Download Assignment_week_3_for_AR

Assignment week 3 for AR
1.Is your protein found only in primates? All mammals? How about amphibians and reptiles?
Are there homologs in bacteria? (You can search these types of organisms individually in blast).
Organism list:
Rattus norvegicus (Rat)
Mus musculus (Mouse)
Mus musculus (Mouse)
Canis familiaris (Dog) (Canis lupus familiaris)
Crocuta crocuta (Spotted hyena)
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Macaca mulatta (Rhesus macaque)
Homo sapiens (Human)
Pan troglodytes (Chimpanzee)
Papio hamadryas (Hamadryas baboon)
Eulemur fulvus collaris (Collared brown lemur) (Eulemur collaris)
Oryctolagus cuniculus (Rabbit)
Sus scrofa (Pig)
Rana catesbeiana (American bullfrog) (Lithobates catesbeiana)
2. Find out as much as you can about your protein and the conserved domains in your protein of
interest:
Androgen receptor isoform 1 contains a ligand binding site, coactivator recognition site,
zinc binding site, DNA binding site, and a dimer interface.
Information concerning these domains from NCBI:
Ligand binding domain of the nuclear receptor androgen receptor, ligand activated
transcription regulator: The ligand binding domain of the androgen receptor (AR): AR is a
member of the nuclear receptor family. It is activated by binding either of the androgenic
hormones, testosterone or dihydrotestosterone, which are responsible for male primary sexual
characteristics and for secondary male characteristics, respectively. The primary mechanism of
action of ARs is by direct regulation of gene transcription. The binding of an androgen results in
a conformational change in the androgen receptor which causes its transport from the cytosol
into the cell nucleus, and dimerization. The receptor dimer binds to a hormone response element
of AR-regulated genes and modulates their expression. Another mode of action is independent of
their interactions with DNA. The receptors interact directly with signal transduction proteins in
the cytoplasm, causing rapid changes in cell function, such as ion transport. Like other members
of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, AR has a
central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible
hinge and a C-terminal ligand binding domain (LBD). The LBD is not only involved in binding
to androgen, but also involved in binding of coactivator proteins and dimerization. A ligand
dependent nuclear export signal is also present at the ligand binding domain.
DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers:
DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers. Each
zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. To
regulate gene expression, AR interacts with a palindrome of the core sequence 5'-TGTTCT-3'
with a 3-bp spacer. It also binds to the direct repeat 5'-TGTTCT-3' hexamer in some androgen
controlled genes. AR is activated by the androgenic hormones, testosterone or
dihydrotestosterone, which are responsible for primary and for secondary male characteristics,
respectively. The primary mechanism of action of ARs is by direct regulation of gene
transcription. The binding of androgen results in a conformational change in the androgen
receptor which causes its transport from the cytosol into the cell nucleus, and dimerization. The
receptor dimer binds to a hormone response element of AR regulated genes and modulates their
expression. Another mode of action of androgen receptor is independent of their interactions
with DNA. The receptor interacts directly with signal transduction proteins in the cytoplasm,
causing rapid changes in cell function, such as ion transport. Like other members of the nuclear
receptor (NR) superfamily of ligand-activated transcription factors, AR has a central well
conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a Cterminal ligand binding domain (LBD).
Submit:
1. The FASTA file for your protein.
>gi|21322252|ref|NP_000035.2| androgen receptor isoform 1 [Homo sapiens]
MEVQLGLGRVYPRPPSKTYRGAFQNLFQSVREVIQNPGPRHPEAASAAPPGASLLLLQQQQQQQQQQQQQ
QQQQQQQQQQETSPRQQQQQQGEDGSPQAHRRGPTGYLVLDEEQQPSQPQSALECHPERGCVPEPGAAVA
ASKGLPQQLPAPPDEDDSAAPSTLSLLGPTFPGLSSCSADLKDILSEASTMQLLQQQQQEAVSEGSSSGR
AREASGAPTSSKDNYLGGTSTISDNAKELCKAVSVSMGLGVEALEHLSPGEQLRGDCMYAPLLGVPPAVR
PTPCAPLAECKGSLLDDSAGKSTEDTAEYSPFKGGYTKGLEGESLGCSGSAAAGSSGTLELPSTLSLYKS
GALDEAAAYQSRDYYNFPLALAGPPPPPPPPHPHARIKLENPLDYGSAWAAAAAQCRYGDLASLHGAGAA
GPGSGSPSAAASSSWHTLFTAEEGQLYGPCGGGGGGGGGGGGGGGGGGGGGGGEAGAVAPYGYTRPPQGL
AGQESDFTAPDVWYPGGMVSRVPYPSPTCVKSEMGPWMDSYSGPYGDMRLETARDHVLPIDYYFPPQKTC
LICGDEASGCHYGALTCGSCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGAR
KLKKLGNLKLQEEGEASSTTSPTEETTQKLTVSHIEGYECQPIFLNVLEAIEPGVVCAGHDNNQPDSFAA
LLSSLNELGERQLVHVVKWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNVNSRMLYFAPDLV
FNEYRMHKSRMYSQCVRMRHLSQEFGWLQITPQEFLCMKALLLFSIIPVDGLKNQKFFDELRMNYIKELD
RIIACKRKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSG
KVKPIYFHTQ
2. Report how far back evolutionarily you can find homologs for your protein.
Biology Workbench
1. Do a multiple alignment and display the results with BOXSHADE. Do the conserved areas of
the protein align with certain domains?
2. Display the evolutionary relationships in a rooted and unrooted tree.