BAALC: Difference between revisions
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{{infobox protein | {{infobox protein | ||
|name=brain and acute leukemia, cytoplasmic | |name=brain and acute leukemia, cytoplasmic | ||
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'''BAALC''' is a gene that codes for the: brain and acute leukemia cytoplasmic protein.<ref name=" | '''BAALC''' is a gene that codes for the: brain and acute leukemia cytoplasmic protein.<ref name="Tanner_2001">{{cite journal | vauthors = Tanner SM, Austin JL, Leone G, Rush LJ, Plass C, Heinonen K, Mrózek K, Sill H, Knuutila S, Kolitz JE, Archer KJ, Caligiuri MA, Bloomfield CD, de La Chapelle A | display-authors = 6 | title = BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 24 | pages = 13901–6 | date = November 2001 | pmid = 11707601 | doi = 10.1073/pnas.241525498 | pmc=61139}}</ref> The official symbol (BAALC) and official name (brain and acute leukemia cytoplasmic) is maintained by the [[HUGO Gene Nomenclature Committee|HGNC]].<ref>{{cite web|url=https://www.proteinatlas.org/ENSG00000164929-BAALC/tissue#gene_information|title=Tissue expression of BAALC - Summary - The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-11-15}}</ref> The function of BAALC is not fully understood yet but has been suggested to have synaptic roles involving the post synaptic lipid raft.<ref name="Wang_2005">{{cite journal | vauthors = Wang X, Tian QB, Okano A, Sakagami H, Moon IS, Kondo H, Endo S, Suzuki T | title = BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with alpha, but not beta, subunit of Ca/calmodulin-dependent protein kinase II | journal = Journal of Neurochemistry | volume = 92 | issue = 3 | pages = 647–59 | date = February 2005 | pmid = | doi = 10.1111/j.1471-4159.2004.02902.x }}</ref> Lipid rafts are microdomains that are enriched with [[cholesterol]] and [[sphingolipid]]s, [[lipid raft]] functions include membrane trafficking, signal processing, and regulation of the actin cytoskeleton.<ref name="Wang_2005" /> The postsynpatic lipid raft possesses many proteins and is one of the major sites for signal processing and [[postsynaptic density]] (PSD).<ref name="Wang_2005" /> Along with its involvement in the post synaptic lipid rafts, BAALC expression has been associated with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia.<ref name="Tanner_2001" /> | ||
== Genetics == | == Genetics == | ||
[[File:Ideogram human chromosome 8.svg|thumb|324x324px|Location of BAALC is 8q22.3]] | [[File:Ideogram human chromosome 8.svg|thumb|324x324px|Location of BAALC is 8q22.3]] | ||
[[File:BAALC Gene on Chromosome 8.png|thumb|327x327px|8q22.3 marked, this showing the location of BAALC gene]]BAALC gene is located on the long arm (q) of [[Chromosome 8 (human)|chromosome 8]] at position 22.3 (8q22.3).<ref name=" | [[File:BAALC Gene on Chromosome 8.png|thumb|327x327px|8q22.3 marked, this showing the location of BAALC gene]]BAALC gene is located on the long arm (q) of [[Chromosome 8 (human)|chromosome 8]] at position 22.3 (8q22.3).<ref name="genecards" /> The human BAALC gene contains eight exons, spans 89 613 bases of genomic [[DNA]], and the transcript contains 180 [[amino acid]]s.<ref name="genecards" /><ref name="ptglab">{{cite web|url=https://www.ptglab.com/Products/BAALC-Antibody-24997-1-AP.htm#datasheet|title=24997-1-AP|website=www.ptglab.com|access-date=2017-11-15}}</ref> | ||
The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats.<ref name=" | The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats.<ref name="Tanner_2001" /> But ''BAALC'' is not seen in lower organisms such as: ''[[Drosophila melanogaster|Drosophila. melanogaster]], [[Saccharomyces cerevisiae|Saccharomyces. cerevisiae]],'' and ''[[Caenorhabditis elegans|Caenorhabditis. elegans]]''.<ref name="Tanner_2001" /> | ||
BAALC and its protein are expressed highly in neural tissues such as the [[Central nervous system|Central Nervous System]] (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands.<ref name=" | BAALC and its protein are expressed highly in neural tissues such as the [[Central nervous system|Central Nervous System]] (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands.<ref name="Tanner_2001" /> The BAALC protein is not expressed in peripheral blood leukocytes (PBL), lymph nodes, or nonneural tissues.<ref name="Tanner_2001" /><ref name="genecards">{{cite web | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=BAALC | title=BAALC Gene - GeneCards {{!}} BAALC Protein {{!}} BAALC Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-11-15}}</ref> BAALC expression has only been found in [[Bone marrow|Bone Marrow]] (BM) when expressed from [[CD34|CD34+ progenitor cells]], besides this BAALC expression has not been visualized.<ref name="Tanner_2001" /> The expression of BAALC from the CD34+ [[progenitor cell]]s suggest the gene has [[neuroectoderm]]al and [[Hematopoietic stem cell|hematopoietic]] cell functions.<ref name="Damm_2011">{{cite journal | vauthors = Damm F, Heuser M, Morgan M, Wagner K, Görlich K, Grosshennig A, Hamwi I, Thol F, Surdziel E, Fiedler W, Lübbert M, Kanz L, Reuter C, Heil G, Delwel R, Löwenberg B, Valk PJ, Krauter J, Ganser A | display-authors = 6 | title = Integrative prognostic risk score in acute myeloid leukemia with normal karyotype | journal = Blood | volume = 117 | issue = 17 | pages = 4561–8 | date = April 2011 | pmid = 21372155 | doi = 10.1182/blood-2010-08-303479 }}</ref><ref name="Tanner_2001" /><ref name="Xiao_2015">{{cite journal | vauthors = Xiao SJ, Shen JZ, Huang JL, Fu HY | title = Prognostic significance of the BAALC gene expression in adult patients with acute myeloid leukemia: A meta-analysis | journal = Molecular and Clinical Oncology | volume = 3 | issue = 4 | pages = 880–888 | date = July 2015 | pmid = 26171200 | pmc = 4486884 | doi = 10.3892/mco.2015.562 | via = }}</ref> BAALC expression is higher in [[neuroectoderm]]al-derived tissues such as the frontal part of the brain, more specifically in the [[hippocampus]], and [[neocortex]].<ref name="Wang_2005" /> | ||
The BAALC gene has eight different transcripts that result into six different [[protein isoform]]s.<ref name=" | The BAALC gene has eight different transcripts that result into six different [[protein isoform]]s.<ref name="swissmodel" /> Isoforms that carry the exon number two do not express protein and it is believed that the termination in [[exon]] two results in an unstable protein after [[Translation (biology)|translation]].<ref name="Tanner_2001" /> The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in the above-mentioned mammals.<ref name="Tanner_2001" /> | ||
== Function == | == Function == | ||
The BAALC gene initially was discovered in the neuroderm of both the human and the mouse.<ref name=" | The BAALC gene initially was discovered in the neuroderm of both the human and the mouse.<ref name="Tanner_2001" /> The function of BAALC protein is not understood very well, but it is predicted to be associated with the cytoskeleton network.<ref name="Tanner_2001" /> When expressed in Bone Marrow CD34+ progenitor cells, BAALC has neuroectodermal and hematopoietic cell functions.<ref name="Tanner_2001" /> Differentiation failure caused by cell shape, motility and adhesion in association between cells are all possible outcomes due to the little known effects and unlear mechanism sites of the BAALC genes.<ref name="Xiao_2015"/> The role of the BAALC gene causing leukemia in immature acute leukemic cells has been found by knocking out the function of BAALC gene using hairpin ([[Stem-loop|stem loop]]) [[RNA]] in a human leukemia cell line KG1a.<ref name="Xu_2012">{{cite journal | vauthors = Xu B, Chen G, Shi P, Guo X, Xiao P, Wang W, Zhou S | title = shRNA-Mediated BAALC knockdown affects proliferation and apoptosis in human acute myeloid leukemia cells | journal = Hematology | volume = 17 | issue = 1 | pages = 35–40 | date = January 2012 | pmid = 22549446 | doi = 10.1179/102453312X13221316477499 }}</ref> The result of knocking out BAALC expression is a decrease in uncontrolled cell growth and an increase in programmed cell death.<ref name="Xu_2012" /><ref name="Xiao_2015" /> The BAALC protein isoform 1-6-8, has been found to interact and associate with the CAMKII alpha subunit and not with the beta subunit.<ref name="Wang_2005" /> The interaction with the CAMKII alpha subunit is in the CAMKII protein's regulatory region and near the [[autophosphorylation]] site, this suggested a regulatory function of the 1-6-8 isoform on the alpha subunit.<ref name="Wang_2005" /> BAALC 1-6-8 isoform also gets targeted to post synaptic lipid rafts, which are thought to have functions involved in: signal processing, membrane trafficking, and regulation of the actin cytoskeleton.<ref name="Wang_2005" /> BAALC may play a role in the regulation of the [[Ca2+/calmodulin-dependent protein kinase II|CAMKII]] protein through interactions with the alpha subunit, no interactions have been found with the beta subunit of this protein.<ref name="Wang_2005" /> Evidence has shown the BAALC protein to be an intracellular protein with cytoskeleton network roles, these roles include regulation of the [[actin]] [[cytoskeleton]] which is an associated role of postsynaptic lipid rafts.<ref name="Tanner_2001" /><ref name="Wang_2005" /> | ||
== | == Clinical Significance == | ||
In studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL.<ref name=" | In studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL.<ref name="Tanner_2001" /> BAALC is ruled out as a marker for [[Neoplasm|neoplasia]] because it is not expressed in other cancer cells.<ref name="Tanner_2001" /> BAALC is seen in acute leukemia in immature [[Myocyte|myoblasts]] and early progenitor cells, but is excluded from mature hematopoietic cells.<ref name="Xu_2012" /><ref name="Tanner_2001" /> It has been found in studies that acute myeloid leukemia patients who over expressed BAALC (BAALC Positive) had a median of approximately 5 months of event free survival, but those who were BAALC negative had a median of around 15 months.<ref name="Tanner_2001" /> Research has found when BAALC is combined with the oncogene [[HOXA9|Hoxa9]], BAALC blocks myeloid differentiation.<ref name="Heesch_2010">{{cite journal | vauthors = Heesch S, Schlee C, Neumann M, Stroux A, Kühnl A, Schwartz S, Haferlach T, Goekbuget N, Hoelzer D, Thiel E, Hofmann WK, Baldus CD | title = BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia | journal = Leukemia | volume = 24 | issue = 8 | pages = 1429–36 | date = August 2010 | pmid = 20535151 | doi = 10.1038/leu.2010.130 }}</ref> This blocking induces leukemogenesis. BAALC over-expression is associated with [[IDH1]] and [[IDH2]] wild type in Chinese cytogenetically normal acute myeloid leukemia patients.<ref name="Heesch_2010" /> The results found by Zhou et al. are different than that found by Weber et al. where no difference in mutations in IDH1 and IDH2 where seen depending on expression of BAALC.<ref name="Xu_2012" /> [[IGFBP7]] is another gene involved in leukemia, this was found conducting [[Gene expression profiling|gene expression profiles]] (GEP) with BAALC.<ref name="Heesch_2010" /> This gene has BAALC characteristics and, unlike BAALC, may have a role in drug resistance and the mechanism of leukemogenesis'''.'''<ref name="Heesch_2010" /> It has been found that treatment for some acute leukemias failed due to BAALC and this suggests BAALC to be a potential [[surrogate marker]].<ref name="Heesch_2010" /> The use of BAALC expression in acute leukemia prognosis is unclear and being studied.<ref name="Xiao_2015"/><ref name="Damm_2011" />[[Prognosis]] of patients with AML and BAALC over-expression has been found to be poor or worse than poor.<ref name="Xiao_2015"/> Over-expression of the BAALC gene and considerable accumulation of the gene production has been found to have caused drug resistance in patients.<ref name="Xiao_2015"/> | ||
== Expression in Cancers == | == Expression in Cancers == | ||
| Line 46: | Line 48: | ||
|Over Expression | |Over Expression | ||
|[[Real-time polymerase chain reaction|RT-PCR]] | |[[Real-time polymerase chain reaction|RT-PCR]] | ||
|<ref name=" | |<ref name="Tanner_2001" /> | ||
|- | |- | ||
|Acute Lymphoblastic Leukemia (ALL) | |Acute Lymphoblastic Leukemia (ALL) | ||
|Over Expression | |Over Expression | ||
|RT-PCR | |RT-PCR | ||
|<ref name=" | |<ref name="Tanner_2001" /> | ||
|- | |- | ||
| | | | ||
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|} | |} | ||
Overexpression of the BAALC gene is seen in [[Acute myeloid leukemia|Acute Myeloid Leukemia]] (AML) and [[Acute lymphoblastic leukemia|Acute Lymphoblastic Leukemia]] (ALL).<ref name=" | Overexpression of the BAALC gene is seen in [[Acute myeloid leukemia|Acute Myeloid Leukemia]] (AML) and [[Acute lymphoblastic leukemia|Acute Lymphoblastic Leukemia]] (ALL).<ref name="Heesch_2010" /><ref name="Weber_2016">{{cite journal | vauthors = Weber S, Haferlach T, Alpermann T, Perglerová K, Schnittger S, Haferlach C, Kern W | title = Feasibility of BAALC gene expression for detection of minimal residual disease and risk stratification in normal karyotype acute myeloid leukaemia | journal = British Journal of Haematology | volume = 175 | issue = 5 | pages = 904–916 | year = 2016 | pmid = 27662611 | doi = 10.1111/bjh.14343 }}</ref> It has been found that BAALC can cause the start of Leukemia (leukemogenesis) by stopping the differentiation of [[Myeloid tissue|myeloid]].<ref name="Heuser_2012">{{cite journal | vauthors = Heuser M, Berg T, Kuchenbauer F, Lai CK, Park G, Fung S, Lin G, Leung M, Krauter J, Ganser A, Humphries RK | display-authors = 6 | title = Functional role of BAALC in leukemogenesis | journal = Leukemia | volume = 26 | issue = 3 | pages = 532–6 | date = March 2012 | pmid = 21869843 | doi = 10.1038/leu.2011.228 }}</ref> Silencing BAALC lowers the amount of proliferation and increased cell death ([[apoptosis]]) in leukemic cell lines KG1a<ref name="Xu_2012" /> It has also been found with the over-expression of the BAALC genes to cause low levels of complete remission in cancer patients, and low amount of overall survival in patients.<ref name="Xiao_2015" /> | ||
== Structure == | == Structure == | ||
The human BAALC gene contains eight exons, spans 89 613 bases of genomic [[DNA]], and the transcript contains 180 [[amino acid]]s. | The human BAALC gene contains eight exons, spans 89 613 bases of genomic [[DNA]], and the transcript contains 180 [[amino acid]]s.<ref name="genecards" /><ref name="ptglab" /> This gene codes for eight different transcripts that are translated into six different protein isoforms.<ref name="Tanner_2001" /><ref name="swissmodel">{{Cite web|url=https://swissmodel.expasy.org/repository/uniprot/Q8WXS3?csm=380183E0F188F684|title=SWISS-MODEL {{!}} Q8WXS3|website=swissmodel.expasy.org|language=en|access-date=2017-11-30}}</ref> Isoforms containing exon number two (1-2-6-8 and 1-2-5-6-8) do not code protein and so exon two contains a termination codon.<ref name="Tanner_2001" /> The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in mammals.<ref name="Tanner_2001" /> | ||
BAALC protein isoform 1-6-8 is modified by [[myristoylation]] an [[palmitoylation]] at the [[N-terminus|N-terminal]].<ref name=" | BAALC protein isoform 1-6-8 is modified by [[myristoylation]] an [[palmitoylation]] at the [[N-terminus|N-terminal]].<ref name="Wang_2005" /> These modifications occur on the [[Glycine]] 2 and [[Cysteine]] 3 amino acids of the protein.<ref name="Wang_2005" /> These modifications are used for targeting the protein to the lipid rafts.<ref name="Wang_2005" /> Little phosphorylation of the BAALC isoform 1-6-8 by the CAMK2A protein has been found as well.<ref name="Wang_2005" /> | ||
== Interactions == | == Interactions == | ||
[[CAMK2A]]<ref name=" | [[CAMK2A]]<ref name="ptglab" /><ref name="genecards" /> | ||
== See also == | == See also == | ||
CAMK2A<ref name=" | CAMK2A<ref name="Wang_2005" /> | ||
Acute Myeloid Leukemia<ref name=" | Acute Myeloid Leukemia<ref name="Tanner_2001" /> | ||
Acute lymphoblastic Leukemia<ref name=" | Acute lymphoblastic Leukemia<ref name="Tanner_2001" /> | ||
CD34<ref name=" | CD34<ref name="Tanner_2001" /> | ||
IGFBP7<ref name=" | IGFBP7<ref name="Heesch_2010" /> | ||
== References == | == References == | ||
{{Reflist}} | |||
Revision as of 18:43, 27 March 2018
| brain and acute leukemia, cytoplasmic | |
|---|---|
| Identifiers | |
| Symbol | BAALC |
| Entrez | 79870 |
| HUGO | 14333 |
| OMIM | 606602 |
| RefSeq | NP_079088.1&rn=1 NP_001019543.1 NP_079088.1 |
| UniProt | Q8WXS3 |
| Other data | |
| Locus | Chr. 8 q22.3 |
BAALC is a gene that codes for the: brain and acute leukemia cytoplasmic protein.[1] The official symbol (BAALC) and official name (brain and acute leukemia cytoplasmic) is maintained by the HGNC.[2] The function of BAALC is not fully understood yet but has been suggested to have synaptic roles involving the post synaptic lipid raft.[3] Lipid rafts are microdomains that are enriched with cholesterol and sphingolipids, lipid raft functions include membrane trafficking, signal processing, and regulation of the actin cytoskeleton.[3] The postsynpatic lipid raft possesses many proteins and is one of the major sites for signal processing and postsynaptic density (PSD).[3] Along with its involvement in the post synaptic lipid rafts, BAALC expression has been associated with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia.[1]
Genetics
BAALC gene is located on the long arm (q) of chromosome 8 at position 22.3 (8q22.3).[4] The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids.[4][5]
The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats.[1] But BAALC is not seen in lower organisms such as: Drosophila. melanogaster, Saccharomyces. cerevisiae, and Caenorhabditis. elegans.[1]
BAALC and its protein are expressed highly in neural tissues such as the Central Nervous System (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands.[1] The BAALC protein is not expressed in peripheral blood leukocytes (PBL), lymph nodes, or nonneural tissues.[1][4] BAALC expression has only been found in Bone Marrow (BM) when expressed from CD34+ progenitor cells, besides this BAALC expression has not been visualized.[1] The expression of BAALC from the CD34+ progenitor cells suggest the gene has neuroectodermal and hematopoietic cell functions.[6][1][7] BAALC expression is higher in neuroectodermal-derived tissues such as the frontal part of the brain, more specifically in the hippocampus, and neocortex.[3]
The BAALC gene has eight different transcripts that result into six different protein isoforms.[8] Isoforms that carry the exon number two do not express protein and it is believed that the termination in exon two results in an unstable protein after translation.[1] The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in the above-mentioned mammals.[1]
Function
The BAALC gene initially was discovered in the neuroderm of both the human and the mouse.[1] The function of BAALC protein is not understood very well, but it is predicted to be associated with the cytoskeleton network.[1] When expressed in Bone Marrow CD34+ progenitor cells, BAALC has neuroectodermal and hematopoietic cell functions.[1] Differentiation failure caused by cell shape, motility and adhesion in association between cells are all possible outcomes due to the little known effects and unlear mechanism sites of the BAALC genes.[7] The role of the BAALC gene causing leukemia in immature acute leukemic cells has been found by knocking out the function of BAALC gene using hairpin (stem loop) RNA in a human leukemia cell line KG1a.[9] The result of knocking out BAALC expression is a decrease in uncontrolled cell growth and an increase in programmed cell death.[9][7] The BAALC protein isoform 1-6-8, has been found to interact and associate with the CAMKII alpha subunit and not with the beta subunit.[3] The interaction with the CAMKII alpha subunit is in the CAMKII protein's regulatory region and near the autophosphorylation site, this suggested a regulatory function of the 1-6-8 isoform on the alpha subunit.[3] BAALC 1-6-8 isoform also gets targeted to post synaptic lipid rafts, which are thought to have functions involved in: signal processing, membrane trafficking, and regulation of the actin cytoskeleton.[3] BAALC may play a role in the regulation of the CAMKII protein through interactions with the alpha subunit, no interactions have been found with the beta subunit of this protein.[3] Evidence has shown the BAALC protein to be an intracellular protein with cytoskeleton network roles, these roles include regulation of the actin cytoskeleton which is an associated role of postsynaptic lipid rafts.[1][3]
Clinical Significance
In studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL.[1] BAALC is ruled out as a marker for neoplasia because it is not expressed in other cancer cells.[1] BAALC is seen in acute leukemia in immature myoblasts and early progenitor cells, but is excluded from mature hematopoietic cells.[9][1] It has been found in studies that acute myeloid leukemia patients who over expressed BAALC (BAALC Positive) had a median of approximately 5 months of event free survival, but those who were BAALC negative had a median of around 15 months.[1] Research has found when BAALC is combined with the oncogene Hoxa9, BAALC blocks myeloid differentiation.[10] This blocking induces leukemogenesis. BAALC over-expression is associated with IDH1 and IDH2 wild type in Chinese cytogenetically normal acute myeloid leukemia patients.[10] The results found by Zhou et al. are different than that found by Weber et al. where no difference in mutations in IDH1 and IDH2 where seen depending on expression of BAALC.[9] IGFBP7 is another gene involved in leukemia, this was found conducting gene expression profiles (GEP) with BAALC.[10] This gene has BAALC characteristics and, unlike BAALC, may have a role in drug resistance and the mechanism of leukemogenesis.[10] It has been found that treatment for some acute leukemias failed due to BAALC and this suggests BAALC to be a potential surrogate marker.[10] The use of BAALC expression in acute leukemia prognosis is unclear and being studied.[7][6]Prognosis of patients with AML and BAALC over-expression has been found to be poor or worse than poor.[7] Over-expression of the BAALC gene and considerable accumulation of the gene production has been found to have caused drug resistance in patients.[7]
Expression in Cancers
| Cancer | Under or Over expression | Evaluation Method | Reference |
|---|---|---|---|
| Acute Myeloid Leukemia (AML) | Over Expression | RT-PCR | [1] |
| Acute Lymphoblastic Leukemia (ALL) | Over Expression | RT-PCR | [1] |
Overexpression of the BAALC gene is seen in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).[10][11] It has been found that BAALC can cause the start of Leukemia (leukemogenesis) by stopping the differentiation of myeloid.[12] Silencing BAALC lowers the amount of proliferation and increased cell death (apoptosis) in leukemic cell lines KG1a[9] It has also been found with the over-expression of the BAALC genes to cause low levels of complete remission in cancer patients, and low amount of overall survival in patients.[7]
Structure
The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids.[4][5] This gene codes for eight different transcripts that are translated into six different protein isoforms.[1][8] Isoforms containing exon number two (1-2-6-8 and 1-2-5-6-8) do not code protein and so exon two contains a termination codon.[1] The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in mammals.[1]
BAALC protein isoform 1-6-8 is modified by myristoylation an palmitoylation at the N-terminal.[3] These modifications occur on the Glycine 2 and Cysteine 3 amino acids of the protein.[3] These modifications are used for targeting the protein to the lipid rafts.[3] Little phosphorylation of the BAALC isoform 1-6-8 by the CAMK2A protein has been found as well.[3]
Interactions
See also
CAMK2A[3]
Acute Myeloid Leukemia[1]
Acute lymphoblastic Leukemia[1]
CD34[1]
IGFBP7[10]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 Tanner SM, Austin JL, Leone G, Rush LJ, Plass C, Heinonen K, et al. (November 2001). "BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia". Proceedings of the National Academy of Sciences of the United States of America. 98 (24): 13901–6. doi:10.1073/pnas.241525498. PMC 61139. PMID 11707601.
- ↑ "Tissue expression of BAALC - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-11-15.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 Wang X, Tian QB, Okano A, Sakagami H, Moon IS, Kondo H, Endo S, Suzuki T (February 2005). "BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with alpha, but not beta, subunit of Ca/calmodulin-dependent protein kinase II". Journal of Neurochemistry. 92 (3): 647–59. doi:10.1111/j.1471-4159.2004.02902.x.
- ↑ 4.0 4.1 4.2 4.3 4.4 Database, GeneCards Human Gene. "BAALC Gene - GeneCards | BAALC Protein | BAALC Antibody". www.genecards.org. Retrieved 2017-11-15.
- ↑ 5.0 5.1 5.2 "24997-1-AP". www.ptglab.com. Retrieved 2017-11-15.
- ↑ 6.0 6.1 Damm F, Heuser M, Morgan M, Wagner K, Görlich K, Grosshennig A, et al. (April 2011). "Integrative prognostic risk score in acute myeloid leukemia with normal karyotype". Blood. 117 (17): 4561–8. doi:10.1182/blood-2010-08-303479. PMID 21372155.
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Xiao SJ, Shen JZ, Huang JL, Fu HY (July 2015). "Prognostic significance of the BAALC gene expression in adult patients with acute myeloid leukemia: A meta-analysis". Molecular and Clinical Oncology. 3 (4): 880–888. doi:10.3892/mco.2015.562. PMC 4486884. PMID 26171200.
- ↑ 8.0 8.1 "SWISS-MODEL | Q8WXS3". swissmodel.expasy.org. Retrieved 2017-11-30.
- ↑ 9.0 9.1 9.2 9.3 9.4 Xu B, Chen G, Shi P, Guo X, Xiao P, Wang W, Zhou S (January 2012). "shRNA-Mediated BAALC knockdown affects proliferation and apoptosis in human acute myeloid leukemia cells". Hematology. 17 (1): 35–40. doi:10.1179/102453312X13221316477499. PMID 22549446.
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Heesch S, Schlee C, Neumann M, Stroux A, Kühnl A, Schwartz S, Haferlach T, Goekbuget N, Hoelzer D, Thiel E, Hofmann WK, Baldus CD (August 2010). "BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia". Leukemia. 24 (8): 1429–36. doi:10.1038/leu.2010.130. PMID 20535151.
- ↑ Weber S, Haferlach T, Alpermann T, Perglerová K, Schnittger S, Haferlach C, Kern W (2016). "Feasibility of BAALC gene expression for detection of minimal residual disease and risk stratification in normal karyotype acute myeloid leukaemia". British Journal of Haematology. 175 (5): 904–916. doi:10.1111/bjh.14343. PMID 27662611.
- ↑ Heuser M, Berg T, Kuchenbauer F, Lai CK, Park G, Fung S, et al. (March 2012). "Functional role of BAALC in leukemogenesis". Leukemia. 26 (3): 532–6. doi:10.1038/leu.2011.228. PMID 21869843.