Wikipedia

TMEM61

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.

TMEM61
Identifiers
AliasesTMEM61, transmembrane protein 61
External IDsMGI: 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 MbChr 4: 106.36 – 106.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

edit

Aliases

edit

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

Location

edit

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

edit

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.

Name Accession Number[10] Number of Exons Domain Size (bp)
Transcript Variant 1 NM_182532.3 3 2 1256
Transcript Variant X1 XM_011540911.3 0 0 971
Transcript Variant X2 XM_005270586.5 0 0 844
Transcript Variant X2 XM_011540912.3 0 0 1747
Transcript Variant X1 XM_054334900.1 0 0 998
Transcript Variant X2 XM_054334901.1 0 0 865
Transcript Variant X2 XM_054334902.1 0 0 1747

Protein

edit

Isoforms

edit
 
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.

Name Accession Number[10] Size (aa) Predicted Molecular Weight (kDa)[11]
Isoform 1 NP_872338.1 210 22.2
Isoform X1 XP_011539213.1 210 22.2
Isoform X2 XP_005270643.1 205 21.6
Isoform X2 XP_011539214.1 205 21.6
Isoform X1 XP_054190875.1   210 22.2
Isoform X2 XP_054190876.1 205 21.6
Isoform X2 XP_054190877.1 205 21.6

Protein characteristics

edit
 
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

Domains

edit

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 Name Amino 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

Secondary structure

edit

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

Tertiary structure

edit

No confident model for tertiary structure for TMEM61.

Post-translational modifications

edit
 
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 Sites Kinase Tools
V26-30 N/A GPS-Sumo
K90 N/A GPS-Sumo
S10 AGC GPS
S14 AGC GPS
T15 AGC GPS
T21 AGC GPS
T23 AGC GPS
T25 AGC GPS
T32 AGC GPS
S39 AGC GPS
T44 AGC GPS
T54 AGC GPS
 
I-TASSER Predicted 3D model of TMEM61

Subcellular localization

edit
 
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

edit

Transcription factors

edit
Position Score strand TranscriptionFactor Name
473 682 + E2F6\
376 528 - TFAP2B\
58 514 - KLF4\
170 522 - NFIC\
564 548 + Tbx6\
488 537 + PLAG1\
235 512 - THAP1\
376 510 + TFAP2C\
59 494 + KLF10\
376 493 - TFAP2A\
53 489 - ZNF707\
60

469

+ ZNF816\
376 465 + TFAP2B\
477 463 - ZNF460\
132 471 + Prdm5\
201 469 + TWIST1\
59 446 + KLF14\
203 419 - HAND2\
308 472 + PBX1\

Tissue specificity

edit

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

edit

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

edit
 
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

edit

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 Protein Interaction Database Publication notes
YAP1 K on 118 of the sequence In vitro direct interaction BioGrID

InTACT

Protein-peptide
HSPA2 Positive interaction via two hybrid array, pooling INTACT 32814053

10.1016/j.celrep.2020.108050

TMEM45B TMEM61 domain 2 region binding String PMID 34638224
FGFR3 Two hybrid array pooling, with physical association INTACT Interactome 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 affiliation INTACT Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains[1]
TMEM213 Interacts with TMEM61 second domain String PMID 34638224
 
Protein evolution
 
Orthologs of TMEM61

Homology and evolution

edit

Orthologs and paralogs

edit

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

edit

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

edit

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

edit

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.

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000143001 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "Human hg38 chr1:54,979,264-54,990,924 UCSC Genome Browser v457". genome.ucsc.edu.
  6. ^ "GeneCard". GeneCard.
  7. ^ a b 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. ^ a b c "GDS3626 / ILMN_1667115". www.ncbi.nlm.nih.gov. Retrieved 2023-12-16.
  9. ^ "UniProt". www.uniprot.org. Retrieved 2023-12-16.
  10. ^ a b c d e f "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. ^ a b "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. ^ a b c "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. ^ a b "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.
Retrieved from "https://en.wikipedia.org/w/index.php?title=TMEM61&oldid=1251341496"