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.
Plasma kallikrein (EC 3.4.21.34) and coagulation factor XI (EC 3.4.21.27) are two related plasma serine proteases activated by factor XIIA and which share the same domain topology: 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) (PUBMED:1998667) ] that three disulfide bonds link the first and sixth, second and fifth, and third and fourth cysteines. The domain can be drawn in the shape of an apple (see below) and has been accordingly called the 'apple domain'.
The apple domains of plasma prekallikrein are known to mediate its binding to high molecular weight kininogen [ (PUBMED:8662705) ], the apple domains of factor XI bind to factor XIIa, platelets, kininogen, factor IX and heparin [ (PUBMED:9632702) ].
The apple domains display some sequence similarity with the N domain of plasminogen/hepatocyte growth factor (HGF) and to some nematode and protozoan proteins [ (PUBMED:10561497) ]. They all belong to the same domain superfamily that have been called the PAN module [ (PUBMED:11376658) ]. The N domain of hepatocyte growth factor binds to the c-Met receptor and to the heparin molecule. The structure of the PAN module of HGF has been solved. It contains a characteristic hairpin-loop structure stabilised by two disulfide bridges, Cys-1 and 6 are not conserved in HGF PAN modules [ (PUBMED:9493272) ].
Apart from the cysteines, there are a number of other conserved positions in the apple domain. This entry represents the PAN domain of the plasma kalllikrein/coagulation factor XI subgroup proteins.
Family alignment:
There are 16227 PAN_AP domains in 10380 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing PAN_AP domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with PAN_AP domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing PAN_AP domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
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)
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%.
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
