Details for: ALAS1

Gene ID: 211

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: ALAS1

Ensembl ID: ENSG00000023330

Description: 5'-aminolevulinate synthase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • multi-ciliated epithelial cell CL0005012
    CSI 7.63
    rCSI 7.61%
    PRS 40.23
  • myeloid leukocyte CL0000766
    CSI 6.9
    rCSI 6.36%
    PRS 46.86
  • hepatocyte CL0000182
    CSI 6.85
    rCSI 12.26%
    PRS 44.4
  • acinar cell CL0000622
    CSI 6.04
    rCSI 8.85%
    PRS 57.22
  • respiratory suprabasal cell CL4033048
    CSI 5.41
    rCSI 6.94%
    PRS 50.71
  • centrilobular region hepatocyte CL0019029
    CSI 5.24
    rCSI 13.67%
    PRS 53.72
  • placental villous trophoblast CL2000060
    CSI 5.24
    rCSI 8.09%
    PRS 43.75
  • vascular associated smooth muscle cell CL0000359
    CSI 4.99
    rCSI 16.18%
    PRS 48.75
  • group 2 innate lymphoid cell CL0001069
    CSI 4.47
    rCSI 24.17%
    PRS 80.36
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 4.13
    rCSI 5.42%
    PRS 59.02
  • lung interstitial macrophage CL4033043
    CSI 3.89
    rCSI 8.74%
    PRS 65.64
  • epithelial cell of lung CL0000082
    CSI 3.7
    rCSI 3.06%
    PRS 44.48
  • paneth cell CL0000510
    CSI 3.46
    rCSI 5.1%
    PRS 63.45
  • squamous epithelial cell CL0000076
    CSI 3.11
    rCSI 7.38%
    PRS 51.58
  • ciliated cell CL0000064
    CSI 3.11
    rCSI 5.03%
    PRS 44.4
  • ciliated epithelial cell CL0000067
    CSI 2.94
    rCSI 2.58%
    PRS 35.22
  • midzonal region hepatocyte CL0019028
    CSI 2.85
    rCSI 6.69%
    PRS 54.64
  • interneuron CL0000099
    CSI 2.8
    rCSI 5.63%
    PRS 35.94
  • periportal region hepatocyte CL0019026
    CSI 2.79
    rCSI 10.87%
    PRS 54.62
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.79
    rCSI 2.15%
    PRS 44.84
  • hepatic stellate cell CL0000632
    CSI 2.67
    rCSI 9.98%
    PRS 39.06
  • elicited macrophage CL0000861
    CSI 2.63
    rCSI 2.41%
    PRS 53.41
  • pancreatic D cell CL0000173
    CSI 2.62
    rCSI 2.57%
    PRS 48.41
  • pro-B cell CL0000826
    CSI 2.6
    rCSI 2.15%
    PRS 46.94
  • mucous neck cell CL0000651
    CSI 2.39
    rCSI 3.45%
    PRS 59.34
  • perivascular cell CL4033054
    CSI 2.39
    rCSI 3.27%
    PRS 51.01
  • ON-bipolar cell CL0000749
    CSI 2.31
    rCSI 3.44%
    PRS 48.31
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.31
    rCSI 2%
    PRS 49.76
  • secretory cell CL0000151
    CSI 2.3
    rCSI 2.4%
    PRS 46.51
  • respiratory basal cell CL0002633
    CSI 2.3
    rCSI 2.38%
    PRS 51.82
  • neural crest cell CL0011012
    CSI 2.3
    rCSI 1.82%
    PRS 33.85
  • lung macrophage CL1001603
    CSI 2.29
    rCSI 5.12%
    PRS 52.51
  • bronchus fibroblast of lung CL2000093
    CSI 2.25
    rCSI 1.82%
    PRS 46.61
  • melanocyte of skin CL1000458
    CSI 2.24
    rCSI 3.05%
    PRS 23.61
  • pulmonary ionocyte CL0017000
    CSI 2.21
    rCSI 2.68%
    PRS 53.65
  • rod bipolar cell CL0000751
    CSI 2.2
    rCSI 3.95%
    PRS 39.41
  • renal alpha-intercalated cell CL0005011
    CSI 2.17
    rCSI 2.9%
    PRS 54.4
  • group 3 innate lymphoid cell CL0001071
    CSI 2.09
    rCSI 1.57%
    PRS 49.55
  • ionocyte CL0005006
    CSI 2.09
    rCSI 2.24%
    PRS 44.02
  • enterocyte CL0000584
    CSI 2.08
    rCSI 3.36%
    PRS 54.4
  • Kupffer cell CL0000091
    CSI 2.07
    rCSI 4.73%
    PRS 45.33
  • suprabasal keratinocyte CL4033013
    CSI 2.04
    rCSI 3.34%
    PRS 24.45
  • cerebral cortex endothelial cell CL1001602
    CSI 2.02
    rCSI 3.49%
    PRS 36.89
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.98
    rCSI 1.79%
    PRS 42.63
  • nasal mucosa goblet cell CL0002480
    CSI 1.95
    rCSI 2.26%
    PRS 56.33
  • plasmacytoid dendritic cell, human CL0001058
    CSI 1.93
    rCSI 1.35%
    PRS 47.79
  • common myeloid progenitor CL0000049
    CSI 1.92
    rCSI 1.55%
    PRS 46.59
  • colon epithelial cell CL0011108
    CSI 1.91
    rCSI 2%
    PRS 43.07
  • early lymphoid progenitor CL0000936
    CSI 1.89
    rCSI 1.66%
    PRS 51.04
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 1.83
    rCSI 1.86%
    PRS 59.23
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.81
    rCSI 2.19%
    PRS 40.54
  • kidney epithelial cell CL0002518
    CSI 1.8
    rCSI 3.43%
    PRS 69.13
  • stem cell CL0000034
    CSI 1.79
    rCSI 1.72%
    PRS 36.82
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.72
    rCSI 2.14%
    PRS 28.79
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.68
    rCSI 3.7%
    PRS 60.38
  • M cell of gut CL0000682
    CSI 1.68
    rCSI 1.78%
    PRS 60.66
  • mesodermal cell CL0000222
    CSI 1.67
    rCSI 2.01%
    PRS 44
  • intestine goblet cell CL0019031
    CSI 1.66
    rCSI 1.47%
    PRS 44.92
  • colonocyte CL1000347
    CSI 1.65
    rCSI 2.36%
    PRS 52.86
  • transit amplifying cell of colon CL0009011
    CSI 1.61
    rCSI 1.89%
    PRS 49.58
  • alternatively activated macrophage CL0000890
    CSI 1.56
    rCSI 1.96%
    PRS 59.44
  • basal cell of epidermis CL0002187
    CSI 1.55
    rCSI 2.74%
    PRS 28.29
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.55
    rCSI 1.99%
    PRS 43.9
  • duct epithelial cell CL0000068
    CSI 1.52
    rCSI 2.22%
    PRS 49.13
  • club cell CL0000158
    CSI 1.5
    rCSI 2.19%
    PRS 45.27
  • promyelocyte CL0000836
    CSI 1.49
    rCSI 2.15%
    PRS 56
  • chondrocyte CL0000138
    CSI 1.48
    rCSI 2.35%
    PRS 39.09
  • intestinal tuft cell CL0019032
    CSI 1.47
    rCSI 2.25%
    PRS 50.6
  • alveolar macrophage CL0000583
    CSI 1.46
    rCSI 2.41%
    PRS 51.38
  • lung ciliated cell CL1000271
    CSI 1.46
    rCSI 1.69%
    PRS 36.29
  • intermediate monocyte CL0002393
    CSI 1.44
    rCSI 2.18%
    PRS 48.02
  • granulocyte CL0000094
    CSI 1.43
    rCSI 2.19%
    PRS 55.26
  • tuft cell of colon CL0009041
    CSI 1.38
    rCSI 3.22%
    PRS 63.15
  • helper T cell CL0000912
    CSI 1.33
    rCSI 1.88%
    PRS 54.51
  • retina horizontal cell CL0000745
    CSI 1.28
    rCSI 1.95%
    PRS 42.67
  • pancreatic ductal cell CL0002079
    CSI 1.25
    rCSI 2.43%
    PRS 48.05
  • promonocyte CL0000559
    CSI 1.21
    rCSI 2.08%
    PRS 55.31
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.2
    rCSI 2.12%
    PRS 29.38
  • type B pancreatic cell CL0000169
    CSI 1.14
    rCSI 2.52%
    PRS 43.41
  • foveolar cell of stomach CL0002179
    CSI 1.12
    rCSI 2.39%
    PRS 60.78
  • syncytiotrophoblast cell CL0000525
    CSI 1.07
    rCSI 3.07%
    PRS 63.44
  • basophil CL0000767
    CSI 1.06
    rCSI 2.25%
    PRS 66.39
  • enterocyte of epithelium of large intestine CL0002071
    CSI 1.03
    rCSI 5.43%
    PRS 59.99
  • pancreatic PP cell CL0002275
    CSI 0.8
    rCSI 3.17%
    PRS 61.28
  • tracheal goblet cell CL1000329
    CSI 0.74
    rCSI 1.62%
    PRS 65.1
  • kidney connecting tubule epithelial cell CL1000768
    CSI 0.71
    rCSI 1.81%
    PRS 36.59
  • myelocyte CL0002193
    CSI 0.61
    rCSI 4%
    PRS 78.3
  • eosinophil CL0000771
    CSI 0.58
    rCSI 3.83%
    PRS 76.43
  • Hofbauer cell CL3000001
    CSI 0.48
    rCSI 0.91%
    PRS 56.21
  • erythroid progenitor cell CL0000038
    CSI 0.36
    rCSI 2.09%
    PRS 56.72

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 [ALAS1](/details-gene/211) (5'-aminolevulinate synthase 1) is a protein-coding gene located on chromosome 3p21.2. It encodes a critical mitochondrial enzyme that catalyzes the first and rate-limiting step in the heme biosynthesis pathway. As the "housekeeping" isoform of 5-aminolevulinate synthase, [ALAS1](/details-gene/211) is responsible for producing heme for a wide variety of hemoproteins, such as cytochromes, which are essential for cellular respiration and metabolism ([Link](https://doi.org/10.1093/nar/18.23.7187)). Consistent with this fundamental role, the gene exhibits significant expression across a diverse array of metabolically active cell types. **Overall**, it is a top marker in `[multi-ciliated epithelial cells](/details-cell/CL0005012)`, `[myeloid leukocytes](/details-cell/CL0000766)`, and `[hepatocytes](/details-cell/CL0000182)`, highlighting its importance in cellular energy production, innate immunity, and systemic metabolic regulation. Dysregulation of [ALAS1](/details-gene/211) is clinically associated with certain forms of porphyria ([125290](https://omim.org/entry/125290)). ## Cellular Roles and Expression Landscape The expression profile of [ALAS1](/details-gene/211) underscores its foundational role in cells with high metabolic or biosynthetic demands. Its significance is not restricted to a single lineage but is instead a common feature of functionally diverse, high-energy cell types. **Overall**, the gene's highest significance is observed in several key functional groups: * **Metabolically Active Tissues:** [ALAS1](/details-gene/211) shows prominent significance in `[hepatocytes](/details-cell/CL0000182)`, including `[centrilobular region hepatocytes](/details-cell/CL0019029)`, which are central to detoxification and metabolism, processes heavily reliant on heme-containing cytochrome P450 enzymes. Its expression is also high in secretory `[acinar cells](/details-cell/CL0000622)`, which require substantial energy for protein synthesis and export. * **Epithelial and Barrier Cells:** The gene is a top marker in `[multi-ciliated epithelial cells](/details-cell/CL0005012)` and other `[ciliated cells](/details-cell/CL0000064)`, likely reflecting the high mitochondrial energy demand required to power ciliary beating for mucociliary clearance. Its significance in `[epithelial cells of the lung](/details-cell/CL0000082)` and `[squamous epithelial cells](/details-cell/CL0000076)` further suggests a role in maintaining epithelial integrity and function. * **Innate Immune System:** [ALAS1](/details-gene/211) is highly significant in `[myeloid leukocytes](/details-cell/CL0000766)` and more specific subsets like `[CD14-positive, CD16-positive monocytes](/details-cell/CL0002397)` and `[lung interstitial macrophages](/details-cell/CL4033043)`. This indicates that heme synthesis is crucial for supporting the energetic requirements of phagocytosis, respiratory burst, and other key functions of these innate immune cells. This broad but specific expression pattern solidifies the role of [ALAS1](/details-gene/211) as a fundamental housekeeping gene essential for the bioenergetic capacity of many of the body's most active cells. ## Pathways and Molecular Function The function of [ALAS1](/details-gene/211) is centered on its `5-aminolevulinate synthase activity` ([GO:0003870](https://www.ebi.ac.uk/QuickGO/term/GO:0003870)), a molecular function that initiates the `Heme biosynthetic process` ([GO:0006783](https://www.ebi.ac.uk/QuickGO/term/GO:0006783)). This process, detailed in the `Heme biosynthesis` pathway ([R-HSA-189451](https://reactome.org/content/detail/R-HSA-189451)), occurs within the `[Mitochondrion](/details-cell/GO:0005739)`, specifically in the `[Mitochondrial matrix](/details-cell/GO:0005759)`, where the ALAS1 protein is localized. The gene's activity is tightly linked to broader metabolic networks. Its involvement in pathways like `Transcriptional activation of mitochondrial biogenesis` ([R-HSA-2151201](https://reactome.org/content/detail/R-HSA-2151201)) and `Metabolism of lipids` ([R-HSA-556833](https://reactome.org/content/detail/R-HSA-556833)) highlights the coordination between heme production and the cell's overall energy status. Furthermore, its annotation in `Regulation of lipid metabolism by pparalpha` ([R-HSA-400206](https://reactome.org/content/detail/R-HSA-400206)) and `Response to bile acid` ([GO:1903412](https://www.ebi.ac.uk/QuickGO/term/GO:1903412)) is consistent with its high expression in `[hepatocytes](/details-cell/CL0000182)`, where bile acids are known to regulate its transcription ([Link](https://doi.org/10.1002/hep.21879)). These connections suggest that [ALAS1](/details-gene/211) acts as a metabolic sensor, integrating signals from lipid and bile acid metabolism to control the supply of heme for essential cellular functions. ## Research Directions The widespread and critical role of [ALAS1](/details-gene/211) provides multiple avenues for future investigation, particularly concerning its function in specific cellular contexts beyond its canonical role in the liver. ### Proposed Hypotheses 1. **Impaired Mucociliary Clearance:** The high significance of [ALAS1](/details-gene/211) in `[multi-ciliated epithelial cells](/details-cell/CL0005012)` suggests that localized defects in heme synthesis could impair mitochondrial respiration, leading to reduced ciliary beat frequency and compromised mucociliary clearance in the respiratory tract. 2. **Myeloid Cell Effector Function:** The expression of [ALAS1](/details-gene/211) in `[myeloid leukocytes](/details-cell/CL0000766)` may be essential for their effector functions. It is hypothesized that [ALAS1](/details-gene/211)-derived heme is a necessary cofactor for hemoproteins involved in the respiratory burst (e.g., cytochrome b-245) and that limiting heme availability could selectively dampen pro-inflammatory myeloid activity. ### Experimental Approach To test the hypothesis regarding mucociliary clearance (Hypothesis 1), a robust *in vitro* model could be employed. Primary human bronchial epithelial cells could be cultured at an air-liquid interface (ALI) to induce differentiation into a polarized, ciliated epithelium. [ALAS1](/details-gene/211) expression could then be knocked down using lentiviral-delivered shRNA. The functional consequences would be evaluated by measuring ciliary beat frequency (CBF) via high-speed video microscopy and assessing mitochondrial function through Seahorse XF analysis of oxygen consumption rates. A significant reduction in both CBF and mitochondrial respiration following [ALAS1](/details-gene/211) knockdown would support the hypothesis. ### Therapeutic Potential [ALAS1](/details-gene/211) is a well-established therapeutic target, but primarily for **inhibition** in the context of acute intermittent porphyria (AIP). In this disease, downstream defects in the heme pathway lead to a feedback-driven overexpression of [ALAS1](/details-gene/211) and the accumulation of toxic precursors. Therapeutic strategies, such as the FDA-approved siRNA drug Givosiran, are designed to specifically target and degrade [ALAS1](/details-gene/211) mRNA in `[hepatocytes](/details-cell/CL0000182)`, thereby reducing the toxic burden. Due to its essential housekeeping function across many tissues, systemic inhibition of [ALAS1](/details-gene/211) would likely be highly toxic. Therefore, its therapeutic potential is limited to diseases of overexpression and relies on targeted delivery mechanisms to confine its inhibitory effects to the specific cell type driving the pathology.

Genular Protein ID: 2229501242

Symbol: HEM1_HUMAN

Name: 5-aminolevulinate synthase, non-specific, mitochondrial

UniProtKB Accession Codes:

P13196

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 1 EMBL 4 Ensembl 4 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 4 RefSeq 4 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2263504

Title: Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes.

PubMed ID: 2263504

DOI: 10.1093/nar/18.23.7187

PubMed ID: 3671094

Title: Sequence of human 5-aminolevulinate synthase cDNA.

PubMed ID: 3671094

DOI: 10.1093/nar/15.20.8563

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: 16234850

Title: Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition.

PubMed ID: 16234850

DOI: 10.1139/o05-045

PubMed ID: 17975826

Title: Regulation of human liver delta-aminolevulinic acid synthase by bile acids.

PubMed ID: 17975826

DOI: 10.1002/hep.21879

Sequence Information:

  • Length: 640
  • Mass: 70581
  • Checksum: 5E952DCCFFD6873F
  • Sequence:
    • MESVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRALST AAVHYQQIKE 
TPPASEKDKT AKAKVQQTPD GSQQSPDGTQ LPSGHPLPAT SQGTASKCPF LAAQMNQRGS 
SVFCKASLEL QEDVQEMNAV RKEVAETSAG PSVVSVKTDG GDPSGLLKNF QDIMQKQRPE 
RVSHLLQDNL PKSVSTFQYD RFFEKKIDEK KNDHTYRVFK TVNRRAHIFP MADDYSDSLI 
TKKQVSVWCS NDYLGMSRHP RVCGAVMDTL KQHGAGAGGT RNISGTSKFH VDLERELADL 
HGKDAALLFS SCFVANDSTL FTLAKMMPGC EIYSDSGNHA SMIQGIRNSR VPKYIFRHND 
VSHLRELLQR SDPSVPKIVA FETVHSMDGA VCPLEELCDV AHEFGAITFV DEVHAVGLYG 
ARGGGIGDRD GVMPKMDIIS GTLGKAFGCV GGYIASTSSL IDTVRSYAAG FIFTTSLPPM 
LLAGALESVR ILKSAEGRVL RRQHQRNVKL MRQMLMDAGL PVVHCPSHII PVRVADAAKN 
TEVCDELMSR HNIYVQAINY PTVPRGEELL RIAPTPHHTP QMMNYFLENL LVTWKQVGLE 
LKPHSSAECN FCRRPLHFEV MSEREKSYFS GLSKLVSAQA

Genular Protein ID: 845292504

Symbol: B4DVA0_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DVA0

Database IDs:

ARBA 16 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 7 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 7 Gene3D 2 InterPro 8 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 1 Pfam 4 RefSeq 2 Rhea 2 SAM 1 SUPFAM 1 UniPathway 1

Sequence Information:

  • Length: 657
  • Mass: 72624
  • Checksum: 53A1CDE8C9B1144A
  • Sequence:
    • MDEWLLLHLD EPAYFLNMES VVRRCPFLSR VPQAFLQKAG KSLLFYAQNC PKMMEVGAKP 
APRALSTAAV HYQQIKETPP ASEKDKTAKA KVQQTPDGSQ QSPDGTQLPS GHPLPATSQG 
TASKCPFLAA QMNQRGSSVF CKASLELQED VQEMNAVRKE VAETSAGPSV VSVKTDGGDP 
SGLLKNFQDI MQKQRPERVS HLLQDNLPKS VSTFQYGRFF EKKIDEKKND HTYRVFKTVN 
RRAHIFPMAD DYSDSLITKK QVSVWCSNDY LGMSRHPRVC GAVMDTLKQH GAGAGGTRNI 
SGTSKFHVDL ERELADLHGK DAALLFSSCF VANDSTLFTL AKMMPGCEIY SDSGNHASMI 
QGIRNSRVPK YIFRHNDVSH LRELLQRSDP SVPKIVAFET VHSMDGAVCP LEELCDVAHE 
FGAITFVDEV HAVGLYGARG GGIGDRDGVM PKMDIISGTL GKAFGCVGGY IASTSSLIDT 
VRSYAAGFIF TTSLPPMLLA GALESVRILK SAEGRVLRRQ HQRNVKLMRQ MLMDAGLPVV 
HCPSHIIPVR VADAAKNTEV CDELMSRHNI YVQAINYPTV PRGEELLRIA PTPHHTPQMM 
NYFLENLLVT WKQVGLELKP HSSAECNFCR RPLHFEVMSE REKSYFSGLS KLVSAQA