Transmembrane protein 131-like(TMEM131L protein), alternatively named uncharacterized protein KIAA0922 (KIAA0922 protein), is an integral transmembrane protein[1] encoded by the human gene KIAA0922 that is significantly conserved at least through protists.[2][3][4] Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses. Research into its relation to its known and well studied paralog, Prolyl endopeptidase (PREP), may allow its function to be further elucidated.

Paralogs edit

Prolyl Endopeptidase edit

The enzyme Prolyl endopeptidase (PREP) is 13.4% identical to transmembrane protein 131L.[5][6][7][8] PREP acts in the cytosol by cleaving peptide bonds on the C-terminus of short prolyl residues (approx. 30 amino acids long).[9] [10] PREP has been found to be involved with the maturation and degredation of neuropeptides and peptide hormones.[11] PREP and its general funtions are conserved through flavobateria.[12]

Of particular interest, the highest areas of amino acid conservation between PREP and KIAA0922 are the areas most conserved in KIAA0922 #REDIRECT KIAA0922#Conservation are the esterase lipase region (483...706)[13] and peptidase S9 N region (7...423)[13]

This connection may help direct the efforts to elucidate the function of transmembrane protein 131L.

Transmembrane Protein 131 edit

Transmembrane protein 131L is 36% identical and 54% similar to transmembrane protein 131. The gene for transmembrane protein 131 is found on chromosomal location 2q11.2 and the protein is 1883 amino acids long and is also an integral membrane protein.[14][15] However, research indicates that the TMEM131L protein is more highly methylated than the TMEM protein. [16]

Conservation edit

 
Divergence of KIAA0922 protein amino acid conservation over time to show high conservation of a significant portion of the KIAA0922 protein. (Percent identity and percent similarity values for orthologs found using NCBI Blast and SDSC Biology Workbench CLUSTALW. *Time since divergence is based on values estimated by the bioinformatics tool TimeTree.org)

Following Biology Workbench[5] multialign CLUSTAL W[4] analyses, certain regions of TMEM131L protein are highly conserved through Eukaryotes as distantly as single-celled protists (24% identity with Dictyostelium fasciculatum).[17] These exact same regions also appear to be conserved in the KIAA0922 paralog Prolyl endopeptidase (PREP), a gene for a cytostolic enzyme that cleaves the C-terminus of short polyl proteins. [18]

Genus and Species Name common Name mRNA Accession Number[19] Sequence Length (amino acids)[19] Sequence Identity to human mRNA[17] Sequence Similarity to human mRNA[17]
Homo sapiens Humans NM_001131007.1 1624
Pongo abelii Sumatran orangutan XP_002815269.1 1608 98% 99%
Loxodonta africana Elephant XP_003417575.1 1610 86% 92%
Mus musculus Mouse NP_766269.3 1597 77% 86%
Ornithorhynchus anatinus Platypus XP_001514395.2 1609 71% 82%
Gallus gallus Chicken XP_420366.3 1610 63% 79%
Anolis carolinensis Carolina anole XP_003221762.1 1606 61% 75%
Xenopus tropicalis Western clawed toad XP_002933525.1 1610 48% 65%
Oreochromis niloticus Nile tilapia XP_003444335.1 1755 36% 53%
Drosophila melanogaster Fruit fly NP_611073.2 1567 30% 51%
Dictyostelium fasciculatum Dictyostelium (unicellular protist) EGG18468.1 2317 26% 52%
Polysphondylium pallidum Slime mold EFA75514.1 1234 24% 42%


General Attributes edit

Gene edit

 
KIAA0922 Labelled on Annotated Chromosome 4. (Original image from NCBI Map View, edited to highlight KIAA0922 location)

The KIAA0922 gene is found in the human genome at chromosomal location 4q31.3 on the plus strand and is 170,364 base pairs (bp) in length.[20] The gene has the aliases TMEM131L, FLJ10592, DKFZp586H1322, and LOC23240 [21] The gene includes 44 distinct introns (with an additional 6 probable non-overlapping alternative last exons).[21] The function of this gene is not yet fully understood.

The gene includes the Domain of unknown function 3651 (DUF3651) and a confirmed signal peptide region.[16]

mRNA edit

KIAA0922 mRNA is around 5 kilo-base pairs(kbp) in length.[22] Thirteen splice variants are supported by ACEVIEW analysis but only two have been experimentally identified.[21] Mostly, different variants seem to vary based on differing truncation of the 3' and 5' ends (especially due to the presence of an upstream stop codon in the exonic region).[21]

Protein edit

Protein TMEM131L is an integral membrane protein[1] and is also known as OTTHUMP00000205136.[21] The protein TMEM131L Isoform I is 1,610 amino acids in length[23] and its primary structure weighs 179.209 kilo-Dalton (unit) (kDa). [20] Twelve different isoforms of this protein have been predicted (one partial, six COOH complete, and five complete) however there have been only 5 experimentally observed.[21]

Expression edit

The protein TMEM131L shows highest levels of expression in immune related cells and tissues such as lymphocytes and bone marrow.[3]. Levels of TMEM131L protein have been shown to significantly increase under certain immune responses, such as increasing over time after introduction of measels virus to the immune cells dendritic cells[24] and in peripheral blood lymphocytes from kidney tranplants displaying acute rejection.[25]

Transmembrane Region edit

There is only one confirmed transmembrane domain region in protein TMEM131L.[16] This domain exists near the center of the protein, at 871-891 amino acid of the 1610 amino acid long protein sequence (for isoform I).[16]

There is a dramatic switch from hydrophobic to hydrophilic amino acid density at this confirmed transmembrane region [26]. There is also a switch to a higher density of predicted N-linked glycosylation sites across this confirmed transmembrane region (0.0136 to 0.0069 predicted N-glycosylation sites/amino acid) at this region[27]. Furthermore, the only confirmed phosphorylation site is on the latter half of the protein (1,123 aa in isoform I)[16] and predicted phosphorylation sites increase in density across the confirmed transmembrane region (from 0.0386 to 0.0905 predicted phosphorylation sites/amino acid).[28]


References edit

  1. ^ a b "EMBL-EBI: KIAA0922".
  2. ^ Ota T, Suzuki Y, Nishikawa T, Otsuki T; et al. (2003). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat Genet. 36 (1): 40–45. doi:10.1093/dnares/6.3.197. PMID 14702039. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  3. ^ a b "GeneCards: KIAA0922".
  4. ^ a b Julie D. Thompson, Desmond G. Higgins and Toby J. Gibson (1993). "CLUSTAL W (program v 3.5c)". PHYLIP (Phylogeny Inference Package). {{cite web}}: Missing or empty |url= (help)
  5. ^ a b "SDSC Biology Workbench".
  6. ^ E. W. Myers and W. Miller (1989). "ALIGN algorithm (1)". CABIOS. 4: 11-17.
  7. ^ {{cite journal | author = W.R. Pearson & D.J. Lipman | journal = PNAS | date = 1988 | volume = 85 | page = 2444-2448 | title = ALIGN algorithm (2)]}
  8. ^ W. R. Pearson (1990). "Rapid and Sensitive Sequence Comparison with FASTP and FASTA". Methods in Enzymology. 183: 63-98.
  9. ^ {{cite journal | title = Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography | author = Koida M, Walter R. | journal = The Journal of Biological Chemistry (J Biol Chem} | date = 1975 | volume = 251 | number = 23 | pages = 7593-9 | url = http://www.ncbi.nlm.nih.gov/pubmed/12173 }
  10. ^ "NCBI Gene: PREP". Retrieved April, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  11. ^ Mentlein R. (July, 1988). FEBS Letters. 234 (2): 251–6 http://www.ncbi.nlm.nih.gov/pubmed/3292288. {{cite journal}}: Check date values in: |date= (help); Missing or empty |title= (help)
  12. ^ "ExPASy ENZYME: PREP". Retrieved May, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  13. ^ a b "NCBI Protein: PREP". Retrieved April, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  14. ^ "NCBI Gene: TMEM131".
  15. ^ "WolframAlpha: TMEM131". Retrieved April, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  16. ^ a b c d e "NCBI Nucleotide: KIAA0922". {{cite web}}: Unknown parameter |NCBI Reference Sequence= ignored (help)
  17. ^ a b c "NCBI Blast".
  18. ^ "NCBI Nucleotide: PREP". {{cite web}}: Unknown parameter |NCBI Reference Sequence= ignored (help)
  19. ^ a b "NCBI National Center for Biotechnology Information". Retrieved 9 May 2011.
  20. ^ a b "WolframAlpha: KIAA0922". Retrieved April, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  21. ^ a b c d e f "Aceview: KIAA0922".
  22. ^ "NCBI Gene: KIAA0922".
  23. ^ "NCBI Protein: KIAA0922". Retrieved April, 2012. {{cite web}}: Check date values in: |accessdate= (help)
  24. ^ Zilliox MJ, Parmigiani G, Griffin DE (2006). "Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens". Proc Natl Acad Sci. 103 (9): 3363-8. PMID 16492729.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ Flechner SM, Kurian SM, Head SR, Sharp SM; et al. (September 2004). "Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes". American Journal of Transplant. 9: 1475-89. PMID 15307835. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  26. ^ Kyte J., Doolittle R.F. (1982). "Amino acid scale: Hydropathicity". Journal of Molecular Biology. 157: 105-132.
  27. ^ Gupta, E. Jung and S. Brunak (2004). "Prediction of N-glycosylation sites in human proteins". {{cite journal}}: Cite journal requires |journal= (help)
  28. ^ "Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351-1362. 1999. {{cite journal}}: Unknown parameter |Author= ignored (|author= suggested) (help)