Kinesin Nomenclature:

1
Kinesin Nomenclature Perspectives from Other
Protein Families
Holly Goodson Department of Chemistry and
Biochemistry University of Notre Dame
2
Three reasons for an organized nomenclature

• Unify vocabulary
• mention one protein, all know what talking
  about!
• Create framework for understanding family
• phylogenetic trees provide framework, but
  unified nomenclature
• helps convey it
• Convey functional information

Myosin I Arp2  classification
conveys set of common attributes  name itself
may have meaning ideal but difficult to achieve
3

• Two common approaches to nomenclature
• 1) Uncoordinated name as we go
• Present state of kinesin field.

? chaos.
Similar Families - Kinases - GTPases
(rabs) - Ion channels
No organizing principle - multiple
synonyms - logic behind names is different
? names convey little functional information -
difficult to relate proteins between
organism ? hard to learn, confuses
EVERYONE ? inhibits scientific process
Path of least resistance
4
2) Name/rename based on evolutionary
relationships

• Actins
• Myosins
• - Histone Deacetylases

Nomenclature enhances understanding of protein
function Protein names ? evolutionary
relationships ? function
5
Approaches to Phylogenetic Nomenclature
1. Name proteins/genes on basis of phylogenetic
relationships
Nice, but the horse is already out of the
barn Useful for naming otherwise
uncharacterized proteins
2. REname proteins/genes on basis of
phylogenetic relationships
 NOT trivial WAS done for actin family
Act3p ? Arp1p

• Establish phylogentically based classification
  system
• on top of existing nomenclature

most common approach compromise MYO3 is
a myosin 1
6
Actin Family
Initial state No consistency in family within
or between organisms ARPs not differentiated
from conventional actins
Lots of synonyms
7
Actin Solution (Schroer et al, JCB 1994,
Goodson and Hawse, JCS 2002) Separate ARPs
into groups by phylogenetic analysis
(deepest well-supported nodes valid groups
must have sequences from divergent organisms)
REname proteins based on group they
belong to Act3p ? Arp1p
How name groups???
- By distance from actin (ARP1 .Arp10) - If
group contains subgroups, use a, b, g
? Approach works well because most proteins DO
fall into obvious and significant groups well
behaved
What if multiple ARPs are equally divergent?

• Choose reference organism S. cerevisiae

What about orphan proteins???
- Establish membership in group by other methods
(Arp10) - Leave group as undefined -- default
to chaos approach
8
Myosin Solution (Cheney et al. CMC 1993, Hodge
and Cope JCS 2000) Separate ARPs into classes
by phylogenetic analysis (deepest
well-supported nodes classes can
contain single sequences) Impose class
structure on top no renaming individual
proteins
How name classes???

• By chronological order of identification
• Use a, b, c to name subclasses, or adhere to
  tradition (a cardiac..)

• Again, most proteins
• DO fall into obvious
• and significant groups
• well behaved

What about orphan proteins?

• Given them their own group!
• - some extraneous classes
• - DOES convey functional information

9
Histone Deacetylase Approach (Gregoretti et al.,
submitted)
? Example of messier system
4 classes humans?bacteria
Eukaryotes have many subclasses AND limits
not easily defined weak bootstrapping.
Solution Adopt myosin system except  Use
humans as reference organism to sort out
subclasses yeast-human relationships is
unclear - Define group as subclass if has
members from vertebrates and
invertebrates - Subclasses named by human
proteins contained within HDAC1/3 contains
HsHDAC1 and HsHDAC3
10
Possible solutions for kinesin family Combine
aspects of all three approaches
? Impose class system on top of existing names
Define classes by - deepest well-supported
node and - additional biological evidence
? Include ScSMY1 in kinesin group
orphans??
Name classes by - first identified member
or - number in order of identification
Name subclasses by - name in reference
organism (humans??) - a, b, g in order of
discovery??
Define subclasses by - presence of protein
in vertebrates and invertebrates ? any other
gene duplication ? subtype
11
Acknowledgements
Goodson Lab
CLIP-170 and ClipRs Molecular
Evolution/ Computational Biology Eric
Folker Ivan Gregoretti Gergana Ugrinova Bill
Hawse Susan Skube-Barr Kelly Gallagher
Caroline Blessing Adam Willis Adreas Weiss
Technician Jose Chaverri

Collaborators
B. Baker and Biochemistry Group K. Vaughan and
the Cell Biology Group Mark Alber and the
Biocomplexity Center G. Borisy, Y. Komorova
Northwestern Medical School

Funding  NIH  AHA
Funding

• NIH
• American Heart Association
• Biocomplexity Center
• Walther Cancer Center/DOD-I