TM9SF2 Membrane Protein Introduction

Introduction of TM9SF2

TM9SF2 belongs to the transmembrane 9 superfamily. Transmembrane 9 (TM9) proteins, or nonaspanins, are a family of proteins conserved throughout evolution and characterized by 9 transmembrane domains. This family is highly conserved through evolution and comprises three members in Saccharomyces cerevisiae, Dictyostelium discoideum, and Drosophila melanogaster, and four members are reported in mammals (TM9SF1-TM9SF4).

Basic Information of TM9SF2
Protein Name	Transmembrane 9 superfamily member 2
Gene Name	TM9SF2
Aliases	p76
Organism	Homo sapiens (Human)
UniProt ID	Q99805
Transmembrane Times	9
Length (aa)	663
Sequence	MSARLPVLSPPRWPRLLLLSLLLLGAVPGPRRSGAFYLPGLAPVNFCDEEKKSDECKAEIELFVNRLDSVESVLPYEYTAFDFCQASEGKRPSENLGQVLFGERIEPSPYKFTFNKKETCKLVCTKTYHTEKAEDKQKLEFLKKSMLLNYQHHWIVDNMPVTWCYDVEDGQRFCNPGFPIGCYITDKGHAKDACVISSDFHERDTFYIFNHVDIKIYYHVVETGSMGARLVAAKLEPKSFKHTHIDKPDCSGPPMDISNKASGEIKIAYTYSVSFEEDDKIRWASRWDYILESMPHTHIQWFSIMNSLVIVLFLSGMVAMIMLRTLHKDIARYNQMDSTEDAQEEFGWKLVHGDIFRPPRKGMLLSVFLGSGTQILIMTFVTLFFACLGFLSPANRGALMTCAVVLWVLLGTPAGYVAARFYKSFGGEKWKTNVLLTSFLCPGIVFADFFIMNLILWGEGSSAAIPFGTLVAILALWFCISVPLTFIGAYFGFKKNAIEHPVRTNQIPRQIPEQSFYTKPLPGIIMGGILPFGCIFIQLFFILNSIWSHQMYYMFGFLFLVFIILVITCSEATILLCYFHLCAEDYHWQWRSFLTSGFTAVYFLIYAVHYFFSKLQITGTASTILYFGYTMIMVLIFFLFTGTIGFFACFWFVTKIYSVVKVD

Function of TM9SF2 Membrane Protein

The transmembrane 9 (TM9) proteins (also known as nonaspanins) are a group of highly conserved proteins with 9 transmembrane domains. They include 3 members in the amoeba Dictyostelium discoideum (Phg1A, B, C), in the yeast Saccharomyces cerevisiae (TMN1-3) and in Drosophila melanogaster flies (TM9SF2, TM9SF3, TM9SF4) and 4 members in humans (TM9SF1-TM9SF4). TM9 proteins mediate signal transduction events, playing a role in the regulation of cell development, growth, activationand motility. In Drosophila, TM9SF4 and its closest paralogue, TM9SF2, contribute to phagocytosis of various types of particles, while TM9SF4 displays non-redundant requirement in Gram-negative bacteria engulfment. The closely related protein TM9SF2 acts redundantly with TM9SF4 in the phagocytosis of various types of particles and in the control of the actin cytoskeleton.

TM9SF2 Membrane Protein Introduction Fig.1 Spatial arrangement between TM9 and the periplasmic cleft. (Bolla, 2014)

Application of TM9SF2 Membrane Protein in Literature

Tanaka A., et al. Genome-wide screening uncovers the significance of N-sulfation of heparan sulfate as a host cell factor for chikungunya virus infection. J Virol. 2017, 91(13): e00432-17. PubMed ID: 28404855

TM9SF2 is involved in the N-sulfation of heparan sulfate through ensuring NDST1 activity when CHIKV infects to HAP1 cells.
Breton C.V., et al. Particulate matter, the newborn methylome, and cardio-respiratory health outcomes in childhood. Environ Epigenet. 2016, 2(2): dvw005. PubMed ID: 29492287

A higher methylation level in TM9SF2 (cg02015529) and UBE2S (cg00035623), respectively, is associated with a 2SD increase in prenatal PM and is also associated with 36% and 98% increased odds of asthma; whereas methylation of TDRD6 (cg22329831) is negatively associated with PM and a 24% decreased odds of asthma.
Perrin J., et al. The nonaspanins TM9SF2 and TM9SF4 regulate the plasma membrane localization and signalling activity of the peptidoglycan recognition protein PGRP-LC in Drosophila. J Innate Immun. 2015, 7(1): 37-46. PubMed ID: 25139117

Silencing TM9SF4 has a role in preventing pgrp-lc localization of the plasma membrane, while silencing TM9SF2 does not, which may explain the non-redundant role of TM9SF4 in gram-negative bacterial phagocytosis.
Ross C.T., et al. Evolutionary distance of amino acid sequence orthologs across macaque subspecies: identifying candidate genes for SIV resistance in Chinese rhesus macaques.. PLoS One. 2015, 10(4): e0123624. PubMed ID: 25884674

Four of the strongest candidate genes for SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32. Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 are identified as possible candidates.
Pruvot B. Comparative analysis of nonaspanin protein sequences and expression studies in zebrafish. Immunogenetics. 2010, 62(10): 681-699. PubMed ID: 20820770

TM9SF proteins may play a regulatory role in a specific and ancient cellular mechanism that is involved in innate immunity.

TM9SF2 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TM9SF2 antibody development services.

Creative Biolabs' skillful scientists are glad to leverage our expertise and advanced technologies to help you with the member protein research. If you are interested, please feel free to contact us for more details.

Reference

Bolla J R, et al. (2014). Crystal sructure of the Neisseria gonorrhoeae MtrD inner membrane multidrug efflux pump. PLoS ONE. 9(6), e97903.

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