UniProt CAUTION Notes — Extracted Data

Auto-generated by extract_caution_notes.py. Do not edit by hand.

• Records with >=1 CAUTION note: 201
• Total CAUTION notes: 209
• Curation-relevant notes (excludes WGS/lacks-conserved boilerplate): 151
• Retracted-reference notes: 12

Notes by category

contested-function (44)

• DANRE/cpt2 (Q5U3U3): It is uncertain whether Met-1 or Met-2 is the initiator
• DANRE/glceb (F1QR43): It is uncertain whether Met-1 or Met-2 is the initiator
• DANRE/pcif1 (A0A0R4IKJ1): The role of N(6),2'-O-dimethyladenosine cap (m6A(m)) on transcripts is unclear and subject to discussion. According to a report, m6A(m) promotes the translation of capped mRNAs (PubMed:30467178). However, another study did not observe a clear effect on mRNA translation, but reported an increased stability of a subset of m6A(m) transcripts (By similarity). According to a third report, m6A(m) inhibits mRNA translation without affecting mRNA stability (By similarity) [PMIDs: 30467178]
• DANRE/tomt (A0A193KX02): Despite its name, the zebrafish TOMT protein is not predicted to contain a transmembrane region in contrast to primate orthologs
• POPTR/ycf15-A (A4GYV5): Could be the product of a pseudogene
• PSEPK/ttgA (Q88N30): There are 4 nearly identical operons in various strains of P.putida. The ttgABC operon of strain DOT-T1E and the mepABC operon of strain KT2442-TOL function in solvent and antibiotic efflux; however in strain S12 the arpABC operon functions only in antibiotic efflux. This may be due to different protein expression levels. In KT2400 this operon does not seem to function in toluene efflux
• PSEPK/ttgB (Q88N31): There are 4 nearly identical operons in various strains of P.putida. The ttgABC operon of strain DOT-T1E and the mepABC operon of strain KT2442-TOL function in solvent and antibiotic efflux; however in strain S12 the arpABC operon functions only in antibiotic efflux. This may be due to different protein expression levels. In KT2400 this operon does not seem to function in toluene efflux
• PSEPK/ttgC (Q88N32): There are 4 nearly identical operons in various strains of P.putida. The ttgABC operon of strain DOT-T1E and the mepABC operon of strain KT2442-TOL function in solvent and antibiotic efflux; however in strain S12 the arpABC operon functions only in antibiotic efflux. This may be due to different protein expression levels. In KT2400 this operon does not seem to function in toluene efflux
• human/ABCD3 (P28288): Mutation in ABCD3 have been found in two individuals affected by Zellweger syndrome (PubMed:1301993). Later studies, however, showed unambiguously that a PEX1 defect was the underlying cause of the defect in peroxisome biogenesis in these patients (PubMed:9539740) [PMIDs: 1301993, 9539740]
• human/ASAH2 (Q9NR71): Was proposed to be mitochondrial, based on experiments with an N-terminal GFP-tag (PubMed:10781606). The in vivo localization to the mitochondrion could not be confirmed (PubMed:15845354). However, it has been observed for the mouse (AC Q9JHE3) and rat (AC Q91XT9) orthologs [PMIDs: 10781606, 15845354]
• human/ATF2 (P15336): Appears to have histone acetyltransferase (HAT) activity, specifically towards histones H2B and H4 in vitro (PubMed:10821277). However, it is not clear if this activity is genuine or caused by contamination with other histone acetyltransferases in the assay [PMIDs: 10821277]
• human/ATP6V0A2 (Q9Y487): The N-terminal peptide may increase IL1B secretion by peripheral blood monocytes; however as this region is probably in the cytosol, the in vivo relevance of this observation needs to be confirmed
• human/BAIAP2 (Q9UQB8): It is uncertain whether Met-1 or Met-59 is the initiator
• human/CPT1C (Q8TCG5): In contrast to its paralogs, CPT1A and CPT1B, does not have, or at very low levels, carnitine O-palmitoyltransferase activity (EC:2.3.1.21) in vivo, being unable to catalyze the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine. This is in agreement with its expression specific to neurons which is a cell-type that does not use fatty acids as fuel to any major extent and the fact that it locates to endoplasmic reticulum instead of mitochondria [PMIDs: 12376098, 30135643]
• human/DNAJC24 (Q6P3W2): It is uncertain whether Met-1 or Met-2 is the initiator
• human/EDEM2 (Q9BV94): Has similarity to alpha 1,2-mannosidases, but the catalytic activity of this protein is controversial (PubMed:15537790, PubMed:25092655). One study shows that it is important for a specific oligosaccharide trimming step from Man9GlcNAc2 to Man8GlcNAc2, suggesting activity as a mannosidase (PubMed:25092655). However, another study reports that this protein has no mannosidase activity (PubMed:15537790) [PMIDs: 15537790, 25092655]
• human/FKBP8 (Q14318): It is uncertain whether Met-1 or Met-58 is the initiator
• human/GPATCH11 (Q8N954): It is uncertain whether Met-1 or Met-27 is the initiator
• human/HMGB1 (P09429): Inconsistent experimental results may reflect the use of inconsistently defined redox forms. A recombinant fully reduced form has been used in a number of experiments. However, the redox states of HMGB1 administered in vivo, may interconvert among each other. Purified HMGB1 by itself has only weak pro-inflammatory activity
• human/IL13 (P35225): It is uncertain whether Met-1 or Met-15 is the initiator
• human/IL21 (Q9HBE4): It is uncertain whether Met-1 or Met-8 is the initiator
• human/IL4I1 (Q96RQ9): According to a report, acts as a negative regulator of T-cell activation independently of its enzymatic activity (PubMed:28891065). However, authors of this study only tested enzyme activity via phenylalanine (Phe) deprivation and not via tryptophan (Trp). As IL4I1 immunoregulator activity is mediated via Trp degradation and subsequent activation of the transcription factor AHR, additional experiments are required to confirm this statement (PubMed:32818467, PubMed:32866000) [PMIDs: 28891065, 32818467, 32866000]
• human/ISCU (Q9H1K1): [Isoform 1]: Previous publications report that ISCU could provide the architecture on which both [2Fe-2S] and [4Fe-4S] clusters could be assembled (PubMed:16517407, PubMed:16527810, PubMed:23940031). Recent reports confirm that only [2Fe-2S] clusters are formed by the core ISC assembly complex (PubMed:34824239) [PMIDs: 16517407, 16527810, 23940031, 34824239]
• human/KEAP1 (Q14145): The mechanism of inactivation of the BCR(KEAP1) complex by covalent modifications of reactive cysteines is unclear. Covalent modifications were initially thought to disrupt interaction between KEAP1 and NFE2L2/NRF2 (By similarity). Recent publications suggest that cysteine modifications disrupt the interaction between KEAP1 and CUL3 without affecting the interaction between KEAP1 and NFE2L2/NRF2 (PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:24896564) [PMIDs: 16006525, 17127771, 18251510, 24896564]
• human/MAN1B1 (Q9UKM7): It is uncertain whether Met-1 or Met-37 is the initiator
• human/NME2 (P22392): Originnally, in addition to its DNA binding activity, some reports shown that exhibited an intrinsic nuclease activity (PubMed:11121025, PubMed:11694515). Bound DNA within the nuclease hypersensitive element (NHE) III(1) region and cleaved the phosphodiester bond by transiently forming a covalent protein-DNA intermediate through a nucleophilic attack (PubMed:11121025). However, this nuclease activity has not been confirmed (PubMed:19435876) [PMIDs: 11121025, 11694515, 19435876]
• human/PARK7 (Q99497): Glyoxalase activity has been reported (PubMed:22523093, PubMed:31653696). It may however reflect its deglycase activity (PubMed:25416785) [PMIDs: 22523093, 25416785, 31653696]
• human/PEX13 (Q92968): It is uncertain whether Met-1 or Met-40 is the initiator
• human/PPIB (P23284): It is uncertain whether Met-1 or Met-9 is the initiator
• human/SH3GLB1 (Q9Y371): It is uncertain whether Met-1 or Met-4 is the initiator
• human/SLC40A1 (Q9NP59): Manganese Mn(2+) transport by SLC40A1 remains controversial. Some in vitro studies have suggested that SLC40A1 transports minimal amounts of Mn(2+) (PubMed:22178646, PubMed:30247984). Other groups have suggested that it does not (PubMed:24304836, PubMed:29792530). The affinity of SLC40A1 for Mn(2+) is extremely low compared with iron, implying that any SLC40A1-mediated Mn(2+) transport in vivo would likely be trivial (PubMed:24304836). A recent study examined the role of SLC40A1 in Mn(2+) homeostasis by using Tmprss6-O mice, which express high levels of hepcidin/HAMP and therefore have very low SLC40A1 levels in their tissues. These mice show frank iron deficiency and reduced iron levels in most tissues, but manganese levels are largely unaffected (By similarity). These studies suggest that manganese is propably not the physiological substrate of SLC40A1 [PMIDs: 22178646, 24304836, 29792530, 30247984]
• human/STAT1 (P42224): Has been shown to be mono-ADP-ribosylated at Glu-657 and Glu- 705 by PARP14 which prevents phosphorylation at Tyr-701 (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question (PubMed:29858569). It has been suggested that the lack of phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569) [PMIDs: 27796300, 29858569]
• human/SYN2 (Q92777): There are several mRNAs and ESTs supporting this gene model. However, the genome sequence encoding the N-terminal part contains several sequence discrepancies
• human/SYNGAP1 (Q96PV0): It is uncertain whether Met-1 or Met-16 is the initiator methionine
• human/TPM3 (P06753): It is uncertain whether Met-1 or Met-2 is the initiator
• human/UBAP1 (Q9NZ09): According to a report, can also be a component of ESCRT-I complexes containing VPS37B, VPS37C or VPS37D (PubMed:22405001). However, another publication showed that UBAP1 has specificity for complexes containing VPS37A and not VPS37 paralogs (PubMed:24284069) [PMIDs: 22405001, 24284069]
• human/UCHL1 (P09936): PubMed:9774100 reports the association of mutation Ile93Met with Parkinson disease. However, according to PubMed:16450370 this association is uncertain and UCHL1 is not a susceptibility gene for Parkinson disease [PMIDs: 9774100, 16450370]
• human/UCHL1 (P09936): The homodimer may have ATP-independent ubiquitin ligase activity (PubMed:12408865). However, in another study, UCHL1 was shown to lack ubiquitin ligase activity (PubMed:23359680) [PMIDs: 12408865, 23359680]
• human/VCP (P55072): It is unclear how it participates in the recruitment of TP53BP1 at DNA damage sites. According to a first report, participates in the recruitment of TP53BP1 by promoting ubiquitination and removal of L3MBTL1 from DNA damage sites (PubMed:22120668). According to a second report, it acts by removing 'Lys-48'-linked ubiquitination from sites of DNA damage (PubMed:22020440) [PMIDs: 22020440, 22120668]
• mouse/Stat1 (P42225): Has been shown to be mono-ADP-ribosylated at Glu-657 and Glu- 705 by PARP14 which prevents phosphorylation at Tyr-701 (By similarity). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question (By similarity). It has been suggested that the lack of phosphorylation may be due to sumoylation of Lys-703 (By similarity)
• mouse/Trp53 (P02340): It is uncertain whether Met-1 or Met-4 is the initiator
• worm/P54811 (P54811): The role of cdc-48.1 in the regulation of kinase air-2, a component of the chromosomal passenger complex (CPC), is controversial. One study suggests that cdc-48.1 inactivates air-2 at the end of mitosis whereas a second study shows that cdc-48.1 is not implicated in the regulation of air-2 [PMIDs: 18097415, 18854144]
• worm/cdc-48 (P54811): The role of cdc-48.1 in the regulation of kinase air-2, a component of the chromosomal passenger complex (CPC), is controversial. One study suggests that cdc-48.1 inactivates air-2 at the end of mitosis whereas a second study shows that cdc-48.1 is not implicated in the regulation of air-2 [PMIDs: 18097415, 18854144]
• yeast/TOR1 (P35169): It is uncertain whether Met-1 is the initiator

wgs-preliminary (39)

• 9BACT/HMPREF1058_RS08555 (I9U7L5): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9BACT/I9U7L5 (I9U7L5): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS10166 (A0A811MX19): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS1270 (A0A811M8A5): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS1765 (A0A811M5M6): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS27674 (A0A811PC48): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS29329 (A0A811PKG6): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS3088 (A0A811MJ28): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• 9POAL/NCGR_LOCUS67308 (A0A811SRM7): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• ECOLX/SNIPE (A0A8T9CRB7): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaA622 (A0A314KUK7): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaA622_candidate_IFRH_0 (A0A1J6I5H4): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaAO2_candidate_AO_0 (A0A1J6KBX2): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaAO2_candidate_AO_1 (A0A314LIN0): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBBL1_candidate_FOX1_0 (A0A1J6JGR6): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBBL2_candidate_FOX1_2 (A0A1J6KPK0): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBBL_candidate_FOX1_4 (A0A1J6KZ94): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBBL_candidate_FOX2_2 (A0A314LBC4): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBBL_candidate_FOX2_4 (A0A1J6KAK0): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBGL1_candidate_BGLU18_6 (A0A1J6KFZ7): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBGL1_candidate_BGLU42 (A0A314LBF6): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaBGL2_candidate_BGLU18_1 (A0A314KWB2): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaMATE1_candidate_DTX40_3 (A0A314KVN4): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaMPO1_candidate_AMO_3 (A0A314KPU1): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaODC_candidate_DCOR (A0A1J6ITS2): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaODC_candidate_ODC (A0A314KUM9): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaQPT2_candidate_QPT_0 (A0A1J6KEF3): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• NICAT/NaQPT2_candidate_QPT_1 (A0A1J6IKI8): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• POLH7/AJ80_06654 (A0A2B7XTR7): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• PRORE/fosA3 (A0AB35LIB0): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_00650 (A0A1D1UDY8): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_00651 (A0A1D1UKR0): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_01767 (A0A1D1USM4): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_03754 (A0A1D1UP68): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_03757 (A0A1D1UP59): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_09480 (A0A1D1VEY6): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_10893 (A0A1D1VE88): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_15948 (A0A1D1VWP9): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data
• RAMVA/RvY_17310 (A0A1D1W3Y1): The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data

other (38)

• BPT4/rI (P13304): It was first thought (PubMed:17693511) that the antiholin possesses a SAR domain, but it undergoes normal processing of its N- terminal signal sequence [PMIDs: 17693511, 34456892]
• BPT4/uvsW (P0DXF1): Originally thought to also encode the following gene uvsW1 (PubMed:17092935) [PMIDs: 17092935]
• ECOLI/mbiA (P28697): This gene is encoded entirely within the yaaW gene on the opposite strand (PubMed:18226237). Disruptions of one gene are also usually disruptions in the other [PMIDs: 18226237]
• POPTR/rps12-A (A4GYT5): There is 1 gene for this protein in each of the chloroplast inverted repeats; while they are usually identical, in this organism they are not. The other copy is AC A4GYN8
• POPTR/rps12-B (A4GYN8): There is 1 gene for this protein in each of the chloroplast inverted repeats; while they are usually identical, in this organism they are not. The other copy is AC A4GYT5
• human/ACIN1 (Q9UKV3): Structural and functional studies of the ASAP complex have been conducted with a chimeric complex involving a conserved fragment of Drosophila melanogaster Acinus/hkl [PMIDs: 22388736]
• human/ADRM1 (Q16186): Although initially described as a cell membrane glycoprotein, ADRM1 is intracellular and non-glycosylated, and has probably no direct role in cell adhesion
• human/AGK (Q53H12): According to a report, the N-terminal hydrophobic region forms a transmembrane region that crosses the mitochondrion inner membrane (PubMed:28712726). According to another report, the N-terminal hydrophobic region associates with the membrane without crossing it (PubMed:28712724) [PMIDs: 28712724, 28712726]
• human/AGRN (O00468): The unknown residue 'x' in the transmembrane isoform is probably a proline residue by similarity to mouse and rat sequences
• human/AKT1 (P31749): In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain
• human/BRCA1 (P38398): An article that concluded that AURKA-mediated phosphorylation of BRCA1 Ser-308 plays a role in the normal cell cycle G2/M transition was withdrawn due to data manipulation of flow cytometry data [PMIDs: 14990569, 26341884]
• human/COLGALT1 (Q8NBJ5): Has no glucosyltransferase activity
• human/COLGALT2 (Q8IYK4): Has no glucosyltransferase activity
• human/CRBN (Q96SW2): Although it contains a Lon N-terminal domain also found in proteases of the peptidase S16 family, it does not contain the ATP- binding and catalytic domains, suggesting that it has no protease activity
• human/CWC27 (Q6UX04): Despite the fact that it belongs to the cyclophilin-type PPIase family, a report has shown that it has probably no peptidyl- prolyl cis-trans isomerase activity [PMIDs: 20676357]
• human/DNAJB11 (Q9UBS4): PubMed:11584023 reported a cytosolic, as well as nuclear subcellular location. This result was obtained using an N-terminally GFP-tagged construct which most probably affected signal peptide-driven targeting to the ER. As a consequence, the in vivo revelance of the observed interaction with APOBEC1, a nuclear protein, is dubious. This holds true for the interaction with PWP1 [PMIDs: 11584023]
• human/DNAJC13 (O75165): In human, WASHC2 has undergone evolutionary duplication giving rise to highly homologous family members. A WASHC2C construct with WASHC2A-specific sequence insertions (of 2 aa and 21 aa length resulting in a construct length of 1341 aa similar to WASHC2A length) has been used to demonstrate the interaction with WASHC2 (PubMed:24643499) [PMIDs: 24643499]
• human/DSCAM (O60469): Has been reported to enhance netrin-induced phosphorylation of PAK1 and FYN; and the interaction between DSCAM, PAK1 and RAC1 has been described. This article has been withdrawn by the authors [PMIDs: 15169762, 26048998]
• human/ERP27 (Q96DN0): Does not contain a CXXC active site motif indicating that it is a catalytically redox-inactive member of the protein disulfide isomerase family
• human/FBXL8 (Q96CD0): While the gene symbol and protein names are indicative of the presence of LRR repeats, such repeats are not present in this protein
• human/GDPD2 (Q9HCC8): The catalytic domain of GDPD2 is oriented extracellularly; Glycerophosphoinositol is hydrolyzed in the medium of cells overexpressing Gdpd2, whereas intracellular levels of glycerophosphoinositol is not affected
• human/IFNL4 (K9M1U5): The reference genome assembly, GRCh37, describes the non- functional copy of that gene, frameshifted at position 22, that is more frequent in human populations
• human/KCTD11 (Q693B1): A N-terminal fragment of KCTD11 isoform 2 (comprising residues 15 - 115) has been used for some KCTD11:CUL3 interaction studies [PMIDs: 25974686]
• human/MAGI1 (Q6P9H4): The gene name MAGI1, shown in this entry as a synonym, is an obsolete human gene nomenclature committee-approved name. It should be noted that MAGI1 currently is the official name for the unrelated membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1
• human/MUC1 (P15941): O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats. Experimental sites were determined in a synthetic peptide glycosylated in vitro (PubMed:7744025, PubMed:9597769) [PMIDs: 7744025, 9597769]
• human/PEX11B (O96011): PubMed:9792670 states that both the N- and the C-terminus are located in the cytoplasm [PMIDs: 9792670]
• human/PHYKPL (Q8IUZ5): Does not seem to possess aminotransferase activity [PMIDs: 22241472]
• human/PIP5K1B (O14986): There is confusion in the literature with phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due to the fact that frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5- kinase type I alpha
• human/PLD4 (Q96BZ4): Exhibits no phospholipase activity, despite two HKD motifs
• human/PMPCA (Q10713): Does not seem to have protease activity as it lacks the zinc- binding site
• human/SLC7A11 (Q9UPY5): In the PMID:15151999, a typographical error has been introduced leading to L-cysteine spelling instead of L-cystine [PMIDs: 15151999]
• human/UQCRFS1 (P47985): Several peptides are generated during UQCRFS1 insertion (PubMed:28673544). According to some authors, the identification of the transit peptide as the subunit 9, does not necessary imply that it must be considered as a structural subunit of the complex III dimer as additional fragments from UQCRFS1 are also present (PubMed:28673544) [PMIDs: 28673544]
• mouse/Akt1 (P31750): In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain
• mouse/Dnajb11 (Q99KV1): PubMed:11584023 reported a cytosolic, as well as nuclear subcellular location. This result was obtained using an N-terminally GFP-tagged construct which most probably affected signal peptide-driven targeting to the ER. As a consequence, the in vivo revelance of the observed interaction with APOBEC1, a nuclear protein, is dubious [PMIDs: 11584023]
• mouse/Pld4 (Q8BG07): Exhibits no phospholipase activity, despite two HKD motifs [PMIDs: 30111894]
• rat/Akt1 (P47196): In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain
• rat/Hsd11b2 (P50233): Rats and mice do not produce appreciable cortisol, because they do not express the 17-alpha hydroxylase (Cyp17a1) enzyme in the adrenals [PMIDs: 1312193]
• yeast/ESA1 (Q08649): The catalytic mechanisms is still under debate. Cys-304 was proposed to function as a nucleophile that forms a covalent intermediate with acetyl-CoA during the reaction (PubMed:12368900), and indeed the residue can be acetylated (in vitro) (PubMed:12368900, PubMed:17223684). Depending on the assay system, mutation of Cys-304 leads to reduced or undetectable activity, indicating that is plays an important role. Still, mutation of Cys-304 has only a minor effect on the catalytic activity of the NuA4 histone acetyltransferase (HAT) complex (PubMed:17223684), making it unlikely that this residue functions as the catalytic nucleophile [PMIDs: 12368900, 17223684]

reclassified-function (37)

• ARATH/CRY1 (Q43125): Was originally thought to be a DNA photolyase [PMIDs: 8232555]
• ARATH/CRY2 (Q96524): Was originally thought to be a DNA photolyase [PMIDs: 9003312]
• ECOLI/GroEL (P0A6F5): Was originally designated as the ams protein [PMIDs: 2578448]
• ECOLI/Skp (P0AEU7): Was originally thought to bind DNA. It was probably an artifact due to the cationic nature of skp
• ECOLI/ftsI (P0AD68): Was originally thought to be a bifunctional enzyme with transglycosylase and transpeptidase activities [PMIDs: 7030331]
• ECOLI/rbsD (P04982): Was originally thought (PubMed:3011793) to be a high affinity ribose transport protein, but further analysis (PubMed:15060078) shows that it is a D-ribose pyranase [PMIDs: 3011793, 15060078]
• MAIZE/ABP1 (P13689): Was originally thought to have a disulfide bond between Cys-40 and Cys-99 [PMIDs: 11749971]
• SCHPO/aah1 (O74922): Was originally thought to exhibit alpha-amylase activity, but this activity is not detectable in S.pombe cell lysates or culture media [PMIDs: 16751704]
• SCHPO/pol5 (O60094): Was originally thought to belong to the DNA polymerase type-B family based on conserved motifs (PubMed:12093911). Has later been shown to be unrelated to B class DNA polymerases (PubMed:12695662) [PMIDs: 12093911, 12695662]
• human/ABHD2 (P08910): Was originally thought to be a G-coupled receptor [PMIDs: 2843827]
• human/AIFM2 (Q9BRQ8): Conflicting data exist on the pro-apoptotic function of the protein. It was initially claimed that overexpression of FSP1 induces caspase-independent apoptosis, but new evidence disputes this function [PMIDs: 11980907, 12135761, 15958387, 26689472, 31634899, 31634900]
• human/ARIH1 (Q9Y4X5): The RING-type 2 zinc finger was initially reported to only bind 1 zinc ion instead of 2 compared to classical RING-types (PubMed:15236971). But it was later shown that it is not the case and binds 2 zinc ions (PubMed:23707686, PubMed:24058416) [PMIDs: 15236971, 23707686, 24058416]
• human/ATP13A1 (Q9HD20): Was initially thought to mediate manganese transport (PubMed:24392018). However, it was later shown to specifically bind moderately hydrophobic transmembrane with short hydrophilic lumenal domains that misinsert into the endoplasmic reticulum (PubMed:32973005) [PMIDs: 24392018, 32973005]
• human/BBIP1 (A8MTZ0): Was previously thought to be non-coding and described as 'non- protein coding RNA 81', abbreviated NCRNA00081
• human/BOLA3 (Q53S33): Was initially reported to be secreted via a non-classical export pathway (PubMed:18548201). It was however later shown that it localizes to mitochondria, in agreement with other members of the family (PubMed:22746225) [PMIDs: 18548201, 22746225]
• human/CALR (P27797): Was originally thought to be the 52 kDa Ro autoantigen [PMIDs: 2332496]
• human/CAPG (P40121): This protein was originally thought to be a DNA-binding protein with a helix-loop-helix domain
• human/CHMP1A (Q9HD42): Was originally (PubMed:8863740) thought to be a metalloprotease (PRSM1). This was based on a wrong translation of the ORF which gave rise to a putative protein of 318 AA containing a pattern reminiscent of zinc metalloproteases [PMIDs: 8863740]
• human/CLU (P10909): Isoform 4 has been previously detected in cytosol and in the nuclei of apoptotic cells and promoted apoptosis following irradiation (PubMed:12551933). However the nuclear localization and apoptosis promotion has not been confirmed in other cell types (PubMed:24073260) [PMIDs: 12551933, 24073260]
• human/EIF2D (P41214): Was previously erroneously called ligatin, a trafficking receptor for phosphoglycoproteins, while ligatin is actually a distinct 10 kDa filamentous membrane protein encoded by a still unidentified gene [PMIDs: 20566627]
• human/ENDOU (P21128): Was originally (PubMed:2350438) thought to be a serine protease. However, PubMed:18936097 showed it is not the case [PMIDs: 2350438, 18936097]
• human/HDAC6 (Q9UBN7): Was originally thought to be a histone deacetylase (PubMed:10220385). However, subsequent work has shown that it is predominantly cytoplasmic and deacetylates a range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:38534334, PubMed:39567688) [PMIDs: 10220385, 12024216, 18606987, 20308065, 24882211, 26246421, 30538141, 31857589, 38534334, 39567688]
• human/HSPB8 (Q9UJY1): Was reported to have a protein kinase activity and to act as a Mn(2+)-dependent serine-threonine-specific protein kinase [PMIDs: 10833516]
• human/NBR1 (Q14596): Was originally thought to be the ovarian carcinoma antigen CA125 [PMIDs: 8069304]
• human/NDUFA4 (O00483): Was initially believed to be a subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I) [PMIDs: 12611891]
• human/NF1 (P21359): Was originally thought to be associated with LEOPARD (LS), an autosomal dominant syndrome [PMIDs: 8807336]
• human/PGRMC1 (O00264): Was initially identified as sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation (PubMed:21730960, PubMed:22292588, PubMed:28007569). However, it was later shown that it is not the case (PubMed:28007569). The sigma-2 receptor has been identified as TMEM97 (AC Q5BJF2) (PubMed:28559337) [PMIDs: 21730960, 22292588, 28007569, 28559337]
• human/PHTF1 (Q9UMS5): The PHTF domain was initially defined as an atypical homeodomain, suggesting that this protein could act as a transcription regulator (PubMed:10395808). However, the protein is not found in the nucleus and mainly localizes in the endoplasmic reticulum membrane, suggesting that it does not act as a transcription factor (By similarity) [PMIDs: 10395808]
• human/SH3GLB1 (Q9Y371): Was originally thought to have lysophosphatidic acid acyltransferase activity, but by homology with SH3GL2/endophilin A1 is unlikely to have this activity [PMIDs: 12456676]
• human/TCF25 (Q9BQ70): Was reported to have DNA-binding activity (PubMed:16574069). However, this is uncertain as it was shown with the protein fused to the yeast GAL4 DNA-binding domain [PMIDs: 16574069]
• human/UBA5 (Q9GZZ9): Was initially reported to mediate activation of SUMO2 in addition to UFM1 (PubMed:18442052). However, it was later shown that it is specific for UFM1 (By similarity) [PMIDs: 18442052]
• human/UFSP1 (Q6NVU6): UFSP1 initiates at a non-canonical GUG codon (PubMed:35525273, PubMed:35926457). Was initially thought to initiate from Met-77 and constitute a inactive isopeptidase that lacks a functional protease domain (PubMed:35525273, PubMed:35926457) [PMIDs: 35525273, 35926457]
• human/YWHAZ (P63104): Was originally thought to have phospholipase A2 activity [PMIDs: 1577711]
• mouse/Tert (O70372): Was originally thought to originate from rat [PMIDs: 13679242]
• yeast/NAP1 (P25293): NAP-I was previously referred to as AP-I
• yeast/PAP2 (P53632): Was originally thought to have DNA polymerase activity
• yeast/SIR2 (P06700): Was originally thought to be an ADP-ribosyltransferase [PMIDs: 10619427]

lacks-conserved-residue (19)

• 9INFA/M2 (A0A1S7IWC7): Lacks conserved residue(s) required for the propagation of feature annotation
• 9POAL/NCGR_LOCUS10166 (A0A811MX19): Lacks conserved residue(s) required for the propagation of feature annotation
• 9POAL/NCGR_LOCUS27674 (A0A811PC48): Lacks conserved residue(s) required for the propagation of feature annotation
• DESRO/K9IIP0 (K9IIP0): Lacks conserved residue(s) required for the propagation of feature annotation
• DESRO/K9IJK6 (K9IJK6): Lacks conserved residue(s) required for the propagation of feature annotation
• DESRO/K9IUF6 (K9IUF6): Lacks conserved residue(s) required for the propagation of feature annotation
• DESRO/K9IWX5 (K9IWX5): Lacks conserved residue(s) required for the propagation of feature annotation
• DORPE/TDO (A0A7G4RN94): Lacks conserved residue(s) required for the propagation of feature annotation
• METEA/pckA (C5B045): Lacks conserved residue(s) required for the propagation of feature annotation
• MISSI/atpH (A0A0S2RM82): Lacks conserved residue(s) required for the propagation of feature annotation
• MISSI/d8 (A0A0A0UMC1): Lacks conserved residue(s) required for the propagation of feature annotation
• MISSI/ndhA (A0A0S2RMT7): Lacks conserved residue(s) required for the propagation of feature annotation
• PSEPK/aroA (Q88M05): Lacks conserved residue(s) required for the propagation of feature annotation
• PSEPK/aroE (Q88IJ7): Lacks conserved residue(s) required for the propagation of feature annotation
• PSEPK/mexB (Q88HA4): Lacks conserved residue(s) required for the propagation of feature annotation
• PSEPK/rpoH (Q7CCA6): Lacks conserved residue(s) required for the propagation of feature annotation
• PSEPK/zwf (Q88C32): Lacks conserved residue(s) required for the propagation of feature annotation
• RHOPA/nosZ (Q6N843): Lacks conserved residue(s) required for the propagation of feature annotation
• worm/lrx-1 (Q22179): Lacks conserved residue(s) required for the propagation of feature annotation

degenerate-domain (16)

• ARATH/TOC1 (Q9LKL2): Lacks the phospho-accepting Asp (here Glu-71), present in the receiver domain, which is one of the conserved features of the two- component response regulators (ARRs) family
• MISSI/psbN (A0A0S2RMA5): Originally thought to be a component of PSII; based on experiments in Synechocystis, N.tabacum and barley, and its absence from PSII in T.elongatus and T.vulcanus, this is probably not true
• POPTR/psbN (A4GYT9): Originally thought to be a component of PSII; based on experiments in Synechocystis, N.tabacum and barley, and its absence from PSII in T.elongatus and T.vulcanus, this is probably not true
• SACEN/eryCII (A4F7P2): Although related to the cytochrome P450 family, lacks the heme-binding sites
• SCHPO/Epe1 (O94603): In contrast to other JHDM1 histone demethylases, it lacks the iron catalytic His in position 370 which is replaced by a Tyr residue and has no histone demethylase activity in vitro (PubMed:16362057). It therefore may not be functional in vivo [PMIDs: 16362057]
• SCHPO/cts2 (Q9C105): Lacks the conserved Glu residue in position 166 essential for chitinase activity. Its enzyme activity is therefore unsure
• SCHPO/spt16 (O94267): Although related to the peptidase M24 family, this protein lacks conserved active site residues suggesting that it may lack peptidase activity
• human/ABCF2 (Q9UG63): Lacks transmembrane domains and is probably not involved in transport
• human/ABRAXAS2 (Q15018): Although strongly related to the ABRAXAS1 protein, lacks the C-terminal pSXXF that constitutes a specific recognition motif for the BRCT domain of BRCA1
• human/ADAMTSL4 (Q6UY14): Although similar to members of the ADAMTS family, it lacks the metalloprotease and disintegrin-like domains which are typical of that family
• human/AKTIP (Q9H8T0): Lacks the conserved Cys residue necessary for ubiquitin- conjugating enzyme E2 activity
• human/CSNK1D (P48730): Was shown to phosphorylate and activate DCK in vitro but probably not in vivo [PMIDs: 20637175]
• human/PLD5 (Q8N7P1): In contrast to other members of the family, it lacks the conserved active sites, suggesting that it has no phospholipase activity
• human/RNF14 (Q9UBS8): Lacks the His residue in the RING-type domain 2 that is one of the conserved features of the family
• worm/lys-7 (O16202): Lacks conserved active site residues, suggesting it has no catalytic activity
• yeast/SPT16 (P32558): Although related to the peptidase M24 family, this protein lacks conserved active site residues suggesting that it may lack peptidase activity

retracted-reference (12)

• ARATH/BAK1 (Q94F62): An article reported the role of autophosphorylation of Tyr-610 in brassinosteroid signaling; however, this paper was later retracted. A second article from the same group reported the role of phosphorylation; however, this paper was also retracted [PMIDs: 20876109, 21350342, 27325779, 27603314]
• ARATH/FT (Q9SXZ2): An article reported that transcripts can move in the phloem from leaves to shoot apex to induce flowering; however, this paper was later retracted [PMIDs: 16099949, 17446370]
• human/ACTB (P60709): Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203) [PMIDs: 19377461, 24336203]
• human/AKT1 (P31749): PUBMED:20231902 has been retracted because there was evidence of data fabrication and/or falsification in multiple figure panels [PMIDs: 20231902, 37490513]
• human/AKT1 (P31749): PUBMED:19940129 has been retracted because the same data were used to represent different experimental conditions [PMIDs: 19940129, 27825096]
• human/APP (P05067): Was reported to bind TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (PubMed:19225519). This work was later retracted (PubMed:38110576) [PMIDs: 19225519, 38110576]
• human/ATG4D (Q86TL0): A paper describing ATG4D tissue expression has been retracted, due to concerns of image duplication in some of the figures [PMIDs: 12446702, 30808002]
• human/CHAF1A (Q13111): Was reported to form, during DNA replication, a S phase- specific complex that would facilitate methylation of H3 'Lys-9' during replication-coupled chromatin assembly and vould be at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1 (PubMed:15327775). However, this paper has been retracted because some data, results and conclusions are not reliable (PubMed:30849389) [PMIDs: 15327775, 30849389]
• human/MAP3K5 (Q99683): Reported to be phosphorylated by AKT2 (PubMed:12697749). However, the publication has been retracted due to image duplication in figures [PMIDs: 12697749, 27825085]
• human/RARA (P10276): Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203) [PMIDs: 19377461, 24336203]
• human/STAT3 (P40763): Was shown to be S-palmitoylated by ZDHHC19, leading to STAT3 homodimerization. However, this study was later retracted [PMIDs: 31462771, 32555452]
• human/TP53 (P04637): Interaction with BANP was reported to enhance phosphorylation on Ser-15 upon ultraviolet irradiation (PubMed:15701641). However, the publication has been retracted due to image duplication and manipulation. Interaction with BANP has been confirmed in mouse studies (By similarity). Phosphorylation at Ser-15 has been confirmed by other studies (PubMed:10570149, PubMed:11554766, PubMed:15866171, PubMed:16219768, PubMed:17317671, PubMed:17954561, PubMed:20959462, PubMed:25772236). Its nuclear and cytoplasmic localization has been confirmed by other studies (PubMed:15340061, PubMed:17170702, PubMed:17591690, PubMed:18206965, PubMed:19011621, PubMed:21597459, PubMed:22726440) [PMIDs: 10570149, 11554766, 15340061, 15701641, 15866171, 16219768, 17170702, 17317671, 17591690, 17954561, 18206965, 19011621, 20959462, 21597459, 22726440, 25772236, 32144153]

possible-artifact (4)

• human/C1QBP (Q07021): The subcellular location has been matter of debate. After being reported to be exclusively localized to mitochondria, demonstrations of promiscuous associations and locations were considered as artifactual due to the extremely acidic character and the use of different tagged versions of the protein (PubMed:11493647, PubMed:9305894). However, its location to multiple compartments linked to diverse functions is now accepted. The N-termini of the surface and secreted forms are identical to the reported processed mitochondrial form [PMIDs: 9305894, 11493647]
• human/GTF2F2 (P13984): GTF2F2 appears to have ATP-dependent DNA-helicase activity; however this is probably an artifact that happened during the protein purification [PMIDs: 2477704]
• human/PARK7 (Q99497): The protein deglycation activity is controversial. It has been ascribed to a TRIS buffer artifact by a publication (PubMed:27903648) and as a result of the removal of methylglyoxal by glyoxalase activity that leads to a subsequent decomposition of hemithioacetals and hemianimals due to the shift in equilibrium position by another one (PubMed:31653696). However, biochemical experiments showing that PARK7 is a bona fide deglycase have been performed (PubMed:25416785, PubMed:28013050, PubMed:28596309) [PMIDs: 25416785, 27903648, 28013050, 28596309, 31653696]
• human/UCHL1 (P09936): The oxidation forms of Met-1, Met-6, Met-12, Met-124, Met-179 and Cys-220 are subject of controversy and could be the artifactual results of sample handling [PMIDs: 14722078]