XB-FEAT-22164454

tff3.5

This is the Xenbase community wiki page for Xenopus tff3.5 genes. Please feel free to record here any relevant information about these ones, that is not already represented on the gene page or elsewhere on Xenbase.

Tff proteins in Xenopus

The early work on these proteins by Werner Hoffmann’s lab (PMID: 31979419, PMID: 9394039; PMID: 31979419) suggested the Xenopus loci, which they consistently call xP1 and xP2, are considered orthologous to TFF1 and TFF2 as they form 2 different complexes (of high v low molecular weight) and probably have different mucosal/immune functions. This nomenclature is still used 25 -30 years later, in Hoffmann’s 2019 and 2020 papers(PMID: 31801293, PMID: 32244312; PMID: 31979419). the genes described in their early papers from etc 1990's are described below.

frog integumentary mucin A.1

First described as frog integumentary mucin A.1, FIM-A.1 by Werner Hoffman's group (Max-Plunck-Institutfur Psychiatrie, Abteilung Neurochemie, W-8033 Martinsried, Federal Republicof Germany) in publication from 1990 the BLAST of the published protein sequence [MKHIILCIHFLLMVVGLGQAQ] from the original paper hits tff3.5.L. These proteins are now referred to as trefoils in the TFF family, and as the fim-a.1 gene symbol wasn't used in the recent genome assemblies, we have merged the legacy names/symbols and added the article the the literature here to the Xenopus tff3.5 gene page.

xP2

Hauser Roeben and Hoffman's 1991, 'xP2, a NewMember of the P-domain Peptide Familyof Potential Growth Factors,Is Synthesized in Xenopus laevis Skin, described another protein, submitted to GenBank under M90095.

The translation of this short protein is: MNHKLFCVHFLLLILSVCYIQGQDAVGPKTEDCKGDPFKRTDCGYPGITEGQCKAKGCCFDSSIVGVKWCFFPRTARAQCLFSPGDREDCGYSSITPMECMKRGCCFDASITGVKWCFHQK

BLASTp, identifies it as Xla.tff3.7.S, aka xP2/p2 and with partial matches/conserved domains with p2 (which links to tff3.6) and tff3.6/tff3.6.L and tff3.5.L

frog integumentary mucin C.1

Hauser and Hoffman's 1992 paper described a 2nd FIM protein in X. laevis, they dubbed it FIM-C.1.

The protein sequence for GenBank: L02115.1

APTTAAAVAATGKDTTAAAEGSAAAEKTAAAGEVSAPPTAAVAATGEDATTAAATAAAETTAAAGEAPTTTTAPATTAAGKAPTTAAATAPTTAAAGAPTTATG KAPATAAAPVPTTAASKAPTTAAAATHSTAAAAAPTTAASAAKSKERSTSSSSEEEHCHVKPSKREMCGSKGITKKQCKKKNCCFDPKGHGGIHCFHRKPKGHS HEEHTTTTTKAPTTIQIATTTTTPTTTTTTTKATPTTTTTTKATPTTTTTTKATTTTTTPTTTTTTTKATTTPTTTTTTTPTTTTTKATTTTTTTSGECKMEPS KREDCGYSGITESQCRTKGCCFDSSIPQTKWCFYTLSQVADCKVEPSQRVDCGFRGITADQCRQKNCCFDSSISGTKWCFYSTSQVAATKTTTTPTTTTTPTTT TTTKATTTTPTTTTTTPTTTTTTTTTTKATTTTPTTTTPTTTTTKATTTTPTTTTTTPTTTTTKATTTTPTTTTTTPTTTTTKATTTTPTTTTTTTTTTKATTT TTSGECKMEPSKRADCGYPGITESQCRSKGCCFDSSIPQTKWCFYSLPQVADCKVAPSSRVDCGFGGITADQCRQRNCCFDSSISGTKWCFYSTSQGNAMCSGP PTKRRDCGYPGISSSVCINRGCCWDNSVMNVPWCFYRT

[see https://www.ncbi.nlm.nih.gov/nuccore/L02115.1/]

BLASTp of this sequence matches/hits/aligns to the 3' tail end of Xtr.tff3.5 as well as the original FIM-C.1 sequences, and 1 instance of a similar Xtr.tff3.7 gene/protein.

summary for TFF family from NCBI

Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. In mammals they are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not well defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. The encoded proteins are predicted to inhibit gastric acid secretion in mammals. In amphibians they have been well studied by the Hoffmann lab, and occur in 4th gastrointestinal tract & stomach.

orthology and gene annotation notes

01APRL2024 [CJZ]

The TFF genes in humans are on Chr 21 (TFF1, TFF2 & TFF3) and are relatively small proteins -492bp.603bp and 867 bp respectively.

In Xenopus, there is a 8-gene expansion on chromsomes 2/2L/2S, where the genes ranges from 2,549 bp (tff3.1.S) to 92,038 bp (Xla.tff3.4).

NCBI does not identify any amphibian orthologs of TFF2, only a Bufo ortholog of TFF1, and a B. bombina gene for TFF3.

Although clearly, Xenopus have these genes too!

Xenopus has an expansion of 8 x ‘’tff3’’ genes, ‘’tff3.1-3.8’’ on chromosome 2/2L/2S

tff3.1, trefoil factor 3, gene 1 XB-GENEPAGE-5897916

tff3.2, trefoil factor 3, gene 2 XB-GENEPAGE-18006555

tff3.3, trefoil factor 3, gene 3 XB-GENEPAGE-22164444

tff3.4, trefoil factor 3, gene 4 XB-GENEPAGE-22164449

tff3.5, trefoil factor 3, gene 5 XB-GENEPAGE-22164454

tff3.6, trefoil factor 3, gene 6 XB-GENEPAGE-22164459

tff3.7, trefoil factor 3, gene 7 XB-GENEPAGE-6462248 (01.04.24 gene name changed from Skin secretory protein xP2 )

tff3.8, trefoil factor 3 gene 8 XB-GENEPAGE-5824117

Note that to apply Xenopus nomenclature conventions to this expansion, we have kept the gene names assigned in the v10 assembly, and have applied new numbers to those genes in this expansions, in serial succession from tff3.1 to tff3.8.

A cursory assessment of the number of PD/trefoil domains nor the number of exons or protein length show that these factors are inconsistent and virtually impossible to apply. Further phylogenetic analysis may (or may not) be needed to resolve parology.

From a basic NCBI /COBALT alignment of the X.trop genes compared to human genes, Xtrop tff3.1 and tff3.2 are quite similar to Hsa.TFF3, especially at the 5’end.

Synteny (see below) doesn't help all that much as it informs us that the Xenopus genes are equally orthologous to TFF3 as they are to TFF1 as the flanking genes are both conserved, namely abcg1/ ABCG1 and tmprss3/TMPRSS3 across taxa (human mouse frog).

synteny

Human: ch21: ABCG1> TFF3< TFF2< TFF1< TMPRSS3<

Mouse: chr17: Abcg1> Tff3< Tff2< Tff1< Tmprss3<

Xtr.ch2: bcl9< tmprss3< tff3.1> tff3.2>. tff3.2> tff3.4 tff3.5> LOC116408572(integ mucA.1like)(tff3.6)> tff3.7> ttf3.8> abcg1<

Xla.chr2L: bcl9.L<. tmprss3.L< LOC121399802(gigfXP1/tff3.1)> LOC121399803(gigfXP1/tff3.2)> LOC121399801(gigfXP4/tff3.3)> LOC121399628(sgp)>. LOC108707398(integ mucin C/tff3.4)> tff3.5> LOC121399618(myb-rtf)< LOC121399808(integ mucinA1like)(tff3.6.L)> LOC121399619(integ mucinA1like)(tff3.7)> tff3.8> abcg1.L<

Xla.chr2S: zbtb21.S> abcg1.S> tff3.8.S< LOC121400379(unch/tff3.7)< LOC1214003809(integ mucinA.1like/tff3.6)< LOC121400381(integ mucinA.1like/tff3.4)< sgp.S< LOC121400417(integ mucinC.1like/tff3.3)< tff3.2.S< tff3.1.S< bcl9.S

tff paralogs and orthologs

Note that the X.laevis ‘gastrointestinal growth factor xP4’ proteins all have 1 or more Tff trefoil domains, so these are the paralogous ‘tff ‘ genes we have in X. tropicalis.

Note the sgp proteins in Xlaevis DO NOT have trefoil motifs, and that there are no Xtropicalis sgp genes in the v10 assembly on Chr2.