TMEM126B

Last updated
TMEM126B
Identifiers
Aliases TMEM126B , HT007, transmembrane protein 126B
External IDs OMIM: 615533 MGI: 1915722 HomoloGene: 10222 GeneCards: TMEM126B
Orthologs
SpeciesHumanMouse
Entrez

55863

68472

Ensembl

ENSG00000171204

ENSMUSG00000030614

UniProt

Q8IUX1

Q9D1R1

RefSeq (mRNA)

NM_001193537
NM_001193538
NM_001256546
NM_001256547
NM_018480

Contents

NM_026734

RefSeq (protein)

NP_081010

Location (UCSC)n/a Chr 7: 90.47 – 90.48 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 126B is a protein that in humans is encoded by the TMEM126B gene. [4] [5] TMEM126B is a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The TMEM126B gene is conserved in mammals. [6] The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. It interacts with NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 13. Naturally occurring mutations in this gene are associated with isolated complex I deficiency. A pseudogene of this gene has been defined on chromosome 9. [4]

Structure

TMEM126B is located on the q arm of chromosome 11 in position 14.1 and has 7 exons. [4] The TMEM126B gene produces a 4.6 kDa protein composed of 54 amino acids. [7] [8] It is a part of the mitochondrial complex I assembly (MCIA) complex, composed of NDUFAF1, ECSIT, and ACAD9 (by similarity). It associates with the intermediate 370 kDa subcomplex of incompletely assembled complex I. [9] Complex I is composed of 45 evolutionally conserved core subunits, including both mitochondrial DNA and nuclear encoded subunits. One of its arms is embedded in the inner membrane of the mitochondria, and the other is embedded in the organelle. The two arms are arranged in an L-shaped configuration. The total molecular weight of the complex is 1MDa. [10] A cartoon representation of the predicted orientation of TMEM126B within cell membrane, tentatively based on the phosphorylation [11] and hydrophobicity data [12] is shown below.

Tmem126B cartoon2.jpg

Function

The TMEM126B gene encodes a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. [4] TMEM126B comigrates with other assembly factors including ACAD9, CIA30, and ECSIT. In the absence of TMEM126B, such assembly factors were not recruited into the mitochondrial membrane, and did not participate in complex I assembly. Dysfunction of TMEM126B has known to cause several complications in complex I characterized by severe difficulties in mitochondrial respiration and the complete failure of complex I assembly. However, it is not known to have significant effect on the assemblies of mitochondrial complexes III, IV, and V. [13]

Clinical Significance

Mutations in TMEM126B is known to result in mitochondrial diseases and associated disorders. It is majorly associated with a complex I deficiency, a deficiency in the first complex of the mitochondrial respiratory chain. [4] A complex I deficiency involving the dysfunction of the mitochondrial respiratory chain may cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, Leigh syndrome, myopathy, liver disease, Leber hereditary optic neuropathy, and some forms of Parkinson disease. [9] In addition to complex I deficiency, TMEM126B mutations also show association with severe multi-system disorders during infancy, such as chronic renal failure and cardiomyopathy, and myopathy in childhood or adulthood. [13]

Discovery

TMEM126B was first discovered in a study of protein expression in tissues of the hypothalamus-pituitary-adrenal axis using full cDNA cloning. [5] It has since been detected in other tissues. [14]

Gene

TMEM126B is located on chromosome 11 in humans, flanked by the following genes: [15]

Translation

A conceptual translation of the TMEM126B protein, including a projection of the secondary structure, [18] predictions of transmembrane regions, [12] and putative phosphorylation [11] and glycation sites [19] is included below:

Human proteins - Conceptual translation of TMEM126B.png

Tissue distribution

TMEM126B is expressed in most tissue types, with the notable exceptions of adipose tissue, ear tissue, the larynx, lymph tissue, nerve tissue, pituitary gland, spleen, thymus, thyroid, trachea, and umbilical cord. [20] It also appears to be highly expressed in parathyroid, bone marrow, and urinary bladder tissue. [20] There is also evidence that one of the isoforms of TMEM126B is expressed in the cell membrane of memory B cells of the adaptive immune system. [21]
Tmem126B expression.png

Predicted properties

The following properties of TMEM126B were predicted using bioinformatic analysis:

Interactions

In addition to co-subunits for complex I, TMEM126B has protein-protein interactions with ECSIT, NDUFAF1, NDUFC2, NDUFA13, and others. [9]

Related Research Articles

Cytochrome c oxidase subunit I Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that in humans is encoded by the MT-CO1 gene. In other eukaryotes, the gene is called COX1, CO1, or COI. Cytochrome c oxidase I is the main subunit of the cytochrome c oxidase complex. Mutations in MT-CO1 have been associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.

SCO1

Protein SCO1 homolog, mitochondrial, also known as SCO1, cytochrome c oxidase assembly protein, is a protein that in humans is encoded by the SCO1 gene. SCO1 localizes predominantly to blood vessels, whereas SCO2 is barely detectable, as well as to tissues with high levels of oxidative phosphorylation. The expression of SCO2 is also much higher than that of SCO1 in muscle tissue, while SCO1 is expressed at higher levels in liver tissue than SCO2. Mutations in both SCO1 and SCO2 are associated with distinct clinical phenotypes as well as tissue-specific cytochrome c oxidase deficiency.

TMEM50A

Transmembrane protein 50A is a protein that in humans is encoded by the TMEM50A gene.

TIMMDC1

TIMMDC1 is a protein that in humans is encoded by the TIMMDC1 gene. It is a chaperone protein involved in constructing the membrane arm of mitochondrial Complex I. A frameshift mutation in an intron of this gene has been shown to cause failure to thrive, retardation of psychomotor development, infantile-onset hypotonia, and severe neurologic dysfunction. High expression of this gene has been associated with migration of lung cancer cells while depletion of the protein has been shown to affect regulation of apoptosis, the cell cycle, and cell migration.

NDUFAF1

Complex I intermediate-associated protein 30, mitochondrial (CIA30), or NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1 (NDUFAF1), is a protein that in humans is encoded by the NDUFAF1 or CIA30 gene. The NDUFAF1 gene encodes a human homolog of a Neurospora crassa protein involved in the assembly of complex I. The NDUFAF1 protein is an assembly factor of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Variants of the NDUFAF1 gene are associated with hypertrophic cardiomyopathy, leukodystrophy, and cardioencephalomyopathy.

NDUFAF3

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3, also known as 2P1, E3-3, or C3orf60, is a protein that in humans is encoded by the NDUFAF3 gene. NDUFAF3 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated severe complex I deficiency and Leigh syndrome.

ACAD9

Acyl-CoA dehydrogenase family member 9, mitochondrial is an enzyme that in humans is encoded by the ACAD9 gene. Mitochondrial Complex I Deficiency with varying clinical manifestations has been associated with mutations in ACAD9.

Transmembrane protein 33 is a protein that in humans, is encoded by the TMEM33 gene, also known as SHINC3. Another name for the TMEM33 protein is DB83.

TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.

DMAC1

Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123 and Distal membrane-arm assembly complex protein 1.

Transmembrane protein 268

Transmembrane protein 268 is a protein that in humans is encoded by TMEM268 gene. The protein is a transmembrane protein of 342 amino acids long with eight alternative splice variants. The protein has been identified in organisms from the common fruit fly to primates. To date, there has been no protein expression found in organisms simpler than insects.

NDUFAF4

NADH:ubiquinone oxidoreductase complex assembly factor 4, (NDUFAF4) also known as Hormone-regulated proliferation-associated protein of 20 kDa, (HRPAP20) or C6orf66 is a protein that in humans is encoded by the NDUFAF4 gene. NDUFAF4 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with complex I deficiency and infantile mitochondrial encephalomyopathy. Elevations in HRPAP20 have also been implicated in breast cancer.

NDUFAF2

NADH:ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2), also known as B17.2L or NDUFA12L is a protein that in humans is encoded by the NDUFAF2, or B17.2L, gene. The NDUFAF2 protein is a chaperone involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.

COA3

Cytochrome c oxidase assembly factor 3, also known as Coiled-coil domain-containing protein 56, or Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa is a protein that in humans is encoded by the COA3 gene. This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function.

Cytochrome c oxidase assembly factor 5 is a protein that in humans is encoded by the COA5 gene. This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency.

Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene. This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.

TMEM70

Transmembrane protein 70 is a protein that in humans is encoded by the TMEM70 gene. It is a transmembrane protein located in the mitochondrial inner membrane involved in the assembly of the F1 and Fo structural subunits of ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalo-cardiomyopathy due to ATP synthase deficiency, causing a wide variety of symptoms including 3-methylglutaconic aciduria, lactic acidosis, mitochondrial myopathy, and cardiomyopathy.

TMEM171

Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.

Transmembrane protein 179

Transmembrane protein 179 is a protein that in humans is encoded by the TMEM179 gene. The function of transmembrane protein 179 is not yet well understood, but it is believed to have a function in the nervous system.

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

References

  1. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030614 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. 1 2 3 4 5 "Entrez Gene: transmembrane protein 126B".
  5. 1 2 Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, et al. (August 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–8. Bibcode:2000PNAS...97.9543H. doi: 10.1073/pnas.160270997 . PMC   16901 . PMID   10931946.
  6. ↑ "HomoloGene Results: TMEM126B transmembrane protein 126B".
  7. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
  8. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-27.
  9. 1 2 3 "Complex I assembly factor TMEM126B, mitochondrial". www.uniprot.org. Retrieved 2018-07-27.
  10. ↑ Rhein VF, Carroll J, Ding S, Fearnley IM, Walker JE (July 2016). "NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I". The Journal of Biological Chemistry. 291 (28): 14851–60. doi: 10.1074/jbc.M116.734970 . PMC   4938201 . PMID   27226634.
  11. 1 2 3 "NetPhos 2.0 predictions for TMEM126B".
  12. 1 2 Persson B, Argos P (March 1994). "Prediction of transmembrane segments in proteins utilising multiple sequence alignments". Journal of Molecular Biology. 237 (2): 182–92. doi:10.1006/jmbi.1994.1220. PMID   8126732.
  13. 1 2 Alston CL, Compton AG, Formosa LE, Strecker V, Oláhová M, Haack TB, et al. (July 2016). "Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype". American Journal of Human Genetics. 99 (1): 217–27. doi:10.1016/j.ajhg.2016.05.021. PMC   5005451 . PMID   27374774.
  14. ↑ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
  15. ↑ "TMEM126B in Map Viewer".
  16. ↑ "Entrez Gene: TMEM126A transmembrane protein 126A".
  17. ↑ "OMIM Zhangfei protein".
  18. ↑ Burgess AW, Ponnuswamy PK, Sheraga HA (1974). "Analysis of conformations of amino acid residues and prediction of backbone topography in proteins". Israel Journal of Chemistry. 12 (1–2): 239–286. doi:10.1002/ijch.197400022.
  19. 1 2 "NetGlycate 1.0 predictions for TMEM126B".
  20. 1 2 "EST profile - Hs.525063".
  21. ↑ "CELLS BELONGING TO THE ADAPTIVE IMMUNE SYSTEM THAT EXPRESS PAQ ISOFORM OF TMEM126B".
  22. ↑ Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. Bibcode:1992PNAS...89.2002B. doi: 10.1073/pnas.89.6.2002 . PMC   48584 . PMID   1549558.
  23. 1 2 "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
  24. ↑ Bendtsen JD, Nielsen H, von Heijne G, Brunak S (July 2004). "Improved prediction of signal peptides: SignalP 3.0". Journal of Molecular Biology. 340 (4): 783–95. CiteSeerX   10.1.1.165.2784 . doi:10.1016/j.jmb.2004.05.028. PMID   15223320.

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