Fu L , Das B , Mathew S , Shi YB .

Intramural NIH HHS

	Figure 1. Phylogenetic tree of X. tropicalis (Xt) and human MMPs. Also included are chicken MMP22 (cMMP22) and Rana catesbeiana MMP1 (Rc-MMP1) as MMP22 was not found in human and Xenopus and Rc-MMP1 has a unique sequence organization (see description on MMP1). Novel X. tropicalis MMPs are highlighted in bold.
	Figure 2. Sequence comparison of MMP1 with MMP N4 and MMP N5. X. tropicalis (Xt) MMP1, N4 and N5, and X. laevis (Xl) MMP1A and 1B were aligned with human (h) MMP1 for comparison. The sequences of the putative signal peptide are underlined. The predicted cleavage site between the signal peptide and the propeptide is indicated by an arrow, and the predicted cleavage site between the propeptide and the catalytic domain is indicated by solid arrowhead. The conserved sequence in the propeptide involved in the "cysteine-switch" is boxed, and the zinc-binding motif within the bracketed catalytic domain is indicated by a solid line on top. The three conserved histidine residues in the zinc binding motif and the conserved methionine residue of the nearby "Met-turn" are indicated by stars below. The 16 aa sequence (shadowed) at the end of the catalytic domain (bracketed) indicates the region whose integrity is important for collagenase specificity for collagen. An insertion of 8 or more aa within this region at the site indicated by an arrowhead is characteristics of stromelysins. The arrow marked "C" shows the beginning of the C-terminal hemopexin-like domain. A dot indicates an identical amino acid as the corresponding one in Xt-MMP1. Gaps (dashes) are introduced to optimize the alignment among proteins. Note that MMP N4 and N5 contain internal deletions in the linker region between the catalytic domain and C-terminal hemopexin-like domain.
	Figure 3. Comparison of Xenopus MMP3 with human MMP1, 3, and 10. Note that the shadowed region at the end of the catalytic domain corresponds to the same region in Fig. 2 except the insertion of 8–14 aa in stromelysins (MMP3, 10) compared to collagenases (e.g., the MMP1 shown here). See Fig. 2 for other information.
	Figure 4. Comparison of frog and human MMP23 with MMP N6. The predicted signal anchor (transmembrane domain) sequences are underlined and the putative furin recognition sequences are in bold. The cysteine residues in the "cysteine-array" unique to MMP23 are in bold and indicated with # below. The amino acid residues characteristic of an Ig (immunoglobulin)-fold are indicated with rectangle boxes below. See Fig. 2 for other information.
	Figure 5. Comparison of MMP21 with MMP N3. The predicted signal peptide is underlined and the putative furin recognition sequences within the propeptide are in bold. The sequence in white on dark background indicates the unique insertion in the propeptide in MMP21. A unique cysteine residue in the catalytic domain is in bold and indicated with a black diamond below. Note that the sequence for Xl-MMP N3 is incomplete at the N-terminus. See Fig. 2 for other information.
	Figure 6. Comparison of MMP N2 with MMP7 and MMP26. Note that like human and Xenopus MMP7 and MMP26, MMP N2 lacks the linker peptide and hemopexin-like domain at the C-terminal. See Fig. 2 for other information.
	Figure 7. Putative alternative splicing variant of X. laevis MMP2 (MMP2asv). A) Nucleotide and deduced amino acid sequences of MMP2asv. The protein contains, from the N-terminus to C-terminus, a signal peptide (underlined), the conserved sequence in the propeptide involved in the "cysteine-switch" (in bold letters), a truncated catalytic domain linked to a truncated hemopexin domain (separated by double slash lines). The predicted cleavage site between the propeptide and the catalytic domain is indicated by an arrow. B) Comparison of the full length and alternatively spliced X. laevis MMP2 exon/intron organization. Solid blocks stand for exons present in the mRNAs and lines are introns.
	Figure 8. Comparison of Xenopus MMP N1 with human MMP1, 3, 12, and X. laevis MMP18. The amino acid sequence in shadowed letters corresponds to the region equivalent of the proline-rich sequences (16 aa) at the end of the catalytic domain in human MMP1 whose integrity is important for the collagenase specificity for collagen. A short peptide insertion (in bold letters) within this region is characteristics of stromelysins as shown here for MMP3. The Xenopus MMP N1 has a 16 aa-insertion within the same region (in bold letters) as well as some additional insertions within the C-terminal hemopexin-like domain (in italics). See Fig. 2 for other information.
	Figure 9. Comparison of the MMPs cluster on X. tropicalis Scaffold_119 to that on human Chromosome 11. X. tropicalis MMP cDNA sequences were used to do BLAST search against the X. tropicalis genomic sequences to locate the genes on the assembly scaffolds. MMP 1, 3, 7, 13, 18, 20, 26, as well as the novel ones MMP N2, N4 and N5 are found on Scaffold_119. They were arranged on the scaffold according to their location and orientation. The human MMPs on Chromosome 11 were arranged according to the annotations for their locations and orientations in Human Genome Build 36.3 on the NCBI website. The MMPs shown above the line for the chromosome/scaffold are MMPs specific to X. tropicalis or human while those shown below are the MMPs present in both species. Mb, mega base pair; kb, kilo base pairs. Note the gene size was not drawn to scale for clarity.

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