PART A

CYP3A4 and CYP3A5 comparative analysis

PCR fragment obtained from CYP3A4 primers. The sequence obtained with the reverse primer is shown below.

CTGTGATCCTAAGAAACCAAATTTTAGGAACTTCTTAGTGCTCTCCACAAAGGGGTCTTGTGGATTGTTGAGAGAGTGAGGTTCACTCCAAATGATGTGCCAGTAATCACATCCATGTTGTTGGCCGACAAAGATGTCTTTCAAGGTGACAGGCTTGCCTTTCTCTGCTTCCCGCCTCAAGTTTCTCACCAATACACCTCCATACTGGGCAATGATGGGGAACATCTCCTTGAGTTTTCCGCTGGGAAGTTGGAAAGCATGCCTTTTTTCATTTTAATCTAACAC

The above sequence was BLAST aligned, at NCBI database.

Human ORFeome Gateway entry vector pENTR223-CYP3A5, complete sequence

Sequence ID: LT741352.1Length: 4296Number of Matches: 1

Related Information

Range 1: 882 to 1139GenBankGraphics Next Match Previous Match

Alignment statistics for match #1
Score / Expect / Identities / Gaps / Strand
407 bits(220) / 9e-110 / 248/260(95%) / 7/260(2%) / Plus/Minus

Query 5 GATCCTAAGAAACCAAATTTTAGGAACTTCTTAGTGCTCTCCACAAAGGGGTCTTGTGGA 64

||| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||

Sbjct 1139 GAT-CTAAGAAACCAAATTTTAGGAACTTCTTAGTGCTCTCCACAAAGGGGTCTTGTGGA 1081

Query 65 TTGTTGAGAGAGT-GAGGTTCACTCCAAATGATGTGCCAGTAATCACATCCATGTTGTTG 123

||||||||||||| || ||||||||||||||||||||||||||||||||||||| ||| |

Sbjct 1080 TTGTTGAGAGAGTCGATGTTCACTCCAAATGATGTGCCAGTAATCACATCCATGCTGTAG 1021

Query 124 GCCGACAAAGATGTCTTTCAAGGTGACAGGCTTGCCTTTCTCTGCTTCCCGCCTCAAGTT 183

||| |||||||||||||||||||||||||||||||||||||||||||||||||||||||

Sbjct 1020 GCCC-CAAAGATGTCTTTCAAGGTGACAGGCTTGCCTTTCTCTGCTTCCCGCCTCAAGTT 962

Query 184 TCTCACCAATACACCTCCATACTGGGCAATGATGGGGAACATCTCCTTGAGTTTTCCGCT 243

||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||

Sbjct 961 TCTCACCAATACATCTCCATACTGGGCAATGATGGGGAACATCTCCTTGAGTTTTCCGCT 902

Query 244 GG-GAAG-TTGGA-A-AGCA 259

|| |||| ||||| | ||||

Sbjct 901 GGTGAAGGTTGGAGACAGCA 882

PART B

To determine sequence similarity between CYP3A4 and CYP3A5, their mRNA sequences were aligned using CLUSTALW tools (CLUSTAL 2.1 Multiple Nucleotide Sequence Alignments). The primers used in the PCR amplification were highlighted in the CYP3A4 transcript.

Sequence 1: CYP3A4 2792 bp

Sequence 2: CYP3A5 1755 bp

Start of Pairwise alignments

Aligning...

Sequences (1:2) Aligned. Score: 85.1282

Guide tree file created: [clustalw.dnd]

There are 1 groups

Start of Multiple Alignment

Aligning...

Group 1: Sequences: 2 Score:30274

Alignment Score 10426

CLUSTAL-Alignment file created [clustalw.aln]

CLUSTAL 2.1 multiple sequence alignment (Forward and reverse primers are highlighted.)

CYP3A4 ------AATCACTGCTGTGCAGGGCAGGAAAGCTCCATGCACA

CYP3A5 ATAAATCTTTCAGCAGCTTGGCTGAAGACTGCTGTGCAGGGCAGGGAAGCTCCAGGCAAA

* ****************** ******** *** *

CYP3A4 TAGCCCAGCAAAGAGCAACACAGAGCTGAAAGGAAGACTCAGAGGAGAGAGATAAGTAAG

CYP3A5 CAGCCCAGCAAACAGCAGCACTCAGCTAAAAGGAAGACTCACAGAACACAGTTGAAGAAG

*********** **** *** **** ************* ** * * ** * * ***

CYP3A4 GAAAGTAGTGATGGCTCTCATCCCAGACTTGGCCATGGAAACCTGGCTTCTCCTGGCTGT

CYP3A5 GAAAGTGGCGATGGACCTCATCCCAAATTTGGCGGTGGAAACCTGGCTTCTCCTGGCTGT

****** * ***** ********* * ***** *************************

(Forward primer)

CYP3A4 CAGCCTGGTGCTCCTCTATCTATATGGAACCCATTCACATGGACTTTTTAAGAAGCTTGG

CYP3A5 CAGCCTGGTGCTCCTCTATCTATATGGGACCCGTACACATGGACTTTTTAAGAGACTGGG

*************************** **** * ****************** ** **

CYP3A4 AATTCCAGGGCCCACACCTCTGCCTTTTTTGGGAAATATTTTGTCCTACCATAAGGGCTT

CYP3A5 AATTCCAGGGCCCACACCTCTGCCTTTGTTGGGAAATGTTTTGTCCTATCGTCAGGGTCT

*************************** ********* ********** * * **** *

CYP3A4 TTGTATGTTTGACATGGAATGTCATAAAAAGTATGGAAAAGTGTGGGGCTTTTATGATGG

CYP3A5 CTGGAAATTTGACACAGAGTGCTATAAAAAGTATGGAAAAATGTGGGGAACGTATGAAGG

** * ******* ** ** ***************** ******* ***** **

CYP3A4 TCAACAGCCTGTGCTGGCTATCACAGATCCTGACATGATCAAAACAGTGCTAGTGAAAGA

CYP3A5 TCAACTCCCTGTGCTGGCCATCACAGATCCCGACGTGATCAGAACAGTGCTAGTGAAAGA

***** *********** *********** *** ****** ******************

CYP3A4 ATGTTATTCTGTCTTCACAAACCGGAGGCCTTTTGGTCCAGTGGGATTTATGAAAAGTGC

CYP3A5 ATGTTATTCTGTCTTCACAAATCGAAGGTCTTTAGGCCCAGTGGGATTTATGAAAAGTGC

********************* ** *** **** ** ***********************

CYP3A4 CATCTCTATAGCTGAGGATGAAGAATGGAAGAGATTACGATCATTGCTGTCTCCAACCTT

CYP3A5 CATCTCTTTAGCTGAGGATGAAGAATGGAAGAGAATACGGTCATTGCTGTCTCCAACCTT

******* ************************** **** ********************

CYP3A4 CACCAGTGGAAAACTCAAGGAGATGGTCCCTATCATTGCCCAGTATGGAGATGTGTTGGT

CYP3A5 CACCAGCGGAAAACTCAAGGAGATGTTCCCCATCATTGCCCAGTATGGAGATGTATTGGT

****** ****************** **** *********************** *****

CYP3A4 GAGAAATCTGAGGCGGGAAGCAGAGACAGGCAAGCCTGTCACCTTGAAAGACGTCTTTGG

CYP3A5 GAGAAACTTGAGGCGGGAAGCAGAGAAAGGCAAGCCTGTCACCTTGAAAGACATCTTTGG

****** ****************** ************************* *******

CYP3A4 GGCCTACAGCATGGATGTGATCACTAGCACATCATTTGGAGTGAACATCGACTCTCTCAA

CYP3A5 GGCCTACAGCATGGATGTGATTACTGGCACATCATTTGGAGTGAACATCGACTCTCTCAA

********************* *** **********************************

CYP3A4 CAATCCACAAGACCCCTTTGTGGAAAACACCAAGAAGCTTTTAAGATTTGATTTTTTGGA

CYP3A5 CAATCCACAAGACCCCTTTGTGGAGAGCACTAAGAAGTTCCTAAAATTTGGTTTCTTAGA

************************ * *** ****** * *** ***** *** ** **

(reverse primer)

CYP3A4 TCCATTCTTTCTCTCAATAACAGTCTTTCCATTCCTCATCCCAATTCTTGAAGTATTAAA

CYP3A5 TCCATTATTTCTCTCAATAATACTCTTTCCATTCCTTACCCCAGTTTTTGAAGCATTAAA

****** ************* * ************* * **** ** ****** ******

CYP3A4 TATCTGTGTGTTTCCAAGAGAAGTTACAAATTTTTTAAGAAAATCTGTAAAAAGGATGAA

CYP3A5 TGTCTCTCTGTTTCCAAAAGATACCATAAATTTTTTAAGTAAATCTGTAAACAGAATGAA

* *** * ********* *** * ************ *********** ** *****

CYP3A4 AGAAAGTCGCCTCGAAGATACACAAAAGCACCGAGTGGATTTCCTTCAGCTGATGATTGA

CYP3A5 GAAAAGTCGCCTCAACGACAAACAAAAGCACCGACTAGATTTCCTTCAGCTGATGATTGA

*********** * ** * ************* * ***********************

CYP3A4 CTCTCAGAATTCAAAAGAAACTGAGTCCCACAAAGCTCTGTCCGATCTGGAGCTCGTGGC

CYP3A5 CTCCCAGAATTCGAAAGAAACTGAGTCCCACAAAGCTCTGTCTGATCTGGAGCTCGCAGC

*** ******** ***************************** ************* **

CYP3A4 CCAATCAATTATCTTTATTTTTGCTGGCTATGAAACCACGAGCAGTGTTCTCTCCTTCAT

CYP3A5 CCAGTCAATAATCTTCATTTTTGCTGGCTATGAAACCACCAGCAGTGTTCTTTCCTTCAC

*** ***** ***** *********************** *********** *******

CYP3A4 TATGTATGAACTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAGGAGGAAATTGATGC

CYP3A5 TTTATATGAACTGGCCACTCACCCTGATGTCCAGCAGAAACTGCAAAAGGAGATTGATGC

* * ***************************************** **** ********

CYP3A4 AGTTTTACCCAATAAGGCACCACCCACCTATGATACTGTGCTACAGATGGAGTATCTTGA

CYP3A5 AGTTTTGCCCAATAAGGCACCACCTACCTATGATGCCGTGGTACAGATGGAGTACCTTGA

****** ***************** ********* * *** ************* *****

CYP3A4 CATGGTGGTGAATGAAACGCTCAGATTATTCCCAATTGCTATGAGACTTGAGAGGGTCTG

CYP3A5 CATGGTGGTGAATGAAACACTCAGATTATTCCCAGTTGCTATTAGACTTGAGAGGACTTG

****************** *************** ******* ************ **

CYP3A4 CAAAAAAGATGTTGAGATCAATGGGATGTTCATTCCCAAAGGGGTGGTGGTGATGATTCC

CYP3A5 CAAGAAAGATGTTGAAATCAATGGGGTATTCATTCCCAAAGGGTCAATGGTGGTGATTCC

*** *********** ********* * *************** ***** *******

CYP3A4 AAGCTATGCTCTTCACCGTGACCCAAAGTACTGGACAGAGCCTGAGAAGTTCCTCCCTGA

CYP3A5 AACTTATGCTCTTCACCATGACCCAAAGTACTGGACAGAGCCTGAGGAGTTCCGCCCTGA

** ************* **************************** ****** ******

CYP3A4 AAGATTCAGCAAGAAGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAG

CYP3A5 AAGGTTCAGTAAGAAGAA---GGACAGCATAGATCCTTACATATACACACCCTTTGGAAC

*** ***** ******** ***** ********************************

CYP3A4 TGGACCCAGAAACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAAT

CYP3A5 TGGACCCAGAAACTGCATTGGCATGAGGTTTGCTCTCATGAACATGAAACTTGCTCTAAT

************************************************************

CYP3A4 CAGAGTCCTTCAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCCTGAAATT

CYP3A5 CAGAGTCCTTCAGAACTTCTCCTTCAAACCTTGTAAAGAAACACAGATCCCCTTGAAATT

**************************************************** *******

CYP3A4 AAGCTTAGGAGGACTTCTTCAACCAGAAAAACCCGTTGTTCTAAAGGTTGAGTCAAGGGA

CYP3A5 AGACACGCAAGGACTTCTTCAACCAGAAAAACCCATTGTTCTAAAGGTGGATTCAAGAGA

* * ************************* ************* ** ***** **

CYP3A4 TGGCACCGTAAGTGGAGCCTGAATTTTCCTAAGGACTTCTGCTTTGCTCTTCAAGAAATC

CYP3A5 TGGAACCCTAAGTGGAGAATGAGTTATTCTAAGGATTTCTACTTTGGTCTTCAAGAAAGC

*** *** ********* *** ** * ******* **** ***** *********** *

CYP3A4 TGTGCCTGAGAACACCAGAGACCTCAAATTACTTTGTGAATAGAACTCTGAAATGAAGAT

CYP3A5 TGTGCCCCAGAACACCAGAGATTTCAA----CTTAGTCAATAAAACCTTGAAATAAAGAT

****** ************* **** *** ** **** *** ****** *****

CYP3A4 GGGCTTCATCCAATGGACTGCATAAATAACCGGGGATTCTGTACATGCATTGAGCTCTCT

CYP3A5 GGGCTTAATCTAATGTACTGCA------

****** *** **** ******

CYP3A4 CATTGTCTGTGTAGAGTGTTATACTTGGGAATATAAAGGAGGTGACCAAATCAGTGTGAG

CYP3A5 ------

CYP3A4 GAGGTAGATTTGGCTCCTCTGCTTCTCACGGGACTATTTCCACCACCCCCAGTTAGCACC

CYP3A5 ------

CYP3A4 ATTAACTCCTCCTGAGCTCTGATAAGAGAATCAACATTTCTCAATAATTTCCTCCACAAA

CYP3A5 ------

CYP3A4 TTATTAATGAAAATAAGAATTATTTTGATGGCTCTAACAATGACATTTATATCACATGTT

CYP3A5 ------

CYP3A4 TTCTCTGGAGTATTCTATAAGTTTTATGTTAAATCAATAAAGACCACTTTACAAAAGTAT

CYP3A5 ------

CYP3A4 TATCAGATGCTTTCCTGCACATTAAGGAGAAATCTATAGAACTGAATGAGAACCAACAAG

CYP3A5 ------

CYP3A4 TAAATATTTTTGGTCATTGTAATCACTGTTGGCGTGGGGCCTTTGTCAGAACTAGAATTT

CYP3A5 ------

CYP3A4 GATTATTAACATAGGTGAAAGTTAATCCACTGTGACTTTGCCCATTGTTTAGAAAGAATA

CYP3A5 ------

CYP3A4 TTCATAGTTTAATTATGCCTTTTTTGATCAGGCACAGTGGCTCACGCCTGTAATCCTAGC

CYP3A5 ------

CYP3A4 AGTTTGGGAGGCTGAGCCGGGTGGATCGCCTGAGGTCAGGAGTTCAAGACAAGCCTGGCC

CYP3A5 ------

CYP3A4 TACATGGTTGAAACCCCATCTCTACTAAAAATACACAAATTAGCTAGGCATGGTGGACTC

CYP3A5 ------

CYP3A4 GCCTGTAATCTCACTACACAGGAGGCTGAGGCAGGAGAATCACTTGAACCTGGGAGGCGG

CYP3A5 ------

CYP3A4 ATGTTGAAGTGAGCTGAGATTGCACCACTGCACTCCAGTCTGGGTGAGAGTGAGACTCAG

CYP3A5 ------

CYP3A4 TCTTAAAAAAATATGCCTTTTTGAAGCACGTACATTTTGTAACAAAGAACTGAAGCTCTT

CYP3A5 ------

CYP3A4 ATTATATTATTAGTTTTGATTTAATGTTTTCAGCCCATCTCCTTTCATATTTCTGGGAGA

CYP3A5 ------

CYP3A4 CAGAAAACATGTTTCCCTACACCTCTTGCATTCCATCCTCAACACCCAACTGTCTCGATG

CYP3A5 ------

CYP3A4 CAATGAACACTTAATAAAAAACAGTCGATTGGTCAATTGATTGAGCAATAAGCCT

CYP3A5 ------

To determine the protein similarities between CYP3A4 and CYP4A5, protein sequences were aligned using CLUSTALW tool.

CLUSTAL 2.1 Multiple protein Sequence Alignments

Sequence 1: CYP3A4 503 aa

Sequence 2: CYP3A5 502 aa

Start of Pairwise alignments

Aligning...

Sequences (1:2) Aligned. Score: 83.6653

Guide tree file created: [clustalw.dnd]

There are 1 groups

Start of Multiple Alignment

Aligning...

Group 1: Sequences: 2 Score:7602

Alignment Score 2691

CLUSTAL-Alignment file created [clustalw.aln]

clustalw.aln

CLUSTAL 2.1 multiple sequence alignment

CYP3A4 MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMF

CYP3A5 MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKF

* ***:**:******************::*****:**********:***:***::*: *

CYP3A4 DMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISI

CYP3A5 DTECYKKYGKMWGTYEGQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISL

* **:*****:** *:** *********:*:***************.:***********:

CYP3A4 AEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYS

CYP3A5 AEDEEWKRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIFGAYS

********:****************.*******************.********:*****

CYP3A4 MDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICV

CYP3A5 MDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILFPFLTPVFEALNVSL

*****.*******************.***:*:*.****:**** :**** *::*.**:.:

CYP3A4 FPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSI

CYP3A5 FPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMIDSQNSKETESHKALSDLELAAQSI

**::. *** ***:***:***:*.****:**************************.****

CYP3A4 IFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVV

CYP3A5 IFIFAGYETTSSVLSFTLYELATHPDVQQKLQKEIDAVLPNKAPPTYDAVVQMEYLDMVV

**************** :**************:***************:*:*********

CYP3A4 NETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFS

CYP3A5 NETLRLFPVAIRLERTCKKDVEINGVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFS

********:*:****.*********:***** :*:**:****:*********:* *****

CYP3A4 KKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLG

CYP3A5 KK-KDSIDPYIYTPFGTGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQ

** **.**********:****************************************.

CYP3A4 GLLQPEKPVVLKVESRDGTVSGA

CYP3A5 GLLQPEKPIVLKVDSRDGTLSGE

********:****:*****:**