Target+-+Carbonic+Anhydrase+IX

http://plasmid.med.harvard.edu/PLASMID/GetCloneDetail.do?cloneid=44271&species= http://dnasu.asu.edu/DNASU/GetCloneDetail.do?cloneid=44271&species=Homo%20sapiens
 * Organism: Homo sapiens**
 * Target: Carbonic Anhydrase IX (CA9)**
 * NCBI ID #: 768**
 * EC#: 4.2.1.1**
 * PDB # : 3IAI**
 * Link to Harvard PSI Page:**
 * Link to ASU PSI Page:**


 * Background/Disease:**

Carbonic Anhydrase IX (CA9), also called membrane antigen MN, is a transmembrane protein that is part of the Carbonic Anhydrase (CA) family. Carbonic Anhydrases, which are metalloenzymes, catalyze the reversible hydration of carbon dioxide. Therefore, they participate in a wide variety of physical and biological processes. CA9 is made of a signal peptide, a CA domain with a highly conserved active site, a proteoglyclan-related region, a transmembrane anchor, and an intracytoplasmic tail. CA9 is evidenced to be involved in rapid cellular reproduction and cellular transformation. It is overexpressed in tumors of several forms of cancers and is so far the only known Carbonic Anhydrase isoenzyme that is associated with cancer. CA9 is involved with increased metastasis, or the spreading of cancer to other parts of the body, and poor prognosis in aggressive carcinomas, or malignant tumors derived from epithelial tissue. CA9 is cell density dependent and has shown to be strongly induced by hypoxia, the deprivation of adequate oxygen supply. Therefore, it allows for the adaptation of tumor cells to hypoxic conditions which make them much more hard to treat through chemotherapy or radiation.

Because CA9 is expressed in cancers but not in most normal tissues, it is an attractive target for virtual drug screening. CA9 inhibition can prove to be key in therapeutic drugs for cancer and may increase success in chemotherapy and radiation treatment.


 * Image of protein (PyMol or etc):**

atggctcccctgtgccccagcccctggctccctctgttgatcccggcccctgctccaggc ctcactgtgcaactgctgctgtcactgctgcttctggtgcctgtccatccccagaggttg ccccggatgcaggaggattcccccttgggaggaggctcttctggggaagatgacccactg ggcgaggaggatctgcccagtgaagaggattcacccagagaggaggatccacccggagag gaggatctacctggagaggaggatctacctggagaggaggatctacctgaagttaagcct aaatcagaagaagagggctccctgaagttagaggatctacctactgttgaggctcctgga gatcctcaagaaccccagaataatgcccacagggacaaagaaggggatgaccagagtcat tggcgctatggaggcgacccgccctggccccgggtgtccccagcctgcgcgggccgcttc cagtccccggtggatatccgcccccagctcgccgccttctgcccggccctgcgccccctg gaactcctgggcttccagctcccgccgctcccagaactgcgcctgcgcaacaatggccac agtgtgcaactgaccctgcctcctgggctagagatggctctgggtcccgggcgggagtac cgggctctgcagctgcatctgcactggggggctgcaggtcgtccgggctcggagcacact gtggaaggccaccgtttccctgccgagatccacgtggttcacctcagcaccgcctttgcc agagttgacgaggccttggggcgcccgggaggcctggccgtgttggccgcctttctggag gagggcccggaagaaaacagtgcctatgagcagttgctgtctcgcttggaagaaatcgct gaggaaggctcagagactcaggtcccaggactggacatatctgcactcctgccctctgac ttcagccgctacttccaatatgaggggtctctgactacaccgccctgtgcccagggtgtc atctggactgtgtttaaccagacagtgatgctgagtgctaagcagctccacaccctctct gacaccctgtggggacctggtgactctcggctacagctgaacttccgagcgacgcagcct ttgaatgggcgagtgattgaggcctccttccctgctggagtggacagcagtcctcgggct gctgagccagtccagctgaattcctgcctggctgctggtgacatcctagccctggttttt ggcctcctttttgctgtcaccagcgtcgcgttccttgtgcagatgagaaggcagcacaga aggggaaccaaagggggtgtgagctaccgcccagcagaggtagccgagactggagcctag
 * CDS Gene Sequence:** (1380 bp)


 * Amino Acid Sequence:** (459 aa)

MAPLCPSPWLPLLIPAPAPGLTVQLLLSLLLLVPVHPQRLPRMQEDSPLGGGSSGEDDPL GEEDLPSEEDSPREEDPPGEEDLPGEEDLPGEEDLPEVKPKSEEEGSLKLEDLPTVEAPG DPQEPQNNAHRDKEGDDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFCPALRPL ELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMALGPGREYRALQLHLHWGAAGRPGSEHT VEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLSRLEEIA EEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLS DTLWGPGDSRLQLNFRATQPLNGRVIEASFPAGVDSSPRAAEPVQLNSCLAAGDILALVF GLLFAVTSVAFLVQMRRQHRRGTKGGVSYRPAEVAETGA

Dr. B - the 3IAI uses a truncated protein since part of the protein is intermembrane and won't express and purify well. PDB a.a. sequence: GPDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFSPALRPLELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMAL GPGREYRALQLHLHWGAAGRPGSEHTVEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLS RLEEIAEEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLSDTLWGPGDSRLQLN FRATQPLNGRVIEASFP

ASU/PSI sequence translated on the Sequence Manipulation Suite using the Standard Code MAPLCPSPWLPLLIPAPAPGLTVQLLLSLLLLMPVHPQRLPRMQEDSPLGGGSSGEDDPL GEEDLPSEEDSPREEDPPGEEDLPGEEDLPGEEDLPEVKPKSEEEGSLKLEDLPTVEAPG DPQEPQNNAHRDKEGDDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFCPALRPL ELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMALGPGREYRALQLHLHWGAAGRPGSEHT VEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLSRLEEIA EEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLS DTLWGPGDSRLQLNFRATQPLNGRVIEASFPAGVDSSPRAAEPVQLNSCLAAGDILALVF GLLFAVTSVAFLVQMRRQHRRGTKGGVSYRPAEVAETGA*

BLASTP with 31A1 pdb on top and ASU/PSI translated on the bottom Ordered plasmid: Clone ID: HsCD00044271

TAC TTC CAA TCC ATG GGG GAT GAC CAG AGT CAT

TAT CCA CCT TTA CTG CTA AGG GAA GGA GGC CTC