Bruger:Drlectin/sandkasse4

• Bruger:Drlectin/væsentligebidrag
• bruger:Drlectin/sandkasse
• Biokemi UNDER UDARBEJDELSE. Bruger:Drlectin/sandkasse1
• Peptider UNDER UDARBEJDELSE. Bruger:Drlectin/sandkasse2
• Hormoner og vækstfaktorer. UNDER UDARBEJDELSE Bruger:Drlectin/sandkasse3
• Trimer, IgSF, TMD. UNDER UDARBEJDELSE Bruger:Drlectin/sandkasse4
• Molekylær evolution UNDER UDARBEJDELSE bruger:Drlectin/sandkasse5

• Bruger:Drlectin/sandkasse6Trimer proteins

https://en.wikipedia.org/wiki/Protein_trimer

Trimer

I biokemien er trimer betegnelsen for et makromolekylært kompleks dannet af tre ikke-kovalent bundne proteiner eller af tre ikke-kovalent bundne nukleinsyrer.

En homo-trimer består af identiske molekyler. En hetero-trimer består af forskellige makromolekyler.

Trimere makromolekylære komplekser er vidt udbredt blandt alle levende organismer (virus inkluderet).

Virus

• Nipah virus F glycoprotein forms a trimer, which mediates membrane fusion.

• Spike https://www.sciencedirect.com/science/article/pii/S0092867420302622#undfig1

The viral spike (S) protein is a metastable prefusion homotrimer, comprising two subunits, the N-terminal S1 and C-terminal S2 subunit [35]. The S1 subunit contains the receptor binding domains, an N-terminal domain and a C-domain, while the S2 subunit contains the fusion domain

• NP fra influenzavirus https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0021740.g005

• Hemagglutinin HA fra influenzavirus https://en.wikipedia.org/wiki/Hemagglutinin_(influenza) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2114319/

• SU = surface gp og TM = transmembrane gp fra HTLV (Tcelle leukemivirus) https://www.researchgate.net/profile/David_Brighty/publication/6551348_An_antibody_that_blocks_human_T-cell_leukemia_virus_type_1_six-helix-bundle_formation_in_vitro_identified_by_a_novel_assay_for_inhibitors_of_envelope_function/links/564c9cc108ae352ab55a090d/An-antibody-that-blocks-human-T-cell-leukemia-virus-type-1-six-helix-bundle-formation-in-vitro-identified-by-a-novel-assay-for-inhibitors-of-envelope-function.pd

• Env fra HIV —with 3 cap-like subunits called glycoprotein 120 (gp120) and 3 stem-like subunits called glycoprotein 41 (gp41) https://www.nih.gov/news-events/nih-research-matters/structure-dynamics-hiv-surface-spikes

• SLEV St. Louis encefalitis virus E dimer to posfusion trimer conformation # TBEV, DENV1, DENV2, SLEV (E) and SFV (E1)

• Trimer-of-hairpins structures in viral membrane fusion proteins. Ebola, Moloney murine leukemia (Mo-MLV), and human T-cell leukemia virus type 1 (HTLV-1), simian immunodeficiency virus (SIV), HIV-1, and Visna (this work), influenza and human respiratory syncytial virus (HRSV), simian parainfluenza virus 5 (SV5), and Newcastle disease virus (NDV-F). Fusion model. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC37465/

• Rabies virus RABV Spike = gp = G ectodomain is a homotrimer, and trimers are often called spikes. https://www.hindawi.com/journals/bmri/2016/

• σ1,The homotrimeric reovirus attachment protein σ1 binds directly within the dimer interface of the membrane distal D1 domain of human JAM-A and disrupts the JAM-A–JAM-A interface

• Fiber, dsRNA reovirus and dsDNA adenovirus [13]. Both attachment proteins, σ1 and fiber, are trimeric proteins that comprised large globular heads formed by an 8-stranded β barrel structure and long fibrous tails, referred to as the “knob” and “shaft” in adenovirus

Bakteriofager

• T4 tail lysozyme complex (gp27-gp5). https://jb.asm.org/content/185/14/4022

• P5 fra fag PBD1 https://www.researchgate.net/figure/a-Major-coat-protein-P3-trimer-high-resolution-structure-orange-Benson-et-al-2002_fig1_10729382

• Fag P22 tailspike adhesin

• Fag adhesins

• Fag tail proteins https://jb.asm.org/content/185/14/4022/figures-only

• foldon from the T4-phage fibritin

Bakterier

• Nitrite Reductase

• PNPase from E. coli

• Maltoporin

• esterase PDB 1ZOI fra Pseudomonas [51668919_Mechanism_and_Function_of_the_Outer_Membrane_C]

• Fenna-Matthews-Olson (FMO) complex of green sulfur bacteria [1]

• TolC, outer membrane efflux protein (OEP) i Gram-negative bakterier

hannel_TolC_in_Multidrug_Resistance_and_Physiology_of_Enterobacteria

Andre

• Syncytins

• ASCT2 (receptor for Syncytin-1) is organised as a homo-trimeric multi-membrane spanning protein with each monomer consisting of five extracellular loops

• zebrafish CRP

• Adenylyl cyclase

• TNF tumor necrosis factor og TRAIL (TNF-Related Apoptosis-Inducing Ligand) like most TNF family members, TRAIL forms homotrimers that bind three receptors.

• TNFR1 og TNFR2

• CNT3 er trimer af 13TM?

• KDPG aldolase billede https://en.wikipedia.org/wiki/2-dehydro-3-deoxy-phosphogluconate_aldolase

• Stoma SLAC1 anion channel = slow anion channel 1 (med 10 helix TM) i planter https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548404/

• alkyl hydroperoxidase D-like proteins from different species https://www.researchgate.net/figure/a-Examples-of-hexamers-and-trimer-molecular-units-found-in-the-crystal-for-alkyl_fig7_51168506

• Poriner https://en.wikipedia.org/wiki/Porin_(protein)

• Ara h 1 Structural and Immunologic Characterization of Ara h 1, a Major Peanut Allergen

• Proliferating cell nuclear antigen (PCNA) is a DNA clamp https://en.wikipedia.org/wiki/Proliferating_cell_nuclear_antigen

• collagen I

• Kollagen Type II

• Type XIV collagen

Heteromeric proteins

• G-protein coupled receptors (GPR)
• sweet taste receptors, which are heterotrimeric G-protein coupled receptors (GPR) consisting of two subunits, namely taste receptor type 1 member 2 (T1R2) and 3 (T1R3)
• α-gustducin - Upon interaction of sweet compounds to the sweet receptor T1R2/T1R3, the heterotrimeric G protein, α-gustducin, is activated

IgSF, Immunoglobulin superfamilie

Evolution, se [https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cd7 Immunoglobin Superfamily A.N. Barclay, in Brenner's Encyclopedia of Genetics (Second Edition), 2013 How Did IgSF Domains Evolve?]

12 immunoglobulin domains make up the two heavy chains (red and blue) and the two light chains (green and yellow) of an antibody. The immunoglobulin domains are composed of between 7 (for constant domains) and 9 (for variable domains) β-strands.

https://en.wikipedia.org/wiki/Immunoglobulin_superfamily https://en.wikipedia.org/wiki/Antibody

Der kendes mere end 750 proteiner med fra et til 112 immunoglobulinlignende domæner https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/immunoglobulin-domaint

Et immunglobulinlignende domæne består typisk af 70-100 aminosyrer arrangeret i en sandwich af to beta-sheets med 7-9 beta-kæder i et fast meander-mønster (se billedet).

Nogle proteiner i IgSF

112 immunoglobulinlignende domæner

• Titin, muskelprotein, det største protein der kendes, se en:Titin

Titin Ig domains. a) Schematic of part of a sarcomere b) Structure of Ig domains c) Topology of Ig domains.

Protein domains of Titin A-band. White boxes are Fn3 domains, red boxes are Ig domains, yellow boxes are Fn3 domains with the -AVNKYG- sequence, and the black box is protein kinase domain.

70 immunoglobulinlignende domæner

• IgM (20 peptidkæder)

28 immunoglobulinlignende domæner

• IgA (otte peptidkæder)

Femten immunoglobulinlignende domæner

• SIGLEC-1/Sialoadhesin/Sialic acid-binding immunoglobulin-type lectin-1

Fjorten immunoglobulinlignende domæner

• IgE (fire peptidkæder)
• IgY/Immunoglobuliner i fugle, krybdyr og lungefisk (fire peptidkæder)

Tolv immunoglobulinlignende domæner

• IgG, IgA (fire peptidkæder)
• IgNAR/“New Antigen Receptor”/“heavy-chain antibody”/haj-immunoglobulin (to peptidkæder)

Ti immunoglobulinlignende domæner

• DSCAM

Ni immunoglobulinlignende domæner

• ICAM-5/TLCM/Telencephalin

Syv immunoglobulinlignende domæner

• VCAM-7 https://en.m.wikipedia.org/wiki/IgSF_CAM
• CEA/CEACAM-5

Seks immunoglobulinlignende domæner

• L1/NgCAM
• PECAM
• CNTN/Contactin
• CD-22/Siglec-2/Sialic acid-binding immunoglobulin-type lectin-2
• Camelid IgG-2 og IgG-3/Llama immunoglobulin (to peptidkæder)

Fem immunoglobulinlignende domæner

• NCAM
• ICAM-1/Rhinovirus receptor
• MAG/Myelin associative glycoprotein/SIGLEC-4?
• Robo
• Poly-Immunoglobulinreceptor
• Rst-protein, Drosophila celleadhæsionsmolekyle

Fire immunoglobulinlignende domæner

• CD-4
• PSG1
• MAG/Siglec-4?

Tre immunoglobulinlignende domæner

• CADM1
• Nectin
• CEACAM-6, CEACAM-8
• LAMP
• NEGR1
• Ntm
• OBCAM
• KIR3DL1/Killer-Cell Immunoglobulin-Like Receptor
• Siglec-10, Siglec-11, Siglec-16
• SynCAM

To immunoglobulinlignende domæner

• BT-IgSF
• CD-2
• CAR/Coxsackie virus and adenovirus receptor
• CTX
• ICAM-?
• JAM
• LFA-3
• CEACAM-7
• KIR2DL1/Killer-Cell Immunoglobulin-Like Receptor
• Siglec-5, Siglec-6, Siglec-7, Siglec-8, Siglec-9, Siglec-XII, Siglec-14
• CD-8 (to peptidkæder)

Et immunoglobulinlignende domæne

• Izumo
• CD-3
• CD-33/Siglec-3, Siglec-15
• CD66a/CEACAM1, se en:CEACAM1
• Thy-1

TMD, transmembrane domain

TMD, Transmembrandomæner

Se

• Proteindomæne#Transmembrane domæner
• Membranprotein

https://en.wikipedia.org/wiki/Transmembrane_domain Integrale membranproteiner https://en.wikipedia.org/wiki/Integral_membrane_protein Transmembranprotein https://en.wikipedia.org/wiki/Transmembrane_protein

Eksempler

• ACE https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193637/
• ACE2

Generelt

About 30% of all proteins have transmembrane domains. 27% of the total human proteome are alpha-helical transmembrane proteins.

We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups: receptors (63 groups, 1,352 members), transporters (89 groups, 817 members) or enzymes (7 groups, 533 members). Also, 74 miscellaneous groups with 697 members were determined. Interestingly, we find that 41% of the membrane proteins are singlets with no apparent affiliation or identity to any human protein family. Our results identify major differences between the human membrane proteome and the ones in unicellular organisms and we also show a strong bias towards certain membrane topologies for different functional classes: 77% of all transporters have more than six helices while 60% of proteins with an enzymatic function and 88% receptors, that are not GPCRs, have only one single membrane spanning α-helix. Further, we have identified and characterized new gene families and novel members of existing families. .... important membrane protein groups such as the G-protein coupled receptors (GPCR), Aquaporins, Ion channels, ATPases, their structure and topology [7,8]. .... RECEPTORS: 1,352 receptors into 63 groups (Figure 3). Most of these families can be placed in one of four superfamilies; G protein-coupled receptors (901 proteins), Receptor type tyrosine kinases (72 proteins), Receptors of the immunoglobulin superfamily and related (149 proteins) and Scavenger receptors and related (63 proteins). The remaining 167 receptors, in 20 groups, are annotated as Other receptors... TRANSPORTERS: Transporters perform the movement of a substrate across membranes by utilizing electrochemical gradients or energy from chemical reactions. We identified 817 transporters and placed them in 89 groups (Figure 4). The groups have been primarily arranged into three major functional classes: Channels (247 proteins), Solute carriers (393 proteins), and Active transporters (81 proteins). The remaining eight groups are annotated as Other transporters (51 proteins). Here we also include 42 auxiliary transport proteins in 9 groups that modulate the activity of other transporters... ENZYMES: 533 enzymes (Figure 5). They have been classified based on the EC system, which classifies enzymes performing a similar type of reaction into six major classes: Oxidoreductases (123 proteins), Transferases (194 proteins), Hydrolases (178 proteins), Lyases (17 proteins), Isomerases (8 proteins) and Ligases (7 proteins). An additional six enzymes belong to multiple classes...

FORSKELLIGT: The 74 protein families that did not fit into any of the 3 major functional classes were gathered in a class called Miscellaneous. This class contains 697 proteins and is further divided into four subclasses: Ligands (57 proteins), Other (272 proteins), Structural/Adhesion proteins (187 proteins) and Proteins of unknown function (181 proteins) Figure 6.  

http://www.biomedcentral.com/1741-7007/7/50

In humans, 27% of all proteins have been estimated to be alpha-helical membrane proteins.

Type I transmembrane proteins (single pass) are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains targeted to the ER lumen during synthesis (and the extracellular space, if mature forms are located on plasmalemma). Type II (single pass) and III (single pass) are anchored with a signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen. Type IV (multiple pass) is subdivided into IV-A, with their N-terminal domains targeted to the cytosol and IV-B, with an N-terminal domain targeted to the lumen.[

Chloride channel subunits contain between 1 and 12 transmembrane segments.

Beta-BARREL og TMB, Transmembrane beta-barrel

W Beta-barrel proteins are found in outer membranes of gram-negative bacteria, cell wall of gram-positive bacteria, and outer membranes of mitochondria and chloroplasts. All beta-barrel transmembrane proteins have simplest up-and-down topology, which may reflect their common evolutionary origin and similar folding mechanism. I mitochondrier og chloroplastre[2]

• Outer membrane proteins from Gram-negative bacteria, 8-26 beta-strænge. Top row: OmpX 8; PagP 8; tOmpA (transmembrane domain of OmpA 8; OmpW 8; OmpT 10; EspP (β-domain) 12. Middle row: OmpLA 12; OmpG 14; FadL 14; OmpF 16; BamA 16; Bottom row: LamB 18; FhuA 22; FimD 24; LptD 26.[3]

• Tom40. Del af translocase of the outer mitochondrial membrane (TOM complex).

• Tim22. Del af translocase of the inner mitochondrial membrane

• Tim23. Del af translocase of the inner mitochondrial membrane

• SAM50 [4]

• TOM40 [5]
• TOM = Translocase of the Outer Membrane. [6]

• lipocaliner

• Retinolbindende protein [7]

• Major urinary proteins, 0 i mennesker til mindst 21i mus[8]

• Poriner [9][10]

• Gram-negative bakteriers ydre membran. The OMP family shows substantial differences in its size and structural complexity; the smallest member OmpX has 8 β-strands, and the largest member LptD has 26 β-strands. E. coli the most abundant OMPs are OmpF, OmpC, LamB, and OmpA.

• OmpA og OmpA-like TMD. Eight-stranded beta barrel.[1] OmpA is the predominant cell surface antigen in enterobacteria found in about 100,000 copies per cell.

• C9, MAC reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming β-barrel.Structure of the poly-C9 component of the complement membrane attack complex. Nature 2016 MAC, Membrane attack complex/perforin-like (MACPF) proteins comprise the largest superfamily of pore-forming proteins, playing crucial roles in immunity and pathogenesis. Soluble monomers assemble into large transmembrane pores via conformational transitions. MAC, the membrane attack complex/perforin (MACPF) domain, and revealed an evolutionary link to the cholesterol-dependent cytolysin (CDC) family of bacterial toxins despite limited sequence identity [40,41]. As such, proteins across a wide range of genera and species that share this fold are often referred to as belonging to the MACPF/CDC superfamily [42]. The MACPF/CDC fold is composed of approximately 350 amino acids and includes a central antiparallel, twisted β-sheet. The central β-sheet is bent nearly 90° and is flanked by two clusters of α-helices. During conversion to the pore, both clusters unfurl to form two antiparallel transmembrane β-hairpins (TMHs) that comprise the final β-barrel [43–45] (figure 2f).[11][12]

• Pleurotolysin MACPF, 13 monomers each with two beta-hairpins > beta-barrel with 52 beta-tråde [13]

• Pore-forming toxin

• • CDC, cholesterol dependant cytolysins. the pore complex in which each CDC monomer contributes two amphipathic β-hairpins (transmembrane β-hairpins or TMHs), which are derived from the two α-helical bundles (αHBs) in D3 (Figure 1a,b). In a cooperative manner, these hairpins assemble into and insert the membrane-spanning β-barrel pore, which is composed of 35–45 monomers (dependent on the CDC) The Unique Molecular Choreography of Giant Pore Formation by the Cholesterol-Dependent Cytolysins of Gram-Positive Bacteria

• • • Clostridium perfringens perfringolysin O (PFO or θ-toxin) is a cytolytic toxin that binds to cholesterol-containing membranes and then self-associates to spontaneously form aqueous pores of varying size in the bilayer. [14]

MANGE TMD

ATPase, eubakterier, mitokondrier, grønkorn http://palaeos.com/bacteria/glossary/glossary.html F ATPase=urformen af ATPase. In Eubacteria, the F-ATPase normally runs in "reverse," allowing ions (usually H+, sometimes Na+) at high concentration to enter the cytoplasm, driving ATP synthesis. ATP syntetase. The FO region of ATP synthase is a proton pore that is embedded in the mitochondrial membrane. It consists of three main subunits A, B, and C, and (in humans) six additional subunits, d, e, f, g, F6, and 8 (or A6L). Mitokondrie ATP synthase (F1F0 ATPase). Fo = rotating ring C = 12 domæner, PP

BETA BARREL OG ALPHA HELIX

Scramblase

Tubby protein

ALPHA HELIX

60 TMD

NADH Dehydrogenase Mechanism: 1. The seven primary iron sulfur centers serve to carry electrons from the site of NADH dehydration to ubiquinone. Note that N7 is not found in eukaryotes. 2. There is a reduction of ubiquinone (CoQ) to ubiquinol (CoQH₂). 3. The energy from the redox reaction results in conformational change allowing hydrogen ions to pass through four transmembrane helix channels.

• Respiratory complex I, EC 1.6.5.3 (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial Complex I) translocates protons across the inner mitochondrial membrane in prokaryotes or the plasma membrane of bacteria.The structure is an "L" shape with a long membrane domain (with around 60 trans-membrane helices) and a hydrophilic (or peripheral) domain, which includes all the known redox centres and the NADH binding site.

36 TMD

Piezo as Mechanosensitive Channels. Ref. https://www-annualreviews-org.wikipedialibrary.idm.oclc.org/doi/full/10.1146/annurev-neuro-070918-050509 Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms. Annual Review of Neuroscience Volume 43, 2020

24 TMD

• Voltage-Gated Ion Channels

Three major families of VGICs are expressed in the animal kingdom and they are most readily distinguished by the cation that they pass:

- sodium (NaV),

- potassium (KV), or

- calcium (CaV) [15]

• voltage-gated sodium channel as a specific example of a protein embedded in the plasma membrane. This type of protein is found in the nerve and muscle cells and is used in the rapid electrical signalling found in these cells. The principle subunit of the voltage-gated sodium channel is a polypeptide chain of more than 1800 amino acids. [http://courses.washington.edu/conj/membrane/nachan.htm

20 TMD

• Bestrophiner. Fem identiske subunits med hver fire TMD. a Cl− channel that can be activated by Ca2+. Stable pentamer of protomers /4 membrane alpha helices.[16], se figure [17][18]

• theEscherichia coli BtuCD protein, an ABC transporter mediating vitamin B12 uptake.

14 TMD

• Tet(L), antibiotic resistance protein, a tetracycline efflux protein with 14 transmembrane segments (TMS). Antiporter.http://jb.asm.org/content/183/8/2667/F1.expansion.html se 12 TMD Variant.

• Lac permease

http://www.pnas.org/content/97/16/8938/F1.expansion.html

12 TMD

• GluT1 [19]

• ATP-binding cassette<se fig og exempler. ATP binding cassette (ABC) and major facilitator superfamily (MFS)

• • Cystic fibrosis transmembrane conductance regulator (CFTR)[20]

• • P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) or ABC transporter of the MDR/TAP subfamily is an important protein of the cell membrane that pumps many foreign substances out of cells.

• PTC, Patched Ptch, receptor for Hh ("Hedghog")-homologe SHH, DHH, IHH. The seven transmembrane domain containing protein smoothened (SMO, 7 pass) serves as the key player for signal transduction of this pathway, whose function is inhibited by another transmembrane protein Patched (PTC) in the absence of Hh ligands. In the presence of active Hh ligands, binding of Hh to its receptor PTC releases this inhibition, allowing SMO to signal downstream.[21] Kræftrelateret? Ja, a tumour suppressor gene implicated in basal cell carcinomas and medullablastomas.[22]

• Tet(L) antibiotic resistance protein (12TMS variant)[23]

• Monoamine transporters
• * norepinephrine transporter, NET (=noradrenalin)

https://en.wikipedia.org/wiki/Norepinephrine_transporter

• * Dopamintransporter DAT symporter 12TMD http://www.nature.com/nature/journal/v503/n7474/full/nature12533.html

https://en.wikipedia.org/wiki/Dopamine_transporter

• * Norepinephrintransporter, NET

Simplified structure of the norepinephrine transporter protein.

• * norepinephrine transporter (NET), also known as solute carrier family 6 member 2 (SLC6A2). NET is a monoamine transporter and is responsible for the sodium-chloride (Na+/Cl–)-dependent reuptake of extracellular norepinephrine(NE), which is also known as noradrenaline. NET can also reuptake extracellular dopamine (DA).

The norepinephrine transporter is composed of 12 transmembrane domains (TMDs). The intracellular portion contains an amino (-NH₂) group and carboxyl (-COOH) group. In addition, there is a large extracellular loop located between TMD 3 and 4. The protein is composed of 617 amino acids.

12 eller 10TMD

• Chloride channels https://en.wikipedia.org/wiki/Chloride_channel

10+2TMD

• Flippases

http://www.mdpi.com/1422-0067/14/4/7897/htm P4 ATPases: Flippases

10+1TMD

• GASTRIC PROTON PUMP?? P-type ATPase H+/K+ ATPase

http://www.biokemi.org/biozoom/issues/531/articles/2433 PUMPKIN Aarhus Uni

10 eller 12TMD

• Chloride channels https://en.wikipedia.org/wiki/Chloride_channel

10TMD

• Sec61α is composed of 10 transmembrane helices [24]. alpha subunit af SEC61 complex, del af ER protein translocon [25]

• P4 ATPases In all eukaryotic cells, P4 ATPases, also named phospholipid flippases, generate phospholipid asymmetry across biological membranes. This process is essential for cell survival, as it is required for vesicle budding and fusion in the secretory pathway.[26]

• Na,K-ATPase alpha subunit

9TMD

• Presenilin [27] regulate the cleavage of other transmembrane proteins, notably the receptor Notch and the β-amyloid precursor protein. Mutations in presenilin genes increase the production of neurotoxic forms of the amyloid β peptide and contribute to 20-50% of early-onset cases of inherited Alzheimer's disease.[28]

8 eller 10TMD

• ABC3 exporters (undergruppe af ATP-binding cassette transporters, forkortet til ABC transporters) evolved from a 4 TMS precursor which duplicated either extragenicly to give two 4 TMS proteins, both required for transport function, or intragenicly to give 8 or 10 TMS proteins. The 10 TMS proteins appear to have two extra TMSs between the two 4 TMS repeat units.

7TMD

• GPCR

Adrenaline receptors

• vomeronasal receptors, tetramers, pheromon-receptorer.
• glucagon' receptor

• SMO. The seven transmembrane domain containing protein smoothened (SMO) serves as the key player for signal transduction of the hedgehog pathway, whose function is inhibited by another transmembrane protein Patched (PTC, 12 pass) in the absence of Hh ligands. In the presence of active Hh ligands, binding of Hh to its receptor PTC releases this inhibition, allowing SMO to signal downstream.

6TMD

• TRP, Transient receptor potential calcium channel W [29] Transient Receptor Potential (TRP) channels are evolutionarily conserved integral membrane proteins. The mammalian TRP superfamily of ion channels consists of 28 cation permeable channels that are grouped into six subfamilies based on sequence homology [30]

• TRPM8, cold sensor. TRPV1, also named vanilloid receptor 1 or capsaicin receptor 1, is activated by capsaicin and temperature above 42 [31] TRPM8 Transient receptor potential channel melastatin, homotetramer [32]

• De fleste TRP transient receptor potential (TRP) channels, calcium-permeable cation channels with polymodal activation properties, wasabi receptor, capsaicin receptor=TRPV1. Tetramere, monomer = 6TM.[33]
• TRPA
• TRPC
• TRPM
• TRPML
• TRPP
• TRPV

• Calciumactivated Cl- channels CaCC bestrophins (6TMD) and anoctamins

• Aquaporin proteins [34] are made up of six transmembrane α-helicesarranged in a right-handed bundle, with the amino and the carboxyl termini located on the cytoplasmic surface of the membrane... There are thirteen known types of aquaporins in mammals, and six of these are located in the kidney, but the existence of many more is suspected. .. AQP1... Aquaporins in plants are separated into five main homologous subfamilies, or groups:
  • Plasma membrane Intrinsic Protein (PIP)[26]
  • Tonoplast Intrinsic Protein (TIP)[27]
  • Nodulin-26 like Intrinsic Protein (NIP)[28]
  • Small basic Intrinsic Protein (SIP)[29]
  • X Intrinsic Protein (XIP)

• Rhomboid proteases cleave other transmembrane proteins within their transmembrane domains. [35]

• ABC1 exporters (undergruppe af ATP-binding cassette transporters, forkortet til ABC transporters) evolved by intragenic triplication of a 2 TMS precursor.

• ABC2 exporters (undergruppe af ATP-binding cassette transporters, forkortet til ABC transporters) evolved by intragenic duplication of a 3 TMS precursor.

5TMD

• E. coli methionine ABC transporter - usædvanligt da de fleste ABC transportere har 6 TMD.

• YIPF-proteiner, lokaliseret først og fremmest i Golgi Characteristics and Functions of the Yip1 Domain Family (YIPF), Multi-Span Transmembrane Proteins Mainly Localized to the Golgi Apparatus. REVIEW ARTICLE. Front. Cell Dev. Biol., 30 July 2019

4TMD

• TIM22 [36]

• gamma subunit af TRAP complex [37]

• KCP2 subunit af STT3A/OSTC complex [38]

• TUSC3 subunit og MAGT1 subunit af STT3B/OSTC complex [39]

• 5Ht receptor (pentamer) Serotonin receptors = 5-HT receptorer (dog 5-HT 3 w= ligand-gated ion channels in the central or peripheral nervous system)[40]

3TMD

• SEC63 [41]

• DC2/OSTC subunit af STT3A/OSTC complex [42]

• DAD1 subunit og RPN1 subunit af STT3A/OST complex og af STT3B/OST complex [43]

2TMD

• SEC62 del af ER protein translocon [44]

• TMEM258 subunit af STT3A/OST complex og af STT3B/OST complex [45]

• Subunits af alpha pore-dannende toksiner. Identification and structural analysis of the tripartite α-pore forming toxin of Aeromonas hydrophila [46]

• ENaC, epithelial Na Channel subunit, trimer. three homologous subunits α or δ, β, and γ, ASIC subunit, trimer (The epithelial sodium channel/degenerin (ENaC/DEG)-superfamily proteins are voltage-insensitive, sodium-selective channels, including vertebrate ENaC and acid-sensitive channels (ASICs)[47] [48]

1TMD homodimere

• Cytokine receptors [49]
  • GHR, growth hormone receptor
  • PRLR, prolaktin receptor
  • EPOR, erythropoietin receptor

• Currently available homodimer structures of mammalian WT SPTMR‐TMDs.[50]
  • APP, amyloid precursor protein
  • TLR3, Toll‐like receptor 3
  • GpA, glycophorin A
  • EphA1 og EphA2, ephrin receptor
  • ErbB1, ErbB2, ErbB3 og ErbB4, epidermal growth factor receptor
  • VEGFR2, vascular endothelium growth factor receptor 2
  • PDGFR, platelet‐derived growth factor receptor
  • FGFR3, fibroblast growth factor receptor
  • ζζ
  • DAP12, lymphoid/myeloid receptor signaling module

1TMD Type I (single pass)

[51] [52] [53]

• ACE2 er et membranprotein af type 1, såkaldt single-pass med et enzymatisk aktivt domæne eksponeret på celleoverfladen. Enzymatisk er det et zink-holdigt metalloenzym med det ekstracellulære domæne som virushæfter for coronavirus der binder med spike

• CD155 poliovirusreceptor CD155 is a transmembrane protein with 3 extracellular immunoglobulin-like domains, D1-D3, where D1 is recognized by the virus.

• CD4 HIV receptor [54]

• Integrin subunits, heterodimers. Integrins have two different chains, the α (alpha) and β (beta) subunits, and are called obligate heterodimers. In mammals, there are eighteen α and eight β subunits, in Drosophila five α and two β subunits, and in Caenorhabditisnematodes two α subunits and one β subunit. The α and β subunits each penetrate the plasma membrane and possess small cytoplasmic domains.[55]

• β-amyloid precursor protein APP is a single-pass transmembrane protein expressed at high levels in the brain [[56]]

• Spike trimer

• Syncytin-1

• Neuropilin-1, værtsreceptor for SARS-CoV-2.

• Toll-like receptors (TLRs) ... single pass, forms dimers ... are important innate immune proteins responsible for the identification and clearance of invading pathogens. They are pattern recognition receptors (PRRs) capable of recognizing specific pathogen-associated molecular patterns (PAMPs) conserved among micro-organisms and also recognize damage-associated molecular patterns (DAMPs) from tissue injury or cell death resulting from inflammation, oxidative stress, necrosis, etc. Ultimately, TLRs act as sentinels, providing an immediate first line of defense against invading microbes leading to the activation of defense mechanisms of the innate immune system. They are also important for developing B and T cell-mediated, pathogen-specific adaptive immune “memories”.

• leptin receptor (LEP-R), a single-transmembrane-domaíin receptor of the cytokine receptor family.[4]

• Furin

• Receptortyrosinkinaser, bl.a. insulinreceptoren.
  • Receptor tyrosine kinases RTK ELLER TRK single-pass membrane proteins that form dimers within the membrane. [57]] 58 forskellige receptorer i omkring 20 klasser [58]
  • GROWTH FACTOR RECEPTORS Receptorer for vækstfaktorer] - Tyrosine kinase-linked receptors. Growth factors (GFs) are small molecular weight soluble mediators controlling proliferation, survival, metabolism and tissue differentiation. They have also important implications in tumor. [Signal Transduction (Medical Biotechnology) [59]
  • Fibroblast growth factor receptor 3 (FGFR3) is of interest as a G380R mutation in its TMD is the underlying cause of ~99% of the cases of achondroplasia, the most common form of human dwarfism. (FGFR3) is of interest as a G380R mutation in its TMD is the underlying cause of ~99% of the cases of achondroplasia, the most common form of human dwarfism.[60]

• Complement receptor 1

• Mange medlemmer af Immunglobulin-superfamilien
  • Monomer T cell receptor, covalent heterodimer binder antigener[61]
  • Celleadhesionsmolekyler, en:Cell Adhesion Molecules CAM (calcium-uafhængige): ICAM, NCAM, PECAM-1, VCAM-1.

• • ? CD4 (cluster of differentiation 4) is a glycoproteinfound on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. I
  • ? CD8

• Selectins (CAM) are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding.[2] Selectins bind to sugar moieties and so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymers.[3]

• Cadherins (named for "calcium-dependent adhesion") are a class of type-1 transmembrane proteins. /There are at least 100 cadherins, and most are expressed in the developing vertebrate brain on immature cells, neurons, and glia. Their functions are numerous, including cell sorting, boundary formation, target recognition, synaptogenesis, and synapse function. / They play important roles in cell adhesion, forming adherens junctions to bind cells within tissues together. They are dependent on calcium (Ca2+) ions to function, hence their name. The cadherin superfamily includes cadherins, protocadherins, desmogleins, and desmocollins, and more.Axonal Pathfinding: Extracellular Matrix Role. Cadherins. Encyclopedia of Neuroscience, 2009

• cytokinreceptor-superfamilien
  • Type I cytokine receptor
  • Receptor protein serine/threonine kinase
  • Receptor tyrosine kinase. FGFR. http://www.rndsystems.com/cb_detail_objectname_SP96_FGF.aspx
  • Tumor necrosis factor receptor, TNFR, trimer

• Membran-Tumor necrosis factor, mTNF, trimer

• Glycophoriner. image = PDB 1afo EBI.jpg. CD235a (Glycophorin A) is member of the glycophorin A family. It is a type I sialoglycoprotein with a molecular weight of 10 kD, present in the cell membrane as a homodimer. A Glycophorin is a sialoglycoprotein of the membrane of a red blood cell. It is a membrane-spanning protein and carries sugar molecules. It is heavily glycosylated (60%). Glycophorins are rich in sialic acid, which gives the red blood cells a very hydrophilic-charged coat. glycophorins constitute ~2% of the total erythrocyte membrane protein mass.
  • Glycophorin B type I.
  • Glycophorin C type III.

• Notch receptor Notch Receptor. ScienceDirect 2017

• Notch ligands. Notch ligands are plasma single-pass transmembrane proteins named Delta-like and Jagged.

• A Disintegin And Metalloproteinase (ADAM) familien Substrater include growth factors, cytokines, chemokines and adhesion molecules, and, as such, many ADAM proteins play crucial roles in cell-cell adhesion, extracellular and intracellular signaling, cell differentiation and cell proliferation. [Ectodomain shedding and ADAMs in development http://dev.biologists.org/content/139/20/3693.full.pdf]

• proteins of SNARE family that mediate fusion between vesicles and organelles. Most SNAREs have a single TMD, and these all have the same type II topology. Individual SNAREs all perform the same general fusogenic role but are located to different organ- elles within the exocytic and endocytic pathways.

• beta subunit og gamma subunit af SEC61,[62]

• alpha subunit, beta subunit og delta subunit af TRAP complex [63]

• OST4 subunit, RPN1 subunit og OST48/DDOST subunit af STT3A/OST complex og af STT3B/OST complex [64]