIDFA ISAKPLTRYM PQNRHTFQYR VWHFVVSPSF EYTIMAMIAL NTVVLMMKYY 
SAPCTYELAL KYLNIAFTMV FSLECVLKVI AFGFLNYFRD TWNIFDFITV IGSITEIILT 
DSKLVNTSGF NMSFLKLFRA ARLIKLLRQG YTIRILLWTF VQSFKALPYV CLLIAMLFFI 
YAIIGMQVFG NIKLDEESHI NRHNNFRSFF GSLMLLFRSA TGEAWQEIML SCLGEKGCEP 
DTTAPSGQNE NERCGTDLAY VYFVSFIFFC SFLMLNLFVA VIMDNFEYLT RDSSILGPHH 
LDEFVRVWAE YDRAACGRIH YTEMYEMLTL MSPPLGLGKR CPSKVAYKRL VLMNMPVAED 
MTVHFTSTLM ALIRTALDIK IAKGGADRQQ LDSELQKETL AIWPHLSQKM LDLLVPMPKA 
SDLTVGKIYA AMMIMDYYKQ SKVKKQRQQL EEQKNAPMFQ RMEPSSLPQE IIANAKALPY 
LQQDPVSGLS GRSGYPSMSP LSPQDIFQLA CMDPADDGQF QERQSLEPEV SELKSVQPSN 
HGIYLPSDTQ EHAGSGRASS MPRLTVDPQV VTDPSSMRRS FSTIRDKRSN SSWLEEFSME 
RSSENTYKSR RRSYHSSLRL SAHRLNSDSG HKSDTHRSGG RERGRSKERK HLLSPDVSRC 
NSEERGTQAD WESPERRQSR SPSEGRSQTP NRQGTGSLSE SSIPSVSDTS TPRRSRRQLP 
PVPPKPRPLL SYSSLIRHAG SISPPADGSE EGSPLTSQAL ESNNACLTES SNSPHPQQSQ 
HASPQRYISE PYLALHEDSH ASDCGEEETL TFEAAVATSL GRSNTIGSAP PLRHSWQMPN 
GHYRRRRRGG PGPGMMCGAV NNLLSDTEED DKC

Genular Protein ID: 2342004387

Symbol: Q59FG1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q59FG1

Database IDs:

ARBA 16 BioGRID-ORCS 1 CTD 1 ChEBI 2 DNASU 1 DisGeNET 1 EMBL 2 GO 7 Gene3D 3 InterPro 8 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSR 1 PRINTS 2 PROSITE 2 PeptideAtlas 1 Pfam 3 RefSeq 3 RuleBase 1 SAM 3 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 1869
  • Mass: 211937
  • Checksum: 22262D31FB729EA0
  • Sequence:
    • AGTSALEVLR RATIKRSRTE AMTRDSSDEH CVDISSVGTP LARASIKSAK VDGVSYFRHK 
ERLLRISIRH MVKSQVFYWI VLSLVALNTA CVAIVHHNQP QWLTHLLYYA EFLFLGLFLL 
EMSLKMYGMG PRLYFHSSFN CFDFGVTVGS IFEVVWAIFR PGTSFGISVL RALRLLRIFK 
ITKYWASLRN LVVSLMSSMK SIISLLFLLF LFIVVFALLG MQLFGGRFNF NDGTPSANFD 
TFPAAIMTVF QILTGEDWNE VMYNGIRSQG GVSSGMWSAI YFIVLTLFGN YTLLNVFLAI 
AVDNLANAQE LTKDEQEEEE AFNQKHALQK AKEVSPMSAP NMPSIERDRR RRHHMSMWEP 
RSSHLRERRR RHHMSVWEQR TSQLRKHMQM SSQEALNREE APTMNPLNPL NPLSSLNPLN 
AHPSLYRRPR AIEGLALGLA LEKFEEERIS RGGSLKGDGG DRSSALDNQR TPLSLGQREP 
PWLARPCHGN CDPTQQEAGG GEAVVTFEDR ARHRQSQRRS RHRRVRTEGK ESSSASRSRS 
ASQERSLDEA MPTEGEKDHE LRGNHGAKEP TIQEERAQDL RRTNSLMVSR GSGLAGGLDE 
ADTPLVLPHP ELEVGKHVVL TEQEPEGSSE QALLGNVQLD MGRVISQSEP DLSCITANTD 
KATTESTSVT VAIPDVDPLV DSTVVHISNK TDGEASPLKE AEIREDEEEV EKKKQKKEKR 
ETGKAMVPHS SMFIFSTTNP IRRACHYIVN LRYFEMCILL VIAASSIALA AEDPVLTNSE 
RNKVLRYFDY VFTGVFTFEM VIKMIDQGLI LQDGSYFRDL WNILDFVVVV GALVAFALAN 
ALGTNKGRDI KTIKSLRVLR VLRPLKTIKR LPKLKAVFDC VVTSLKNVFN ILIVYKLFMF 
IFAVIAVQLF KGKFFYCTDS SKDTEKECIG NYVDHEKNKM EVKGREWKRH EFHYDNIIWA 
LLTLFTVSTG EGWPQVLQHS VDVTEEDRGP SRSNRMEMSI FYVVYFVVFP FFFVNIFVAL 
IIITFQEQGD KMMEECSLEK NERACIDFAI SAKPLTRYMP QNRHTFQYRV WHFVVSPSFE 
YTIMAMIALN TVVLMMKYYS APCTYELALK YLNIAFTMVF SLECVLKVIA FGFLNYFRDT 
WNIFDFITVI GSITEIILTD SKLVNTSGFN MSFLKLFRAA RLIKLLRQGY TIRILLWTFV 
QSFKALPYVC LLIAMLFFIY AIIGMQVFGN IKLDEESHIN RHNNFRSFFG SLMLLFRSAT 
GEAWQEIMLS CLGEKGCEPD TTAPSGQNEN ERCGTDLAYV YFVSFIFFCS FLMLNLFVAV 
IMDNFEYLTR DSSILGPHHL DEFVRVWAEY DRAACGRIHY TEMYEMLTLM SPPLGLGKRC 
PSKVAYKRLV LMNMPVAEDM TVHFTSTLMA LIRTALDIKI AKGGADRQQL DSELQKETLA 
IWPHLSQKML DLLVPMPKAS DLTVGKIYAA MMIMDYYKQS KVKKQRQQLE EQKNAPMFQR 
MEPSSLPQEI IANAKALPYL QQDPVSGLSG RSGYPSMSPL SPQDIFQLAC MDPTDDGQFQ 
ERQSLVVTDP SSMRRSFSTI RDKRSNSSWL EEFSMERSSE NTYKSRRRSY HSSLRLSAHR 
LNSDSGHKSD THRSGGRERG RSKERKHLLS PDVSRCNSEE RGTQADWESP ERRQSRSPSE 
GRSQTPNRQG TGSLSESSIP SVSDTSTPRR SRRQLPPVPP KPRPLLSYSS LIRHAGSISP 
PADGSEEGSP LTSQALESNN ACLTESSNSP HPQQSQHASP QRYISEPYLA LHEDSHASDC 
GEEETLTFEA AVATSLGRSN TIGSAPPLRH SWQMPNGHYR RRRRGGPGPG MMCGAVNNLL 
SDTEEDDKC