{PDOC00198}
{PS00226; IF_ROD_1}
{PS51842; IF_ROD_2}
{BEGIN}
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* Intermediate filament (IF) rod domain signature and profile *
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Intermediate filaments  (IF)  [1,2,3,4]  are  proteins  which  are  primordial
components of  the cytoskeleton and the nuclear envelope.  They generally form
filamentous structures  8  to  14  nm  wide. IF proteins are members of a very
large multigene family of proteins which has been subdivided in six types:

 - Type   I: Acidic cytokeratins.
 - Type  II: Basic cytokeratins.
 - Type III: Vimentin,  desmin,   glial  fibrillary  acidic  protein   (GFAP),
   peripherin, and plasticin.
 - Type  IV: Neurofilaments L, H and M, alpha-internexin and nestin.
 - Type   V: Nuclear lamins A, B1, B2 and C.
 - Type  VI: 'Orphan' IF proteins, which are more distant in terms of their
   amino acid sequences.

All IF proteins  are structurally  similar in  that they consist of: a central
rod domain comprising  some 300 to  350 residues which is  arranged in coiled-
coiled alpha-helices,  with at least two short characteristic interruptions; a
N-terminal non-helical  domain  (head)  of variable  length; and a  C-terminal
domain (tail)  which is also   non-helical,  and which   shows  extreme length
variation between different IF proteins.

While IF proteins are evolutionary and structurally related, they have limited
sequence homologies    except in several regions of the rod domain. The IF rod
domain is  approximately  310 residues long in all cytoplasmic IF proteins and
close to  350  residues  in  the  nuclear  ones. The IF rod domain exhibits an
interrupted alpha-helical   conformation   (see   <PDB:3G1E>)  and  reveals  a
pronounced seven-residue  periodicity  in the distribution of apolar residues.
The heptad periodicity within the rod domain is interrupted in several places,
which generates  four  consecutive  alpha-helical  segments:  1A and 1B, which
together form the so-called coil 1, and 2A and 2B, which form coil 2. The four
alpha-helical segments   are  interconnected  by  relatively  short,  variable
linkers L1, L12 and L2 [5,6].

IF proteins  have  a  very strong tendency to dimerize via the formation of an
alpha-helical coiled coil (CC) by their rod domains [6].

We use,  as  a sequence pattern for this class of proteins, a conserved region
situated at  the  very  end of the 2B segment, which is critically involved in
specific dimer-dimer  interactions  within  the  mature  filament [5]. We also
developed a profile that covers the whole IF rod domain.

-Consensus pattern: [IV]-{K}-[TACI]-Y-[RKH]-{E}-[LM]-L-[DE]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for Drosophila lamin DM0 and filensin.
-Other sequence(s) detected in Swiss-Prot: 19.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: In the third position of  the pattern, Ala is found in type IV and V IF
 proteins, Thr is found in IF proteins of  type I, II, III, and VI,  Cys in IF
 from snails, and Ile in IF from worms.   In the first position of the pattern
 Val is found in type VI, Ile is found in all other types.

-Last update: September 2017 / Text revised; profile added.

[ 1] Quinlan R., Hutchison C., Lane B.
     Protein Prof. 2:801-952(1995).
[ 2] Steiner P.M., Roop D.R.
     Annu. Rev. Biochem. 57:593-625(1988).
[ 3] Stewart M.
     "Intermediate filaments: structure, assembly and molecular
     interactions."
     Curr. Opin. Cell Biol. 2:91-100(1990).
     PubMed=2183847
[ 4] Guzenko D., Chernyatina A.A., Strelkov S.V.
     "Crystallographic Studies of Intermediate Filament Proteins."
     Subcell. Biochem. 82:151-170(2017).
     PubMed=28101862; DOI=10.1007/978-3-319-49674-0_6
[ 5] Strelkov S.V., Herrmann H., Aebi U.
     "Molecular architecture of intermediate filaments."
     Bioessays 25:243-251(2003).
     PubMed=12596228; DOI=10.1002/bies.10246
[ 6] Chernyatina A.A., Nicolet S., Aebi U., Herrmann H., Strelkov S.V.
     "Atomic structure of the vimentin central alpha-helical domain and its
     implications for intermediate filament assembly."
     Proc. Natl. Acad. Sci. U.S.A. 109:13620-13625(2012).
     PubMed=22869704; DOI=10.1073/pnas.1206836109
{END}