View source for KIAA0922

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{cs1 config|name-list-style=vanc}}
{{Infobox_gene}}
'''Transmembrane protein 131-like''' (TMEM131L protein), alternatively named '''uncharacterized protein KIAA0922''' (KIAA0922 protein), is an integral [[transmembrane protein]]<ref name="EMBL-EBI: KIAA0922" />  encoded by the human [[gene]] '''''KIAA0922''''' that is significantly conserved in [[eukaryotes]], at least through [[protists]].<ref name="Ota_2004" /><ref name="GeneCards: KIAA0922" /><ref name="CLUSTAL W" />  Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses.  Furthermore, its [[paralog]], [[prolyl endopeptidase]] (PREP) whose function is known, provides clues as to the function of TMEM131L.
== Gene ==
[[File:KIAA0922 Labelled Annotated Chromosome 4.jpg|thumb|right| 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, spanning from 154,387,498 to 154,557,863<ref name="NCBI Gene: KIAA0922" /> along chromosome 4 (NC_000004.11).<ref name="WolframAlpha: KIAA0922"/> The gene has the aliases TMEM131L, FLJ10592, DKFZp586H1322, and LOC23240 <ref name="Aceview: KIAA0922"/> The gene includes 44 distinct [[introns]] (with an additional 6 probable non-overlapping alternative last [[exons]]).<ref name="Aceview: KIAA0922"/> The function of this gene is not yet fully understood.
The gene includes the [[Domain of unknown function]] 3651 (DUF3651) which is part of the transmembrane associated family pfam12371 and of the superfamily cl13764.<ref name="NCBI CDD: DUF3651" />  The mature mRNA of certain transcript variants have a confirmed [[signal peptide]] region.<ref name="NCBI Nucleotide: KIAA0922" /> although protein localization remains unknown.
== mRNA ==
KIAA0922 [[mRNA]] is around 5 kilo-[[base pairs]](kbp) in length.<ref name="NCBI Gene: KIAA0922" /> Thirteen splice variants are supported by ACEVIEW analysis but only two have been experimentally identified.<ref name="Aceview: KIAA0922"/> 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).<ref name="Aceview: KIAA0922"/>
== Protein ==
Protein TMEM131L is an integral membrane protein<ref name="EMBL-EBI: KIAA0922"/> and is also known as OTTHUMP00000205136.<ref name="Aceview: KIAA0922"/>  The protein TMEM131L Isoform I is 1,610 amino acids in length<ref name="NCBI Protein: KIAA0922" /> and its primary structure weighs 179.209 kilo-[[Dalton (unit)]] (kDa).<ref name="WolframAlpha: KIAA0922"/>  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.<ref name="Aceview: KIAA0922"/>
=== Expression ===
The protein TMEM131L shows highest levels of expression in [[immune]] related cells and tissues such as [[lymphocytes]] and [[bone marrow]].<ref name="GeneCards: KIAA0922" />  Levels of TMEM131L protein have been shown to significantly increase under certain immune responses, such as increasing over time after introduction of [[measles]] virus to the immune cells [[dendritic cells]]<ref name="Zilliox et. al; 2006" /> and in peripheral blood [[lymphocytes]] from [[kidney transplants]] displaying [[acute rejection]].<ref name ="Flechner et. al; 2004" />
=== Transmembrane region ===
There is only one confirmed [[transmembrane domain]] region in protein TMEM131L.<ref name="NCBI Nucleotide: KIAA0922" />  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).<ref name="NCBI Nucleotide: KIAA0922" />
There is a dramatic switch from hydrophobic to hydrophilic amino acid density at this confirmed transmembrane region.<ref name="ProtScale: Hydrophobicity (Kyte & Doolittle)" />  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.<ref name="NetNGlyc" /> Furthermore, the only confirmed [[phosphorylation]] site is on the latter half of the protein (1,123 aa in isoform I)<ref name="NCBI Nucleotide: KIAA0922" /> and predicted phosphorylation sites increase in density across the confirmed transmembrane region (from 0.0386 to 0.0905 predicted phosphorylation sites/amino acid).<ref name="NetPhos 2.0" />  These results together indicate that the first half of the protein (1-871 aa of isoform I) is outside of the membrane while the second half (891-1610 aa of isoform I) is inside of the membrane, although experimentation is necessary to confirm this deduction.
== Paralogs ==
=== Prolyl endopeptidase ===
The enzyme [[prolyl endopeptidase]] (PREP) is 13.4% identical to transmembrane protein 131L.<ref name ="SDSC Biology Workbench" /><ref name ="Align 1" /><ref name ="Align 2" /><ref name ="Align 3" /> PREP acts in the [[cytosol]] by cleaving peptide bonds on the [[C-terminus]] of short prolyl residues (approx. 30 amino acids long).<ref name="Koida_Walter_1976" /><ref name = "NCBI Gene: PREP" /> PREP has been found to be involved with the maturation and degradation of neuropeptides and peptide hormones.<ref name = "Mentlein_1988" /> PREP and its general functions are conserved through flavobateria.<ref name="ExPASy Enzyme: PREP" />
Of particular interest, the highest areas of amino acid conservation between PREP and KIAA0922 are the areas most conserved in KIAA0922 ([[KIAA0922#Conservation]]) are the esterase lipase region (483...706)<ref name = "NCBI Protein: PREP" /> and [[peptidase]] S9 N region (7...423)<ref name = "NCBI Protein: PREP" />
This connection may help direct the efforts to elucidate the function of transmembrane protein 131L.
=== Transmembrane protein 131 ===
{{main|TMEM131}}
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.<ref name = "NCBI Gene: TMEM131" /><ref name = "WolframAlpha: TMEM131" />  However, research indicates that the TMEM131L protein is more highly [[methylated]] than the TMEM protein.<ref name="NCBI Nucleotide: KIAA0922"/>
== Conservation ==
[[File:Divergence of KIAA0922 protein amino acid conservation over time.jpg|thumb|left|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<ref name="SDSC Biology Workbench"/> multialign CLUSTAL W<ref name="CLUSTAL W" /> analyses, certain regions of TMEM131L protein are highly conserved through [[Eukaryotes]] as distantly as single-celled [[protists]] (24% identity with ''Dictyostelium fasciculatum'').<ref name = "NCBI Blast" />  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.<ref name="NCBI Nucleotide: KIAA0922" />
{| class="wikitable" | title = "Percent Conservation of TMEM131L Protein in Orthologs"
|-
! Genus and Species Name !! common Name !! mRNA Accession Number<ref name=NCBI>{{cite web|title=NCBI National Center for Biotechnology Information|url=https://www.ncbi.nlm.nih.gov/|access-date=9 May 2011}}</ref>  !! Sequence Length (amino acids)<ref name="NCBI"/> !!Sequence Identity to human mRNA<ref name="NCBI Blast" /> !!Sequence Similarity to human mRNA<ref name="NCBI Blast" />
|-
| ''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%
|}
==References==
{{Reflist|colwidth=35em|refs=
<ref name="Ota_2004">{{cite journal  |vauthors=Ota T, Suzuki Y, Nishikawa T, etal | title = Complete sequencing and characterization of 21,243 full-length human cDNAs | journal = Nat. Genet. | volume = 36 | issue = 1 | pages = 40–5 |date=January 2004 | pmid = 14702039 | doi = 10.1038/ng1285 | doi-access = free }}</ref>
<ref name="Mentlein_1988">{{cite journal | author = Mentlein R | title = Proline residues in the maturation and degradation of peptide hormones and neuropeptides | journal = FEBS Lett. | volume = 234 | issue = 2 | pages = 251–6 |date=July 1988 | pmid = 3292288 | doi = 10.1016/0014-5793(88)80092-9| s2cid = 39590213 | doi-access = free }}</ref>
<ref name="Koida_Walter_1976">{{cite journal |vauthors=Koida M, Walter R | title = Post-proline cleaving enzyme. Purification of this endopeptidase by affinity chromatography | journal = J. Biol. Chem. | volume = 251 | issue = 23 | pages = 7593–9 |date=December 1976 | doi = 10.1016/S0021-9258(17)32893-4 | pmid = 12173 | doi-access = free }}</ref>
<ref name="WolframAlpha: TMEM131">{{cite web | title = WolframAlpha: TMEM131 | url = http://www.wolframalpha.com/input/?i=TMEM131 | access-date =8 May 2012}}</ref>
<ref name="GeneCards: KIAA0922">{{GeneCard|KIAA0922}}</ref>
<ref name="WolframAlpha: KIAA0922">{{cite web | title = WolframAlpha: KIAA0922| url = http://www.wolframalpha.com/input/?i=TMEM131L | access-date = 8 May 2012}}</ref>
<ref name="Aceview: KIAA0922">{{cite web | title = Aceview: KIAA0922| url = https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=KIAA0922&submit=Go}}</ref>
<ref name="NCBI Nucleotide: KIAA0922">{{cite web | title = Homo sapiens KIAA0922 (KIAA0922), transcript variant 1, mRNA| date = 20 October 2018| url = https://www.ncbi.nlm.nih.gov/nuccore/NM_001131007.1|id=NCBI Reference Sequence: NM_001131007.1 }}</ref>
<ref name="NCBI CDD: DUF3651">{{cite web | title = NCBI Conserved Domain Database; DUF3651 | url = https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=204895 | access-date =8 May 2012}}</ref>
<ref name="NCBI Gene: KIAA0922">{{EntrezGene|23240}}</ref>
<ref name="EMBL-EBI: KIAA0922">{{cite web | title = EMBL-EBI: KIAA0922| url = http://www.ebi.ac.uk/s4/summary/molecular?term=KIAA0922&classification=9606&tid=synENSMUSG00000033767}}</ref>
<ref name="NCBI Gene: TMEM131">{{cite web | url = https://www.ncbi.nlm.nih.gov/protein/NP_056163.1 | title = NCBI Gene: TMEM131}}</ref>
<ref name="NCBI Blast">{{cite web | title = NCBI Blast | url = http://blast.ncbi.nlm.nih.gov/Blast.cgi}}</ref>
<ref name="SDSC Biology Workbench">{{cite web| title = SDSC Biology Workbench| url = http://workbench.sdsc.edu/}}</ref>
<ref name="CLUSTAL W">{{cite journal | title = CLUSTAL W (program v 3.5c) |author1=Julie D. Thompson |author2=Desmond G. Higgins |author3=Toby J. Gibson | year = 1993 | journal = PHYLIP (Phylogeny Inference Package)}}</ref>
<ref name="Align 1">{{cite journal |author1=E. W. Myers EW |author2=Miller W | year = 1988 | journal = CABIOS | volume = 4 |issue=1 | pages = 11–17 | title = Optimal alignments in linear space  | doi = 10.1093/bioinformatics/4.1.11 |pmid=3382986 }}</ref>
<ref name="Align 2">{{cite journal |vauthors=Pearson WR, Lipman DJ | title = Improved tools for biological sequence comparison | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 8 | pages = 2444–8 |date=April 1988 | pmid = 3162770 | pmc = 280013 | doi = 10.1073/pnas.85.8.2444| bibcode = 1988PNAS...85.2444P | doi-access = free }}</ref>
<ref name="Align 3">{{cite book | author = Pearson WR | title = &#91;5&#93; Rapid and sensitive sequence comparison with FASTP and FASTA | volume = 183 | pages = [https://archive.org/details/molecularevoluti0000unse_d5p9/page/63 63–98] | year = 1990 | pmid = 2156132 | doi = 10.1016/0076-6879(90)83007-V | series = Methods in Enzymology | isbn = 978-0-12-182084-8 | url = https://archive.org/details/molecularevoluti0000unse_d5p9/page/63 }}</ref>
<ref name="NCBI Protein: PREP">{{cite web | title = NCBI Protein: PREP| url = https://www.ncbi.nlm.nih.gov/protein/41349456 | access-date = 8 May 2012}}</ref>
<ref name="NCBI Protein: KIAA0922">{{cite web | title = NCBI Protein: KIAA0922| url = https://www.ncbi.nlm.nih.gov/protein/AAI31506.1 | access-date =8 May 2012}}</ref>
<ref name="ExPASy Enzyme: PREP">{{cite web | title = ExPASy ENZYME: PREP | url = http://enzyme.expasy.org/EC/3.4.21.26 | access-date =8 May 2012}}</ref>
<ref name="NCBI Gene: PREP">{{cite web | title = NCBI Gene: PREP| url = https://www.ncbi.nlm.nih.gov/gene/5550 | access-date =8 May 2012}}</ref>
<ref name="NetPhos 2.0">{{cite journal |vauthors=Blom N, Gammeltoft S, Brunak S | title = Sequence and structure-based prediction of eukaryotic protein phosphorylation sites | journal = J. Mol. Biol. | volume = 294 | issue = 5 | pages = 1351–62 |date=December 1999 | pmid = 10600390 | doi = 10.1006/jmbi.1999.3310 | url = http://www.cbs.dtu.dk/services/NetPhos/ }}</ref>
<ref name="NetNGlyc">{{cite journal | title = Prediction of N-glycosylation sites in human proteins |vauthors=Jung GE, Brunak S | year = 2004 | url = http://www.cbs.dtu.dk/services/NetNGlyc/}}</ref>
<ref name="ProtScale: Hydrophobicity (Kyte & Doolittle)">{{cite journal |vauthors=Kyte J, Doolittle RF | title = A simple method for displaying the hydropathic character of a protein | journal = J. Mol. Biol. | volume = 157 | issue = 1 | pages = 105–32 |date=May 1982 | pmid = 7108955 | doi = 10.1016/0022-2836(82)90515-0| url = http://web.expasy.org/protscale/ }}</ref>
<ref name="Zilliox et. al; 2006">{{cite journal |vauthors=Zilliox MJ, Parmigiani G, Griffin DE | title = Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens | journal = Proc. Natl. Acad. Sci. USA | year = 2006 | volume = 103 | number = 9 | pages = 3363–8 | pmid = 16492729 | url = https://www.ncbi.nlm.nih.gov/geo/gds/profileGraph.cgi?&dataset=BAHEEFLHDOK5zd&dataset=VV_YYY3_V41ckf$&gmin=54.691573&gmax=309.725539&absc=&uid=17799123&gds=1681&idref=39929_at&annot=KIAA0922 | doi=10.1073/pnas.0511345103 | pmc=1413941| bibcode = 2006PNAS..103.3363Z | doi-access = free }}</ref>
<ref name ="Flechner et. al; 2004">{{cite journal  |vauthors=Flechner SM, Kurian SM, Head SR, Sharp SM, etal | title = Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes | journal = American Journal of Transplantation | date = September 2004  | volume =  4| issue = 9 | pages = 1475–89 | pmid = 15307835 | url = https://www.ncbi.nlm.nih.gov/geo/gds/profileGraph.cgi?&dataset=X3ONFNLO93zXdDPNSHPPPMN0K0SLYWWDBEDECCABCHEEBGMBBBACAADBBCDBCA&dataset=fi86V657ljsfpR-6aZ88856i3hb3feeSOVSROQLMS_VTNW4NLLLQLLRONRTNQL$&gmin=84.800000&gmax=859.182000&absc=26836p1p1p1p1p1p1p1p1p1p17p1p1p2&uid=5866823&gds=724&idref=39929_at&annot=KIAA0922 | doi=10.1111/j.1600-6143.2004.00526.x | pmc=2041877}}</ref>
}}