Medha Banerjee 1660091 IMTH-7(A)

Bioinformatics assignment

A1)

The given peptide sequence was “RVLSLGR”. After using BLAST for the sequence against the Uniprot
database, no results were found. Even after changing various parameters such as E-value, filtering and
different matrices, result was not found.

PROTIEN NAME -E3 ubiquitin-protein ligase TRIM56

ORGANISM - Homo sapiens LENGTH- 755 Match to RVLSLGR -

@311
A2)

Breast cancer type 1 susceptibility protein or BRCA1 is a tumor suppression protein encoded in humans.
BRCA1 and BRCA2 are proteins found in the human breast cells but are unrelated.Both are involved in the
DNA repair of double stranded breaks. A heterodimer formed by the association of BRCA1-BARD
coordinated a wide range of molecular pathways, repair mechanisms, ubiquitination etc. It also helps in the
progression of cells from their G2 phase to M phase. The tumor suppressor protein P21 is also regulated by
it. A few genes like, BRCA and P53, are required by the cells for normal progression of mitosis. The ch2
kinase and its targets are potential CIN (Chromosomal instabililty) genes. Depletion of ch2 or removal of its
kinase activity leads to improper division, abnormal mitotic spindle assembly formation etc. However in the
presence of BRCA it does not occur. Similarly absence of BRCA leads to defective spindle formation and
CIN.Individuals with Breast or Ovarian cancer have a mutation in their BRCA1 & 2 genes. PALB2 which
acts as a scaffold for the binding of BRCA 1 and 2 forms a heterodimer with BRCA1in vivo via apolar
bonding. Cells with defective interactions of these proteins showed defective homologous recombination.
via its direct interaction with PALB2, BRCA1 fine-tunes recombinational repair partly through its
modulatory rolein the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA
breaks.BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage–induced G2/M arrest.
Thus, BRCA1 controls the expression, phosphorylation and cellular localization of Cdc25C and Cdc2/cyclin
B kinase—proteins that are crucial for the G2/M transition.

A3)

The Ankyrin or ANK1 is a protein encoded by the human ANK1 gene.They are a family of proteins that link
the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities
such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane
domains. Mutation is the ANK1 gene is related to many different diseases such as spherocytosis,
Alzheimer's and in some cases pancreatic cancer.

ANK1 role in spherocytosis:

Hereditary spherocytosis is a hereditary heterogenous disorder which is identified by the presence of

spherical red blood cells instead of the usualy bi concave shape. It is an important membrane protein in red
blood cells and interact with transmembrane proteins and membrane skeleton. A de novo nonsense mutation
at codon 266, which caused substitution glutamic acid to stop codon (G to T).This mutation is causative to HS
which play an important role in supplmenting the mutational spectrum of ANK1.

ANK1 role in Alzheimer’s:

Alzheimer’s disease is a chronic neurodegenerative disease characterized by the cognitive decline and
progressive neuropathy. Differently methylated regions in ANK1 is associated in neuropathy in the
entorhinal cortex. The same methylated regions were not present in the cerebellum. The methylated
modifications in the cortex are associated with AD.

ANK1 role in Pancreatic cancer:

The promoter methylation influences the expression of the gene and tumor development. ANK1 is usually
hypomethylated. In cases of pancreatic cancers, it was shown that cells which overexpressed ANK1
developed the disease as opposed to normal/healthy cells. It is also co expressed with miR-486 in panreatic
cancer cells. When stable knockdown of the gene was done it led to changes in cell morphology and
decrease in colony formation in vitro. It showed reduced growth of tumors in mice.

A4)

(i) Huntington’s disease:

The gene for Huntington’s disease (HD) is called as Huntington gene. It is present on the short arm of
chromosome 4. It is associated with a triple nucleotide repeat CAG. Onset of HD occurs if the CAG repeats
exceed 41, and if less than 35 it is considered normal. Incomplete expression being between 35-41. It was
previously thought that HD may be caused by haploinsufficiency but it was scrapped out as terminal
deletion or physical disruption of the HD gene in man does not cause Huntington’s disease. In vitro evidence
for HD shows that the polyglutamine strands due to the repeats lead to aggregation of huntingtin in the cells.
The mutated protein is subject to proteolysis which truncates it and this leads to the aggregation. Once an
aggregate is formed, it becomes toxic and translocates to the nucleus. Prolonged aggregation leads to its
evasion via autophagic vacuolization. It recruits other normal functioning proteins into the aggregate too.
This leads to the loss of transcription regulation, apoptosis etc. Mutant huntingtin might cause harm to a
neuron, by disrupting the function of nearby neurons or glia that provide important support to that neuron.

(ii) Sickle cell disease:

Sickle cell disease or sickle cell anemia is an autosomal recessive disease. It occurs in the short arm of the
chromosome 11 at the β-globin gene. A single nucleotide polymorphism occurs which changes the GAG
codon to GTG resulting in glutamic acid being substituted by valine.It results in an abnormality in the
oxygen-carrying protein haemoglobin found in red blood cells.This leads to a rigid, sickle-like shape under
certain circumstances. This is normally a benign mutation, causing no apparent effects on
the secondary, tertiary, or quaternary structures of haemoglobin in conditions of
normal oxygen concentration. However, under low oxygen concentration, HbS polymerizes and forms
fibrous precipitates because the deoxy form of haemoglobin exposes a hydrophobic patch on the protein
between the E and F helices.

(iii) Cystic fibrosis:- 

Cystic fibrosis is a genetic disorder which affects the lungs, pancreas liver and kidneys. It may also lead to
difficulty in breating and mucosal buildup. It is an autosomal recessive diseaseIt is caused when mutations
are present in both the cystic fibrosis transmembrane conductance (CFTR) gene. The gene is present on the
long arm of the chromosome 7.

A5)

Gorilla:-
Chimpanzee

Dog
Cat
A6)

Step 1:Sign in and create a NCBI account.

Step 2:Successfully signed in:

Step 3: then give the contact information

Step 4:Then fill the sequencing technology with the corrosponding sequence for the same.
Step5:Fill the information for the organism for which the DNA is:

Step 6: Fill the submission category to verify it’s authenticity

Step 7:Mention the source of organism for which the gene has been sequenced.

Step 8:Mentioned the nature of the sequence and went on to add the protein sequence of the coding gene
Step9:Review and correction of the data which were filled .

Step 10:Submission of the sequence was successful through Bankit but I did not submit the sequence
through sequin because the software could not be installed on my computer.