Transmembrane protein 42 (TMEM42) is a protein which in humans is encoded by the TMEM42 gene. TMEM42 and its associated proteins may play a role in development and maintenance of the retina.
Gene The TMEM42 gene is located on the plus strand of the short arm on human chromosome 3 at cytogenetic band 3p21.31. The gene spans 3,752 base pairs. The gene contains 3 exons.
Regulation TMEM42 has a ubiquitous variable expression, with approximately a 5x range. It is expressed across all human tissues.
mRNA TMEM42 only has one transcript variant. This transcript is 977 nucleotides long. The transcript has a short 5' UTR. It has one predicted polyadenylation signal and site location.
Protein
There is only one TMEM42 isoform. The TMEM42 protein is 159 amino acids long and has 4 transmembrane regions.
It has a molecular weight of about 17 kDa and an isoelectric point of about 9 pI. Based on its highest scoring predicted structure, the TMEM42 protein has four alpha helices. Topological predictions point to the majority of the protein being on the inside of the cell, with only 7 amino acids being on the extracellular side.
TMEM42 has two standard deviations lower amounts of aspartate compared to the average human protein.
Regulation Experimental evidence points TMEM42 subcellular localization to the nucleoplasm, whereas computational predictions point to the endoplasmic reticulum and Golgi apparatus. Due to TMEM42 being largely intercellular, it has 26 predicted phosphorylation sites.
Homology and evolution
Paralogs There are no known human paralogs of this gene. There is an animal paralog, TMEM42a, estimated to appear 429 million years ago in zebrafish.
Orthologs As seen in the table below, TMEM42 first appeared in fungi 1.27 billion years ago. This following table represents small selection of TMEM42 orthologs, identified via NCBI BLAST. Across 20 orthologs in the table below, seven amino acids are conserved across all 20 organisms. Genus and speciesCommon nameTaxonomic groupMedian date of divergence from humans (mya)Accession numberSequence length (aa)Sequence identity (%) to human proteinSequence similarity (%) to human proteinHomo sapiensHumanPrimates0NP_653239.1159100100Pan troglodytesChimpanzeePrimates6NP_001229549.315999.499.4Manis pentadactylaChinese pangolinPholidota94XP_036739795.215981.184.3Euleptes europaeaTarantolinoSquamata319XP_056713860.114733.945.7Heteronotia binoeiPrickly geckoSquamata319XP_060104087.114732.342.5Carettochelys insculptaPitted-shelled turtleTestudines319XP_074842191.114932.143.7Calidris pugnaxRuffCharadriiformes319XP_014813517.115234.347.4Dromaius novaehollandiaeEmuCasuariiformes319XP_064362502.113531.043.7Manacus vitellinusGolden-collared manakinPasseriformes319XP_029817613.117526.235.7Rhinatrema bivittatumTwo-lined caecilian Gymnophiona352XP_029445552.117833.251.1Spea bombifronsPlains spadefoot toadAnura352XP_053324228.114431.344.5Pleurodeles waltlIberian ribbed newtUrodela352XP_069067612.115831.944.5Lates calcariferBarramundi perchCarangiformes429XP_018536264.115029.842.0Coregonus clupeaformisLake whitefishSalmoniformes429XP_041707945.112729.441.2Electrophorus electricusElectric eelGymnotiformes429XP_026886815.115527.740.0Zootermopsis nevadensisNevada termiteBlattodea686XP_021923555.112529.841.7Anabrus simplexMormon cricketOrthoptera686XP_067001956.212925.038.1Aedes albopictusAsian tiger mosquitoDiptera686XP_029713444.113521.136.7Coemansia javaensisN/AZoopagomycotan1275KAJ2786225.112728.237.1Coemansia spiralisN/AZoopagomycotan 1275KAJ2708432.115322.032.4
Interacting proteins +Notable protein interactions of human TMEM42Protein NameExtended NameDescriptionTLCD5TLC Domain Containing 5Role in human retina and lipid metabolismCCDC24Coiled-Coil Domain Containing 24Retinal developmentWFDC5WAP Four-Disulfide Core Domain 5Protease inhibitorUBE2ISUMO-conjugating enzyme UBC9Performs conjugation step of sumoylation processKIF15Kinesin family member 15Maintains spindle apparatus during mitosis
Clinical significance TMEM42 contains two cis-eQTLs, one on the promoter sequence and one on the 5' UTR. TMEM42 has been implicated as a protective factor against papillary renal cell carcinoma.
RNA-binding protein MBNL1 has 8 predicted binding sites on the TMEM42 transcript. Impairments in MBNL1 function are associated with myotonic dystrophy. Vastus lateralis biopises showed significantly reduced TMEM42 abundance in those with myotonic dystrophy type 2.
References