CRACD-like protein

CRACDL is a protein-coding gene.{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA1211L|title=KIAA1211L Gene - GeneCards {{!}} K121L Protein {{!}} K121L Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-02-24}} The table above presents the gene's alias, location, size and accession number.

There are 11 splice isoforms of the CRACDL. The validated isoform has 10 exons.

File:Conceptual Translation KIAA1211L Part 1.jpg

File:Conceptual Translation KIAA1211L Part 2.0.jpg

The table above presents the protein's alias, size, and accession number. The CRACD-L protein is proline rich and asparagine, isoleucine, phenylalanine, and tyrosine poor.

File:MyDomain.png

The CRACD-L protein has one domain called the DUF4592 motif and spans amino acids 131–239.{{Cite web|url=http://pfam.xfam.org/family/PF15262|title=Pfam: Family: DUF4592 (PF15262)|website=pfam.xfam.org|access-date=2017-04-23}} This domain is highly conserved among the CRACDL orthologs. The DUF4592 motif is depicted in both the conceptual translation and schematic figures.

CRACDL is phosphorylated at the Ser92 and Ser490 amino acids.{{Cite web|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_207362.2|title=Homo sapiens KIAA1211 like (KIAA1211L), mRNA - Nucleotide - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2017-04-23}} The KIAA1211L protein is also predicted to have five different SUMOylation sites located at Lys134, Lys375, Lys866, Lys874, and Lys914.{{Cite web|url=http://www.abgent.com/sumoplot|title=SUMOplot™ Analysis Program {{!}} Abgent|website=www.abgent.com|language=en|access-date=2017-04-23}} Both the phosphorylated sites and the SUMOylation sites are depicted in the conceptual translation and schematic figures.

The CRACD-L protein predicted secondary structure is composed of 50% alpha helixes, 8.9% beta sheets, and 17.9% turns.{{Cite web|url=http://www.biogem.org|title=BioGem.Org - Ashok Kumar's Bioinformatics Portal... {{!}} Home|last=Kumar|first=Prof. T. Ashok|website=www.biogem.org|access-date=2017-04-23}} The high number of turns is consistent with the fact that CRACD-L is proline rich.

The CRACD-L protein is predicted to be located in the nucleus.{{Cite web|url=https://psort.hgc.jp/cgi-bin/runpsort.pl|title=GenScript Protein Subcellular Location Prediction Tool}}{{Dead link|date=February 2020 |bot=InternetArchiveBot |fix-attempted=yes }} The orthologs, including the elephant shark, horse, rock dove, and chimp, are also predicted to be located in the nucleus. The nuclear location signal is located on amino acids 25-43 which is depicted in both the conceptual translation and schematic figures. . This signal is conserved throughout the orthologs. Additionally, this location (amino acids 24-43) is positively charged, probably due to the high amount of lysine at this location. Finally, it is predicted that CRACD-L is mainly localized to the microtubules and centrosome and sometimes localized to the cytokinetic bridge.{{Cite web|url=http://www.proteinatlas.org/ENSG00000196872-KIAA1211L/cell|title=Cell atlas - KIAA1211L - The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-04-23}}

The gene is highly expressed in the cerebral cortex of the brain. The CRACD-L protein is located in many different tissue types, including the brain, the hippocampus, the lung, breast carcinoma, the islets of Langerhans, the pancreas, the kidney, and 38 other tissues.{{Cite web|url=http://www.proteinatlas.org/ENSG00000196872-KIAA1211L/tissue|title=Tissue expression of KIAA1211L - Summary - The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-04-23}} Additionally, it is expressed an average amount compared to other human proteins.{{Cite web|url=http://pax-db.org/protein/1858538|title=KIAA1211L protein abundance in PaxDb|website=pax-db.org|language=en|access-date=2017-04-23}}

The promoter region of CRACDL is approximately 1340 base pairs with various predicted transcription factors.{{Cite web|url=https://www.genomatix.de/|title=Genomatix - NGS Data Analysis & Personalized Medicine|website=www.genomatix.de|access-date=2017-05-07|archive-date=2001-02-24|archive-url=https://web.archive.org/web/20010224072831/http://www.genomatix.de/|url-status=dead}} The glial cells missing homolog 1 and the oligodendrocyte lineage transcription factors are notable because CRACDL is highly expressed in the brain. Furthermore, the Estrogen-related receptor alpha is also a notable transcription factor due to CRACDL's low expression levels when estrogen receptors are knocked down.{{cite journal | vauthors = Al Saleh S, Al Mulla F, Luqmani YA | title = Estrogen receptor silencing induces epithelial to mesenchymal transition in human breast cancer cells | journal = PLOS ONE | volume = 6 | issue = 6 | pages = e20610 | date = 2011 | pmid = 21713035 | pmc = 3119661 | doi = 10.1371/journal.pone.0020610 | bibcode = 2011PLoSO...620610A | doi-access = free }} Furthermore, CRACDL is predicted to be SUMOylated. The 3' UTR of CRACDL is predicted to be a targeted by miRNA-132, which is depicted in the conceptual translation figure.{{Cite journal|last=Alvarez-Saavedra|first=M|date=2010|title=MicroRNA-132-Dependent Post-Transcriptional Regulation of Clock Entrainment Physiology Via Modulation of Chromatin Remodeling and Translational Control Gene Targets|journal=University of Ottawa}}

Glycogen Synthase Kinase 3 Beta (GSK3B)

GSK3B is a protein kinase that regulates transcription factors and microtubules.{{Cite web|url=https://www.uniprot.org/uniprot/P49841|title=GSK3B - Glycogen synthase kinase-3 beta - Homo sapiens (Human) - GSK3B gene & protein|website=www.uniprot.org|language=en|access-date=2017-04-23}} As such, it phosphorylates proteins, decreasing their ability to bind and stabilize microtubules. The proteins it phosphorylates are the principle components of neurofibrillary tangles in Alzheimer disease. The protein is needed for the establishment of neuronal polarity and axon outgrowth and phosphorylates proteins in neuroblastoma cells. Furthermore, it is associated with bipolar disease and is active in breast cancer cells.{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=GSK3B|title=GSK3B Gene - GeneCards {{!}} GSK3B Protein {{!}} GSK3B Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-04-23}}

As such, the predicted interaction between CRACDL and GSK3B is likely because CRACDL is highly expressed in the brain, associated with bipolar disorder and breast cancer, and is localized on the microtubules. The interaction between GSK3B and CRACDL was predicted using anti bait coimmunoprecipitation, pull down, tandem affinity purification, fluorescence polarization spectroscopy, protein kinases assay, two hybrid, and confocal microscopy experiments.{{Cite web|url=http://www.ebi.ac.uk/intact/|title=IntAct|website=www.ebi.ac.uk|access-date=2017-04-23}}

CRACD-L protein is also predicted to interact with Alpha-synuclein (SNCA), E3 Ubiquitin-Protein Ligase Mdm2 (MDM2), Serine/Threonine-Protein Kinase PAK 1 (PAK 1), and DNA Replication Factor Cdt1 (CDT1).

CRACDL is associated with depression, bipolar disorder, and schizophrenia.{{cite journal | vauthors = Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T | title = Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders | journal = Molecular Psychiatry | volume = 9 | issue = 4 | pages = 406–16 | date = April 2004 | pmid = 14743183 | doi = 10.1038/sj.mp.4001437 | doi-access = }} Additionally, CRACDL is associated with various cancers including ovarian, breast, etc.{{cite thesis | vauthors = Spurrell CH | degree = Doctor of Philosophy | publisher = University of Washington |date=2013|title=Identifying New Genes for Inherited Breast Cancer by Exome Sequencing.|url=https://digital.lib.washington.edu/researchworks/handle/1773/25172 }}

KIAA1211 is the paralog to KIAA1211L. KIAA1211 is located on chromosome 4 and has 1233 amino acids.{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA1211|title=KIAA1211 Gene - GeneCards {{!}} K1211 Protein {{!}} K1211 Antibody|last=Database|first=GeneCards Human Gene|website=www.genecards.org|access-date=2017-04-23}} Its percent identity to KIAA1211L is 21%.{{cite journal | vauthors = Myers EW, Miller W | title = Optimal alignments in linear space | journal = Computer Applications in the Biosciences | volume = 4 | issue = 1 | pages = 11–7 | date = March 1988 | pmid = 3382986 | doi = 10.1093/bioinformatics/4.1.11}} The KIAA1211 has an ortholog in the bacteria Proteus vulgarism, indicating the paralog duplicated 4290 million years ago, before KIAA1211L.{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/?term=XP_007889338.1|title=kiaa1211l KIAA1211 like [Callorhinchus milii (elephant shark)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2017-02-24}}{{Cite web|url=http://www.timetree.org|title=TimeTree :: The Timescale of Life|website=www.timetree.org|access-date=2017-02-24}}

Below is the table of various KIAA1211L orthologs. It includes closely, intermediately, and distantly related orthologs. The most distant ortholog is the elephant shark, indicating KIAA1211L duplicated 473 MYA. The amino acids conserved among all the KIAA1211L orthologs are depicted in the conceptual translation.

The CRACDL gene is similar and conserved in mammals, birds, reptiles, amphibians, and fish. It is not conserved in bacteria, archaea, protists, plants, fungus, trichoplax, and invertebrates.

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Category:Human proteins