Transmembrane protein 89
TMEM89 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | TMEM89, transmembrane protein 89 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 1916634; HomoloGene: 52857; GeneCards: TMEM89; OMA:TMEM89 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane protein 89 (TMEM89) is a protein that in humans is encoded by the TMEM89 gene.
Gene
[edit]Structure
[edit]The TMEM89 gene is found on the minus strand of chromosome 3 (3p21.31) from 48,658,192 to 48,659,288 and is 1,011 nucleotides long.[5][6] The gene has two exons.[5][6] These two exons are not predicted to be alternatively spliced.[5][6]
Gene expression
[edit]The TMEM89 gene is most highly expressed in the testis.[5][6] TMEM89 is also found to be expressed at low levels in other tissues such as the stomach, kidneys, heart, ovaries, thyroid, colon, bone marrow, and in adrenal tissues.[5] This gene is also expressed in fetal heart, stomach, kidney, and intestine tissues.[5] Immunohistochemistry data has also found TMEM89 located in the cell membranes of the colon, fallopian tube, kidney, and testis tissues.[7][8] Expression of the TMEM89 gene has also been found in low amounts in the brain tissue from a mouse cerebellum.[9]
Gene expression neighborhood
[edit]Human TMEM89 is a part of the Human Protein Atlas expression cluster 23: SpermatidS - Flagellum & Golgi organization.[7][10] The 15 closest expression neighbors include OR4M1, ANTXRL, TGIF2LX, CPXCR1, C3orf84, CXorf66, CLDN17, C11orf94, USP50, SPDYE4, MMP20, SSMEM1, SPMAP1, SPACA1, and LYZL1.[10]
Differential gene expression
[edit]TMEM89 expression is much higher in amniotic fluid derived hAKPC-P cells compared with immortalized hIPod line cells.[11] TMEM89 expression is higher in cells that have macrophage migration inhibitory factor (MIF) knocked down compared to the control.[12] TMEM89 expression is the lowest in cardiomyocytes from human embryonic stem cells, compared to expression in human embryonic stem cells, embryoid bodies with beating cardiomyocytes, and cardiomyocytes from fetal hearts.[13]
Clinical significance
[edit]Gene expression of TMEM89 was found to be upregulated in upper tract urothelial carcinomas, and therefore predicted as a possible biomarker secretory protein for these types of carcinomas.[14] The TMEM89 gene was found to be a potential modifier of autism spectrum disorder severity in a SNP analysis.[citation needed] Gene expression of TMEM89 was also used in a model that predicted the risk score for a potential relapse in stage 1 testicular germ cell tumors.[15]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Wiki_concep_trans-1.jpg/220px-Wiki_concep_trans-1.jpg)
Protein
[edit]Structure
[edit]Primary
[edit]The human TMEM89 protein is 159 amino acids long.[5] This protein has a molecular mass of ~17.5kDa and an isoelectric point of ~10 pI.[6][22] Proteins with a more basic pI are usually associated with the mitochondria or the plasma membrane and have fewer protein interactions.[23][24] The protein structure contains two topological domains (extracellular and cytoplasmic) and a helical transmembrane domain.[17][25][26] The human TMEM89 protein is rich in the amino acids histidine, leucine, and tryptophan.[18] The amino acids aspartate, asparagine, and phenylalanine are present in low amounts in the human TMEM89 protein.[18] Amino acid patterns such as ED are present in the human TMEM89 protein at low amounts, while the pattern KR-ED is present in high amounts.[18] Within the extracellular domain of the human TMEM89 protein, there are 3 cysteines with regular spacing.[18] In the cytoplasmic domain, there are two positive amino acid runs from amino acids 3-5 and 25-27.[18] These different amino acid patterns and protein domains can be visualized in the figures to the right.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/f/f1/TMEM89_hydrophobicity.jpg/220px-TMEM89_hydrophobicity.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/9d/TMEM89_TM_wheel.jpg/220px-TMEM89_TM_wheel.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/f/fc/Protter_TMM89_HUMAN.png/220px-Protter_TMM89_HUMAN.png)
Secondary
[edit]The TMEM89 protein is only made up of α-helices and strands.[27][28] The α-helices are distributed all throughout the protein in all three domains.[27][28]
Tertiary
[edit]The tertiary structure of Human TMEM89 was predicted using Alphafold and I-Tasser software.[27][28] These structures can be seen on the right.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/4/48/Human_TMEM89_Tertiary_Structure.jpg/220px-Human_TMEM89_Tertiary_Structure.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/a/a2/Human_TMEM89_protein_colored_by_charge.jpg/220px-Human_TMEM89_protein_colored_by_charge.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/0/05/ITasser_TMEM89_Signal_Peptide_and_Extracellular_Region_Prediction.jpg/220px-ITasser_TMEM89_Signal_Peptide_and_Extracellular_Region_Prediction.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/9d/ITasser_and_Alphafold_TMEM89_singnal_peptide_and_extracellular_region_comparison.jpg/220px-ITasser_and_Alphafold_TMEM89_singnal_peptide_and_extracellular_region_comparison.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/f/f4/Itasser_tmem89_cyt_pic.jpg/220px-Itasser_tmem89_cyt_pic.jpg)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/8/82/Itasser_alphafold_cyt.jpg/220px-Itasser_alphafold_cyt.jpg)
Post-translational modifications
[edit]The TMEM89 protein has a predicted N-myristylation site from amino acids 47-52, a predicted Src homology 3 (SH3) binding domain from amino acids 106-111, and one conserved predicted phosphorylation site at amino acid S117.[19][21][20] N-myristylation is a protein lipid modification that has roles in protein-protein interactions, cell signaling, and targeting proteins to endomembranes and the plasma membrane.[30] Proteins with SH3 binding domains are usually involved in signal transduction pathways, cytoskeleton organization, membrane trafficking, or organelle assembly.[31] Protein phosphorylation is an important process involved with signal transduction, protein synthesis, cell division, cell growth, development, and aging.[32]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/2/28/PS4_motif_schematic.png/220px-PS4_motif_schematic.png)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/31/TMEM89_N-myristoylation_site_alignment.png/220px-TMEM89_N-myristoylation_site_alignment.png)
Interactions
[edit]The human TMEM89 protein interacts with the proteins C4A, RBM15B, GOLGA6A, PFKFB4, DOCK3, MAPKAPK3, ZNF557, and ZBTB47.[35][36]
Homologs
[edit]Orthologs
[edit]Orthologs of TMEM89 are only found in mammals.[5] The only mammalian taxon that does not contain a TMEM89 ortholog is the monotremes.
Below is a table with information on some of the orthologs of human TMEM89. These orthologs were used to make the multiple sequence alignment and N-myristylation site alignment to the right.
Genus and Species | Common Name | Taxon | Date of Divergence (MYA) | NCBI Accession Number | Sequence Length (aa) | % Identity | % Similarity |
---|---|---|---|---|---|---|---|
Homo sapiens | Humans | Primate | 0 | NP_001008270.1 | 159 | 100 | 100 |
Castor canadensis | American beaver | Rodentia | 87 | XP_020018275.1 | 158 | 73.1 | 81.2 |
Urocitellus parryii | Arctic ground squirrel | Rodentia | 87 | XP_026239733.1 | 155 | 66.0 | 74.8 |
Orcinus orca | Orca | Artiodactyla | 94 | XP_004283952.1 | 159 | 71.9 | 80.0 |
Bos taurus | Cow | Artiodactyla | 94 | NP_001104538.1 | 159 | 63.5 | 73.5 |
Odobenus rosmarus divergens | Pacific walrus | Carnivora | 94 | XP_004399365.2 | 159 | 67.9 | 77.4 |
Canis lupus familiaris | Dog | Carnivora | 94 | XP_038283783.1 | 159 | 65.6 | 76.2 |
Talpa occidentalis | Spanish mole | Eulipotphyla | 94 | XP_037376292.1 | 162 | 66.7 | 75.3 |
Condylura cristata | Star-nosed mole | Eulipotphyla | 94 | XP_004676653.1 | 162 | 63.0 | 74.1 |
Pteropus alecto | Black flying fox | Chiroptera | 94 | XP_006909233.1 | 156 | 65.2 | 74.5 |
Desmodus rotundus | Common vampire bat | Chiroptera | 94 | XP_024421609.1 | 159 | 63.8 | 74.4 |
Ceratotherium simum simum | Southern white rhinoceros | Perissodactyla | 94 | XP_004419716.1 | 159 | 64.2 | 78.0 |
Equus caballus | Horse | Perissodactyla | 94 | XP_003363167.2 | 207 | 49.8 | 58.9 |
Manis javanica | Malayan pangolin | Pholidota | 94 | KAI5937412.1 | 158 | 53.8 | 67.5 |
Manis pentadactyla | Chinese pangolin | Pholidota | 94 | XP_036733472.1 | 158 | 53.1 | 66.0 |
Orycteropus afer afer | Aardvark | Tubulidentata | 99 | XP_007953489.1 | 160 | 68.9 | 77.0 |
Loxodonta africana | African bush elephant | Proboscidea | 99 | XP_003409726.1 | 160 | 68.8 | 79.4 |
Dasypus novemcinctus | Nine-banded armadillo | Cingulata | 99 | XP_004451990.1 | 157 | 67.5 | 75.0 |
Sarcophilus harrisii | Tasmanian devil | Dasyuromorphia | 160 | XP_031794457.1 | 168 | 41.0 | 52.2 |
Trichosurus vulpecula | Common brushtail possum | Diprotodontia | 160 | XP_036595517.1 | 168 | 40.8 | 51.4 |
![](http://upload.wikimedia.org/wikipedia/commons/thumb/f/f6/PS2_tree_image.png/220px-PS2_tree_image.png)
Conserved regions
[edit]Regions within the cytoplasmic and extracellular domains of the human TMEM89 protein seem to be the most conserved, as seen in figures on the right.[34][37] Some of these conserved amino acids are part of α-helices in the cytoplasmic and extracellular regions.[34][37]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/d/d4/TMEM89_Multiple_Sequences_Alignment.png/220px-TMEM89_Multiple_Sequences_Alignment.png)
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