TMPRSS2 Lab Notebook

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Purpose

TMPRSS2 primes the SARS-CoV-2 spike protein by cleavage of S1/S2 sites which is necessary for virus-cell membrane fusion and cell entry. The purpose of this study is to examine the role of TMPRSS2 polymorphisms and potential impacts they may contribute to SARS-CoV-2.

Combined Method and Results

  • Performed a literature search of possible TMPRSS2 SNPs and compiled data into a table
  • Examine databases for information and data on relevant SNPs

Regulation of TMPRSS2

  • TMPRSS2 is mainly expressed in the luminal cells of the prostate epithelium, positively regulated by androgens
  • Enhancer located 13 kb upstream of the transcription start site crucial for androgen regulation (Clinckemalie et. al 2013)
  • Chromatin looping of E1 and E2 enhancers with PRCAT38 (prostate cancer transcript) and TMPRSS2 promoters (Chen et.al)
  • L formation and enhancer activity were mediated by AR/FOXA1 binding and the activity of acetyltransferase p300 (Chen et.al)
  • TMPRSS2 has no overt phenotype and mice KO of TMPRSS2 shows no apparent problems, indicate that there might be some functional redundancy with other type II transmembrane serine protease family (TTSP) members. (Thunders and Delahunt 2020)


Gene Map

  • We created a gene map using Google Slides. TMPRSS2 Gene Diagram
    • Text boxes and arrows were used to display regulatory regions and exons.
  • Information about exons and regulatory regions were taken from the NCBI gene viewer.
  • Isoforms were added to the map.

Isoforms

  • TMPRSS2 was searched on Uniprot (UniProtKB - O15393)
    • Two isoforms are shown under sequences
    • Sequences were compared by clicking the Align button (Alignment)
    • Isoform 1 is shown to be lacking the first 37 A.A.
  • TMPRSS2 was also searched on NCBI Gene (Gene ID: 7113)
    • Navigated to “Genomic regions, transcripts, and products” section and clicked “Switch ON mode ‘show All’ for Gene tracks” in the toolbar
    • 3 isoforms were seen

TMPRSS2 Summary

  • Full Name: Transmembrane Serine Protease 2
    • Chromosome Region: 21q22.3 Location: 41,464,305-41,508,158
    • Exons: 14
    • Promoter Location: 41,507,255-41,508,648
    • Regulatory Regions: 41,508,250-41,508,276
    • Enhancers:41,508,128-41,509,135
    • Terminator: location unknown
  • Has 3 isoforms as a result of alternative splicing
  1. Isoform 1 is believed to be the most relevant due to its expression in viral target cells.
    1. DUF3824: Domain of unknown function (44-91 bp)
    2. LDLa: “Low Density Lipoprotein Receptor Class A” domain: a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism (150-185 bp)
    3. SRCR_2: "Scavanger Receptor Cysteine Rich Domain"(190-283 bp)
    4. Tryp_SPc: “Trypsin-like serine protease”: active site found within this region (293-524 bp)
  2. Isoform 2 is a 492 amino acid protein that is not yet characterized.
  3. Isoform 3 is a 498 amino acid protein that is not yet characterized.

ClinVar SNPs

Previous Research on TMPRSS2 Structure

Structure

Figure 1. Molecular structure of TMPRSS2. (A) Scaled schematic representation of the functional domains of TMPRSS2 protein (B) XtalPred analysis where blue line represents the least probability of the crystallization (C) Ramachandran plot of the model (D) ProSA analysis of the model where the Z score of the model is indicated by black dot, whereas Z scores of resolved structures are shown with dark blue (NMR) and light blue (X-ray) shades. Superimposition of the full length TMPRSS2 model with template in (E) ribbon (F) Cα backbone conformations. Ribbon conformation (G) and surface topology (H) of TMPRSS2 structure where domains are coloured differently and labelled at the corresponding positions. (I) Functionally important residues are shown in green, blue, red and yellow sticks representing calcium binding sites, substrate binding sites, catalytic sites and proteolytic cleavage site, respectively. (J) Molecular dynamic simulation of TMPRSS2 model showing reasonable stability of the molecule after 10000 picoseconds of the simulation run.

Figure 2. TMPRSS2 and SARS-CoV-2 spike protein Molecular Complex. Ribbon diagram of complexes between TMPRSS2 (magenta) and SARS-CoV-2 spike protein (gold) for (A) site1 (Arg685/Ser686) and (B) site2 (Arg815/Ser816), residues of TMPRSS2 (magenta sticks) and spike protein (gold sticks) involved in the intermolecular interactions are shown in the respective boxes. PDB files of the complexes are made available in supplementary materials Model and Complexes.

I-TASSER

  • I-TASSER is a protein modeling resource created by Zhang Lab. Uses threading to predict protein secondary and 3D models
    • submit protein sequence in FASTA format
    • program predicts secondary structure
    • predicts if hydrophobic or hydrophilic residues
    • Predicts 3D models
    • takes about 20 to 60 hours to complete, need to register with the Zhang Lab.
  • TMPRSS2 and TMPRSS4 FAFSA sequence were inputted into database.

  • TMPRSS2 model in I-TASSER

  • TMPRSS4 model in I-TASSER

Swiss-Model

  • Protein structure homology-modelling
    • Has TMPRSS2 modeled already for isoform 1 ID:O15393

Swiss-Model Run for TMPRSS2 & rs12329760

Input FASTA data for TMPRSS2 with and without rs12339760 mutation (V160 --> M)

  • FASTA format for TMPRSS2 was obtained from Uniprot:O15393
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
  • rs12329760 mutation was made on the A.A. sequence (V160 --> M)
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQMYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG

HADDOCK 2.4

  • Software from BonvinLab - models interaction between two molecular structures and how they fit together.
  • Must register to the website, submit a new job, fill out required field (job name, type of structures), click Next and generate results.
  • ClusPro is another website to look at protein-protein docking, needs PDB and chains
  • SARS-Cov-2 S protein was inputted into HADDOCK using the ID: 7DK3, chain A, Protein-Protein Ligand Docking
  • TMPRSS2 3D structure was inputted into HADDOCK using the PDB file obtained from I-TASSER, Protein-Protein Ligand Docking
  • Known cleavage site of S2' region put in for "Active Residues" of SARS-CoV-2 Arg815-Ser816
  • "Active residues of TMPRSS2": (from Hussain 2020).
    • His296, Asp345, Ser441 (catalytic triad)
    • Asp435, Ser460, Gly462 (substrate binding site)

RaptorX Structure Prediction

  • RaptorX is a protein structure prediction server developed by the Xu group. When a sequence is input, RaptorX can predict secondary and tertiary protein structures, contacts, solvent accessibility, disordered regions and binding sites.
  • To submit a job to RaptorX users should
    • Register with email for quick retrieval of results
    • Input a protein sequence or upload a FASTA file. Wait time is 2-3 days.
    • Retrieve results with job ID, email, or sequence
    • Results will include a predicted contact map, a contact result file, and five predicted 3D models assisted by the predicted contacts

RaptorX prediction of TMPRSS2 (Isoform 2) and rs12329760

  • FASTA format for TMPRSS2 was obtained from Uniprot: O15393
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
  • rs12329760 mutation was made on the A.A. sequence (V160 --> M)
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQMYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
  • FASTA sequences were separately input into RaptorX
  • Predicted contact and 3D models were generated

HHpred

  • HHpred can be utilized for detecting remote protein homology and structure prediction, including secondary and tertiary structure.
  • Involves information from databases including PDB, SCOP, Pfam, SMART, COGs, and CDD.
  • To visualize a protein structure, users can:
    • Input the protein sequence in A3M/FASTA/CLUSTAL/STOCKHOLM format into the Input field and select submit.
    • Using the results generated, select the templates you would like to visualize and then select Create Model Using Selection.
    • This will generate a PIR file, which can be pasted into the MODDELLER software under 3ary structure.
      • To download and run the MODDELLER software, users need to register for a license key
    • Inputing this license key into Custom Job ID and clicking Submit will generate results.

HHpred for TMPRSS2 in the absence and presence of rs12329760

  • FASTA format for TMPRSS2 was obtained from Uniprot:O15393
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
  • rs12329760 mutation was made on the A.A. sequence (V160 --> M)
>sp|O15393-2|TMPS2_HUMAN Isoform 2 of Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2
MPPAPPGGESGCEERGAAGHIEHSRYLSLLDAVDNSKMALNSGSPPAIGPYYENHGYQPE
NPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKK
ALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGE
DENRCVRLYGPNFILQMYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGIVDD
SGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNSSRQSRIVGGESAL
PGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEKPLNNPWHWTAFAGILRQSFMFYG
AGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISG
WGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGG
PLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG
  • FASTA sequences were imputed into HHpred in separate runs and submitted.
  • The protein templates generated from these runs were visualized using MODDELLER.

  • HHpred shows no effect on protein structure on rs12329760. Both proteins did not have A.A. 160 included in their structure

PredMP

  • PredMP is a de novo prediction and visualization of membrane proteins
    • TMPRSS2 is a transmembrane serine protease
  • FASTA sequence for TMPRSS2 was imputted into the server

  • First de novo prediction model of TMPRSS2

SNPs of interest

  • Possible SNPs of interest include ones listed in ClinVar
    • Synonymous: rs142750000, rs2298658, rs141788162, rs61735789, rs199824558
    • Missense: rs61735793, rs201679623, rs61735790
    • Frameshift: rs193920966
  • SNP rs12329760 which has been seen in multiple papers that is a V --> M mutation
  • SNP rs2070788 and rs383510 has been cited in multiple papers as conferring higher risk for severe influenza A virus infection (G-->A)
  • SNP rs456142 and rs462574 are 3' UTR variants that are located in mRNA target sites.
  • SNP rs456298 is a 3' UTR variant that has a different frequency for Asian populations and may be correlated with immune response to rubella vaccine.
  • SNP rs75603675 has been cited in multiple papers that might be associated with SARS-CoV-2 entry
  • SNP rs139010197 is a TMPRSS11a missense variant and has been cited to may increase infection risk [1]
  • SNP rs977728 is a TMPRSS11a initiator codon missense variant and may increase infection risk [2]
  • SNP rs353163 is a TMPRSS11a missense variant that has been cited by multiple papers to increase risk to esophageal cancer.
  • Russo et. al stated that the SNP rs1475908, whose alternative allele (A) is associated with low TMPRSS2 expression, and the two variants rs74659079 (allele T) and rs2838057 (allele A), both associated with high TMPRSS2 expression. Interestingly, the eQTL rs1475908 shows the highest AF among EAS (A:0.38) and EUR (A:0.35) and the lowest frequency among Latinos (0.17) These findings agree with a previous study that demonstrated the association of two high TMPRSS2 expression-variants, rs2070788 (allele G) and rs383510 (allele T), with increased susceptibility to the influenza virus infection A (H7N9)

SNP Population Frequencies

Allele frequencies for each SNP from above was found by searching the SNP on dbSNP and looking under “Frequency”.

  • For consistency across SNPs, Allele Frequency Aggregator ALFA was used for the collection of data.

Frameshift

Intron Variants

Intron SNP Population Frequency
Population European African Asian Latin American 2 Total
rs2070788 G=0.461512 A=0.538488 G=0.3100 A=0.6900 G=0.325 A=0.675 G=0.5271 A=0.4729 G=0.459889 A=0.540111
rs383510 T=0.4817 C=0.5183 T=0.33 C=0.67 T=0.5 C=0.5 T=0 C=0 T=0.4771 C=0.5229

Missense

Missense SNP Population Frequency
Population European African Asian Latin American 2 Total
rs61735793 G=0.9901 A=0.0099 G=0.999 A=.001 G=1.000 A=0.000 G=1.00 A=0.00 G=0.99025 A=0.00975
rs201679623 A=0.9999 C=0.00001 A=1.000 C=0.000 A=1.000 C=0.000 A=1.000 C=0.000 A=1.000 C=0.000
rs61735790 T=0.99996 C=0.00004 T=0.993 C=0.007 T=1.000 C=0.000 T=1.00 C=0.00 T=0.99989 C=0.00011
rs12329760 C=0.777704 T=0.2222 C=0.7093 t=0.2907 C=0.620 T=0.380 C=0.8536 T=0.1464 C=0.777066 T=0.2229
rs75603675 C=0.6017 A=0.3983 C=0.68 A=0.32 C=1.0 A=0.0 C=0 A=0 C=0.6059 A=0.3941
rs139010197 T=0.97531 C=0.02469 T=0.982 C=0.018 T=1.000 C=0.000 T=1.00 C=0.00 T=0.97552 C=0.02448
rs977728 C=0.823458 T=0.176542 C=0.8676 T=0.1324 C=0.824 T=0.176 C=0.65 T=0.35 C=0.823073 T=0.176927
rs353163 T=0.33089 C=0.66911 T=0.1788 C=0.8212 T=0.173 C=0.827 T=0.4638 C=0.5362 T=0.329175 C=0.670825

3' UTR Variant

3' UTR Variant SNP Population Frequency
Population European African Asian Latin American 2 Total
rs456142 T=0.1481 C=0.8300 T=0.406 C=0.594 T=0.67 C=0.33 T=0.33 C=0.67 T=0.1700 C=0.8300
rs462574 A=0.02352 G=0.97648 A=0.1818 G=0.8182 A=0.516 G=0.484 A=0.2661 G=0.7339 A=0.05383 G=0.94617
rs456298 T=0.1515 A=0.8485 T=0.43 A=0.57 T=0.8 A=0.2 T=0 A=0 T=0.1654 A=0.8346

Synonymous

Synonymous SNP Population Frequency
Population European African Asian Latin American 2 Total
rs142750000 C=0.99555 T=0.00445 C=0.999 T=0.001 C=1.000 T=0.000 C=1.00 T=0.00 C=0.99574 T=0.00426
rs2298658 C=1.0000 T=0.0000 C=1.00 T=1.00 C=1.0 T=0.0 C=0 T=0 C=1.000 T=0.000
rs141788162 G=0.9951 A=0.0049 G=0.988 A=0.012 G=0.98 A=0.02 no data G=0.99436 A=0.00564
rs61735789 G=0.98298 A=0.01702 G=0.987 A=0.013 G=1.00 A=0.00 no data G=0.98327 A=0.01673
rs199824558 G=0.9980 A=0.0020 G=0.999 A=0.001 G=1.00 A=0.00 no data G=0.99821 A=0.00179

PolyPhen-2

  • PolyPhen2 predicts whether certain amino acid substitutions will be damaging or non-damaging to the protein
  • TMPRSS2 SNPs of interest were submitted into queries to see if they are expected to be damaging

TMPRSS2 SNP Predictions

SIFT

  • dbSNP ID was entered
  • SIFT score and SIFT predictions were recorded
    • SIFT scores range from 0 to 1. The amino acid substitution is considered damaging if the score is less than 0.05 and is tolerated if the score is greater than 0.05.
  • PolyPhen-2 scores and predictions were recorded
  • Polyphen-2 scores range from 0 to 1. The amino acid substitution is considered benign if the score is less than 0.05, possibly damaging if the score is between 0.5 and 0.9, and probably damaging if the score is between 0.9 and 1.


TMPRSS2 SNP Predictions
rs Number SIFT score SIFT prediction PolyPhen-2 score PolyPhen-2 prediction
rs61735793 0.238 tolerated 0.015 Benign
rs75603675 G8V 0.201 tolerated 0.167 Benign
rs61735790 0.231 tolerated 0.033 Benign
rs12329760 0.009 deleterious 0.937 Probably Damaging
rs200291871 0.817 Tolerated 0.011 Benign
rs61735791 0.199 Tolerated 0.029 Benign
rs148125094 0.171 Tolerated 0.098 Benign
rs114363287 0.383 Tolerated 0.109 Benign
rs147711290 L128G Not Found - 0.920 Probably Damaging
rs147711290 L91P 0.005 Deleterious 1.000 Probably Damaging
rs147711290 L91R Not Found - Not Found -
rs150554820 0.004 Deleterious 0.549 Possibly Damaging
rs61735796 0.34 Tolerated 0.017 Benign
rs138651919 0.021 Deleterious 0.833 Possibly Damaging
rs61735795 0.551 Tolerated 0.086 Benign
rs142446494 0.015 Deleterious 0.294 Benign
rs201093031 1 Tolerated 0.00 Benign
rs768173297 Not Found - 0.131 Benign

TMPRSS4

  • TMPRSS4 may serve a similar function in viral entry as TMPRSS2, as it also codes for a membrane bound serine protease that was observed to recognize the SARS-CoV-2 spike protein and help facilitate its entry into cells.
  • SNPS of interest: rs142842357 (ClinVar),
  • High expression (>90%) in tissues such as the nasal cavity, esophagus, bronchus epithelium, colon, intestine, and oral cavity. Source
  • TMPRSS4 snps were filtered on the NCBI dnSNP database by frequency in populations (MAF 0.05-0.1)
    • 84 SNPs were found as of January 19th 2021
    • None of the SNPs had citations or Clinvar significance.


TMPRSS4 and SARS-CoV-2

Structural Model of TMPRSS4

  • 3D Visualization of TMPRSS4 was generated by importing the FASTA sequence into HHPred's MODELLER software.
    • The FASTA sequence of TMPRSS4 was taken from Uniprot: Q9NRS4
  >sp|Q9NRS4|TMPS4_HUMAN Transmembrane protease serine 4 OS=Homo sapiens OX=9606 GN=TMPRSS4 PE=1 SV=2
  MLQDPDSDQPLNSLDVKPLRKPRIPMETFRKVGIPIIIALLSLASIIIVVVLIKVILDKY
  YFLCGQPLHFIPRKQLCDGELDCPLGEDEEHCVKSFPEGPAVAVRLSKDRSTLQVLDSAT
  GNWFSACFDNFTEALAETACRQMGYSSKPTFRAVEIGPDQDLDVVEITENSQELRMRNSS
  GPCLSGSLVSLHCLACGKSLKTPRVVGVEEASVDSWPWQVSIQYDKQHVCGGSILDPHWV
  LTAAHCFRKHTDVFNWKVRAGSDKLGSFPSLAVAKIIIIEFNPMYPKDNDIALMKLQFPL
  TFSGTVRPICLPFFDEELTPATPLWIIGWGFTKQNGGKMSDILLQASVQVIDSTRCNADD
  AYQGEVTEKMMCAGIPEGGVDTCQGDSGGPLMYQSDQWHVVGIVSWGYGCGGPSTPGVYT
  KVSAYLNWIYNVWKAEL

iC3nD

  • Interaction between TMPRSS2 and SARS-CoV-2 highlighted in yellow and green.
    • Upload docked PDB file into iC3nD, click Analysis, View Sequence, Interactions, go to the Details, then highlight the relevant interactions in the bottom bar. Interactions will be highlighted in the model view.

  • Interaction Network was shown by clicking Analysis, H-bonds and Interactions, For the first set pick Structure A and then for the second set Structure B, click Interaction Network to generate the network image.

TMPRSS2 missense SNPs in FASTA format

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs61735793
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGIVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs201679623
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYDPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs61735790
MALNSGSPPAIGPYYENRGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs12329760
MALNSGSPPAIGPYYENRGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQMYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG  

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs61735791
MALNSGSPPAIGPYYENHGYQPENPYPTQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs148125094
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYIYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs114363287
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSRTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs147711290 
(L91R)
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTRGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs147711290 
(L91P)
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTPGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs147711290 
(L91Q)
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTQGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs150554820
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSIMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG 

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs61735796
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGKSALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG 

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs138651919
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHLAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs61735795
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQSEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs142446494
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHMCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs201093031
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVAPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

>sp|O15393|TMPS2_HUMAN Transmembrane protease serine 2 OS=Homo sapiens OX=9606 GN=TMPRSS2 PE=1 SV=3 rs768173297
MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
PLNNPWHWMAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
TDWIYRQMRADG

TMPRSS2 Multiple Sequence Alignment

CLUSTAL FORMAT: MUSCLE (3.8) multiple sequence alignment 


s_147Q          MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_147P          MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_147R          MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_63            MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s.O.TMPS2       MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_65            MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_14812509      MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_61            MALNSGSPPAIGPYYENHGYQPENPYPTQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_12329760      MALNSGSPPAIGPYYENRGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_60            MALNSGSPPAIGPYYENRGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_2679623       MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYDPSPVPQYAPRVLTQA
s_11436328      MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_15055482      MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_66            MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_13865191      MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHLAQYYPSPVPQYAPRVLTQA
s_2093031       MALNSGSPPAIGPYYENHGYQPENPYPAQPTVAPTVYEVHPAQYYPSPVPQYAPRVLTQA
s_76817329      MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
s               MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVPQYAPRVLTQA
                *****************.*********:****.******* *** ***************

s_147Q          SNPVVCTQPKSPSGTVCTSKTKKALCITLTQGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_147P          SNPVVCTQPKSPSGTVCTSKTKKALCITLTPGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_147R          SNPVVCTQPKSPSGTVCTSKTKKALCITLTRGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_63            SNPVVCTQPKSPSGIVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s.O.TMPS2       SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_65            SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_14812509      SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_61            SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_12329760      SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_60            SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_2679623       SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_11436328      SNPVVCTQPKSPSRTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_15055482      SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_66            SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_13865191      SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_2093031       SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s_76817329      SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
s               SNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAALAAGLLWKFMGSKCSNSGIEC
                *************  *************** *****************************

s_147Q          DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_147P          DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_147R          DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_63            DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s.O.TMPS2       DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_65            DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_14812509      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_61            DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_12329760      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQMYSSQRKSWHPVCQDDWNENY
s_60            DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_2679623       DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_11436328      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_15055482      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_66            DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_13865191      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_2093031       DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s_76817329      DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
s               DSSGTCINPSNWCDGVSHCPGGEDENRCVRLYGPNFILQVYSSQRKSWHPVCQDDWNENY
                ***************************************:********************

s_147Q          GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_147P          GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_147R          GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_63            GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s.O.TMPS2       GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_65            GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_14812509      GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_61            GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_12329760      GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_60            GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_2679623       GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_11436328      GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_15055482      GRAACRDMGYKNNFYSSQGIVDDSGSTSIMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_66            GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_13865191      GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_2093031       GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s_76817329      GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
s               GRAACRDMGYKNNFYSSQGIVDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLR
                ****************************:*******************************

s_147Q          CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_147P          CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_147R          CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_63            CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s.O.TMPS2       CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHMCGGSIITPEWIVTAAHCVEK
s_65            CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_14812509      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_61            CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_12329760      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_60            CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_2679623       CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_11436328      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_15055482      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_66            CIACGVNLNSSRQSRIVGGKSALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_13865191      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_2093031       CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s_76817329      CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
s               CIACGVNLNSSRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK
                *******************:*******************:********************

s_147Q          PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_147P          PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_147R          PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_63            PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s.O.TMPS2       PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_65            PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_14812509      PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_61            PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_12329760      PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_60            PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_2679623       PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_11436328      PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_15055482      PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_66            PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_13865191      PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_2093031       PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s_76817329      PLNNPWHWMAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
s               PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMKLQKPLTFNDL
                ******** ***************************************************

s_147Q          VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_147P          VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_147R          VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_63            VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s.O.TMPS2       VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_65            VKPVCLPNPGMMLQSEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_14812509      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYIYDNLI
s_61            VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_12329760      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_60            VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_2679623       VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_11436328      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_15055482      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_66            VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_13865191      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_2093031       VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s_76817329      VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
s               VKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAAKVLLIETQRCNSRYVYDNLI
                **************.***************************************:*****

s_147Q          TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_147P          TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_147R          TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_63            TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s.O.TMPS2       TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_65            TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_14812509      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_61            TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_12329760      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_60            TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_2679623       TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_11436328      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_15055482      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_66            TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_13865191      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_2093031       TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s_76817329      TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
s               TPAMICAGFLQGNVDSCQGDSGGPLVTSKNNIWWLIGDTSWGSGCAKAYRPGVYGNVMVF
                ************************************************************

s_147Q          TDWIYRQMRADG
s_147P          TDWIYRQMRADG
s_147R          TDWIYRQMRADG
s_63            TDWIYRQMRADG
s.O.TMPS2       TDWIYRQMRADG
s_65            TDWIYRQMRADG
s_14812509      TDWIYRQMRADG
s_61            TDWIYRQMRADG
s_12329760      TDWIYRQMRADG
s_60            TDWIYRQMRADG
s_2679623       TDWIYRQMRADG
s_11436328      TDWIYRQMRADG
s_15055482      TDWIYRQMRADG
s_66            TDWIYRQMRADG
s_13865191      TDWIYRQMRADG
s_2093031       TDWIYRQMRADG
s_76817329      TDWIYRQMRADG
s               TDWIYRQMRADG
                ************

PredictProtein

PredictProtein is a program that can be used to predict secondary structure, solvent accessibility, transmembrane helices, globular region, and much more.

  • FASTA format of TMPRSS2 was inputted into text box
  • Results can be seen [Here]

SNPs on TMPRSS2-SARS-CoV-2 Docking Analysis

SNPs below are from most frequent to low frequent:

  • V160M- not near interactions but in SRCR conserved domain, predicted to be lethal using PredictProtein heatmap and PolyPhen2 & SIFT
  • Thr75Ile- not near interactions
  • Ala28Thr- not near interactions
  • Val415Ile- close to interaction sites, in the serine protease domain, predicted to have little-no effect on PredictProtein
  • Val280Met- This is an interaction site. It is located on a beta sheet and interacts with K790 on the Spike Protein (right after fusion peptide). Valine to Methionine are both nonpolar amino acids, but there is a gain of a sulfur atom which could potentially unfavorably bind to nearby amino acids.
  • Glu260Lys- somewhat close to interactions with the spike protein, in the serine protease domain. Predicted to be tolerated in SIFT and PolyPhen2.
  • Phe209Ile- not near interactions but in SRCR conserved domain, predicted to be deleterious/lethal in PolyPhen2 and SIFT, and a red signal in the PredictProtein heatmap.
  • Pro41Leu- not near interactions
  • His18Arg- not near interactions
  • Thr309Met- This is partially close to several interaction sites (302,301,300). It is located in a beta sheet and predicted have little/no effect in PredictProtein heatmap. (PolyPhen-2 and SIFT could not be determined).
  • Pro275Ser- not near interactions
  • Val33Ala- not near interactions
  • Leu91Gln- not near interactions
  • Leu91Pro- not near interactions
  • Leu91Arg- not near interactions
  • Gly74Arg- not near interactions
  • Leu81Arg- not near interactions

Secondary Structure Alignment

  • HH=HHPred, SM=SWISS-MODEL, RX=RaptorX, I-T=I-TASSER, AA= amino acid sequence
  • H = helix, B = beta strand, - = random coil, space = not modeled
RX  --------------------------------------------------
I-T --------------------------------------------------
HH  
SM  
AA  MALNSGSPPAIGPYYENHGYQPENPYPAQPTVVPTVYEVHPAQYYPSPVP 50

RX  -----------------------------HHHHHHHHHHHHHHHHHHHHH
I-T --------------------------------------------------
HH  
SM   
AA  QYAPRVLTQASNPVVCTQPKSPSGTVCTSKTKKALCITLTLGTFLVGAAL 100

RX  HHHHHHHH---------BBBHHH-BBB---------------HHHHHH--
I-T ------------------------------------------------BB
HH  
SM                                             -----BB
AA  AAGLLWKFMGSKCSNSGIECDSSGTCINPSNWCDGVSHCPGGEDENRCVR 150

RX  -------------HHH-----------HHHHHHHHHH-------------
I-T B------BBBBBHHH-BBBB------HHHHHHHHHHHH----BBBBBBBB
HH         -BBBBB---BBBB------HHHHHHHHHHHH----BBBBBBBB
SM  B------BBBBB----BBBB------HHHHHHHHHHHH----BBBBBBBB
AA  LYGPNFILQVYSSQRKSWHPVCQDDWNENYGRAACRDMGYKNNFYSSQGI 200

RX  ----------------------------HHHHHHHHHHHHHHH-------
I-T ----------------------------------BBBBBBB---------
HH  --------BBBB---HHHH--HHHHBBBB-----BBBBBBB---------
SM  HHHH-----BBB---HHH---HHHHBBB------BBBBBBB---------
AA  VDDSGSTSFMKLNTSAGNVDIYKKLYHSDACSSKAVVSLRCIACGVNLNS 250

RX  ---------BB--------BBBBBB--BBBBBBBBBB--BBBBBHHH---
I-T --------BBB--------BBBBBB--BBBBBBBBBB--BBBB-HHHH--
HH  ----------BB-------BBBBBB--BBBBBBBB----BBBB-HHH--H
SM  -------------------BBBBBB---BBBBBBBBB--BBB--HHHH-H
AA  SRQSRIVGGESALPGAWPWQVSLHVQNVHVCGGSIITPEWIVTAAHCVEK 300

RX  -------BBBBB--------HHHBBBBBBBBBB------------BBBBB
I-T ----HHHBBBBB-----------BBB-BBBBBB-------------BBBB
HH  HH--HHHBBBBB-----------BBB-BBBBBB-------------BBBB
SM  HH--HHHBBBBB-----------BBB-BBBBBB-------------BBBB
AA  PLNNPWHWTAFAGILRQSFMFYGAGYQVEKVISHPNYDSKTKNNDIALMK 350

RX  ---------------------------BBBBBBB------------BBBB
I-T B--------------------------BBBBBB--------------BBB
HH  ---------------------------BBBB----------------BB-
SM  B--------------------------BBBBBB--------------BBB
AA  LQKPLTFNDLVKPVCLPNPGMMLQPEQLCWISGWGATEEKGKTSEVLNAA 400
RX  BBBBB-HHHH--HHH--------BBBBB---------HHH--BBBBBBB-
I-T BBBBB------------------BBBBB---------------BBBBBB-
HH  BBBBB-HHHHH------------BBBB----------------BBBBBB-
SM  BBBBB-HHHH-------------BBBB----------------BBBBB--
AA  KVLLIETQRCNSRYVYDNLITPAMICAGFLQGNVDSCQGDSGGPLVTSKN 450

RX  -BBBBBBBBBBBHHH------BBBBBHHH-HHHHHHHHHHH
I-T -BBBBBBBBBB----------BBBBBHHHHHHHHHHH-----
HH  -BBBBBBBBBB----------BBBBBHHHHHHHHHHHHHH-
SM  --BBBBBBBBB----------BBBBBHHHHHHHHHHHHHH
AA  NIWWLIGDTSWGSGCAKAYRPGVYGNVMVFTDWIYRQMRADG 492

Assessment of TMPRSS2 Model

  • Ramachandran(phi/psi) plots can be used to understand which secondary structures of proteins are sterically allowed/favored to occur
  • Comparing the structures of TMPRSS2 generated to a Ramachandran plot of TMPRSS2 allows us to see if the predicted structure contains elements that would/would not be sterically allowed to occur and therefore judge the accuracy of our structure
  • Ramachandran plot generating softwares:

MolProbity

  • To generate Ramachandran plots, PDB files of TMPRSS2 from each modelling software (RaptorX, I-Tasser, HHpred, Swiss-Model) was uploaded onto MolProbity by selecting Choose File, uploading the file, then selecting Upload
  • After PDB has uploaded, select Analyze geometry without all-atom contacts
  • 'RaptorX_TMPRSS2.pdb' was selected and all default outputs were run

Summary Table Cutoffs

RaptorX

  • Summary Statistics of Predicted Structure

  • Ramachandran Plot for TMPRSS2 generated by Raptor X
   Ramachandran Plot (PDF)

I-TASSER

  • Summary Statistics of Predicted Structure

  • Ramachandran plot of TMPRSS2 generated by I-TASSER
  Ramachandran plot (PDF)

SWISS-MODEL

  • Summary statistics of Predicted Structure

  • Ramachandran plot of structure generated by SWISS-MODEL
Ramachandran plot (pdf)

HH-Pred

  • Summary Statistics of Predicted Structure

  • Ramachandran plot of structure generated by HH-Pred
 Ramachandran plot (pdf)

Truncated I-TASSER

  • Residues 149-487
  • Summary Statistics of Predicted Structure

  • Ramachandran plot of structure generated by I-TASSER
 Ramachandran plot (pdf)


To Do

  • fix secondary structure alignment to take out spaces
  • look at Ramachandran plots
    • divide number of outliers by number of amino acids modeled
      • Raptor X: 14 outliers / 492 = 2.65%
      • I-TASSER: 65 outliers / 492 = 13.27%
      • SWISS-Model: 2 outliers / 492 = 0.57%
      • HHPred: 6 outliers / 492 = 1.81%
    • look at iTasser to see if most of the outliers are in the random coil at the beginning of the structure
      • Most I-TASSER outliers occur from 8-150 aa
    • the shortest model is HH, so look to see what proportion of outliers are in all of them for the length of HH (HHPred models from 158 aa to 491 aa)
      • Raptor X: 13 outliers / 332 = 3.92%
      • I-TASSER: 18 outliers / 332 = 5.42%
      • Swiss-Model: 2 outliers / 332 = 0.60%
  • if it's easy, you could chop off the random coil part of the iTasser model and just run that through the Ramachandran plots


Chimera

How to Mutate a Residue

  • Input docked model, select TMPRSS2 chain, select Chain B (if chain B is TMPRSS2)
  • To model SNPS go to Favorites -> Command Line
  • In the command line type select: 123 where 123 is the specific residue (so for a SNP at aa 75, type select: 75)
  • Turn the residue into a stick Actions → Atoms/Bonds → Show
  • Then, click Tools → Structure Editing → Rotamers
  • This will bring up a selection box. Change the rotamer type to the SNP amino acid, click Ok. Click the highest probability rotamer, then under Existing side chain(s) box should be changed to retain to keep the original SNP on there. Click Ok.
  • Then highlight the original residue under Actions -> Color
  • The changed color (I chose green) is the original, and the branching that remained the same color shows the new residue SNP (hopefully).

How to Check for Clashes/Hindrance

Instructions for mutating a residue, checking for clashes, and structure minimization were derived from NIAID Bioinformatics video tutorials: Part 1 and Part 2

  • Steric Analysis was performed on mutated residue to observe clashing residues
  1. Select mutated residue by holding down “Control” and left clicking on residue. Use up arrow to ensure that entire residue is selected.
  2. Click Tools -> Surface Binding Analysis -> Find Clashes and Contacts
  3. On the pop-up window, click "Designate" and check the designated atoms against “all other atoms”. Leave Default Parameters.
  4. Under “Treatment of Clash/Contact Atoms”, ensure the boxes next to “Select”, “Color”, “Draw pseudobonds of…” and “Write information to reply…” are checked, then click apply.
  5. Clashing atoms are highlighted in red and psuedobonds between them are highlighted in yellow. Hovering over each residue will show which residue is involved in the clash.

How to Find Energy Minimization

  • Hydrogen bonds were removed by Favorites --> Command Line --> and type in "del H"
  1. Mutated residue and clashes were selected with the up arrow
  2. Click Tools -> Structure Editing --> Minimize Structure
  3. Due to time, Steepest Descent Steps was changed to 15, Conjugate Gradient Steps was changed to 0, Fixed Atoms were changed to unselected, and Update Interval was changed to three
  4. Under the Find Clashes/ Contacts window, Select was deselected, Pseudobonds were changed to red, and Check... after relative motions was selected
  5. To begin, Minimize was clicked
  6. OK was pressed to add hydrogens, followed by charges
  7. 2 clashes are shown below, interacting with itself (Leu 302)

Images

V280M

  • rs142446494 V280M mutation was visualized using Chimera using the methodology listed above
  • this mutation does not appear to cause steric hinderance with neighboring residues, however further steric analysis shows that it will clash with neighboring residues on itself

Default Visualization

  • entire residue is highlighted in green, residues in white are original residue (V), residues in yellow are mutated residue (M)

Designated Color Visualization

  • blue= TMPRSS2, SARS-CoV-2= magenta, green residue indicates wildtype (V280), blue residue is the mutation (M280)

  • Focused in on residues

Clashes/Contacts

  • Multiple clashes were shown with neighboring residues of TMPRSS2
  • This may prevent proper binding of TMPRSS2 to SARS-CoV-2

  • Clashes viewed with hydrogen bonds

Minimization

  • cornflower blue = SARS-CoV-2, tan = TMPRSS2
  • 2 clashes can be viewed with the red psuedobonds

ConSurf

Results

Active Sites

Data and Files

Link to SNP Table
TMPRSS2 Structure
TMPRSS2 and SARS-Cov-2 Interactions
TMPRSS2 Gene Map
Link to Fall 2020 Research Summary
Link to Abstract

Capstone

Annotated Bib

Annika's Annotated Bibliography
Jessica's Annotated Bibliography
Madeleine's Annotated Bibliography

Outline

Madeleine's Outline
Annika's Outline
Jessica's Outline

Results

Madeleine's Results (draft)
Annika's Results
Jessica's Results Draft 1

Discussion

Jessica's Discussion Draft 1
Madeleine's Discussion Draft
Annika's Results + Discussion Draft

Introduction

Jessica's Introduction Draft
Annika's Introduction Draft
Madeleine's Introduction Draft

Materials & Methods

Madeleine's Materials & Methods Draft
Annika's Materials & Methods Draft
Jessica's Materials & Methods Draft

Appendix

Data & Graphs

  • SNP Frequency & Location Table
    • Population frequencies of the 18 SNPs of interest were gathered on Excel using ALFA and split according to ALFA defined populations and shown in “All SNPs”. “All SNPs Location” discloses the location and amino acid change of the 18 SNPs, where also recorded from …. “Deleterious SNPs” displays a list of seven of the 18 SNPs that had been classified as “Deleterious” or “possibly damaging” according to SIFT and PolyPhen-2 .
  • SNP Interaction Table
    • Table displaying the bonding interactions between TMPRSS2 SNPs and SARS-CoV-2 virus. iCn3d was used to visualize the interactions.
  • SNP Frequency Graphs
    • These Excel sheets group the SNPs based on their frequencies. “No. of SNPs vs. Allele Frequency” plots the SNPs against their frequencies in ranges of 0.0001. “No. SNPs v. 10^x freq.” plots the SNPs in frequencies that correlate with the base 10 of one another. “No. SNPs v. (log(freq))^-1” plots SNPs against the negative inverse of the logarithm (base 10) of the SNP frequencies, grouping them in ranges of 0.1.
  • SIFT/PolyPhen2 Results
    • This table shows the effect of each of the 18 SNPs amino acid substitution on protein function, according to results from SIFT and PolyPhen--2. SIFT defines SIFT scores range from 0 to 1: the amino acid substitution is considered damaging if the score is less than 0.05 and is tolerated if the score is greater than 0.05. Polyphen-2 scores range from 0 to 1: the amino acid substitution is considered benign if the score is less than 0.05, possibly damaging if the score is between 0.5 and 0.9, and probably damaging if the score is between 0.9 and 1.


Software Files & Images

  • Biorender TMPRSS2 Gene Map
    • Gene map diagram and Isoform 1 of TMPRSS2. TMPRSS2 is located on Chromosome 21 at q 22.3. It has an enhancer, regulatory region, and promoter located before the transcribed portion of the gene. After splicing, there are 14 exons in Isoform 1. Each of the SNP amino acid substitutions are plotted along Isoform 1, which contains 4 domains.
  • Chimera
    • Chimera is a software used to visualize molecular structures. It was used to visualize rs142446494 V280M mutation and check for steric hindrance, clashing, and contacts with SARS-CoV-2.
  • CLUSPRO Docking Models
    • ClusPro was used for protein-protein docking. It was used to dock TMPRSS2 and SARS-Cov-2.
  • Haddock Spike Protein TMPRSS2 Summary
    • Haddock models the interactions of 2 molecular structures and how they fit together. It was used to model the interaction between TMPRSS2 and the SARS-Cov-2 spike glycoprotein.
  • HHpred
    • HHpred is a software utilized for detecting remote protein homology and structure prediction, including secondary and tertiary structure. It was used to generate a model and Ramachandran plot of TMPRSS2.
  • iCn3D
    • iCn3d is a software used to display the 3-D structures of biomolecular structures as well as their interactions and sequences. It was used to visualize the interaction between TMPRSS2 and SARS-CoV-2.
  • i-TASSER
    • I-TASSER is a protein modeling resource that uses threading to predict protein secondary and 3D models. It was used to generate models for TMPRSS2 and TMPRSS4, and generate a Ramachandran plot.
  • Predict Protein Heat Map
    • Predict Protein is a software that predicts the effect mutations may have on a protein’s structure and function. It was used to determine the possible effects of the SNPs in the protein.
  • RaptorX
    • RaptorX is a protein structure prediction server developed that can predict secondary and tertiary protein structures, contacts, solvent accessibility, disordered regions and binding sites. It was used to generate a model and Ramachandran plot of TMPRSS2.
  • Swiss Model
    • Swiss Model is a protein structure homology modeling software. It was used to generate a model and Ramachandran plot of TMPRSS2.
  • TMPRSS2 FASTA files
    • FASTA files were found on UnitPro and edited to reflect each SNPs amino acid change. Was input into other softwares to predict protein models and interactions.


Posters, Abstracts, Recordings

Box Folder

Capstone

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