Table 3. DIA1-family motifs.

Motif*	Alignment consensus**	Human DIA1 sequence***	Comment
1	F-L-x-L	FLqL	This motif is conserved in DIA1 and DIA1R proteins, but less-strongly conserved in DIA1L proteins (which are not targeted to the secretory pathway). The penultimate leucine in the motif is absent from Drosophila DIA1 proteins.
2	C-x-A-C-x-G-x(3,5)-C	CpACfGtswC	Motif contains two of the absolutely conserved DIA1-family residues.
3	A-x-Y-x(6,15)-L	AqYgepreggrrrvvklrL	The tyrosine is conserved in 73% of DIA1-family members. In some family members it is replaced by a tryptophan or phenylalanine, or there is an adjacent (or nearby) residue that is a tyrosine.
4	I-C-x(8,10)-C	ICkratgrprC	Absent from DIA1 from Drosophila species.
5	V-x(4,11)-C-x-S-x(6,10)-Y-x-E	VegwsdlvhCpSqrlldrlvrrYaE	The tyrosine is conserved in 85% of DIA1-family proteins.
6	L-x(3)-L-x-x-N-x-x-P-L-V-L-Q	LlltLafNpePLVLQ	The proline and glutamine residues of this motif are absent from DIA1L proteins from amphioxus.
7	G-W-P-x(5)-G-x-C-G	GWPfakylGaCG	Motif contains one of the absolutely conserved DIA1-family residues.
8	L-x-x-Y	LwsY	The tyrosine is conserved in 77% of DIA1-family members. In some family members it is replaced by a tryptophan or phenylalanine, or there is an adjacent (or nearby) tyrosine residue.
9	R-x-D-L-A-x-Q-L-M-x-I-x(3)-L	RvDLAwQLMeIaeqL	The first amino acid (R) of this motif is poorly conserved in DIA1R proteins.
10	F-x-L-Y-x-x-D-x(5)-F-A-V	FaLYlldvsfdnFAV	The tyrosine is conserved in 73% of DIA1-family members. In some family members it is replaced by a tryptophan or phenylalanine, or there is an adjacent (or nearby) residue that is a tyrosine. The aspartate of this motif is absent from DIA1R proteins.
11	K-V-x-I-D-x-E-x-V-x-V-x-D	KViIvDaEnVlVaD	The central glutamate is not conserved in DIA1R proteins.
12	C-x(3,4)-A-C-x(6,8)-C	CdkeAClsfskeilC	The final cysteine is well-conserved, but the remainder of motif is poorly conserved in insect and tunicate DIA1. Motif absent from DIA1L proteins.
13	[D-x-N-x-Y-x-x]-C-x-x-L-L	[DhNyYav]CqnLL	Motif contains one of the absolutely conserved DIA1-family residues. An expanded, tyrosine-containing motif [in square brackets] is found in this position in DIA1 and DIA1L, but not DIA1R, proteins (see Figures S8 and S9).
14	G-x-L-H-x(3,4)-E	GlLHDPPsE	Motif found in DIA1 only, with the exception of Drosophila DIA1 proteins. Absent from DIA1R and DIA1L.
15	L-x-E-x(16,18)-L	LdEcanpkkrygrfqaakeL	Consensus is conserved in more than 80% of DIA1 family but, while the final leucine is highly conserved, the first leucine is absent from 75% of DIA1R proteins. The charged residue is poorly conserved in DIA1 of insects.

*Motifs numbered in amino- to carboxy-terminal direction.

**Consensus motif is that from the Boxshade consensus line using 80% similarity threshold (Figure S8), unless otherwise indicated. Underlined residues  = 100% conserved. Standard single-letter amino acid abbreviations are used, where x = any amino acid, and x(6,8) indicates 6, 7, or 8 poorly/non-conserved amino acids present in that position.

***Motif-conforming residues are in upper case; poorly or non-conserved amino acids in lower case.