LOC105377021

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LOC105377021
Identifiers
SymbolUNQ6490, PRO21339, (LOC389102, YPLR6490)

LOC105377021 is a protein which in humans is encoded by the LOC105377021 gene.[1][2] LOC105377021 exhibits expressional pathology related to breast cancer, specifically triple negative breast cancer.[3][4] LOC105377021 contains a serine rich region in addition to predicted alpha helix motifs.[5][2]

Gene and mRNA

LOC105377021 localizes to Homo sapiens chromosome 3 (3p2; antisense strand), approximate to the reading frame of TRIM71.[2][6][7] The corresponding gene has 2,473 nucleotides.[2] There is one exon in the LOC105377021p mRNA.[2] There is no predicted alternative splicing on the NCBI gene database.[2]

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.[8]

File:LOC105377021.png

Amino Acid Count Calculated Isoelectric Point Calculated Molecular Weight Competitive Repeat Unit Over-represented Amino Acids
168[2] 11.438[9] 18.2 kdal[10][11] RARP None[10][11]

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).[5]

File:Secondary Structure Text Outline.png

File:I TASSER 3D Prediction of LOC105377021.png
I TASSER 3D Prediction of LOC105377021

Protein Tertiary Structure

LOC105377021 has a prominent, C-terminus repeat of serine residues, potentially for disulfide bonding.[2] One disulfide bond (139-148) was predicted by DISULFIDE software.[12] 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).[13]

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.[14][15] In addition, there is predicted evidence of O-Linked β-N-acetylglucosamine supplements in the C terminal region.[16][17] There is predicted evidence for a nuclear localization sequence oriented at the N-terminal, provided by PSORT with partial support by PHOBIUS software.[8][18]

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.[6] In humans: cranial, intestinal, ovarian, renal, and testicular tissues corroborate this trend.[6]

Microarray data posits the expression of LOC105377021 in certain breast cancer tissues, including metastases to lymphatic and lung tissue.[4] There is potential evidence for higher expression of LOC105377021 during Triple Negative Breast Cancer, which overshadows normal secretion levels for said protein.[3] 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).

File:NCBI Geo Profile for Triple Negative Breast Cancer and YPLR6490.png

This photo is courtesy of NCBI Geo Profiles Accession GDS4069.

Brain Tissue Expression

Seven key brain tissues express LOC105377021 according to an Allen Brain Atlas probe.[19] 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.

File:Four Allen Brain Atlas Annotations for LOC105377021 Brain Expression.png

File:Three Allen Brain Atlas LOC105377021 Cranial Expression Profiles.png

These photos are courtesy of the Allen Brain Atlas.

Evolutionary Relationships and Homology

Orthologs

The Basic Local Alignment Sequence Tool (BLAST) shows that LOC105377021 orthologs are largely homogenous and mammalian.[20] 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 Name Genus species NCBI Accession Number[21] % Similarity % Identity Protein Length (in amino acids) Ortholog Aliases[21]
Human Homo sapiens XP_011532636.1 100 100 168 LOC389102, YPLR6490, UNQ6490, PRO21339
Sumatran orangutan Pongo abelii XP_002814002.1 98 98 170 LOC100446670
Squirrel Monkey Saimiri boliviensis boliviensis XP_010339850.1 96 96 167 LOC101034964
Golden snub -nosed monkey Rhinopithecus roxellana XP_010352756.1 96 95 170 LOC104655070
Olive baboon Papio anubis XP_003895275.1 96 95 170 LOC101001601
Angolan Black and White Colobus Colobus angolensis palliatus XP_011816934.1 95 92 171 LOC105525785
Mouse lemur Microbus murinus XP_012624670.1 93 92 169 LOC105873906
Northern greater galago Otolemur garnettii XP_012661211.1 89 87 167 LOC100965366
Sunda Flying Lemur Galeopterus variegatus XP_008581853 87 86 151 LOC103599484
Killer Whale Orcinus orca XP_004279764.1 82 80 282 SEC31
Sperm Whale Physeter catodon XP_007125317.1 82 80 230 LOC10299578
Baiji Litotes vexillifer XP_007464989.1 78 76 217 LOC103081437
Star-Nosed Mole Condylura cristata XP_012590632.1 77 74 162 LOC101633309
Aardvark Orycteropus afer afer XP_007946855.1 76 71 186 LOC103203593
Cape Elephant Shrew Elephantulus edwardii XP_006890725.1 71 67 225 LOC102845592
Cape Golden Mole Chrysochloris asiatica XP_006859232.1 69 66 264 LOC102816436
Bactrian camel Camels bactrianus XP_010958002.1 54 54 126 LOC105072685
Common Bottlenose Dolphin Tursiops truncatus XP_004315393.1 50 46 166 LOC101335194

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.

File:LOC105377021 Corrected Divergence Graph.png

The corrected divergences graph above shows three lines: Alpha Fibrinogen in Red, LOC Ortholog (aka 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.[22]

File:SNP's in LOC105377021.png

Polymorphism Chemical Nature prior to Polymorphism Chemical Nature after Polymorphism
G7R Non polar Basic
R8L,P Basic Non polar
L25F Non polar Non polar
L29F Non polar Non polar
A34P Non polar Non polar
L51F Non polar Non polar
P54R Non polar Basic
H96R Basic Basic
L97H Non polar Basic
G128R Non polar Basic
S157F Polar Non polar
Y163F Polar Non 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.[2][23] Genomatix predicts several transcription factors in general. Two select factors predicted include Gli3 and E2F1.[23]

References

  1. ↑ "HGNC database of human gene names | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2016-04-27.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "LOC105377021 putative uncharacterized protein UNQ6490/PRO21339 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-02-06.
  3. ↑ 3.0 3.1 "GDS4069 / 8086024 / YPLR6490". www.ncbi.nlm.nih.gov. Retrieved 2016-04-22.
  4. ↑ 4.0 4.1 "101977830 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-04-22.
  5. ↑ 5.0 5.1 Remmert M. "Ali2D". toolkit.tuebingen.mpg.de. Retrieved 2016-04-27.
  6. ↑ 6.0 6.1 6.2 mieg@ncbi.nlm.nih.gov, Danielle Thierry-Mieg and Jean Thierry-Mieg, NCBI/NLM/NIH,. "AceView a comprehensive annotation of human and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2016-02-20.
  7. ↑ "Human BLAT Search". genome.ucsc.edu. Retrieved 2016-05-06.
  8. ↑ 8.0 8.1 "Phobius". phobius.sbc.su.se. Retrieved 2016-04-24.
  9. ↑ Toldo L, Kindler B (2016). "Isoelectric point determination". EMBL WWW Gateway to Isoelectric Point Service.
  10. ↑ 10.0 10.1 Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. doi:10.1073/pnas.89.6.2002. PMC 48584. PMID 1549558.
  11. ↑ 11.0 11.1 Brendel V (1992). "SAPS". Department of Mathematics, Stanford University.
  12. ↑ Ceroni A, Passerini A, Vullo A, Frasconi P (July 2006). "DISULFIND: a disulfide bonding state and cysteine connectivity prediction server". Nucleic Acids Research. 34 (Web Server issue): W177–81. doi:10.1093/nar/gkl266. PMC 1538823. PMID 16844986.
  13. ↑ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2016-05-06.
  14. ↑ "Motif Scan". myhits.isb-sib.ch. Retrieved 2016-04-27.
  15. ↑ Blom N, Gammeltoft S, Brunak S (1999). "Sequence-and structure-based prediction of eukaryotic protein phosphorylation sites". www.cbs.dtu.dk. Retrieved 2016-04-27.
  16. ↑ Gupta R. "Prediction of glycosylation sites in proteomes: from post-translational modifications to protein function". www.cbs.dtu.dk. Retrieved 2016-05-04.
  17. ↑ Gupta R, Brunak S (2002). "Prediction of glycosylation across the human proteome and the correlation to protein function". Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing: 310–22. PMID 11928486.
  18. ↑ "Welcome to psort.org!". www.psort.org. Retrieved 2016-04-24.
  19. ↑ "Microarray Data :: Allen Brain Atlas: Human Brain". human.brain-map.org. Retrieved 2016-05-03.
  20. ↑ Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990). "Basic local alignment search tool". Journal of Molecular Biology. 215 (3): 403–10. doi:10.1016/S0022-2836(05)80360-2. PMID 2231712.
  21. ↑ 21.0 21.1 "National Center for Biotechnology Information". www.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
  22. ↑ snpdev. "dbSNP Home Page". www.ncbi.nlm.nih.gov. Retrieved 2016-05-03.
  23. ↑ 23.0 23.1 "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Retrieved 2016-04-24.
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