{PDOC50084}
{PS50084; KH_TYPE_1}
{PS50823; KH_TYPE_2}
{BEGIN}
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* KH domain profiles *
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The  K  homology  (KH)  domain was first identified in the human heterogeneous
nuclear  ribonucleoprotein  (hnRNP) K. It is a domain of around 70 amino acids
that  is  present  in  a  wide  variety  of quite diverse nucleic acid-binding
proteins [1]. It has been shown to bind RNA [2,3]. Like many other RNA-binding
motifs,  KH  motifs  are found in one or multiple copies (14 copies in chicken
vigilin) and, at least for hnRNP K (three copies) and FMR-1 (two copies), each
motif is necessary for in vitro RNA binding activity, suggesting that they may
function cooperatively  or,  in  the  case  of  single  KH motif proteins (for
example, Mer1p), independently [1].

According to structural [2,3,4] analysis the KH domain can be separated in two
groups.  The  first group or type-1 contain a beta-alpha-alpha-beta-beta-alpha
structure,  whereas in the type-2 the two last beta-sheet are located in the N
terminal  part  of  the  domain  (alpha-beta-beta-alpha-alpha-beta).  Sequence
similarity  between  these two folds are limited to a short region (VIGXXGXXI)
in  the  RNA  binding  motif.  This motif is located between helice 1 and 2 in
type-1 and between helice 2 and 3 in type-2.

Some proteins known to contain a type-1 KH domain are listed below:

 - Bacterial polyribonucleotide nucleotidyltransferases (EC 2.7.7.8).
 - Vertebrate  fragile  X  mental  retardation protein 1 (FMR1). Associated to
   polysomes and  might be involved in the transport of  mRNA from the nucleus
   to the cytoplasm.
 - Eukaryotic  heterogeneous  nuclear ribonucleoprotein K (hnRNP K), one of at
   least 20  major  proteins  that  are  part  of hnRNP particles in mammalian
   cells. It  is  presumed  to  be  involved in transport and/or processing of
   heterogeneous nuclear  and  mature RNA.
 - Mammalian poly(rC) binding proteins.
 - Artemia salina glycine-rich protein GRP33.
 - Yeast PAB1-binding protein 2 (PBP2).
 - Vertebrate  vigilin.  An  oestrogen-inducible  protein in polysome extracts
   which binds specifically to a segment of the 3'untranslated region (UTR) of
   estrogen-stabilized vitellogenin mRNA.
 - Human high-density lipoprotein binding protein (HDL-binding protein).
 - Human  onconeural  ventral antigen-1 (NOVA-1). May regulate RNA splicing or
   metabolism in a specific subset of developing neurons.

Proteins known to contain a type-2 KH domain are listed below:

 - Eukaryotic and prokaryotic S3 family of ribosomal proteins.
 - Prokaryotic GTP-binding protein era.

To identify  KH domains we developed two profiles, one specific for type-1 and
the other type-2. Both profiles cover the whole domain.

-Sequences known to belong to this class detected by the first profile: ALL.
-Other sequence(s) detected in Swiss-Prot: also detects six KH type-2 domains.

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

-Last update: December 2001 / First entry.

[ 1] Burd C.G., Dreyfuss G.
     "Conserved structures and diversity of functions of RNA-binding
     proteins."
     Science 265:615-621(1994).
     PubMed=8036511
[ 2] Musco G., Kharrat A., Stier G., Fraternali F., Gibson T.J., Nilges M.,
     Pastore A.
     "The solution structure of the first KH domain of FMR1, the protein
     responsible for the fragile X syndrome."
     Nat. Struct. Biol. 4:712-716(1997).
     PubMed=9302998
[ 3] Baber J.L., Libutti D., Levens D., Tjandra N.
     "High precision solution structure of the C-terminal KH domain of
     heterogeneous nuclear ribonucleoprotein K, a c-myc transcription
     factor."
     J. Mol. Biol. 289:949-962(1999).
     PubMed=10369774; DOI=10.1006/jmbi.1999.2818
[ 4] Grishin N.V.
     "KH domain: one motif, two folds."
     Nucleic Acids Res. 29:638-643(2001).
     PubMed=11160884

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