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Protein

Gag-Pol polyprotein

Gene

pol

Organism
Friend murine leukemia virus (isolate 57) (FrMLV)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

Functioni

Gag-Pol polyprotein: Plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag-Pol, or to Gag-Pol binding host factors. Interaction with HECT ubiquitin ligases probably links the viral protein to the host ESCRT pathway and facilitates release.By similarity
Matrix protein p15: Targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the pre-integration complex.By similarity
RNA-binding phosphoprotein p12: Constituent of the pre-integration complex (PIC) which tethers the latter to mitotic chromosomes. This allows the integration of the viral genome into the host DNA.By similarity
Capsid protein p30: Forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex.By similarity
Nucleocapsid protein p10-Pol: Involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization. Acts as a nucleic acid chaperone which is involved in rearrangement of nucleic acid secondary structures during gRNA retrotranscription.By similarity
Protease: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (Potential). Cleaves the translation initiation factor eIF4G leading to the inhibition of host cap-dependent translation (By similarity).PROSITE-ProRule annotationBy similarity
Reverse transcriptase/ribonuclease H: RT is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5' end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPT that has not been removed by RNase H as primers. PPT and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.Sequence analysis
Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step that requires cell division, the PIC enters cell nucleus. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The last step is viral DNA integration into host chromosome.By similarity

Miscellaneous

Gag-Pol polyprotein: This protein is translated as a gag-pol fusion protein by episodic readthrough of the gag protein termination codon. Readthrough of the terminator codon TAG occurs between the codons for 539-Asp and 541-Gly.By similarity
Nucleocapsid protein p10-Pol: Nucleocapsid protein p10-Pol released from Pol polyprotein (NC-pol) is a few amino acids shorter than the nucleocapsid protein p10 released from Gag polyprotein (NC-gag).By similarity
Reverse transcriptase/ribonuclease H: The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template swiching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs.PROSITE-ProRule annotation

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).PROSITE-ProRule annotation
Endonucleolytic cleavage to 5'-phosphomonoester.PROSITE-ProRule annotation

Cofactori

Protein has several cofactor binding sites:
  • Mg2+PROSITE-ProRule annotationNote: The RT polymerase active site binds 2 magnesium ions.PROSITE-ProRule annotation
  • Mg2+By similarityNote: Binds 1 magnesium ions for ribonuclease H (RNase H) activity.By similarity
  • Mg2+By similarityNote: Magnesium ions are required for integrase activity. Binds at least 1, maybe 2 magnesium ions.By similarity

Enzyme regulationi

Protease: Most efficiently inhibited by Amprenavir, which is able to block Gag-Pol processing in infected cells.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei567Protease; shared with dimeric partnerPROSITE-ProRule annotation1
Metal bindingi810Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi884Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi885Magnesium; catalytic; for reverse transcriptase activityPROSITE-ProRule annotation1
Metal bindingi1184Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1222Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1243Magnesium; catalytic; for RNase H activityPROSITE-ProRule annotation1
Metal bindingi1313MagnesiumPROSITE-ProRule annotation1
Metal bindingi1456Magnesium; catalytic; for integrase activityPROSITE-ProRule annotation1
Metal bindingi1515Magnesium; catalytic; for integrase activityPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri503 – 520CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1388 – 1428HHCC-typeBy similarityAdd BLAST41

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAspartyl protease, DNA-binding, DNA-directed DNA polymerase, Endonuclease, Hydrolase, Multifunctional enzyme, Nuclease, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed DNA polymerase, Transferase, Viral nucleoprotein
Biological processDNA integration, DNA recombination, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Viral genome integration, Virus entry into host cell
LigandMagnesium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Cleaved into the following 7 chains:
Alternative name(s):
pp12
Protease (EC:3.4.23.-PROSITE-ProRule annotation)
Reverse transcriptase/ribonuclease H (EC:2.7.7.49PROSITE-ProRule annotation, EC:2.7.7.7PROSITE-ProRule annotation, EC:3.1.26.4PROSITE-ProRule annotation)
Short name:
RT
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Gene namesi
Name:pol
OrganismiFriend murine leukemia virus (isolate 57) (FrMLV)
Taxonomic identifieri11796 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirusMurine leukemia virus
Virus hostiMus musculus (Mouse) [TaxID: 10090]
Proteomesi
  • UP000007776 Componenti: Genome

Subcellular locationi

Gag-Pol polyprotein :
  • Virion By similarity
  • Host cell membrane By similarity; Lipid-anchor By similarity
  • Host late endosome membrane By similarity; Lipid-anchor By similarity
  • host multivesicular body By similarity
  • Note: These locations are probably linked to virus assembly sites.By similarity
Matrix protein p15 :
  • Virion By similarity
Capsid protein p30 :
  • Virion By similarity
Nucleocapsid protein p10-Pol :
  • Virion By similarity
Protease :
  • Virion By similarity
RNA-binding phosphoprotein p12 :
  • Host cytoplasm By similarity
  • Note: Localizes to the host cytoplasm early in infection and binds to the mitotic chromosomes later on.By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Capsid protein, Host cell membrane, Host cytoplasm, Host endosome, Host membrane, Membrane, Viral matrix protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved; by hostSequence analysis
ChainiPRO_00002597252 – 1739Gag-Pol polyproteinAdd BLAST1738
ChainiPRO_00004428912 – 132Matrix protein p15Add BLAST131
ChainiPRO_0000442892133 – 216RNA-binding phosphoprotein p12Add BLAST84
ChainiPRO_0000442893217 – 479Capsid protein p30Add BLAST263
ChainiPRO_0000442894480 – 535Nucleocapsid protein p10-PolAdd BLAST56
ChainiPRO_0000026130536 – 660ProteaseAdd BLAST125
ChainiPRO_0000259726661 – 1331Reverse transcriptase/ribonuclease HAdd BLAST671
ChainiPRO_00002597271332 – 1739IntegraseAdd BLAST408

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine; by hostSequence analysis1
Modified residuei193Phosphoserine; by hostBy similarity1

Post-translational modificationi

Gag-Pol polyprotein: Ubiquitinated by ITCH. Gag can recruit the ubiquitin ligase Itch in an L domain-independent manner to facilitate virus release via a mechanism that involves Gag ubiquitination.By similarity
Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation.By similarity
Capsid protein p30: Sumoylated; which is required for virus replication.By similarity
RNA-binding phosphoprotein p12: Phosphorylated on serine residues.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei132 – 133Cleavage; by viral proteaseBy similarity2
Sitei216 – 217Cleavage; by viral proteaseBy similarity2
Sitei479 – 480Cleavage; by viral proteaseBy similarity2
Sitei535 – 536Cleavage; by viral proteaseBy similarity2
Sitei660 – 661Cleavage; by viral proteaseBy similarity2
Sitei1331 – 1332Cleavage; by viral proteaseBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Capsid protein p30: Homohexamer; further associates as homomultimer (By similarity). Capsid protein p30: The virus core is composed of a lattice formed from hexagonal rings, each containing six capsid monomers (By similarity). Capsid protein p30: Interacts with mouse UBE2I and mouse PIAS4 (By similarity). Gag-Pol polyprotein: Interacts (via PPXY motif) with host NEDD4 (By similarity). Gag-Pol polyprotein: Interacts (via PSAP motif) with host TSG101 (By similarity). Gag-Pol polyprotein: Interacts (via LYPX(n)L motif) with host PDCD6IP (By similarity). Reverse transcriptase/ribonuclease H: The reverse transcriptase is a monomer (Potential). Reverse transcriptase/ribonuclease H: Interacts (via RNase domains) with host release factor ETF1; this interaction is essential for translational readthrough of amber codon between viral gag and pol genes, as well as for viral replication (By similarity). Integrase: Homodimer (By similarity).PROSITE-ProRule annotationBy similarity

Structurei

3D structure databases

ProteinModelPortaliP26810
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini562 – 632Peptidase A2PROSITE-ProRule annotationAdd BLAST71
Domaini742 – 933Reverse transcriptasePROSITE-ProRule annotationAdd BLAST192
Domaini1175 – 1321RNase HPROSITE-ProRule annotationAdd BLAST147
Domaini1445 – 1603Integrase catalyticPROSITE-ProRule annotationAdd BLAST159

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni346 – 394Interaction with host PIAS4By similarityAdd BLAST49
Regioni431 – 436Interaction with host UBE2IBy similarity6

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili439 – 479Sequence analysisAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi112 – 115PTAP/PSAP motifBy similarity4
Motifi131 – 135LYPX(n)L motifBy similarity5
Motifi163 – 166PPXY motifBy similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi93 – 171Pro-richPROSITE-ProRule annotationAdd BLAST79
Compositional biasi441 – 497Arg-richPROSITE-ProRule annotationAdd BLAST57

Domaini

Gag-Pol polyprotein: Late-budding domains (L domains) are short sequence motifs essential for viral particle release. They can occur individually or in close proximity within structural proteins. They interacts with sorting cellular proteins of the multivesicular body (MVB) pathway. Most of these proteins are class E vacuolar protein sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes. RNA-binding phosphoprotein p12 contains one L domain: a PPXY motif which potentially interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase. PPXY motif is essential for virus egress. Matrix protein p15 contains one L domain: a PTAP/PSAP motif, which potentially interacts with the UEV domain of TSG101. The junction between the matrix protein p15 and RNA-binding phosphoprotein p12 also contains one L domain: a LYPX(n)L motif which potentially interacts with PDCD6IP. Both PSAP and LYPX(n)L domains might play little to no role in budding and possibly drive residual virus release. contains.By similarity

Sequence similaritiesi

Belongs to the retroviral Pol polyprotein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri503 – 520CCHC-typePROSITE-ProRule annotationAdd BLAST18
Zinc fingeri1388 – 1428HHCC-typeBy similarityAdd BLAST41

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

OrthoDBiVOG0900018N

Family and domain databases

CDDicd06095 RP_RTVL_H_like, 1 hit
Gene3Di1.10.150.180, 1 hit
1.10.375.10, 1 hit
2.40.70.10, 1 hit
3.30.420.10, 2 hits
InterProiView protein in InterPro
IPR001969 Aspartic_peptidase_AS
IPR000840 G_retro_matrix
IPR036946 G_retro_matrix_sf
IPR002079 Gag_p12
IPR003036 Gag_P30
IPR001584 Integrase_cat-core
IPR001995 Peptidase_A2_cat
IPR021109 Peptidase_aspartic_dom_sf
IPR018061 Retropepsins
IPR008919 Retrov_capsid_N
IPR010999 Retrovr_matrix
IPR012337 RNaseH-like_sf
IPR002156 RNaseH_domain
IPR036397 RNaseH_sf
IPR034145 RP_RTVL-H-like
IPR000477 RT_dom
IPR001878 Znf_CCHC
IPR036875 Znf_CCHC_sf
PfamiView protein in Pfam
PF01140 Gag_MA, 1 hit
PF01141 Gag_p12, 1 hit
PF02093 Gag_p30, 1 hit
PF00075 RNase_H, 1 hit
PF00665 rve, 1 hit
PF00077 RVP, 1 hit
PF00078 RVT_1, 1 hit
PF00098 zf-CCHC, 1 hit
SMARTiView protein in SMART
SM00343 ZnF_C2HC, 1 hit
SUPFAMiSSF47836 SSF47836, 1 hit
SSF47943 SSF47943, 1 hit
SSF50630 SSF50630, 1 hit
SSF53098 SSF53098, 2 hits
SSF57756 SSF57756, 1 hit
PROSITEiView protein in PROSITE
PS50175 ASP_PROT_RETROV, 1 hit
PS00141 ASP_PROTEASE, 1 hit
PS50994 INTEGRASE, 1 hit
PS50879 RNASE_H, 1 hit
PS50878 RT_POL, 1 hit
PS50158 ZF_CCHC, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P26810-1 [UniParc]FASTAAdd to basket

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        10         20         30         40         50
MGQTVTTPLS LTLDHWKDVE RTAHNQSVEI RKRRWVTLCS AEWPTFNVGW
60 70 80 90 100
PRDGTFNPDI ITQVKIKVFS SGPHGHPDQV PYIVTWEALA ADPPPWVKPF
110 120 130 140 150
VHPKPPPLLL PPSAPSLPPE PPFPTPPQSS LYPALTSPLN TKPRPQVLPD
160 170 180 190 200
SGGPLIDLLT EDPPPYRDPG PSSSDGNGGS GEVAPTEGAP DSSPMVSRLR
210 220 230 240 250
GRREPPVADS TTSQAFPLRQ GGNGQFQYWP FSSSDLYNWK NNNPSFSEDP
260 270 280 290 300
AKLTALIESV LLTHQPTWDD CQQLLGTLLT GEEKQRVLLE ARKAVRGEDG
310 320 330 340 350
RPTQLPNDIN DAFPLERPDW DYNTQRGRNH LVHYRQLLLA GLQNAGRSPT
360 370 380 390 400
NLAKVKGITQ GPNESPSAFL ERLKEAYRRY TPYDPEDPGQ ETNVAMSFIW
410 420 430 440 450
QSAPDIGRKL ERLEDLKSKT LGDLVREAEK IFNKRETPEE REERIRRETE
460 470 480 490 500
EKEERRRAED EQREKERDRR RHREMSKLLA TVISGQRQDR QGGERRRPQL
510 520 530 540 550
DHDQCAYCKE KGHWARDCPK KPRGPRGPRP QASLLTLDDQ GGQGQEPPPE
560 570 580 590 600
PRITLKVGGQ PVTFLVDTGA QHSVLTQNPG PLSDKSAWVQ GATGGKRYRW
610 620 630 640 650
TTDRRVHLAT GKVTHSFLHV PDCPYPLLGR HLLTKLKAQI HFEGSGAQVV
660 670 680 690 700
GPMGQPLQVL TLNIEDEYRL HETSKGPDVP LGSTWLSDFP QAWAETGGMG
710 720 730 740 750
LAFRQAPLII SLKATSTPVS IKQYPMSQEA RLGIKPHIQR LLDQGILVPC
760 770 780 790 800
QSPWNTPLLP VKKPGTNDYR PVQDLREVNK RVEDIHPTVP NPYNLLSGLP
810 820 830 840 850
PSHQWYTVLD LKDAFFCLRL HPTSQSLFAF EWKDPEMGIS GQLTWTRLPQ
860 870 880 890 900
GFKNSPTLFD EALHRDLADF RIQHPDLILL QYVDDLLLAA TSELDCQQGT
910 920 930 940 950
RALLQTLGDL GYRASAKKAQ ICQKQVKYLG YLLKEGQRWL TEARKETVMG
960 970 980 990 1000
QPTPKTPRQL REFLGTAGLC RLWIPGFAEM AAPLYPLTKT GTLFKWGPDQ
1010 1020 1030 1040 1050
QKAYQEIKQA LLTAPALGLP DLTKPFELFV DEKQGYAKGV LTQKLGPWRR
1060 1070 1080 1090 1100
PVAYLSKKLD PVAAGWPPCL RMVAAIAVLT KDVGKLTMGQ PLVILAPHAV
1110 1120 1130 1140 1150
EALVKQPPDR WLSNARMTHY QALLLDTDRV QFGPIVALNP ATLLPLPEEG
1160 1170 1180 1190 1200
LQHDCLDILA EAHGTRPDLT DQPLPDADHT WYTDGSSFLQ EGQRRAGAAV
1210 1220 1230 1240 1250
TTETEVIWAK ALPAGTSAQR AELIALTQAL KMAAGKKLNV YTDSRYAFAT
1260 1270 1280 1290 1300
AHIHGEIYRR RGLLTSEGKE IKNKDEILAL LKALFLPKRL SIIHCPGHQK
1310 1320 1330 1340 1350
GNHAEARGNR MADQAAREVA TRETPETSTL LIENSAPYTR EHFHYTVTDI
1360 1370 1380 1390 1400
KDLTKLGATY DDAKKCWVYQ GKPVMPDQFT FELLDFLHQL THLSFSKTKA
1410 1420 1430 1440 1450
LLERSYSPSY MLNRDRTLKD ITETCKACAQ VNASKSAVKQ GTRVRGHRPG
1460 1470 1480 1490 1500
THWEIDFTEV KPGLYGYKYL LVFVDTFSGW VEAFPTKKET AKVVTKKLLE
1510 1520 1530 1540 1550
EIFPRFGMPQ VLGTDNGPAF VSKVSQTVAD LLGVDWKLHC AYRPQSSGQV
1560 1570 1580 1590 1600
ERMNRTIKET LTKLTLATGS RDWVLLLPLA LYRARNTPGP HGLTPYEILY
1610 1620 1630 1640 1650
GAPPPLVNFP DPDMAKVTHN PSLQAHLQAL YLVQHEVWRP LAAAYQEQLD
1660 1670 1680 1690 1700
RPVVPHPFRV GDTVWVRRHQ TKNLEPRWKG PYTVLLTTPT ALKVDGIAAW
1710 1720 1730
IHAAHVKAAD TRIEPPAEST WRVQRSQNPL KIRLTRGTS
Length:1,739
Mass (Da):195,114
Last modified:January 31, 2018 - v2
Checksum:i52D85C40645C1665
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02794 Genomic RNA No translation available.

Keywords - Coding sequence diversityi

RNA suppression of termination

Similar proteinsi

Entry informationi

Entry nameiPOL_MLVF5
AccessioniPrimary (citable) accession number: P26810
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 31, 2018
Last modified: March 28, 2018
This is version 111 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome
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Main funding by: National Institutes of Health