Transmembrane protein 155 is a protein that in humans is encoded by the TMEM155 gene. It is located on human chromosome 4, spanning 6,497 bases. It is also referred to as FLJ30834 and LOC132332. This protein is known to be expressed mainly in the brain, placenta, and lymph nodes and is conserved throughout most placental mammals. The function and structure of this protein is still not well understood, but its level of expression has been studied pertaining to various pathologies.
Gene
Locus TMEM155 is located on the minus strand of human chromosome 4 (4q27) and spans 13,611 base pairs.
Genetic Neighborhood Cytogenetic band: 4q27
TMEM155 is neighbored by TMEM155 is neighbored on chromosome 4 by CCNA2, a gene encoding for cyclin A2, and ANXA5, which encodes annexin A5. It is also neighbored by PP12613 located on the positive strand.
Size The gene on chromosome 4 encoding for TMEM155 spans 6,487 nucleotides. This gene spans from base pairs 121,758,930 and 121,765,427 on chromosome 4. The longest variant ofTMEM155 has 5 exons detailed in the table below: Exon #Base pairsLength (bp)11-3483482349-4571083458-529714530-8843545885-24291544
mRNA
Isoforms There are 7 isoforms of TMEM155 precursor mRNA. TMEM155 isoform 5 is the longest mRNA and is 2,429 bp long. The shortest isoform is variant 4 and this variant is 2,035 bp long. Isoforms are detailed in the table below. Isoform NumberLength (bp)ExonsIsoform 12,2956Isoform 22,1606Isoform 32,1576Isoform 42,035 6Isoform 52,4295Isoform 62,2945Isoform 72,2926
Protein
Primary Structure TMEM155 protein is 130 amino acids in length. The TMEM155 protein in its full form is 14.2 kD in molecular weight with an isoelectric point of 10.29 Without its signal peptide it is 11.8 kD. The protein interacts with the membrane once, with one transmembrane domain as seen below.
Secondary Structure TMEM155 has a secondary structure composed of 23.5% alpha-helices, 67% beta-sheets, 9.5% turns and coils.
Tertiary structure
The tertiary structure of TMEM155 is predicted in the image on the right. This is predicted to be the structure of the N-terminus tail of TMEM155 located inside the ER membrane.
Post-translational modifications TMEM155 has sites for O-glycosylation at ser78, thr79, and pro80. It has sites for O-GlcNac at thr79 and ser121 It is a target for sumoylation from ile126 to val130. There is a glycation site at lys102.
Subcellular Localization TMEM155 contains a sequence which functions as an ER retention signal.
Interacting Proteins TMEM155 interacts with LMBR1 and TMEM259. LMBR1 is a known lipocalin transmembrane receptor. TMEM259 is another transmembrane protein.
Regulation
Gene Level Regulation There are several promoters of the TMEM155 gene. The promoter region of the gene is bound by several transcription factors involved in regulating chromatin structure, development, cell cycle, and immune responses. TMEM155 is expressed highly in the brain, placenta, and lymph nodes. Below is a table detailing the transcription factor binding sites for the GXP_319937 promoter of TMEM155. The table below details the transcription factors that bind the promoter region of TMEM155 and the sequences which they bind. +Orthologs of TMEM155Transcription factorDetailed matrix informationAnchor baseSequenceRUSHSWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 329gtgtACTTttcRUSH716tggaACTTttaBRACT-box transcription factor TBX2096gtgctatgAGGTgtctgagtgHOMFBarx2, homeobox transcription factor that preferentially binds to paired TAAT motifs235aataaatTAATtgggaacgHOMF232tcccaatTAATttatttcgFKHDAlternative splicing variant of FOXP1, activated in ESCs303tttacaaAACAccagtcFKHD16TTTACAAAACACCAGTCTF2BTranscription factor II B (TFIIB) recognition element616ccgCGCCRBP2Jumonji, AT rich interactive domain 1B1083GCACagcgcEVI1MEL1 (MDS1/EVI1-like gene 1) DNA-binding domain 2139cagtgaaGATGgggtctSMADSmad3 transcription factor involved in TGF-beta signaling1071gggGTCTgggcMYODTranscription factor E2a (E12/E47)605CAGCtgETSFEts variant 1702gaagagcaGGAAgaagaaETSF366gtgcccgcGGAAgttcgctccE2FFE2F transcription factor 1562gaggGGCGggagtgcggE2FF868cactGGCGggagggcacNFATNuclear factor of activated T-cells467agctgaGGAAatccggcgcNFAT488ctccgaGGAAacgcgccaaEGRFWilms Tumor Suppressor1018tcctgtgGGAGgcccggggSTATSignal transducer and activator of transcription 3944cagcTTCCaggtgcggggc
Transcript Level Regulation There are 4 splice enhancers of TMEM155. These enhancer sites come on the 5' end of the TMEM155 gene and contain binding sites for transcription factors RCOR1, MILLT1, SIN3A, NFIC, STAT3, JUNB, FOS, EGR1, PHB2, RUNX3, and SRF. Many of these transcription factors are involved with regulation cell growth and tumor suppression.
Mutations There are several notable SNPs in the coding sequence of TMEM155. These mutations include mostly missense and nonsense mutations. The table below summarizes the mutations found in TMEM155 in the conserved bases.
Position in ProteinMutation TypeCodon PositionChange in nucleic acidChange in amino acidRs Number27Missense3G → AM → Irs75413416628Missense1C → GP → Ars105609762334Nonsense1C → TQ → STOPrs14834454744Missense2G → CC → Yrs139645950845Missense2A → GH → Rrs76151069149Missense3T → GF → Lrs74640775951Missense1G → AG → Rrs125112899652Missense2T → CM → Trs116477695655Nonsense3G → AC → STOPrs74941744456Missense1C → AQ → Krs142830188260Missense3G → CL → Frs75635133861Missense1G → TV → Frs126818082865Missense1G → TG → Wrs134453593865Missense2G → TG → Vrs126721074368Missense1C → TL → Frs95733447571Missense2G → AR → Krs1437581701
Evolution
TMEM155 is evolving at the molecular level rather quickly. When compared to fibrinogen protein rate of evolution, the TMEM155 appears to be accumulating more amino acid changes in a shorter amount of time. Because it is faster than the quickly evolving fibrinogen, it is also evolving faster than cytochrome C protein, which is known to evolve slowly.
Homology TMEM155 is conserved across most placental mammals. DoD (MYA) refers to how many million years ago the gene diverged from the human version of the gene.
Genus and SpeciesCommon nameTaxomic groupDoD (MYA)Accession numberSequence length (aa)E-valuePercent Identity Percent SimilarityHomo sapiensHumanHominidae0NP_001304768.21300.00E+00100.00%100.00%Pan troglodytesChimpanzeeHominidae6.4XP_016807629.11542.00E-8799.00%99.00%Pan paniscusBonoboHominidae6.4XP_008967732.11307.00E-8796.90%97.70%Gorilla gorilla gorillaGorillaHominidae8.6XP_004040390.11301.00E-8899.20%99.20%Pongo pygmaeusBornean orangutanHominidae15.2NP_001127639.11302.00E-8596.20%97.70%Hylobates molochSilvery gibbonHylobatidae19.8XP_032002524.11301.00E-8495.40%96.90%Propithecus coquereliCoquerel's sifakaIndriidae74.1XP_012505863.11272.00E-6879.80%84.60%Fukomys damarensisDamara mole-ratBathyeridae89XP_010609341.11321.00E-5269.70%77.30%Oryctolagus cuniculusEuropean rabbitLeporidae89XP_017203042.11092.00E-3952.90%58.80%Camelus dromedariusDromedaryCamelidae94XP_031322500 1067.00E-4773.10%82.70%Lynx canadensisCanada LynxFelidae94XP_0301690021004.00E-4470.20%76.90%Bison bison bisonBisonBovidae94XP_010856646 1903.00E-5469.20%76.90%Delphinapterus leucasBeluga whaleMonodontidae94XP_022452038 1006.00E-4267.30%76.00%Ceratotherium simum simumSouthern white rhinocerosRhinocerotidae94XP_014639974 1924.00E-4767.00%75.50%Ursus arctos horribilisGrizzly bear Ursidae94XP_026355049.11263.00E-5266.20%72.20%Neomonachus schauinslandiHawaiian monk sealPhocidae94XP_0215371761269.00E-5265.40%73.10%Ailuropoda melanoleucaGiant pandaUrsidae94XP_0196600041005.00E-4063.60%70.10%Mustela ermineaStoatMustelidae94XP_032189210 1278.00E-4363.50%69.20%Vicugna pacosAlpacaCamelidae94XP_015106166.11063.00E-4657.60%64.40%Zalophus californianusCalifornia sea lionOtariidae94XP_027455522.11094.00E-4456.90%64.60%Sus scrofaWild boarSuidae94XP_020957297.11047.00E-3856.90%64.60%Monodon monocerosNarwhalMonodontidae94XP_029091564.11001.00E-4253.80%61.50%Panthera pardusLeopardFelidae94XP_019274438.1981.00E-3853.80%60.00%Loxodonta africanaAfrican bush elephantElephantidae102XP_023404270.11272.00E-3661.50%71.20%Dasypus novemcinctusNine-banded armadilloDasypodidae102XP_023439327.11031.00E-4155.70%61.10%
Clinical significance
Ocular tissues The upregulation of TMEM155 has been found in basal cell nevus syndrome fibroblasts. TMEM155 was also found to be upregulated in corneal keratinocytes, which could contribute to the upregulation of the gene being associated with nystagmus.
Brain tissues TMEM155 regulation co-varies with families that have instances of essential tremor,
Female reproductive tissues Hypermethylated TMEM155 is a potential biomarker for HER2+ breast cancer. The expression of TMEM155 was found to be higher in the oocytes of women with low antral follicular count, meaning it could be involved in the regulation of female fertility.
References