TMEM155

Last updated
TMEM155
Identifiers
Aliases TMEM155 , transmembrane protein 155
External IDs HomoloGene: 131149; GeneCards: TMEM155; OMA:TMEM155 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC) Chr 4: 121.76 – 121.77 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

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. [3] It is also referred to as FLJ30834 and LOC132332. [4] This protein is known to be expressed mainly in the brain, placenta, and lymph nodes and is conserved throughout most placental mammals. [5] The function and structure of this protein is still not well understood, but its level of expression has been studied pertaining to various pathologies.

Contents

Gene

Locus

TMEM155 is located on the minus strand of human chromosome 4 (4q27) and spans 13,611 base pairs. [6]

Genetic Neighborhood

Cytogenetic band: 4q27 [3]

TMEM155 is neighbored by TMEM155 is neighbored on chromosome 4 by CCNA2, a gene encoding for cyclin A2, and ANXA5, which encodes annexin A5. [4] It is also neighbored by PP12613 located on the positive strand.

Size

The gene on chromosome 4 encoding for TMEM155 spans 6,487 nucleotides. [5] This gene spans from base pairs 121,758,930 and 121,765,427 on chromosome 4. [3] The longest variant ofTMEM155 has 5 exons detailed in the table below: [5]

Exon #Base pairsLength (bp)
11-348348
2349-457108
3458-52971
4530-884354
5885-24291544

mRNA

Isoforms

There are 7 isoforms of TMEM155 precursor mRNA. [5] TMEM155 isoform 5 is the longest mRNA and is 2,429 bp long. [3] The shortest isoform is variant 4 and this variant is 2,035 bp long. [5] Isoforms are detailed in the table below. [5]

Isoform NumberLength (bp)Exons
Isoform 12,2956
Isoform 22,1606
Isoform 32,1576
Isoform 42,0356
Isoform 52,4295
Isoform 62,2945
Isoform 72,2926

Protein

Primary Structure

TMEM155 protein is 130 amino acids in length. [3] The TMEM155 protein in its full form is 14.2 kD in molecular weight with an isoelectric point of 10.29 [7] Without its signal peptide it is 11.8 kD. [7] The protein interacts with the membrane once, with one transmembrane domain as seen below.

TMEM155 has a single transmembrane domain through the membrane of the ER. Primary structure of TMEM155.png
TMEM155 has a single transmembrane domain through the membrane of the ER.

Secondary Structure

TMEM155 has a secondary structure composed of 23.5% alpha-helices, 67% beta-sheets, 9.5% turns and coils. [9]

Tertiary structure

Predicted tertiary structure of TMEM155 I-TASSER Results.png
Predicted tertiary structure of TMEM155

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. [11] It has sites for O-GlcNac at thr79 and ser121 [12] It is a target for sumoylation from ile126 to val130. [13] There is a glycation site at lys102. [14]

Subcellular Localization

TMEM155 contains a sequence which functions as an ER retention signal. [15]

Interacting Proteins

TMEM155 interacts with LMBR1 and TMEM259. [16]  LMBR1 is a known lipocalin transmembrane receptor. TMEM259 is another transmembrane protein.

Regulation

Gene Level Regulation

There are several promoters of the TMEM155 gene. [17] The promoter region of the gene is bound by several transcription factors involved in regulating chromatin structure, development, cell cycle, and immune responses. [18] TMEM155 is expressed highly in the brain, placenta, and lymph nodes. [5] Below is a table detailing the transcription factor binding sites for the GXP_319937 promoter of TMEM155. [18] The table below details the transcription factors that bind the promoter region of TMEM155 and the sequences which they bind.

Orthologs of TMEM155 [6]
Transcription factor Detailed matrix informationAnchor baseSequence
RUSHSWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 329gtgtACTTttc
RUSH716tggaACTTtta
BRACT-box transcription factor TBX20 96gtgctatgAGGTgtctgagtg
HOMFBarx2, homeobox transcription factor that preferentially binds to paired TAAT motifs235aataaatTAATtgggaacg
HOMF232tcccaatTAATttatttcg
FKHDAlternative splicing variant of FOXP1, activated in ESCs303tttacaaAACAccagtc
FKHD16TTTACAAAACACCAGTC
TF2B Transcription factor II B (TFIIB) recognition element616ccgCGCC
RBP2 Jumonji, AT rich interactive domain 1B1083GCACagcgc
EVI1MEL1 (MDS1/EVI1-like gene 1) DNA-binding domain 2139cagtgaaGATGgggtct
SMAD Smad3 transcription factor involved in TGF-beta signaling 1071gggGTCTgggc
MYOD Transcription factor E2a (E12/E47)605CAGCtg
ETSF Ets variant 1702gaagagcaGGAAgaagaa
ETSF366gtgcccgcGGAAgttcgctcc
E2FF E2F transcription factor 1562gaggGGCGggagtgcgg
E2FF868cactGGCGggagggcac
NFAT Nuclear factor of activated T-cells467agctgaGGAAatccggcgc
NFAT488ctccgaGGAAacgcgccaa
EGRF Wilms Tumor Suppressor 1018tcctgtgGGAGgcccgggg
STAT Signal transducer and activator of transcription 3944cagcTTCCaggtgcggggc

Transcript Level Regulation

There are 4 splice enhancers of TMEM155. [17] 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. [17] 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. [19]

Position in Protein Mutation TypeCodon PositionChange in nucleic acidChange in amino acidRs Number
27 Missense 3G → AM → Irs754134166
28Missense1C → GP → Ars1056097623
34 Nonsense 1C → TQ → STOPrs148344547
44Missense2G → CC → Yrs1396459508
45Missense2A → GH → Rrs761510691
49Missense3T → GF → Lrs746407759
51Missense1G → AG → Rrs1251128996
52Missense2T → CM → Trs1164776956
55Nonsense3G → AC → STOPrs749417444
56Missense1C → AQ → Krs1428301882
60Missense3G → CL → Frs756351338
61Missense1G → TV → Frs1268180828
65Missense1G → TG → Wrs1344535938
65Missense2G → TG → Vrs1267210743
68Missense1C → TL → Frs957334475
71Missense2G → AR → Krs1437581701

Evolution

Divergence rate of TMEM155 compared to known fast diverging gene, fibrinogen, and slowly diverging gene, CytC. This graph shows the percent change in amino acid sequence over the date of divergence of the sequence from humans. Evolution rate of TMEM155.png
Divergence rate of TMEM155 compared to known fast diverging gene, fibrinogen, and slowly diverging gene, CytC. This graph shows the percent change in amino acid sequence over the date of divergence of the sequence from humans.

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. [5] DoD (MYA) refers to how many million years ago the gene diverged from the human version of the gene. [20]

Genus and Species Common nameTaxomic groupDoD (MYA) Accession number Sequence length (aa)E-valuePercent IdentityPercent Similarity
Homo sapiens Human Hominidae 0NP_001304768.21300.00E+00100.00%100.00%
Pan troglodytes Chimpanzee Hominidae6.4XP_016807629.11542.00E-8799.00%99.00%
Pan paniscus Bonobo Hominidae6.4XP_008967732.11307.00E-8796.90%97.70%
Gorilla gorilla gorilla Gorilla Hominidae8.6XP_004040390.11301.00E-8899.20%99.20%
Pongo pygmaeus Bornean orangutan Hominidae15.2NP_001127639.11302.00E-8596.20%97.70%
Hylobates moloch Silvery gibbon Hylobatidae 19.8XP_032002524.11301.00E-8495.40%96.90%
Propithecus coquereli Coquerel's sifaka Indriidae 74.1XP_012505863.11272.00E-6879.80%84.60%
Fukomys damarensis Damara mole-ratBathyeridae89XP_010609341.11321.00E-5269.70%77.30%
Oryctolagus cuniculus European rabbit Leporidae 89XP_017203042.11092.00E-3952.90%58.80%
Camelus dromedarius Dromedary Camelidae 94XP_0313225001067.00E-4773.10%82.70%
Lynx canadensis Canada Lynx Felidae 94XP_0301690021004.00E-4470.20%76.90%
Bison bison bison Bison Bovidae 94XP_0108566461903.00E-5469.20%76.90%
Delphinapterus leucas Beluga whale Monodontidae 94XP_022452038  1006.00E-4267.30%76.00%
Ceratotherium simum simum Southern white rhinoceros Rhinocerotidae 94XP_014639974  1924.00E-4767.00%75.50%
Ursus arctos horribilis Grizzly bear Ursidae 94XP_026355049.11263.00E-5266.20%72.20%
Neomonachus schauinslandi Hawaiian monk seal Phocidae 94XP_0215371761269.00E-5265.40%73.10%
Ailuropoda melanoleuca Giant pandaUrsidae94XP_0196600041005.00E-4063.60%70.10%
Mustela erminea Stoat Mustelidae 94XP_0321892101278.00E-4363.50%69.20%
Vicugna pacos AlpacaCamelidae94XP_015106166.11063.00E-4657.60%64.40%
Zalophus californianus California sea lion Otariidae 94XP_027455522.11094.00E-4456.90%64.60%
Sus scrofa Wild boar Suidae 94XP_020957297.11047.00E-3856.90%64.60%
Monodon monoceros Narwhal Monodontidae 94XP_029091564.11001.00E-4253.80%61.50%
Panthera pardus LeopardFelidae94XP_019274438.1981.00E-3853.80%60.00%
Loxodonta africana African bush elephant Elephantidae 102XP_023404270.11272.00E-3661.50%71.20%
Dasypus novemcinctus Nine-banded armadillo Dasypodidae 102XP_023439327.11031.00E-4155.70%61.10%

Clinical significance

Ocular tissues

The upregulation of TMEM155 has been found in basal cell nevus syndrome fibroblasts. [21] TMEM155 was also found to be upregulated in corneal keratinocytes, [22] 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, [23]

Female reproductive tissues

Hypermethylated TMEM155 is a potential biomarker for HER2+ breast cancer. [24] 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. [25]

Related Research Articles

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<span class="mw-page-title-main">C1orf122</span> Protein-coding gene in the species Homo sapiens

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