"""Per-protein manual decisions for the 418 settled vesicle-type rows (dossiers_settled.yaml). Second pass of the vesicle review: the HDA/HTP vesicle-type rows that reviewers had already set to KEEP_AS_NON_CORE, which pass 1 (decisions_draft.py) did not cover. Written after reading each gene's dossier; nothing here is computed. Same MISEV2018 framework and the same category constants as pass 1. Genes reviewed in both passes get the same call here as there (PDCD6IP, ACTB, AHCY, ALPL, ASS1, ATP6AP2), except APOE: its pass-1 row is a plasma microvesicle sample, where lipoprotein co-isolation applies, while its rows here are not. """ from decisions_draft import CAT1, CAT1_GO, CAT2, CAT2_GO, CAT2A, CAT4, CAT4_SURFACE, CAT5, CAT5_BOUND, CAT5_SURFACE, G as G1, note G = { "A1BG": note(CAT5, "Secreted plasma glycoprotein."), "A2M": note(CAT5, "Secreted plasma protease inhibitor."), "A2ML1": note(CAT5, "Secreted protease inhibitor."), "AASDHPPT": note(CAT2, "Cytosolic phosphopantetheinyl transferase."), "ABHD8": note(CAT2, "Cytoplasmic hydrolase."), "ACAT1": note(CAT4, "Mitochondrial acetyl-CoA acetyltransferase."), "ACTA2": note(CAT2, "Smooth-muscle actin."), "ACTB": note(CAT2, "Cytoplasmic actin."), "ADAM10": note(CAT1, "Plasma-membrane metalloprotease."), "ADIRF": note(CAT4, "UniProt places ADIRF in the nucleus only."), "AGRN": note(CAT5, "Secreted heparan-sulfate proteoglycan; its proteoglycan-binding annotations are by sequence similarity only (ISS)."), "AHCY": note(CAT2, "Cytoplasmic adenosylhomocysteinase."), "AHNAK": note(CAT2_GO, "Large scaffold protein that shuttles to the cytoplasmic face of the plasma membrane."), "AHSA1": note(CAT2, "Cytosolic HSP90 co-chaperone."), "AKR1C4": note(CAT2, "Cytosolic aldo-keto reductase."), "ALAD": note(CAT2, "Cytosolic porphobilinogen synthase."), "ALCAM": note(CAT1, "Plasma-membrane adhesion molecule."), "ALDOA": note(CAT2, "Cytosolic glycolytic aldolase."), "ALPL": note(CAT1, "GPI-anchored plasma-membrane phosphatase; UniProt also records an EV-membrane pool."), "AMN": note(CAT1, "Apical plasma-membrane cubilin partner."), "ANKFY1": note(CAT2A, "Peripheral endosome-membrane protein."), "APLP2": note(CAT1, "Plasma-membrane amyloid precursor-like protein."), "APOE": ("KEEP_AS_NON_CORE", "Secreted apolipoprotein (UniProt). Not a MISEV2018 (PMID:30637094) negative marker (it " "names APOA1/2 and APOB), and these samples are urine, prostatic secretion, B-cell culture " "and CSF rather than plasma. van Niel et al. (PMID:26387950) show ApoE on endosomal " "intraluminal vesicles that are secreted as exosomes, so the location is real; it is " "secondary to APOE's lipoprotein role. True, but not its core location. (Confirms the " "existing KEEP_AS_NON_CORE; the plasma-microvesicle row stays over-annotated in pass 1.)"), "APOH": ("KEEP_AS_NON_CORE", "Secreted plasma beta-2-glycoprotein I, which binds anionic phospholipids. MISEV2018 " "(PMID:30637094) category 5 allows secreted proteins to associate with EVs through promiscuous " "lipid receptors on the EV surface, so the detection is plausible. (Confirms the existing " "KEEP_AS_NON_CORE.)"), "ARL15": ("KEEP_AS_NON_CORE", "Little-characterized Arf-like small GTPase: neither UniProt nor GO records a location " "other than EV proteomes. Arf-family GTPases cycle between the cytosol and membranes, " "and MISEV2018 (PMID:30637094) category 2 treats such proteins as expected EV contents, so " "the detection is plausible. True, but not its core location."), "ARMC3": ("KEEP_AS_NON_CORE", "Little-characterized armadillo-repeat protein: neither UniProt nor GO records a " "location other than EV proteomes; UniProt infers two S-palmitoyl cysteines by similarity, " "a membrane-binding modification. MISEV2018 (PMID:30637094) category 2 treats cytosolic " "and membrane-binding proteins as expected EV contents, so the detection is plausible. " "True, but not its core location."), "ARPC4": note(CAT2, "Arp2/3 complex subunit (cytoskeleton)."), "ARPC5": note(CAT2, "Arp2/3 complex subunit (cytoskeleton)."), "ARSL": note(CAT4, "Golgi-resident arylsulfatase."), "ASAH1": note(CAT5, "Lysosomal lumenal acid ceramidase; UniProt notes secretion is extremely low."), "ASL": note(CAT2_GO, "Cytosolic argininosuccinate lyase."), "ASS1": note(CAT2, "Cytosolic argininosuccinate synthase."), "ATP5F1A": note(CAT4_SURFACE, "Mitochondrial ATP synthase subunit; ecto-ATP synthase plasma-membrane pool by IDA " "(PMID:10077593)."), "ATP5F1B": note(CAT4_SURFACE, "Mitochondrial ATP synthase subunit; ecto-ATP synthase cell-surface pool by IDA " "(PMID:17510399)."), "ATP6AP2": note(CAT1, "Single-pass membrane protein of the endolysosomal V-ATPase assembly."), "ATP6V0A4": note(CAT1, "Plasma-membrane V-ATPase subunit."), "ATP6V0C": note(CAT1_GO, "V-ATPase membrane subunit of endosomal/vesicle membranes."), "ATP6V0D1": note(CAT2A, "Peripheral V-ATPase V0 subunit of endolysosomal membranes."), "ATP6V0D2": note(CAT2A, "Peripheral V-ATPase V0 subunit of endolysosomal and plasma membranes."), "ATP6V1G1": note(CAT2A, "Peripheral V-ATPase V1 subunit at the apical plasma membrane."), "ATRN": note(CAT1, "Plasma-membrane attractin isoform."), "AZGP1": note(CAT5, "Secreted zinc-alpha-2-glycoprotein."), "B4GALT1": note(CAT1, "Golgi galactosyltransferase whose long isoform has an evidenced cell-surface pool."), "BAIAP2": note(CAT2, "Cytoplasmic membrane-deforming adapter."), "BAIAP2L1": note(CAT2, "Cytoplasmic actin-bundling adapter."), "BLVRA": note(CAT2, "Cytosolic biliverdin reductase."), "C5orf46": note(CAT5, "Secreted protein."), "CA2": note(CAT2, "Cytosolic carbonic anhydrase."), "CALM1": note(CAT2, "Calmodulin."), "CALM2": note(CAT2, "Calmodulin."), "CALM3": note(CAT2, "Calmodulin."), "CALR": note(CAT4_SURFACE, "ER-lumen chaperone calreticulin; cell-surface pool by EXP (PMID:10358038)."), "CAPG": note(CAT2, "Cytoplasmic actin-capping protein."), "CD14": note(CAT1, "GPI-anchored plasma-membrane receptor."), "CD19": note(CAT1, "B-cell plasma-membrane receptor."), "CD48": note(CAT1, "GPI-anchored plasma-membrane protein."), "CDH1": note(CAT1, "Plasma-membrane E-cadherin."), "CDK1": note(CAT2, "Cytoplasmic and nuclear cell-cycle kinase."), "CHMP1A": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CHMP2A": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CHMP2B": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CHMP4B": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CHMP5": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CHMP6": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes (as CHMP3 in pass 1)."), "CKB": note(CAT2, "Cytosolic creatine kinase."), "CLTC": note(CAT2, "Clathrin heavy chain on the cytoplasmic face of vesicle membranes."), "COASY": note(CAT2, "Mainly cytosolic CoA synthase."), "COMP": note(CAT5_BOUND, "Secreted matrix protein with experimental heparin and proteoglycan binding (IDA). (Confirms the existing KEEP_AS_NON_CORE.)"), "COPS8": note(CAT2, "Cytoplasmic/nuclear COP9 signalosome subunit."), "CRISPLD1": note(CAT5, "Secreted protein."), "CSK": note(CAT2, "Cytoplasmic tyrosine kinase with a lipid-raft pool."), "CUBN": ("KEEP_AS_NON_CORE", "Apical plasma-membrane endocytic receptor with no membrane span of its own, held at " "the surface by its transmembrane partner AMN (UniProt). Membrane proteins and their " "bound partners are expected EV contents (MISEV2018 (PMID:30637094) categories 1 and " "2a). True, but not its core location."), "DDC": note(CAT2_GO, "Cytosolic aromatic-L-amino-acid decarboxylase."), "DNAJA2": note(CAT2A, "Cytosolic HSP40 co-chaperone, S-farnesylated (UniProt, PubMed:15308774)."), "DNAJB1": note(CAT2, "Cytoplasmic HSP40 co-chaperone."), "DNAJC13": note(CAT2A, "Peripheral endosome-membrane protein."), "DNAJC3": note(CAT4, "ER-resident co-chaperone."), "DPEP1": note(CAT1, "GPI-anchored apical plasma-membrane dipeptidase."), "DPYS": note(CAT2_GO, "Cytosolic dihydropyrimidinase."), "DPYSL2": note(CAT2, "Cytosolic microtubule-associated protein."), "EGF": note(CAT1_GO, "Single-pass membrane pro-EGF precursor."), "EIF3E": note(CAT2, "Cytoplasmic translation initiation factor."), "FAH": note(CAT2_GO, "Cytosolic fumarylacetoacetase."), "FAS": note(CAT1, "Plasma-membrane death receptor."), "FKBP4": note(CAT2, "Cytosolic HSP90 co-chaperone."), "FKBP5": note(CAT2, "Cytoplasmic HSP90 co-chaperone."), "FN1": note(CAT5_BOUND, "Secreted fibronectin with experimental proteoglycan binding (IDA). (Confirms the existing KEEP_AS_NON_CORE.)"), "FTH1": note(CAT2, "Cytoplasmic ferritin heavy chain."), "G6PD": note(CAT2, "Cytosolic glucose-6-phosphate dehydrogenase."), "GALK1": note(CAT2_GO, "Cytosolic galactokinase."), "GALM": note(CAT2, "Cytoplasmic galactose mutarotase."), "GALNS": note(CAT5, "Lysosomal lumenal sulfatase."), "GAS6": ("KEEP_AS_NON_CORE", "Secreted TAM-receptor ligand whose gamma-carboxylated Gla domain binds phosphatidylserine on " "membranes and vesicles. MISEV2018 (PMID:30637094) category 5 allows secreted proteins to " "associate with EVs through promiscuous lipid receptors on the EV surface, so the detection is " "plausible. (Confirms the existing KEEP_AS_NON_CORE.)"), "GBA": note(CAT5, "Lysosomal lumenal glucocerebrosidase."), "GBA1": note(CAT5, "Lysosomal lumenal glucocerebrosidase."), "GET3": note(CAT2, "Cytoplasmic tail-anchored-protein targeting ATPase."), "GFPT1": note(CAT2_GO, "Cytosolic glutamine-fructose-6-phosphate transaminase."), "GGT1": note(CAT1, "Plasma-membrane gamma-glutamyltransferase."), "GLA": note(CAT5, "Lysosomal lumenal alpha-galactosidase."), "GLB1": note(CAT5, "Lysosomal lumenal beta-galactosidase."), "GLIPR2": note(CAT4, "Golgi-membrane protein."), "GLO1": note(CAT2_GO, "Cytosolic glyoxalase."), "GLOD4": note(CAT4, "Mitochondrial glyoxalase-domain protein."), "GM2A": note(CAT5_BOUND, "Lysosomal GM2 activator with experimental lipid chaperone activity (IDA, PMID:11707436, " "PMID:30988135): it extracts GM2 from intralysosomal luminal vesicle membranes, the " "precursors of exosomes."), "GNS": note(CAT5, "Lysosomal lumenal sulfatase."), "GOT1": note(CAT2, "Cytoplasmic aspartate aminotransferase."), "GOT2": note(CAT4_SURFACE, "Mitochondrial aminotransferase; plasma-membrane pool by IDA (PMID:9537447)."), "GPI": note(CAT2, "Cytoplasmic glucose-6-phosphate isomerase."), "GRB2": note(CAT2, "Cytoplasmic signalling adapter."), "GSR": note(CAT2, "Glutathione reductase, cytoplasmic isoform."), "GSS": note(CAT2_GO, "Cytosolic glutathione synthetase."), "GUSB": note(CAT5, "Lysosomal lumenal beta-glucuronidase."), "HEXA": note(CAT5, "Lysosomal lumenal hexosaminidase."), "HGD": note(CAT2_GO, "Cytosolic homogentisate dioxygenase."), "HPD": note(CAT2, "Cytoplasmic 4-hydroxyphenylpyruvate dioxygenase."), "HPRT1": note(CAT2, "Cytoplasmic purine salvage enzyme."), "HPX": note(CAT5, "Secreted plasma hemopexin."), "HSPA12A": note(CAT2, "Cytoplasmic HSP70-family protein."), "HSPA13": note(CAT4, "ER/microsome HSP70-family protein."), "HSPA1B": note(CAT2, "Cytoplasmic HSP70."), "HSPA1L": note(CAT2_GO, "Cytoplasmic HSP70."), "HSPA2": note(CAT2, "Cytoplasmic HSP70."), "HSPA4": note(CAT2, "Cytoplasmic HSP110-family chaperone."), "HSPA6": note(CAT2_GO, "Cytoplasmic HSP70."), "HSPA8": note(CAT2A, "Cytoplasmic HSC70, which also acts at endosomal membranes."), "HSPA9": note(CAT4, "Mitochondrial HSP70 (mortalin)."), "HSPD1": note(CAT4_SURFACE, "Mitochondrial matrix HSP60; cell-surface pool by IDA (PMID:9243807, PMID:10663613, " "PMID:11807771, PMID:15784682)."), "HSPG2": note(CAT5, "Secreted basement-membrane perlecan, itself a proteoglycan, with no recorded binding to EV-surface receptors."), "IDUA": note(CAT5, "Lysosomal lumenal iduronidase."), "ITGB1": note(CAT1, "Plasma-membrane integrin."), "ITIH1": note(CAT5_BOUND, "Secreted plasma inter-alpha-trypsin inhibitor heavy chain with experimental hyaluronan " "binding (GO:0005540, IDA, PMID:20463016)."), "ITIH2": note(CAT5_BOUND, "Secreted plasma inter-alpha-trypsin inhibitor heavy chain with experimental hyaluronan " "binding (GO:0005540, IDA, PMID:20463016)."), "ITIH3": note(CAT5, "Secreted plasma inter-alpha-trypsin inhibitor heavy chain. UniProt says only that it may carry " "hyaluronan, and unlike ITIH1 and ITIH2 it has no hyaluronan-binding annotation."), "ITIH4": note(CAT5, "Secreted plasma inter-alpha-trypsin inhibitor chain."), "KHK": note(CAT2_GO, "Cytosolic ketohexokinase."), "KL": note(CAT1, "Plasma-membrane klotho isoform."), "LAMP1": note(CAT1, "Lysosome/endosome-membrane glycoprotein that also cycles to the plasma membrane."), "LCK": note(CAT1, "Lipid-anchored plasma-membrane kinase."), "LFNG": note(CAT4, "Golgi glycosyltransferase."), "LGALS3": note(CAT2, "Cytoplasmic galectin secreted by a non-classical route."), "LOXL4": note(CAT5, "Secreted lysyl oxidase-like enzyme."), "LPO": note(CAT5_SURFACE, "Secreted lactoperoxidase, with a basolateral plasma-membrane pool by IDA " "(PMID:19059195)."), "LRG1": note(CAT5, "Secreted plasma glycoprotein."), "LRP2": note(CAT1, "Apical plasma-membrane endocytic receptor (megalin)."), "LRRK2": note(CAT2, "Cytoplasmic kinase associated with vesicle and Golgi membranes."), "LYN": note(CAT1, "Lipid-anchored plasma-membrane kinase."), "MAN1B1": note(CAT4, "ER-membrane mannosidase."), "MGP": note(CAT5, "Secreted matrix Gla protein."), "MTHFD1": note(CAT2, "Cytoplasmic C1-tetrahydrofolate synthase."), "MUC1": note(CAT1, "Apical plasma-membrane mucin."), "MVB12A": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "MVB12B": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "NAGLU": note(CAT5, "Lysosomal lumenal N-acetylglucosaminidase."), "NAMPT": note(CAT2, "Cytoplasmic/nuclear enzyme also released extracellularly."), "NAPRT": note(CAT2, "Cytosolic nicotinate phosphoribosyltransferase."), "NCSTN": note(CAT1_GO, "Gamma-secretase membrane subunit of the plasma membrane and endosomes."), "NID1": note(CAT5_BOUND, "Secreted basement-membrane nidogen with experimental proteoglycan binding (IPI). (Confirms the existing KEEP_AS_NON_CORE.)"), "NME2": note(CAT2, "Cytoplasmic nucleoside-diphosphate kinase."), "NPHS2": note(CAT1, "Podocyte plasma-membrane podocin."), "NQO2": note(CAT2, "Cytoplasmic quinone reductase."), "NT5E": note(CAT1, "GPI-anchored plasma-membrane ecto-5'-nucleotidase (CD73)."), "P3H1": note(CAT4, "ER prolyl 3-hydroxylase."), "P4HB": note(CAT4_SURFACE, "ER-lumen protein disulfide isomerase; pool on the external side of the plasma " "membrane by IDA (PMID:21670307)."), "PAFAH1B1": note(CAT2, "Cytoplasmic dynein regulator LIS1."), "PARD6B": note(CAT2A, "Cytoplasmic polarity adapter recruited to the plasma membrane."), "PCBD1": note(CAT2, "Cytoplasmic/nuclear pterin-4a-carbinolamine dehydratase."), "PDCD5": note(CAT2_GO, "Cytoplasmic/nuclear apoptosis regulator."), "PDCD6IP": G1["PDCD6IP"], "PGK1": note(CAT2, "Cytosolic phosphoglycerate kinase."), "PGM1": note(CAT2, "Cytoplasmic phosphoglucomutase."), "PHGDH": note(CAT2_GO, "Cytosolic phosphoglycerate dehydrogenase."), "PI15": note(CAT5, "Secreted protease inhibitor."), "PKLR": note(CAT2_GO, "Cytosolic pyruvate kinase."), "PKM": note(CAT2, "Cytoplasmic pyruvate kinase."), "PLD3": note(CAT1, "Single-pass membrane protein of ER and endolysosomes."), "PM20D1": note(CAT5, "Secreted N-fatty-acyl-amino-acid synthase/hydrolase."), "PNP": note(CAT2, "Cytosolic purine nucleoside phosphorylase."), "PPIB": note(CAT4, "ER-lumen cyclophilin B."), "PPP2CA": note(CAT2, "Cytoplasmic PP2A catalytic subunit."), "PPP2R1B": note(CAT2_GO, "Cytoplasmic PP2A scaffold subunit."), "PRDX4": note(CAT4, "ER-lumen peroxiredoxin."), "PRSS23": note(CAT5, "Secreted serine protease."), "PSAP": note(CAT5_BOUND, "Prosaposin, lysosomal and secreted, with experimental phospholipid binding (IDA). (Confirms the existing KEEP_AS_NON_CORE.)"), "PSAT1": note(CAT2_GO, "Cytosolic phosphoserine aminotransferase."), "PSMA1": note(CAT2, "Cytoplasmic/nuclear proteasome subunit."), "PSMB5": note(CAT2, "Cytoplasmic/nuclear proteasome subunit."), "PTPRC": note(CAT1, "Plasma-membrane phosphatase CD45."), "QDPR": note(CAT2_GO, "Cytosolic dihydropteridine reductase."), "QPRT": note(CAT2_GO, "Cytosolic quinolinate phosphoribosyltransferase."), "RAB15": note(CAT1, "Lipid-anchored small GTPase of the plasma membrane/endocytic system."), "RAB7A": note(CAT1, "Lipid-anchored late-endosome GTPase."), "RAB9A": note(CAT1, "Lipid-anchored late-endosome GTPase."), "SCAMP2": note(CAT1, "Multi-pass membrane carrier of post-Golgi and endosomal recycling membranes."), "SLC3A2": note(CAT1, "Plasma-membrane amino-acid transporter heavy chain (CD98)."), "SMO": note(CAT1, "Plasma-membrane GPCR."), "SMPD1": note(CAT5_SURFACE, "Lysosomal lumenal acid sphingomyelinase, also secreted, with a plasma-membrane " "pool by IDA (PMID:20956541)."), "SOD1": note(CAT2, "Cytoplasmic superoxide dismutase."), "SORL1": note(CAT1, "Single-pass sorting receptor of Golgi, endosome and plasma membranes."), "SPR": note(CAT2, "Cytoplasmic sepiapterin reductase."), "SQSTM1": note(CAT2, "Cytoplasmic autophagy cargo adapter."), "SRC": note(CAT1, "Lipid-anchored plasma-membrane kinase."), "SYPL1": note(CAT1_GO, "Multi-pass membrane protein of cytoplasmic vesicles and melanosomes (UniProt)."), "TALDO1": note(CAT2, "Cytoplasmic transaldolase."), "TFRC": note(CAT1, "Plasma-membrane transferrin receptor, a classic exosome cargo."), "TLN1": note(CAT2, "Cytoskeletal talin."), "TNFAIP3": note(CAT2, "Cytoplasmic ubiquitin-editing enzyme."), "TNFSF10": note(CAT1, "Plasma-membrane TRAIL ligand."), "TPI1": note(CAT2, "Cytoplasmic triosephosphate isomerase."), "TPM3": note(CAT2, "Cytoskeletal tropomyosin."), "TSG101": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes; an EV marker protein, but its " "core location is the endosome."), "TXN": note(CAT2, "Cytoplasmic thioredoxin."), "TXNDC16": note(CAT4, "ER-lumen thioredoxin-domain protein."), "UPB1": note(CAT2, "Cytoplasmic beta-ureidopropionase."), "VCL": note(CAT2, "Cytoskeletal vinculin at the cytoplasmic face of the plasma membrane."), "VCP": note(CAT2, "Cytosolic AAA ATPase p97."), "VPS28": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "VPS37B": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "VPS37C": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "VPS37D": note(CAT2A, "ESCRT-I subunit acting on the cytosolic face of endosomes."), "YWHAZ": note(CAT2, "Cytoplasmic 14-3-3 protein."), } # supported_by entries that argued for the action this review overturned (a previous # reviewer's own judgement rather than evidence); dropped from the row. S = { ("GLA", 21): ["file:human/GLA/GLA-notes.md"], ("PI15", 4): ["file:human/PI15/PI15-deep-research-manual.md"], ("PRDX4", 31): ["file:human/PRDX4/PRDX4-deep-research-falcon.md"], }