ID THG1_HUMAN Reviewed; 298 AA. AC Q9NWX6; D3DQJ5; Q53G12; Q7L5R3; Q9H0S2; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 171. DE RecName: Full=Probable tRNA(His) guanylyltransferase; DE EC=2.7.7.79 {ECO:0000269|PubMed:21059936}; DE AltName: Full=Induced in high glucose-1 {ECO:0000303|PubMed:25008184}; DE Short=IHG-1 {ECO:0000303|PubMed:25008184}; DE AltName: Full=Interphase cytoplasmic foci protein 45; DE AltName: Full=tRNA-histidine guanylyltransferase; GN Name=THG1L; Synonyms=ICF45; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15459185; DOI=10.1074/jbc.m406737200; RA Guo D., Hu K., Lei Y., Wang Y., Ma T., He D.; RT "Identification and characterization of a novel cytoplasm protein ICF45 RT that is involved in cell cycle regulation."; RL J. Biol. Chem. 279:53498-53505(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-232. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-232. RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-232. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-232. RC TISSUE=Brain, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MFN1 AND MFN2. RX PubMed=25008184; DOI=10.2337/db13-1256; RA Hickey F.B., Corcoran J.B., Griffin B., Bhreathnach U., Mortiboys H., RA Reid H.M., Andrews D., Byrne S., Furlong F., Martin F., Godson C., RA Murphy M.; RT "IHG-1 increases mitochondrial fusion and bioenergetic function."; RL Diabetes 63:4314-4325(2014). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 30-298 IN COMPLEX WITH MAGNESIUM; RP TRIPHOSPHATE AND GTP, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND RP MUTAGENESIS OF ASP-58; HIS-63; SER-104; ASP-105; GLU-106; THR-127; HIS-181; RP LYS-216 AND ASN-227. RX PubMed=21059936; DOI=10.1073/pnas.1010436107; RA Hyde S.J., Eckenroth B.E., Smith B.A., Eberley W.A., Heintz N.H., RA Jackman J.E., Doublie S.; RT "tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl RT transferase, shares unexpected structural homology with canonical 5'-3' DNA RT polymerases."; RL Proc. Natl. Acad. Sci. U.S.A. 107:20305-20310(2010). RN [10] RP INVOLVEMENT IN SCAR28, VARIANT SCAR28 ALA-55, CHARACTERIZATION OF VARIANT RP SCAR28 ALA-55, AND FUNCTION. RX PubMed=27307223; DOI=10.1007/s10048-016-0487-z; RA Edvardson S., Elbaz-Alon Y., Jalas C., Matlock A., Patel K., Labbe K., RA Shaag A., Jackman J.E., Elpeleg O.; RT "A mutation in the THG1L gene in a family with cerebellar ataxia and RT developmental delay."; RL Neurogenetics 17:219-225(2016). RN [11] RP VARIANT SCAR28 ALA-55. RX PubMed=31168944; DOI=10.1002/ajmg.a.61196; RA Walker M.A., Lerman-Sagie T., Swoboda K., Lev D., Blumkin L.; RT "Refining the phenotype of the THG1L (p.Val55Ala mutation)-related RT mitochondrial autosomal recessive congenital cerebellar ataxia."; RL Am. J. Med. Genet. A 179:1575-1579(2019). RN [12] RP VARIANT PRO-294. RX PubMed=30214071; DOI=10.1038/s41436-018-0140-3; RA Shaheen R., Maddirevula S., Ewida N., Alsahli S., Abdel-Salam G.M.H., RA Zaki M.S., Tala S.A., Alhashem A., Softah A., Al-Owain M., Alazami A.M., RA Abadel B., Patel N., Al-Sheddi T., Alomar R., Alobeid E., Ibrahim N., RA Hashem M., Abdulwahab F., Hamad M., Tabarki B., Alwadei A.H., Alhazzani F., RA Bashiri F.A., Kentab A., Sahintuerk S., Sherr E., Fregeau B., Sogati S., RA Alshahwan S.A.M., Alkhalifi S., Alhumaidi Z., Temtamy S., Aglan M., RA Otaify G., Girisha K.M., Tulbah M., Seidahmed M.Z., Salih M.A., RA Abouelhoda M., Momin A.A., Saffar M.A., Partlow J.N., Arold S.T., RA Faqeih E., Walsh C., Alkuraya F.S.; RT "Genomic and phenotypic delineation of congenital microcephaly."; RL Genet. Med. 21:545-552(2019). CC -!- FUNCTION: Adds a GMP to the 5'-end of tRNA(His) after transcription and CC RNase P cleavage. This step is essential for proper recognition of the CC tRNA and for the fidelity of protein synthesis (Probable). Also CC functions as a guanyl-nucleotide exchange factor/GEF for the MFN1 and CC MFN2 mitofusins thereby regulating mitochondrial fusion CC (PubMed:25008184, PubMed:27307223). By regulating both mitochondrial CC dynamics and bioenergetic function, it contributes to cell survival CC following oxidative stress (PubMed:25008184, PubMed:27307223). CC {ECO:0000269|PubMed:25008184, ECO:0000269|PubMed:27307223, CC ECO:0000305|PubMed:21059936}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end ribonucleotide-tRNA(His) + ATP + GTP + H2O = a 5'-end CC phospho-guanosine-ribonucleotide-tRNA(His) + AMP + 2 diphosphate + CC H(+); Xref=Rhea:RHEA:54564, Rhea:RHEA-COMP:14193, Rhea:RHEA- CC COMP:14917, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:138282, CC ChEBI:CHEBI:141847, ChEBI:CHEBI:456215; EC=2.7.7.79; CC Evidence={ECO:0000269|PubMed:21059936}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:21059936}; CC Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:21059936}; CC -!- SUBUNIT: Homotetramer (PubMed:21059936). Interacts with MFN1 and MFN2; CC functions as a guanyl-nucleotide exchange factor/GEF for MFN2 and also CC probably MFN1 (PubMed:25008184). {ECO:0000269|PubMed:21059936, CC ECO:0000269|PubMed:25008184}. CC -!- INTERACTION: CC Q9NWX6; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-746510, EBI-739832; CC Q9NWX6; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-746510, EBI-741158; CC Q9NWX6; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-746510, EBI-742388; CC Q9NWX6; O00560: SDCBP; NbExp=3; IntAct=EBI-746510, EBI-727004; CC Q9NWX6; P54274: TERF1; NbExp=2; IntAct=EBI-746510, EBI-710997; CC Q9NWX6; Q9NWX6: THG1L; NbExp=4; IntAct=EBI-746510, EBI-746510; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15459185}. CC Mitochondrion outer membrane {ECO:0000305|PubMed:25008184}. CC -!- TISSUE SPECIFICITY: Expressed in many tissues. CC {ECO:0000269|PubMed:15459185}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 28 (SCAR28) CC [MIM:618800]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR28 patients manifest mild motor CC developmental delay, gait ataxia, and dysarthria. Some patients show CC mildly impaired intellectual development. Disease onset is in early CC childhood. {ECO:0000269|PubMed:27307223, ECO:0000269|PubMed:31168944}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the tRNA(His) guanylyltransferase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH01523.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH01852.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY463216; AAS21134.1; -; mRNA. DR EMBL; AL136669; CAB66604.1; -; mRNA. DR EMBL; AK000553; BAA91249.1; -; mRNA. DR EMBL; AK021663; BAB13870.1; -; mRNA. DR EMBL; CR533503; CAG38534.1; -; mRNA. DR EMBL; AK223119; BAD96839.1; -; mRNA. DR EMBL; CH471062; EAW61590.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61591.1; -; Genomic_DNA. DR EMBL; BC001523; AAH01523.2; ALT_INIT; mRNA. DR EMBL; BC001852; AAH01852.2; ALT_INIT; mRNA. DR EMBL; BC023521; AAH23521.1; -; mRNA. DR CCDS; CCDS4341.1; -. DR RefSeq; NP_001304753.1; NM_001317824.1. DR RefSeq; NP_001304754.1; NM_001317825.1. DR RefSeq; NP_001304755.1; NM_001317826.1. DR RefSeq; NP_060342.2; NM_017872.4. DR PDB; 3OTB; X-ray; 2.95 A; A/B=30-298. DR PDB; 3OTC; X-ray; 3.01 A; A/B=30-298. DR PDB; 3OTD; X-ray; 2.28 A; A/B=30-298. DR PDB; 3OTE; X-ray; 2.56 A; A/B=30-298. DR PDB; 7CV1; X-ray; 4.00 A; A/B/C/D=30-298. DR PDBsum; 3OTB; -. DR PDBsum; 3OTC; -. DR PDBsum; 3OTD; -. DR PDBsum; 3OTE; -. DR PDBsum; 7CV1; -. DR AlphaFoldDB; Q9NWX6; -. DR SMR; Q9NWX6; -. DR BioGRID; 120311; 62. DR DIP; DIP-59479N; -. DR IntAct; Q9NWX6; 15. DR MINT; Q9NWX6; -. DR STRING; 9606.ENSP00000231198; -. DR GlyGen; Q9NWX6; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NWX6; -. DR PhosphoSitePlus; Q9NWX6; -. DR BioMuta; THG1L; -. DR DMDM; 146325755; -. DR EPD; Q9NWX6; -. DR jPOST; Q9NWX6; -. DR MassIVE; Q9NWX6; -. DR MaxQB; Q9NWX6; -. DR PaxDb; 9606-ENSP00000231198; -. DR PeptideAtlas; Q9NWX6; -. DR ProteomicsDB; 82998; -. DR Pumba; Q9NWX6; -. DR Antibodypedia; 28457; 100 antibodies from 23 providers. DR DNASU; 54974; -. DR Ensembl; ENST00000231198.12; ENSP00000231198.7; ENSG00000113272.14. DR GeneID; 54974; -. DR KEGG; hsa:54974; -. DR MANE-Select; ENST00000231198.12; ENSP00000231198.7; NM_017872.5; NP_060342.2. DR UCSC; uc003lxd.4; human. DR AGR; HGNC:26053; -. DR CTD; 54974; -. DR DisGeNET; 54974; -. DR GeneCards; THG1L; -. DR HGNC; HGNC:26053; THG1L. DR HPA; ENSG00000113272; Low tissue specificity. DR MalaCards; THG1L; -. DR MIM; 618800; phenotype. DR MIM; 618802; gene. DR neXtProt; NX_Q9NWX6; -. DR OpenTargets; ENSG00000113272; -. DR PharmGKB; PA162405691; -. DR VEuPathDB; HostDB:ENSG00000113272; -. DR eggNOG; KOG2721; Eukaryota. DR GeneTree; ENSGT00390000011705; -. DR HOGENOM; CLU_044271_0_0_1; -. DR InParanoid; Q9NWX6; -. DR OMA; WKQHTEI; -. DR OrthoDB; 239198at2759; -. DR PhylomeDB; Q9NWX6; -. DR TreeFam; TF325119; -. DR BRENDA; 2.7.7.79; 2681. DR PathwayCommons; Q9NWX6; -. DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. DR SignaLink; Q9NWX6; -. DR BioGRID-ORCS; 54974; 610 hits in 1169 CRISPR screens. DR ChiTaRS; THG1L; human. DR EvolutionaryTrace; Q9NWX6; -. DR GeneWiki; THG1L; -. DR GenomeRNAi; 54974; -. DR Pharos; Q9NWX6; Tbio. DR PRO; PR:Q9NWX6; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9NWX6; Protein. DR Bgee; ENSG00000113272; Expressed in monocyte and 150 other cell types or tissues. DR ExpressionAtlas; Q9NWX6; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:LIFEdb. DR GO; GO:1990234; C:transferase complex; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL. DR GO; GO:0005525; F:GTP binding; IDA:BHF-UCL. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000287; F:magnesium ion binding; IDA:BHF-UCL. DR GO; GO:0016779; F:nucleotidyltransferase activity; EXP:Reactome. DR GO; GO:0000049; F:tRNA binding; TAS:BHF-UCL. DR GO; GO:0008193; F:tRNA guanylyltransferase activity; IDA:UniProtKB. DR GO; GO:0008053; P:mitochondrial fusion; IDA:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB. DR GO; GO:1990046; P:stress-induced mitochondrial fusion; IDA:UniProtKB. DR GO; GO:0006400; P:tRNA modification; ISS:UniProtKB. DR GO; GO:0008033; P:tRNA processing; IDA:UniProtKB. DR Gene3D; 3.30.70.3000; -; 1. DR InterPro; IPR025845; Thg1_C_dom. DR InterPro; IPR024956; tRNAHis_GuaTrfase_cat. DR InterPro; IPR007537; tRNAHis_GuaTrfase_Thg1. DR InterPro; IPR038469; tRNAHis_GuaTrfase_Thg1_sf. DR PANTHER; PTHR12729:SF6; TRNA(HIS) GUANYLYLTRANSFERASE-RELATED; 1. DR PANTHER; PTHR12729; UNCHARACTERIZED; 1. DR Pfam; PF04446; Thg1; 1. DR Pfam; PF14413; Thg1C; 1. DR PIRSF; PIRSF028980; tRNAHis_guanylyltransferase; 1. DR Genevisible; Q9NWX6; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Disease variant; GTP-binding; Magnesium; Membrane; KW Metal-binding; Mitochondrion; Mitochondrion outer membrane; KW Neurodegeneration; Nucleotide-binding; Nucleotidyltransferase; KW Reference proteome; Transferase; tRNA processing. FT CHAIN 1..298 FT /note="Probable tRNA(His) guanylyltransferase" FT /id="PRO_0000284984" FT BINDING 58..63 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 58 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 58 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 59 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 104..105 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 105 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21059936" FT BINDING 105 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21059936" FT VARIANT 55 FT /note="V -> A (in SCAR28; decreased mitochondrial fusion; FT dbSNP:rs201920319)" FT /evidence="ECO:0000269|PubMed:27307223, FT ECO:0000269|PubMed:31168944" FT /id="VAR_083901" FT VARIANT 232 FT /note="L -> P (in dbSNP:rs2270812)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_031871" FT VARIANT 294 FT /note="L -> P (found in a patient with a severe FT multisystemic growth disorder and cerebellar atrophy; FT uncertain significance; dbSNP:rs1581444231)" FT /evidence="ECO:0000269|PubMed:30214071" FT /id="VAR_083902" FT MUTAGEN 58 FT /note="D->A: Reduces activity by 99.5%." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 63 FT /note="H->A: Slightly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 104 FT /note="S->A: Slightly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 105 FT /note="D->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 106 FT /note="E->A: Reduces activity by 95%." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 127 FT /note="T->A: Abolishes oligomerization. Loss of enzyme FT activity." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 181 FT /note="H->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 216 FT /note="K->A: Reduces activity by 98.5%." FT /evidence="ECO:0000269|PubMed:21059936" FT MUTAGEN 227 FT /note="N->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21059936" FT CONFLICT 57 FT /note="L -> Q (in Ref. 5; BAD96839)" FT /evidence="ECO:0000305" FT HELIX 36..41 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 51..59 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 62..68 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 77..93 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 94..103 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 106..111 FT /evidence="ECO:0007829|PDB:3OTD" FT TURN 117..120 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 122..139 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 156..165 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 166..195 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 201..208 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 213..224 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 233..237 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 239..243 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 274..277 FT /evidence="ECO:0007829|PDB:3OTD" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:3OTB" FT HELIX 284..289 FT /evidence="ECO:0007829|PDB:3OTD" FT HELIX 292..295 FT /evidence="ECO:0007829|PDB:3OTD" SQ SEQUENCE 298 AA; 34831 MW; A6C941B75611C448 CRC64; MWGACKVKVH DSLATISITL RRYLRLGATM AKSKFEYVRD FEADDTCLAH CWVVVRLDGR NFHRFAEKHN FAKPNDSRAL QLMTKCAQTV MEELEDIVIA YGQSDEYSFV FKRKTNWFKR RASKFMTHVA SQFASSYVFY WRDYFEDQPL LYPPGFDGRV VVYPSNQTLK DYLSWRQADC HINNLYNTVF WALIQQSGLT PVQAQGRLQG TLAADKNEIL FSEFNINYNN ELPMYRKGTV LIWQKVDEVM TKEIKLPTEM EGKKMAVTRT RTKPVPLHCD IIGDAFWKEH PEILDEDS //