LOC105377021 is a protein which in humans is encoded by the LOC105377021 gene. LOC105377021 exhibits expressional pathology related to breast cancer, specifically triple negative breast cancer. LOC105377021 contains a serine rich region in addition to predicted alpha helix motifs.

Gene and mRNA LOC105377021 localizes to Homo sapiens chromosome 3 (3p2; antisense strand), approximate to the reading frame of TRIM71. The corresponding gene has 2,473 nucleotides. There is one exon in the LOC105377021p mRNA. There is no predicted alternative splicing on the NCBI gene database.

Protein

Protein primary structure The figure below shows the basic primary protein structure, with N-terminus and C-terminus in their respective annotations. The orange domain is a predicted nuclear localization sequence, while the blue domain is the remainder of the LOC105377021 exon.

Amino Acid CountCalculated Isoelectric PointCalculated Molecular WeightCompetitive Repeat UnitOver-represented Amino Acids16811.43818.2 kdalRARPNone

Protein secondary structure According to Ali2D (a multiple sequence alignment structural predictor for proteins), LOC105377021 is predicted to form mostly alpha helix (see red highlight, blue highlight is for Beta Sheet).

Protein tertiary structure LOC105377021 has a prominent, C-terminus repeat of serine residues, potentially for disulfide bonding. One disulfide bond (139-148) was predicted by DISULFIDE software. Additionally, the I TASSER profile shows several alpha helices in a variety of different colors, in addition to potential turn motifs (see I TASSER 3D Prediction of LOC105377021).

Protein modifications and localization A predicted protein modification of LOC105377021 is phosphorylation, with sites throughout the protein, including the serine rich construct near the C-terminus of the protein. In addition, there is predicted evidence of O-Linked β-N-acetylglucosamine supplements in the C terminal region. There is predicted evidence for a nuclear localization sequence oriented at the N-terminal, provided by PSORT with partial support by PHOBIUS software.

Microarray expression pattern and pathology

Basic expression and breast cancer Compared to the average expression of human protein, LOC105377021 is expressed at 0.9%, which is classified as low. In humans: cranial, intestinal, ovarian, renal, and testicular tissues corroborate this trend.

Microarray data posits the expression of LOC105377021 in certain breast cancer tissues, including metastases to lymphatic and lung tissue. There is potential evidence for higher expression of LOC105377021 during Triple Negative Breast Cancer, which overshadows normal secretion levels for said protein. The figure below shows a potential trend line for this pattern (shown in green, with the triple negative microarray on the left). As the figure legend states, the red bars refer to the left axis for sample counts, whereas the blue dots show the percentage of LOC105377021 expression within each sample (the right axis).

Brain tissue expression Seven key brain tissues express LOC105377021 according to an Allen Brain Atlas probe. The temporal lobe, parietal lobe, cingulate gyrus, parahippocampal gyrus, and insula are five overarching regions of the seven brain tissues where expression was highlighted. The annotated figures below serve as fairly holistic representations of cranial expression in the context of LOC105377021. Light blue shaded regions posit more dense expression of LOC105377021, where as darker green and brighter red show less and least amounts of expression respectively. All seven expression areas, including the middle temporal gyrus, the short insular gyrus, the postcentral gyrus, the cingulate gyrus, the inferior temporal gyrus, the parahippocampal gyrus, and the superior temporal gyrus are depicted in Allen Brain Atlas profiles below.

Evolutionary relationships and homology

Orthologs The Basic Local Alignment Sequence Tool (BLAST) shows that LOC105377021 orthologs are largely homogeneous and mammalian. Important orthologs are summarized into three categories: primates, aquatic mammals, and ferrets/ferret-like animals. Pongo abelii and Tursiops truncatus are the most distant and related orthologs respectively. The river dolphin is the first ortholog to detach from the 80% plus similarity cohort. The following includes a list of select orthologs found: Common nameGenus speciesNCBI Accession Number% Similarity% IdentityProtein Length (in amino acids)Ortholog AliasesHumanHomo sapiensXP_011532636.1100100168LOC389102, YPLR6490, UNQ6490, PRO21339Sumatran orangutanPongo abeliiXP_002814002.19898170LOC100446670Squirrel MonkeySaimiri boliviensis boliviensisXP_010339850.19696167LOC101034964Golden snub -nosed monkeyRhinopithecus roxellanaXP_010352756.19695170LOC104655070Olive baboonPapio anubisXP_003895275.19695170LOC101001601Angolan Black and White ColobusColobus angolensis palliatusXP_011816934.19592171LOC105525785Mouse lemurMicrobus murinusXP_012624670.19392169LOC105873906Northern greater galago Otolemur garnettiiXP_012661211.18987167LOC100965366Sunda Flying Lemur Galeopterus variegatusXP_0085818538786151LOC103599484Killer WhaleOrcinus orcaXP_004279764.18280282SEC31Sperm WhalePhyseter catodon XP_007125317.18280230LOC10299578BaijiLitotes vexilliferXP_007464989.17876217LOC103081437Star-Nosed MoleCondylura cristataXP_012590632.17774162LOC101633309AardvarkOrycteropus afer aferXP_007946855.17671186LOC103203593Cape Elephant ShrewElephantulus edwardiiXP_006890725.17167225LOC102845592Cape Golden MoleChrysochloris asiaticaXP_006859232.16966264LOC102816436Bactrian camelCamels bactrianusXP_010958002.15454126LOC105072685Common Bottlenose DolphinTursiops truncatusXP_004315393.15046166LOC101335194

Pace of evolution The pace of evolution of LOC105377021 upon its inception (in humans) is modeled to be slow. This speed is relative to cytochrome c 6A1 and Alpha fibrinogen using corrected divergence methods.

The corrected divergences graph above shows three lines: Alpha Fibrinogen in Red, LOC Ortholog ( LOC105377021) in blue, and Cytochrome c 6A1 in green. These lines associate with evolutionary pace in LOC105377021, as tested using a corrected divergence genomic analysis.

Single nucleotide polymorphisms The following diagram shows single nucleotide polymorphisms (SNP's) in various regions of the protein. SNP's are highlighted green, with SNP coding on the right hand coding for switches in amino acids.

PolymorphismChemical Nature prior to PolymorphismChemical Nature after PolymorphismG7RNon polarBasicR8L,PBasicNon polarL25FNon polarNon polarL29FNon polarNon polarA34PNon polarNon polarL51FNon polarNon polarP54RNon polarBasicH96RBasicBasicL97HNon polarBasicG128RNon polarBasicS157FPolarNon polarY163FPolarNon polar

Promoter and gene regulation According to Genomatix, LOC389102 (synonym to LOC105377021) is proximate to a 601 base pair promoter and a 5'UTR 129 base pairs long consecutively. Genomatix predicts several transcription factors in general. Two select factors predicted include Gli3 and E2F1.

References