Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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PAN_AP divergent subfamily of APPLE domains

SMART accession number:	SM00473
Description:	Apple-like domains present in Plasminogen, C. elegans hypothetical ORFs and the extracellular portion of plant receptor-like protein kinases. Predicted to possess protein- and/or carbohydrate-binding functions.
Interpro abstract (IPR003609):	The apple domain, IPR000177, has an N-terminal region that contains four tandem repeats of about 90 amino acids and a C-terminal catalytic domain. The 90 amino-acid repeated domain contains 6 conserved cysteines. It has been shown [(PUBMED:1998666)] that three disulphide bonds link the first and sixth, second and fifth, and third and fourth cysteines. This entry contains apple-like domains, which are presented in Plasminogen, Caenorhabditis elegans hypothetical ORFs and the extracellular portion of plant S-locus glycoproteins (IPR000858) and S-receptor kinases. The domain is predicted to possess protein- and/or carbohydrate-binding functions.
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 1420 PAN_AP domains in 997 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a PAN_AP domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PAN_AP domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Tordai H, Banyai L, Patthy L
  • The PAN module: the N-terminal domains of plasminogen and hepatocyte growth factor are homologous with the apple domains of the prekallikrein family and with a novel domain found in numerous nematode proteins.
  • FEBS Lett. 1999; 461: 63-7
  • Display abstract

  • Based on homology search and structure prediction methods we show that (1) the N-terminal N domains of members of the plasminogen/hepatocyte growth factor family, (2) the apple domains of the plasma prekallikrein/coagulation factor XI family, and (3) domains of various nematode proteins belong to the same module superfamily, hereafter referred to as the PAN module. The patterns of conserved residues correspond to secondary structural elements of the known three-dimensional structure of hepatocyte growth factor N domain, therefore we predict a similar fold for all members of this superfamily. Based on available functional informations on apple domains and N domains, it is clear that PAN modules have significant functional versatility, they fulfill diverse biological functions by mediating protein-protein or protein-carbohydrate interactions.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 23.68 map04610 Complement and coagulation cascades 23.68 map04080 Neuroactive ligand-receptor interaction 13.16 map04060 Cytokine-cytokine receptor interaction 13.16 map04510 Focal adhesion 13.16 map05211 Renal cell carcinoma 13.16 map05218 Melanoma This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PAN_AP domain which could be assigned to a KEGG orthologous group, and not all proteins containing PAN_AP domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of PAN_AP domains in PDB

  PDB code	Main view	Title
  1bht		Nk1 fragment of human hepatocyte growth factor
  1gmn		Crystal structures of nk1-heparin complexes reveal the basis for nk1 activity and enable engineering of potent agonists of the met receptor
  1gmo		Crystal structures of nk1-heparin complexes reveal the basis for nk1 activity and enable engineering of potent agonists of the met receptor
  1gp9		A new crystal form of the nk1 splice variant of hgf/sf demonstrates extensive hinge movement and suggests that the nk1 dimer originates by domain swapping
  1nk1		Nk1 fragment of human hepatocyte growth factor/scatter factor (hgf/sf) at 2.5 angstrom resolution
  2hgf		Hairpin loop containing domain of hepatocyte growth factor, nmr, minimized average structure
  2qj2		A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist
  2qj4		A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist

• Links (links to other resources describing this domain)

• INTERPRO	IPR003609

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