TMEM61

Last updated
TMEM61
Identifiers
Aliases TMEM61 , transmembrane protein 61
External IDs MGI: 3041156; HomoloGene: 52319; GeneCards: TMEM61; OMA:TMEM61 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

199964

329909

Ensembl

ENSG00000143001

ENSMUSG00000085933

UniProt

Q8N0U2

n/a

RefSeq (mRNA)

NM_182532

NM_001370848

RefSeq (protein)

NP_872338

n/a

Location (UCSC) Chr 1: 54.98 – 54.99 Mb Chr 4: 106.36 – 106.4 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 61 (TMEM61) is a protein that is encoded by the TMEM61 gene in humans. It is located on the first chromosome in humans [5] and is highly expressed in the intestinal regions predominantly the kidney, adrenal gland and pituitary tissues. [6] The protein, unlike other transmembrane protein in the region does not promote cancer growth. [7] However, the TMEM61 protein when inhibited by secondary factors restricts normal activity in the kidney. [8] The human protein shares many Orthologs and has been prevalent on Earth for millions of years.

Contents

Gene

Aliases

There are no known aliases of TMEM61. The human protein can be identified with any tool that uses UniProt by Q8N0U2. [9]

Location

TMEM61 is located on the plus strand of the human chromosome 1 at the locus 1 p32.3. [5] The gene is 11, 661 base pairs long, it ranges from position 54,980,628 to 54,992,288 on chromosome 1. TMEM61 lies between LOC124904184 and BSND. [10]

Transcript variants

NCBI RefSeq contains seven mRNA transcript variants for TMEM61. Transcription variants X1, X2, and X2 both are splices of the original protein, but all three isoforms have their own variants. None of the variants share similar exon boundaries, domain or disordered regions.

NameAccession Number [10] Number of ExonsDomainSize (bp)
Transcript Variant 1NM_182532.3321256
Transcript Variant X1XM_011540911.300971
Transcript Variant X2XM_005270586.500844
Transcript Variant X2XM_011540912.3001747
Transcript Variant X1XM_054334900.100998
Transcript Variant X2XM_054334901.100865
Transcript Variant X2XM_054334902.1001747

Protein

Isoforms

Conceptual Translation of TMEM61 Conceptual Translation of TMEM61.png
Conceptual Translation of TMEM61

There are six known Isoforms of the TMEM61 protein, Isoform X1 is encoded by transcript variant X1, and Isoform X2 with variant X2 and so on. There are two different X2 isoforms, but both have the same amino acid sequence, both the X2 have five less amino acids in the start of the protein, which differs from isoform X1 with same protein sequence and size as the original protein.

NameAccession Number [10] Size (aa)Predicted Molecular Weight (kDa) [11]
Isoform 1NP_872338.121022.2
Isoform X1XP_011539213.121022.2
Isoform X2XP_005270643.120521.6
Isoform X2XP_011539214.120521.6
Isoform X1XP_054190875.1  21022.2
Isoform X2XP_054190876.120521.6
Isoform X2XP_054190877.120521.6

Protein characteristics

MyHits Motif Scan with evalues Domains of TMEM61.png
MyHits Motif Scan with evalues

The Isoform 1 of the TMEM61 protein is made up of 210 amino acids. [12] The protein has a predicted molecular weight of about 22.2 KDa and a theoretical isoelectric point of about 4.54. [13] In terms of amino acid composition, TMEM61 is relatively rich in both the hydrophobic Proline and hydrophilic Serine. The protein is relatively poor in both hydrophilic Asparagine and Lysine. It is also poor in both hydrophobic Isoleucine and Phenylalanine. [14] The protein indicates acid components from it addition of Arginine and Lysine subtracted to the addition of Glutamic Acid and Aspartic Acid. [14]

Ali2D configured Helix Beta distribution Ali2D configured Helix Beta.png
Ali2D configured Helix Beta distribution

Domains

TMEM61 Isoform 1 contains two transmembrane domains one of encompasses a DUF domain. TMEM61 also contains a MTP domain, unlike the transmembrane domain this domains located in the Golgi Apparatus and involves spanning transportation. All four domain regions had low value scores except the second TMEM domain was not able to be scored.

Domain NameAmino Acid
TMEM [10] 18-38
DUF308 [15] 16-37 or 16-41
TMEM [10] 69-89
MTP [16] 124-152
IBS configuration of TMEM61 with post-translation modification IBS configuration of TMEM61 with post-translation modification.png
IBS configuration of TMEM61 with post-translation modification

Secondary structure

The Ali2D, and I-TASSER models predicted that the secondary structure of TMEM61 has both alpha helices and beta strands.

Tertiary structure

No confident model for tertiary structure for TMEM61.

Post-translational modifications

Glycosylation of TMEM61 Glycosylation of TMEM61.png
Glycosylation of TMEM61

While the modification are few, phosphorylation will not result in a change oil the amino acid for TMEM61, this is a result of the lack of glycosylation that takes place in the sequence. Results are represented by graph on bottom right.

TMEM61 SitesKinaseTools
V26-30N/AGPS-Sumo
K90N/AGPS-Sumo
S10AGCGPS
S14AGCGPS
T15AGCGPS
T21AGCGPS
T23AGCGPS
T25AGCGPS
T32AGCGPS
S39AGCGPS
T44AGCGPS
T54AGCGPS
I-TASSER Predicted 3D model of TMEM61 I-TASSER Predicted 3D model of TMEM61.png
I-TASSER Predicted 3D model of TMEM61

Subcellular localization

TMEM61 transcription factors Transcription Factors of TMEM61.png
TMEM61 transcription factors

Immunofluorescent standing experiments have detected the TMEM61 protein in the endocrine tissues, kidney and Urinary bladder, and proximal digestive tract. The experiment also found slight expression in the brain tissues. [17]

Regulation and expression

Transcription factors

PositionScorestrandTranscriptionFactor Name
473682+E2F6\
376528-TFAP2B\
58514-KLF4\
170522-NFIC\
564548+Tbx6\
488537+PLAG1\
235512-THAP1\
376510+TFAP2C\
59494+KLF10\
376493-TFAP2A\
53489-ZNF707\
60

469

+ZNF816\
376465+TFAP2B\
477463-ZNF460\
132471+Prdm5\
201469+TWIST1\
59446+KLF14\
203419-HAND2\
308472+PBX1\

Tissue specificity

According to HumanAtlas, Geoprofile, and NCBI, TMEM61 is highly expressed in the Kidney, Pituitary gland, Salivary gland, Adrenal, and brain tissues in a decreasing order. [17] [10] [18]

Embryonic development

In situ hybridization staining a mouse embryo discovered high levels of TMEM61 in Kidneys and found no other tissues to express the protein. [17]

Immunochemistry

Immunochemistry of TMEM61 and expression in the Human body Immunochemistry of TMEM61.png
Immunochemistry of TMEM61 and expression in the Human body

TMEM61 was found to be very abundant in the human body in comparison to other proteins. [19]

Western blotting showed an over expression of lysate in mammalian, in this case rabbit. [20]

The staining of the human pancreas shows cytoplasmic positivity in exocrine cells. [20]

Interacting proteins

The IntAct, String, and BioGrid database found eight relevant interacting protein to the TMEM61. [21] [22] [23] Other TMEM protein such as TMEM124 are closely monitored together for the cancer expression both in the same region but both did not promote cancer growth.

Interacting ProteinInteractionDatabasePublication notes
YAP1 K on 118 of the sequence In vitro direct interaction BioGrID

InTACT

Protein-peptide
HSPA2 Positive interaction via two hybrid array, poolingINTACT32814053

10.1016/j.celrep.2020.108050

TMEM45B TMEM61 domain 2 region bindingStringPMID 34638224
FGFR3 Two hybrid array pooling, with physical associationINTACTInteractome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains
SARS1 Host organism: Saccharomyces cerevisiae (Baker's yeast), Neurodegeneration testing affiliationINTACTInteractome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains[1]
TMEM213 Interacts with TMEM61 second domainStringPMID 34638224
Protein evolution Gene evolution.png
Protein evolution
Orthologs of TMEM61 Orthologs of TMEM61 Protein.png
Orthologs of TMEM61

Homology and evolution

Orthologs and paralogs

TMEM61 has orthologs in mammals, reptiles, aves, amphibians, and fish. A table of orthologs is beside to the right. There is no known paralog of TMEM61.

Evolutionary history

West African lungfish is the furthest-from-human known organism to express TMEM61 approximately 408 million years ago. [24] The expression of TMEM61 protein throughout its closely related orthologs all indicate high expression in the Kidney.Based on a molecular clock analysis, the protein sequence of TMEM61 has on average evolved faster than Cytochrome C but slower than Fibrinogen alpha.

Clinical significance

TMEM61 was anticipated to be associated with the formation of brain tumors but was later debunked as there was low levels expressed, however the test did indicate its location to be in the mitochondrial neural membrane region. [7] [25] The TMEM61 has been hoped to promote cancer or tumor growth but there has been no clinical research that proves this idea.

The information obtained about the TMEM61 does show expression on the kidney beyond it human organism[ clarification needed ] and the studies show MIF limiting the expression of TMEM61. [8]

The Aquaporin-11 deficiency, closing or breaking of water channels limits the protein expression in the membrane and restricts TMEM61 expression and inhibits kidney function. [8]

Interacting proteins

Very close to other TMEM protein such as TMEM124 was closely monitored for the cancer expression both in the same region but both did not promote cancer growth. PMP22, YAP1.

Related Research Articles

<span class="mw-page-title-main">Interferon-inducible GTPase 5</span> Protein-coding gene in the species Homo sapiens

Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 (IRGC1) is an enzyme that in humans is coded by the IRGC gene. It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.

<span class="mw-page-title-main">Transmembrane protein 134</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 134 is a protein encoded by the TMEM134 gene. TMEM134 does not have any other known aliases. There are two transmembrane domains and a domain of unknown function (DUF872). Evolutionary, the majority of the organisms that have this gene are primates and mammals, although there are some organisms dating back to Drosophila and C. elegans. Through current research, there has not been any confirmed function of TMEM134.

<span class="mw-page-title-main">TMEM176B</span> Protein-coding gene in the species Homo sapiens

Transmembrane Protein 176B, or TMEM176B is a transmembrane protein that in humans is encoded by the TMEM176B gene. It is thought to play a role in the process of maturation of dendritic cells.

<span class="mw-page-title-main">TMCO4</span> Protein-coding gene in the species Homo sapiens

Transmembrane and coiled-coil domains 4, TMCO4, is a protein in humans that is encoded by the TMCO4 gene. Currently, its function is not well defined. It is transmembrane protein that is predicted to cross the endoplasmic reticulum membrane three times. TMCO4 interacts with other proteins known to play a role in cancer development, hinting at a possible role in the disease of cancer.

<span class="mw-page-title-main">C6orf62</span> Protein-coding gene in the species Homo sapiens

Chromosome 6 open reading frame 62 (C6orf62), also known as X-trans-activated protein 12 (XTP12), is a gene that encodes a protein of the same name. The encoded protein is predicted to have a subcellular location within the cytosol.

<span class="mw-page-title-main">Transmembrane protein 44</span>

Transmembrane protein 44 is a protein that in humans is encoded by the TMEM44 gene.

<span class="mw-page-title-main">C16orf86</span> Protein-coding gene in the species Homo sapiens

Uncharacterized protein C16orf86 is a protein in humans that is encoded by the C16orf86 gene. It is mostly made of alpha helices and it is expressed in the testes, but also in other tissues such as the kidney, colon, brain, fat, spleen, and liver. For the function of C16orf86, it is not well understood, however it could be a transcription factor in the nucleus that regulates G0/G1 in the cell cycle for tissues such as the kidney, brain, and skeletal muscles as mentioned in the DNA microarray data below in the gene level regulation section.

<span class="mw-page-title-main">SMCO3</span> Protein-coding gene in the species Homo sapiens

Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.

<span class="mw-page-title-main">C12orf24</span> Protein-coding gene in humans

C12orf24 is a gene in humans that encodes a protein known as FAM216A. This gene is primarily expressed in the testis and brain, but has constitutive expression in 25 other tissues. FAM216A is an intracellular protein that has been predicted to reside within the nucleus of cells. The exact function of C12orf24 is unknown. FAM216A is highly expressed in Sertoli cells of the testis as well as different stage spermatids.

TMEM275 is a protein that in humans is encoded by the TMEM275 gene. TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.

<span class="mw-page-title-main">TMEM101</span>

Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.

<span class="mw-page-title-main">C12orf50</span> Protein-coding gene in humans

Chromosome 12 Open Reading Frame 50 (C12orf50) is a protein-encoding gene which in humans encodes for the C12orf50 protein. The accession id for this gene is NM_152589. The location of C12orf50 is 12q21.32. It covers 55.42 kb, from 88429231 to 88373811, on the reverse strand. Some of the neighboring genes to C12orf50 are RPS4XP15, LOC107984542, and C12orf29. RPS4XP15 is upstream C12orf50 and is on the same strand. LOC107984542 and C12orf29 are both downstream. LOC107984542 is on the opposite strand while C12orf29 is on the same strand. C12orf50 has six isoforms. This page is focusing on isoform X1. C12orf50 isoform X1 is 1711 nucleotides long and has a protein with a length of 414 aa.

<span class="mw-page-title-main">C4orf19</span> Human C4orf19 gene

C4orf19 is a protein which in humans is encoded by the C4orf19 gene.

<span class="mw-page-title-main">TMEM104</span> TMEM104 protein encoding gene

Transmembrane protein 104 (TMEM104) is a protein that in humans is encoded by the TMEM104 gene. The aliases of TMEM104 are FLJ00021 and FLJ20255. Humans have a 163,255 base pair long gene coding sequence, 4703 base pair long mRNA, and 496 amino acid long protein sequence. In Eukaryotes, the TMEM104 gene is conserved.

<span class="mw-page-title-main">THAP3</span> Protein in Humans

THAP domain-containing protein 3 (THAP3) is a protein that, in Homo sapiens (humans), is encoded by the THAP3 gene. The THAP3 protein is as known as MGC33488, LOC90326, and THAP domain-containing, apoptosis associated protein 3. This protein contains the Thanatos-associated protein (THAP) domain and a host-cell factor 1C binding motif. These domains allow THAP3 to influence a variety of processes, including transcription and neuronal development. THAP3 is ubiquitously expressed in H. sapiens, though expression is highest in the kidneys.

<span class="mw-page-title-main">C13orf46</span> C13of46 Gene and Protein

Chromosome 13 Open Reading Frame 46 is a protein which in humans is encoded by the C13orf46 gene. In humans, C13orf46 is ubiquitously expressed at low levels in tissues, including the lungs, stomach, prostate, spleen, and thymus. This gene encodes eight alternatively spliced mRNA transcript, which produce five different protein isoforms.

<span class="mw-page-title-main">TMEM248</span> Transmembrane protein 248/TMEM248 gene

Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers.

<span class="mw-page-title-main">Chromosome 5 open reading frame 47</span> Human C5ORF47 Gene

Chromosome 5 Open Reading Frame 47, or C5ORF47, is a protein which, in humans, is encoded by the C5ORF47 gene. It also goes by the alias LOC133491. The human C5ORF47 gene is primarily expressed in the testis.

<span class="mw-page-title-main">C19orf22</span> Human gene

Chromosome 19 open reading frame 22 (c19orf22) is a protein which in humans is encoded by the c19orf22 gene. The primary alias of the gene is R3H domain containing 4 (R3HDM4), but it is commonly referred to as c19orf22.

<span class="mw-page-title-main">TMEM19</span> Protein encoded by the TMEM19 gene

Transmembrane protein 19 is a protein that in humans is encoded by the TMEM19 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000143001 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000085933 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Human hg38 chr1:54,979,264-54,990,924 UCSC Genome Browser v457". genome.ucsc.edu.
  6. ↑ "GeneCard". GeneCard.
  7. 1 2 Wrzesiński T, Szelag M, Cieślikowski WA, Ida A, Giles R, Zodro E, et al. (July 2015). "Expression of pre-selected TMEMs with predicted ER localization as potential classifiers of ccRCC tumors". BMC Cancer. 15 (1): 518. doi: 10.1186/s12885-015-1530-4 . PMC   5015219 . PMID   26169495.
  8. 1 2 3 "GDS3626 / ILMN_1667115". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  9. ↑ "UniProt". www.uniprot.org. Retrieved 2023-12-16.
  10. 1 2 3 4 5 6 "TMEM61 transmembrane protein 61 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  11. ↑ "Expasy - Compute pI/Mw tool". web.expasy.org. Retrieved 2023-12-16.
  12. ↑ "Homo sapiens transmembrane protein 61 (TMEM61), mRNA". 2022-12-24.{{cite journal}}: Cite journal requires |journal= (help)
  13. ↑ "TMEM61 (human)". www.phosphosite.org. Retrieved 2023-12-16.
  14. 1 2 "EBI Tools: Job not available". www.ebi.ac.uk. Retrieved 2023-12-16.
  15. ↑ "Motif Scan". myhits.sib.swiss. Retrieved 2023-12-16.
  16. ↑ "Error". www.genome.jp. Retrieved 2023-12-16.
  17. 1 2 3 "Tissue expression of TMEM61 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2023-12-16.
  18. ↑ "GDS4164 / CfaAffx.29002.1.S1_at". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  19. ↑ "The Human Protein".
  20. 1 2 "PAXdb: Protein Abundance Database". pax-db.org. Retrieved 2023-12-16.
  21. ↑ "IntAct Portal". www.ebi.ac.uk. Retrieved 2023-12-16.
  22. ↑ "TMEM61 Result Summary | BioGRID". thebiogrid.org. Retrieved 2023-12-16.
  23. ↑ "error ... STRING: functional protein association networks". string-db.org. Retrieved 2023-12-16.
  24. ↑ "TMEM61 transmembrane protein 61 [Protopterus annectens (West African lungfish)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  25. ↑ Ramsbottom SA, Thelwall PE, Wood KM, Clowry GJ, Devlin LA, Silbermann F, et al. (January 2020). "Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome". Proceedings of the National Academy of Sciences of the United States of America. 117 (2): 1113–1118. Bibcode:2020PNAS..117.1113R. doi: 10.1073/pnas.1912602117 . PMC   6969532 . PMID   31879347.
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