PROSITE: PDOC50002 (documentation)

{PDOC50002}
{PS50002; SH3}
{BEGIN}
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* Src homology 3 (SH3) domain profile *
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The Src  homology  3 (SH3) domain is a small protein domain of about 60 amino-
acid residues first  identified as  a  conserved sequence in the non-catalytic
part of several cytoplasmic protein tyrosine kinases (e.g. Src, Abl, Lck) [1].
Since then,  it  has  been  found in a great variety of other intracellular or
membrane-associated proteins [2,3,4,5].

The SH3  domain  has a characteristic fold which consists of five or six beta-
strands arranged  as  two tightly packed anti-parallel beta sheets. The linker
regions may contain short helices [6].

The function  of the SH3 domain is not well understood. The current opinion is
that they  mediate  assembly  of  specific  protein  complexes  via binding to
proline-rich peptides [7].

In general  SH3  domains  are  found  as single copies in a given protein, but
there is  a  significant number of protein with two SH3 domains and a few with
3 or 4 copies.

So far, SH3 domains have been identified in the following proteins:

 - Many  vertebrate,  invertebrate  and  retroviral cytoplasmic (non-receptor)
   protein tyrosine kinases. In particular in the Src, Abl, Bkt, Csk and ZAP70
   families of kinases.
 - Mammalian phosphatidylinositol-specific phospholipase C-gamma-1 and -2.
 - Mammalian phosphatidyl inositol 3-kinase regulatory p85 subunit.
 - Mammalian Ras GTPase-activating protein (GAP).
 - Adaptor  proteins  mediating binding of guanine nucleotide exchange factors
   to growth  factor  receptors: vertebrate GRB2, Caenorhabditis elegans sem-5
   and Drosophila DRK. All of which have two SH3 domains.
 - Mammalian  Vav  oncoprotein,  a  guanine  nucleotide exchange factor of the
   CDC24 family.
 - Some guanine-nucleotide releasing factors of the CDC25 family: yeast CDC25,
   yeast SCD25, fission yeast ste6.
 - MAGUK  proteins. These proteins consist of at least three types of domains:
   one or  more  copies  of  the  DHR  domain,  a  SH3 domain and a C-terminal
   guanylate kinase  domain  (see  <PDOC00670>).  Members  of this family are:
   Drosophila lethal(1)discs  large-1  tumor  suppressor  protein (gene Dlg1),
   mammalian tight  junction  protein  ZO-1,  vertebrate  erythrocyte membrane
   protein p55,  Caenorhabditis  elegans  protein  lin-2, rat protein CASK and
   mammalian synaptic  proteins  SAP90/PSD-95,  CHAPSYN-110/PSD-93, SAP97/DLG1
   and SAP102.
 - Miscellanous   proteins   interacting   with  vertebrate  receptor  protein
   tyrosine kinases: mammalian cytoplasmic protein Nck (3 copies), oncoprotein
   Crk (2 copies).
 - Chicken  Src  substrate  p80/85  protein  (cortactin) and the similar human
   hemopoietic lineage cell specific protein Hs1.
 - Mammalian dihydrouridine-sensitive L-type calcium channel beta (regulatory)
   subunit including the related human myasthenic syndrome antigen B (MSYB).
 - Mammalian  neutrophil  cytosolic  activators of NADPH oxidase: p47 (NCF-1),
   p67 (NCF-2), and a potential homolog from Caenorhabditis elegans (B0303.7).
   NCF-1 and -2 have two copies of the SH3 domain, while B0303.7 has four.
 - Some myosin heavy chains from amoebae, slime molds and yeast (gene MYO3).
 - Vertebrate and Drosophila spectrin and fodrin alpha-chain.
 - Human amphiphysin.
 - Yeast actin-binding protein ABP1.
 - Yeast actin-binding protein SLA1 (3 copies).
 - Yeast protein BEM1 and the fission yeast homolog scd2 (or ral3) (2 copies).
 - Yeast BEM1-binding proteins BOI2 (BEB1) and BOB1 (BOI1).
 - Yeast fusion protein FUS1.
 - Yeast protein RSV167.
 - Yeast protein SSU81.
 - Yeast  hypothetical proteins YAR014c (1 copy), YFR024c (1 copy), YHL002w (1
   copy), YHR016c  (1  copy),  YJL020C  (1  copy),  YHR114w (2 copies) and the
   fission yeast homolog SpAC12C2.05c.
 - Caenorhabditis elegans hypothetical proteins F42H10.3.

The profile developed to detect SH3 domains is based on a structural alignment
consisting of  5  gap-free  blocks  and  4  linker  regions  totaling 62 match
positions.

-Sequences known to belong to this class detected by the profile: ALL.     The
 second SH3 domain in crk is missed at a stringent cut-off.
-Other sequence(s) detected in SWISS-PROT: 2.

-Expert(s) to contact by email:
        Zvelebil M.: marketa@ludwig.ucl.ac.uk

-Last update: November 1997 / Text revised.

[ 1] Mayer B.J., Hamaguchi M., Hanafusa H.
     Nature 332:272-275(1988).
[ 2] Musacchio A., Gibson T., Lehto V.P., Saraste M.
     FEBS Lett. 307:55-61(1992).
[ 3] Pawson T., Schlessinger J.
     Curr. Biol. 3:434-442(1993).
[ 4] Mayer B.J., Baltimore D.
     Trends Cell Biol. 3:8-13(1993).
[ 5] Pawson T.
     Nature 373:573-580(1995).
[ 6] Kuriyan J., Cowburn D.
     Curr. Opin. Struct. Biol. 3:828-837(1993).
[ 7] Morton C.J., Campbell I.D.
     Curr. Biol. 4:615-617(1994).
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