TMEM155

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.

TMEM155
Identifiers
AliasesTMEM155, transmembrane protein 155
External IDsHomoloGene: 131149 GeneCards: TMEM155
Orthologs
SpeciesHumanMouse
Entrez

132332

n/a

Ensembl

ENSG00000164112

n/a

UniProt

Q4W5P6

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

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

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 pairs Length (bp)
1 1-348 348
2 349-457 108
3 458-529 71
4 530-884 354
5 885-2429 1544

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 Number Length (bp) Exons
Isoform 1 2,295 6
Isoform 2 2,160 6
Isoform 3 2,157 6
Isoform 4 2,035 6
Isoform 5 2,429 5
Isoform 6 2,294 5
Isoform 7 2,292 6

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.[8]

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[10]

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 information Anchor base Sequence
RUSH SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3 29 gtgtACTTttc
RUSH 716 tggaACTTtta
BRAC T-box transcription factor TBX20 96 gtgctatgAGGTgtctgagtg
HOMF Barx2, homeobox transcription factor that preferentially binds to paired TAAT motifs 235 aataaatTAATtgggaacg
HOMF 232 tcccaatTAATttatttcg
FKHD Alternative splicing variant of FOXP1, activated in ESCs 303 tttacaaAACAccagtc
FKHD 16 TTTACAAAACACCAGTC
TF2B Transcription factor II B (TFIIB) recognition element 616 ccgCGCC
RBP2 Jumonji, AT rich interactive domain 1B 1083 GCACagcgc
EVI1 MEL1 (MDS1/EVI1-like gene 1) DNA-binding domain 2 139 cagtgaaGATGgggtct
SMAD Smad3 transcription factor involved in TGF-beta signaling 1071 gggGTCTgggc
MYOD Transcription factor E2a (E12/E47) 605 CAGCtg
ETSF Ets variant 1 702 gaagagcaGGAAgaagaa
ETSF 366 gtgcccgcGGAAgttcgctcc
E2FF E2F transcription factor 1 562 gaggGGCGggagtgcgg
E2FF 868 cactGGCGggagggcac
NFAT Nuclear factor of activated T-cells 467 agctgaGGAAatccggcgc
NFAT 488 ctccgaGGAAacgcgccaa
EGRF Wilms Tumor Suppressor 1018 tcctgtgGGAGgcccgggg
STAT Signal transducer and activator of transcription 3 944 cagcTTCCaggtgcggggc

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 Type Codon Position Change in nucleic acid Change in amino acid Rs Number
27 Missense 3 G → A M → I rs754134166
28 Missense 1 C → G P → A rs1056097623
34 Nonsense 1 C → T Q → STOP rs148344547
44 Missense 2 G → C C → Y rs1396459508
45 Missense 2 A → G H → R rs761510691
49 Missense 3 T → G F → L rs746407759
51 Missense 1 G → A G → R rs1251128996
52 Missense 2 T → C M → T rs1164776956
55 Nonsense 3 G → A C → STOP rs749417444
56 Missense 1 C → A Q → K rs1428301882
60 Missense 3 G → C L → F rs756351338
61 Missense 1 G → T V → F rs1268180828
65 Missense 1 G → T G → W rs1344535938
65 Missense 2 G → T G → V rs1267210743
68 Missense 1 C → T L → F rs957334475
71 Missense 2 G → A R → K rs1437581701

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.

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 name Taxomic group DoD (MYA) Accession number Sequence length (aa) E-value Percent Identity Percent Similarity
Homo sapiens Human Hominidae 0 NP_001304768.2 130 0.00E+00 100.00% 100.00%
Pan troglodytes Chimpanzee Hominidae 6.4 XP_016807629.1 154 2.00E-87 99.00% 99.00%
Pan paniscus Bonobo Hominidae 6.4 XP_008967732.1 130 7.00E-87 96.90% 97.70%
Gorilla gorilla gorilla Gorilla Hominidae 8.6 XP_004040390.1 130 1.00E-88 99.20% 99.20%
Pongo pygmaeus Bornean orangutan Hominidae 15.2 NP_001127639.1 130 2.00E-85 96.20% 97.70%
Hylobates moloch Silvery gibbon Hylobatidae 19.8 XP_032002524.1 130 1.00E-84 95.40% 96.90%
Propithecus coquereli Coquerel's sifaka Indriidae 74.1 XP_012505863.1 127 2.00E-68 79.80% 84.60%
Fukomys damarensis Damara mole-rat Bathyeridae 89 XP_010609341.1 132 1.00E-52 69.70% 77.30%
Oryctolagus cuniculus European rabbit Leporidae 89 XP_017203042.1 109 2.00E-39 52.90% 58.80%
Camelus dromedarius Dromedary Camelidae 94 XP_031322500 106 7.00E-47 73.10% 82.70%
Lynx canadensis Canada Lynx Felidae 94 XP_030169002 100 4.00E-44 70.20% 76.90%
Bison bison bison Bison Bovidae 94 XP_010856646 190 3.00E-54 69.20% 76.90%
Delphinapterus leucas Beluga whale Monodontidae 94 XP_022452038   100 6.00E-42 67.30% 76.00%
Ceratotherium simum simum Southern white rhinoceros Rhinocerotidae 94 XP_014639974   192 4.00E-47 67.00% 75.50%
Ursus arctos horribilis Grizzly bear Ursidae 94 XP_026355049.1 126 3.00E-52 66.20% 72.20%
Neomonachus schauinslandi Hawaiian monk seal Phocidae 94 XP_021537176 126 9.00E-52 65.40% 73.10%
Ailuropoda melanoleuca Giant panda Ursidae 94 XP_019660004 100 5.00E-40 63.60% 70.10%
Mustela erminea Stoat Mustelidae 94 XP_032189210 127 8.00E-43 63.50% 69.20%
Vicugna pacos Alpaca Camelidae 94 XP_015106166.1 106 3.00E-46 57.60% 64.40%
Zalophus californianus California sea lion Otariidae 94 XP_027455522.1 109 4.00E-44 56.90% 64.60%
Sus scrofa Wild boar Suidae 94 XP_020957297.1 104 7.00E-38 56.90% 64.60%
Monodon monoceros Narwhal Monodontidae 94 XP_029091564.1 100 1.00E-42 53.80% 61.50%
Panthera pardus Leopard Felidae 94 XP_019274438.1 98 1.00E-38 53.80% 60.00%
Loxodonta africana African bush elephant Elephantidae 102 XP_023404270.1 127 2.00E-36 61.50% 71.20%
Dasypus novemcinctus Nine-banded armadillo Dasypodidae 102 XP_023439327.1 103 1.00E-41 55.70% 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]

References

  1. GRCh38: Ensembl release 89: ENSG00000164112 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Gene: TMEM155 (ENSG00000164112) - Summary - Homo sapiens - Ensembl genome browser 99". useast.ensembl.org. Retrieved 2020-02-06.
  4. "AceView: Gene:TMEM155, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2020-02-06.
  5. "TMEM155 transmembrane protein 155 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-02-06.
  6. "Home - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-04-30.
  7. "SAPS < Sequence Statistics.< EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-04-30.
  8. "SOSUI WWW Server". harrier.nagahama-i-bio.ac.jp. Retrieved 2020-04-30.
  9. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2020-04-30.
  10. "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2020-04-27.
  11. "5E94BCEC00000467232B8478 expired". www.cbs.dtu.dk. Retrieved 2020-04-30.
  12. "5E94B53300000468E744C097 expired". www.cbs.dtu.dk. Retrieved 2020-04-30.
  13. "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". sumosp.biocuckoo.org. Retrieved 2020-04-30.
  14. "NetGlycate 1.0 Server". www.cbs.dtu.dk. Retrieved 2020-04-30.
  15. "PSORT WWW Server". psort.hgc.jp. Retrieved 2020-04-30.
  16. "Results - mentha: the interactome browser". mentha.uniroma2.it. Retrieved 2020-04-30.
  17. "UCSC Genome Browser Home". genome.ucsc.edu. Retrieved 2020-04-30.
  18. "Genomatix: Login Page". www.genomatix.de. Retrieved 2020-04-30.
  19. "SNP linked to Gene (geneID:132332) Via Contig Annotation". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  20. "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-05-02.
  21. Renaud B, Buda M, Lewis BD, Pujol JF (September 1975). "Effects of 5,6-dihydroxytryptamine on tyrosine-hydroxylase activity in central catecholaminergic neurons of the rat". Biochemical Pharmacology. 24 (18): 1739–42. doi:10.1016/0006-2952(75)90018-0. PMID 17.
  22. Toyono T, Usui T, Yokoo S, Taketani Y, Nakagawa S, Kuroda M, et al. (2015-01-26). "Angiopoietin-like 7 is an anti-angiogenic protein required to prevent vascularization of the cornea". PLOS ONE. 10 (1): e0116838. Bibcode:2015PLoSO..1016838T. doi:10.1371/journal.pone.0116838. PMC 4306551. PMID 25622036.
  23. Odgerel Z, Sonti S, Hernandez N, Park J, Ottman R, Louis ED, Clark LN (2019). "Whole genome sequencing and rare variant analysis in essential tremor families". PLOS ONE. 14 (8): e0220512. Bibcode:2019PLoSO..1420512O. doi:10.1371/journal.pone.0220512. PMC 6690583. PMID 31404076.
  24. Lindqvist BM, Wingren S, Motlagh PB, Nilsson TK (August 2014). "Whole genome DNA methylation signature of HER2-positive breast cancer". Epigenetics. 9 (8): 1149–62. doi:10.4161/epi.29632. PMC 4164500. PMID 25089541.
  25. Barragán M, Pons J, Ferrer-Vaquer A, Cornet-Bartolomé D, Schweitzer A, Hubbard J, et al. (August 2017). "The transcriptome of human oocytes is related to age and ovarian reserve". Molecular Human Reproduction. 23 (8): 535–548. doi:10.1093/molehr/gax033. PMID 28586423.
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