Tuesday, April 26, 2011

Gene and Protein Names (Biochemistry)


            I studied chemistry in college.  Not biochemistry, not biology, not anatomy; chemistry.  My first job out of college was as a research technician in a biological research lab.  The techniques, the discussions, and the research topics were 100% foreign to me.  

                “Well, MAPK signaling isn’t turned on in that situation.”

                “Did you get the knockout mice yet?  Are they viable?”

                “Run a northern and tell me about RNA levels.”

                What?

                I quickly figured out some of this stuff, but the most troublesome topic for me was the convention of naming proteins.  In case you didn’t know, our cells are full of proteins, which number into the thousands.  They all need names so scientists and can share information, but, much like naming children or pets, it can be your basic free-for-all. 

                In chemistry, most things have a scientific name: atom, proton, quark, neutron, etc.  New molecules even have a universal convention for naming them.  Granted, the names are huge and bulky, but they are not ambiguous!  Often, they are shortened to something else, but there is always the universal name and, sometimes, a CAS number to fully identify the chemical.

  In biology, everything is named with letters and numbers, sometimes arbitrarily picked (or not), that either stand for longer names (or not).  For example, I worked heavily in graduate school on p53 (Cancerous Mutational Problems post).  Why is it called that?  Because when scientists were trying to isolate a protein known as Large T antigen (this is only one of its names, by the way), another protein kept hanging around.  Scientists didn’t know anything about this other protein except that its size was 53 kilodaltons (don’t worry about what that means for this post) so…

P = protein
53 = weight
Protein name = p53
                 
           Genius. 
               
I hated sitting through talks while I was a technician.  The names of some proteins were ridiculous.  I often wondered why they couldn’t name them all logical things.  Some proteins really do have logical names! 

Example 1: phosphofructokinase
Function: This protein is an enzyme that adds a phosphate group to phosphofructose*.
                Phosphofructo = phosphofructose
                Kinase = adds a phosphate group to
                Name = phosphofructokinase
                Now that makes sense!

              Example 2: E6AP
     Function: This is a protein known to bind to another protein called E6.
     E6AP = E6 Associating Protein
     Logical!
               
                Other names are just completely batty.  My personal favorite is when I started reading about RING proteins.  You think it sounds nice, maybe the proteins form a ring-like structure, maybe they are involved in making rings of something else… maybe??  No.  RING is an acronym for Really Interesting New Gene.  I loved when people asked me in talks what RING meant.


                 
            One name stands out in my mind as one of the most ridiculous, somewhat contentious, but still high profile proteins in science: Sonic Hedgehog.  Bob Riddle of the Harvard Medical School named this fly developmental gene in 1993.  Luckily, Sega isn’t too threatened by it.  However, Velcro and Pokemon don’t want genes or proteins named after them and both have threatened legal action unless their names were removed from recently characterized genes.  Not all advertising is good advertising, apparently.





                Guidelines do exist for unambiguously naming both genes and proteins.  However, just as with chemicals, people tend to use the colloquial names because the correct nomenclature hasn’t caught on yet or it’s simply easier.  It is always fun to read “protein A, more commonly known as protein ABC” in literature.  I once spent several days looking for two papers that I was told existed: structural information about the CH1 and CH3 domains of a protein known as p300 (or CBP, take your pick).  I could not find them and was convinced everyone was delusional.  It was later that someone mentioned they were published under the names TAZ1 and TAZ2.  

Really?  Science.
               

CAS Number – Numbers assigned by the Chemical Abstracts Service to every chemical reported in scientific literature.  Universal names can be long and difficult so some names are shortened.  Different companies will list chemicals under different names, but CAS numbers will always be listed with the chemical so you can be 100% certain of its identity.

Kilodalton – Unit of protein weight.  Proteins can be described by how much they weigh, which is useful information to give scientists an idea how large or small a particular protein is.  The more amino acids a protein has, the heavier it is so the more kilodaltons it has.  

1 Dalton (Da) = 1.66 X 10-24 g
1 kDa = 1.66 x 10-21 g
One protein weighing 53 kDa = 8.8 X 10-20 g   (Really small!)

*Name was shortened from fructose-6-phosphate so people could more easily understand the name

References

Evans et al. “Mutations in the active site of Escherichia coli phosphofructokinase.” Nature (1987) 327, pgs 437 – 439. 

Huibregtse et al. “Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53” Mol. Cell Biol. (1993) 13(2) pgs 775 – 784.

Simonite, T. “Pokemon blocks gene name” Nature (2005) 438 pg 897

Maclean, K. “Humor of gene names lost in translation to patients.” Nature (2006) 439 pg 266

HUGO Gene Nomenclature Committee: www.genenames.org

De Guzman et al. “Solution structure of the TAZ2 (CH3) Domain of the Transcriptional Adaptor Protein p300” J Mol Biol. (2000) 303 pgs 243 – 253

De Guzman et al. “CBP/p300 TAZ1 Domain Forms a Structured Scaffold for Ligand Binding” Biochemistry (2005) 44 pgs 490 – 497 


NOTE: Amedeo needs to take a short break because she is getting married.  I'll return in the middle of May!

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