ID SYG_HUMAN Reviewed; 739 AA. AC P41250; B3KQA2; B4DIA0; Q969Y1; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 01-OCT-2014, entry version 153. DE RecName: Full=Glycine--tRNA ligase; DE EC=6.1.1.14; DE AltName: Full=Diadenosine tetraphosphate synthetase; DE Short=AP-4-A synthetase; DE AltName: Full=Glycyl-tRNA synthetase; DE Short=GlyRS; GN Name=GARS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-42. RX PubMed=7962006; RA Shiba K., Schimmel P., Motegi H., Noda T.; RT "Human glycyl-tRNA synthetase. Wide divergence of primary structure RT from bacterial counterpart and species-specific aminoacylation."; RL J. Biol. Chem. 269:30049-30055(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-42. RX PubMed=7753621; DOI=10.1093/nar/23.8.1307; RA Williams J.H., Osvath S.R., Khong T.-F., Pearse M.J., Power D.A.; RT "Cloning, sequencing and bacterial expression of human glycine tRNA RT synthetase."; RL Nucleic Acids Res. 23:1307-1310(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-42. RC TISSUE=Embryo, and Hippocampus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-42. RC TISSUE=Eye, 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-739, AND VARIANT ALA-42. RX PubMed=7961834; RA Ge Q., Trieu E.P., Targoff I.N.; RT "Primary structure and functional expression of human glycyl-tRNA RT synthetase, an autoantigen in myositis."; RL J. Biol. Chem. 269:28790-28797(1994). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=9524218; DOI=10.1016/S0378-1119(98)00007-9; RA Mudge S.J., Williams J.H., Eyre H.J., Sutherland G.R., Cowan P.J., RA Power D.A.; RT "Complex organisation of the 5'-end of the human glycine tRNA RT synthetase gene."; RL Gene 209:45-50(1998). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-204 AND LYS-501, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 55-739, SUBUNIT, MUTAGENESIS RP OF SER-635, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17544401; DOI=10.1016/j.febslet.2007.05.046; RA Cader M.Z., Ren J., James P.A., Bird L.E., Talbot K., Stammers D.K.; RT "Crystal structure of human wildtype and S581L-mutant glycyl-tRNA RT synthetase, an enzyme underlying distal spinal muscular atrophy."; RL FEBS Lett. 581:2959-2964(2007). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 55-739, VARIANT ARG-580, AND RP SUBUNIT. RX PubMed=17545306; DOI=10.1073/pnas.0703908104; RA Xie W., Nangle L.A., Zhang W., Schimmel P., Yang X.-L.; RT "Long-range structural effects of a Charcot-Marie-Tooth disease- RT causing mutation in human glycyl-tRNA synthetase."; RL Proc. Natl. Acad. Sci. U.S.A. 104:9976-9981(2007). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 55-739 IN COMPLEX WITH ATP; RP SUBSTRATE AND SUBSTRATE ANALOGS, AND FUNCTION. RX PubMed=19710017; DOI=10.1074/jbc.M109.030692; RA Guo R.-T., Chong Y.E., Guo M., Yang X.-L.; RT "Crystal structures and biochemical analyses suggest a unique RT mechanism and role for human glycyl-tRNA synthetase in Ap4A RT homeostasis."; RL J. Biol. Chem. 284:28968-28976(2009). RN [14] RP VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS HMN5A PRO-183 AND RP ARG-580, AND TISSUE SPECIFICITY. RX PubMed=12690580; DOI=10.1086/375039; RA Antonellis A., Ellsworth R.E., Sambuughin N., Puls I., Abel A., RA Lee-Lin S.Q., Jordanova A., Kremensky I., Christodoulou K., RA Middleton L.T., Sivakumar K., Ionasescu V., Funalot B., Vance J.M., RA Goldfarb L.G., Fischbeck K.H., Green E.D.; RT "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type RT 2D and distal spinal muscular atrophy type V."; RL Am. J. Hum. Genet. 72:1293-1299(2003). CC -!- FUNCTION: Catalyzes the attachment of glycine to tRNA(Gly). Is CC also able produce diadenosine tetraphosphate (Ap4A), a universal CC pleiotropic signaling molecule needed for cell regulation CC pathways, by direct condensation of 2 ATPs. CC {ECO:0000269|PubMed:19710017}. CC -!- CATALYTIC ACTIVITY: ATP + glycine + tRNA(Gly) = AMP + diphosphate CC + glycyl-tRNA(Gly). CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 uM for tRNA(Gly(GCC)) {ECO:0000269|PubMed:17544401}; CC KM=15 uM for glycine {ECO:0000269|PubMed:17544401}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17544401, CC ECO:0000269|PubMed:17545306, ECO:0000269|PubMed:19710017}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9524218}. CC Mitochondrion {ECO:0000269|PubMed:9524218}. CC -!- TISSUE SPECIFICITY: Widely expressed, including brain and spinal CC cord. {ECO:0000269|PubMed:12690580}. CC -!- DISEASE: Charcot-Marie-Tooth disease 2D (CMT2D) [MIM:601472]: A CC dominant axonal form of Charcot-Marie-Tooth disease, a disorder of CC the peripheral nervous system, characterized by progressive CC weakness and atrophy, initially of the peroneal muscles and later CC of the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) CC and primary peripheral axonal neuropathies (CMT2). Neuropathies of CC the CMT2 group are characterized by signs of axonal degeneration CC in the absence of obvious myelin alterations, normal or slightly CC reduced nerve conduction velocities, and progressive distal muscle CC weakness and atrophy. Nerve conduction velocities are normal or CC slightly reduced. {ECO:0000269|PubMed:12690580}. Note=The disease CC is caused by mutations affecting the gene represented in this CC entry. CC -!- DISEASE: Neuronopathy, distal hereditary motor, 5A (HMN5A) CC [MIM:600794]: A disorder characterized by distal muscular atrophy CC mainly affecting the upper extremities, in contrast to other CC distal motor neuronopathies. These constitute a heterogeneous CC group of neuromuscular diseases caused by selective degeneration CC of motor neurons in the anterior horn of the spinal cord, without CC sensory deficit in the posterior horn. The overall clinical CC picture consists of a classical distal muscular atrophy syndrome CC in the legs without clinical sensory loss. The disease starts with CC weakness and wasting of distal muscles of the anterior tibial and CC peroneal compartments of the legs. Later on, weakness and atrophy CC may expand to the proximal muscles of the lower limbs and/or to CC the distal upper limbs. {ECO:0000269|PubMed:12690580}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 WHEP-TRS domain. {ECO:0000255|PROSITE- CC ProRule:PRU00531}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA57001.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAA86443.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="http://www.molgen.ua.ac.be/CMTMutations/"; 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; D30658; BAA06338.1; -; mRNA. DR EMBL; U09510; AAA86443.1; ALT_INIT; mRNA. DR EMBL; AK074524; BAG51964.1; -; mRNA. DR EMBL; AK295490; BAG58412.1; -; mRNA. DR EMBL; AC005154; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006969; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004976; AAC71652.1; -; Genomic_DNA. DR EMBL; BC007722; AAH07722.1; -; mRNA. DR EMBL; BC007755; AAH07755.1; -; mRNA. DR EMBL; U09587; AAA57001.1; ALT_INIT; mRNA. DR CCDS; CCDS43564.1; -. DR PIR; A55314; A55314. DR RefSeq; NP_002038.2; NM_002047.2. DR UniGene; Hs.404321; -. DR PDB; 2PME; X-ray; 2.90 A; A=55-739. DR PDB; 2PMF; X-ray; 2.85 A; A=55-739. DR PDB; 2Q5H; X-ray; 3.00 A; A=55-739. DR PDB; 2Q5I; X-ray; 2.80 A; A=55-739. DR PDB; 2ZT5; X-ray; 2.50 A; A=55-739. DR PDB; 2ZT6; X-ray; 3.08 A; A=55-739. DR PDB; 2ZT7; X-ray; 2.70 A; A=55-739. DR PDB; 2ZT8; X-ray; 3.35 A; A=55-739. DR PDB; 2ZXF; X-ray; 3.40 A; A=55-739. DR PDB; 4KQE; X-ray; 2.74 A; A=55-739. DR PDB; 4KR2; X-ray; 3.29 A; A=114-739. DR PDB; 4KR3; X-ray; 3.24 A; A=114-739. DR PDBsum; 2PME; -. DR PDBsum; 2PMF; -. DR PDBsum; 2Q5H; -. DR PDBsum; 2Q5I; -. DR PDBsum; 2ZT5; -. DR PDBsum; 2ZT6; -. DR PDBsum; 2ZT7; -. DR PDBsum; 2ZT8; -. DR PDBsum; 2ZXF; -. DR PDBsum; 4KQE; -. DR PDBsum; 4KR2; -. DR PDBsum; 4KR3; -. DR ProteinModelPortal; P41250; -. DR SMR; P41250; 117-727. DR BioGrid; 108887; 54. DR DIP; DIP-50471N; -. DR IntAct; P41250; 5. DR MINT; MINT-1395438; -. DR STRING; 9606.ENSP00000373918; -. DR DrugBank; DB00145; Glycine. DR PhosphoSite; P41250; -. DR DMDM; 313104283; -. DR MaxQB; P41250; -. DR PaxDb; P41250; -. DR PRIDE; P41250; -. DR DNASU; 2617; -. DR Ensembl; ENST00000389266; ENSP00000373918; ENSG00000106105. DR GeneID; 2617; -. DR KEGG; hsa:2617; -. DR UCSC; uc003tbm.3; human. DR CTD; 2617; -. DR GeneCards; GC07P030600; -. DR GeneReviews; GARS; -. DR H-InvDB; HIX0006570; -. DR HGNC; HGNC:4162; GARS. DR HPA; HPA017896; -. DR HPA; HPA019097; -. DR MIM; 600287; gene. DR MIM; 600794; phenotype. DR MIM; 601472; phenotype. DR neXtProt; NX_P41250; -. DR Orphanet; 99938; Autosomal dominant Charcot-Marie-Tooth disease type 2D. DR Orphanet; 139536; Distal hereditary motor neuropathy type 5. DR PharmGKB; PA28575; -. DR eggNOG; COG0423; -. DR HOGENOM; HOG000242015; -. DR HOVERGEN; HBG036190; -. DR InParanoid; P41250; -. DR KO; K01880; -. DR OMA; LMFQTTI; -. DR OrthoDB; EOG7FBRH1; -. DR PhylomeDB; P41250; -. DR TreeFam; TF343504; -. DR BRENDA; 6.1.1.14; 2681. DR Reactome; REACT_15302; Mitochondrial tRNA aminoacylation. DR Reactome; REACT_15306; Cytosolic tRNA aminoacylation. DR ChiTaRS; GARS; human. DR EvolutionaryTrace; P41250; -. DR GeneWiki; Glycine%E2%80%94tRNA_ligase; -. DR GenomeRNAi; 2617; -. DR NextBio; 10303; -. DR PMAP-CutDB; P41250; -. DR PRO; PR:P41250; -. DR ArrayExpress; P41250; -. DR Bgee; P41250; -. DR CleanEx; HS_GARS; -. DR Genevestigator; P41250; -. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0030141; C:secretory granule; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004820; F:glycine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB. DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW. DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0006426; P:glycyl-tRNA aminoacylation; IEA:InterPro. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. DR Gene3D; 1.10.287.10; -; 1. DR Gene3D; 3.40.50.800; -; 1. DR InterPro; IPR002314; aa-tRNA-synt_IIb_cons-dom. DR InterPro; IPR006195; aa-tRNA-synth_II. DR InterPro; IPR004154; Anticodon-bd. DR InterPro; IPR027031; Gly-tRNA_synthase/POLG2. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR InterPro; IPR002315; tRNA-synt_gly. DR InterPro; IPR000738; WHEP-TRS. DR PANTHER; PTHR10745; PTHR10745; 1. DR Pfam; PF03129; HGTP_anticodon; 1. DR Pfam; PF00587; tRNA-synt_2b; 1. DR Pfam; PF00458; WHEP-TRS; 1. DR PRINTS; PR01043; TRNASYNTHGLY. DR SMART; SM00991; WHEP-TRS; 1. DR SUPFAM; SSF47060; SSF47060; 1. DR SUPFAM; SSF52954; SSF52954; 1. DR TIGRFAMs; TIGR00389; glyS_dimeric; 1. DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1. DR PROSITE; PS00762; WHEP_TRS_1; 1. DR PROSITE; PS51185; WHEP_TRS_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; KW Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm; KW Disease mutation; Ligase; Mitochondrion; Neurodegeneration; KW Neuropathy; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; KW Reference proteome. FT CHAIN 1 739 Glycine--tRNA ligase. FT /FTId=PRO_0000072998. FT DOMAIN 63 119 WHEP-TRS. {ECO:0000255|PROSITE- FT ProRule:PRU00531}. FT NP_BIND 331 333 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 341 346 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 457 458 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 580 583 ATP. {ECO:0000269|PubMed:19710017}. FT REGION 346 350 Substrate binding. FT REGION 576 580 Substrate binding. FT BINDING 213 213 Substrate. {ECO:0000269|PubMed:19710017}. FT BINDING 299 299 Substrate. {ECO:0000269|PubMed:19710017}. FT BINDING 435 435 Substrate; via carbonyl oxygen. FT {ECO:0000269|PubMed:19710017}. FT MOD_RES 204 204 N6-acetyllysine. FT {ECO:0000269|PubMed:19608861}. FT MOD_RES 453 453 Phosphotyrosine. {ECO:0000250}. FT MOD_RES 501 501 N6-acetyllysine. FT {ECO:0000269|PubMed:19608861}. FT VARIANT 42 42 P -> A (in dbSNP:rs1049402). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7753621, FT ECO:0000269|PubMed:7961834, FT ECO:0000269|PubMed:7962006}. FT /FTId=VAR_054865. FT VARIANT 125 125 E -> G (in CMT2D; phenotype overlapping FT with DSMA-V; dbSNP:rs28936972). FT {ECO:0000269|PubMed:12690580}. FT /FTId=VAR_018718. FT VARIANT 183 183 L -> P (in HMN5A). FT {ECO:0000269|PubMed:12690580}. FT /FTId=VAR_018719. FT VARIANT 268 268 T -> I (in dbSNP:rs2230310). FT /FTId=VAR_054866. FT VARIANT 294 294 G -> R (in CMT2D). FT {ECO:0000269|PubMed:12690580}. FT /FTId=VAR_018720. FT VARIANT 388 388 R -> Q (in dbSNP:rs17159287). FT /FTId=VAR_054867. FT VARIANT 580 580 G -> R (in HMN5A; higher dimerization FT stability but loss of activity; FT dbSNP:rs28937323). FT {ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17545306}. FT /FTId=VAR_018721. FT MUTAGEN 635 635 S->L: Reduced activity. FT {ECO:0000269|PubMed:17544401}. FT CONFLICT 9 18 Missing (in Ref. 3; BAG58412). FT {ECO:0000305}. FT CONFLICT 205 205 D -> G (in Ref. 3; BAG51964). FT {ECO:0000305}. FT CONFLICT 530 530 M -> I (in Ref. 2; AAA86443). FT {ECO:0000305}. FT CONFLICT 634 634 L -> S (in Ref. 3; BAG51964). FT {ECO:0000305}. FT HELIX 121 130 FT STRAND 133 136 FT HELIX 139 141 FT STRAND 148 150 FT HELIX 152 168 FT HELIX 170 173 FT STRAND 182 185 FT HELIX 186 191 FT HELIX 194 197 FT STRAND 199 208 FT STRAND 211 213 FT HELIX 214 227 FT STRAND 229 231 FT HELIX 233 243 FT TURN 244 248 FT HELIX 251 260 FT STRAND 266 268 FT STRAND 276 279 FT STRAND 283 285 FT STRAND 287 296 FT STRAND 298 300 FT HELIX 301 305 FT HELIX 308 314 FT TURN 315 317 FT STRAND 321 330 FT HELIX 339 341 FT STRAND 344 355 FT HELIX 357 359 FT HELIX 365 367 FT TURN 368 370 FT STRAND 372 376 FT HELIX 378 382 FT STRAND 388 391 FT HELIX 392 397 FT STRAND 400 402 FT HELIX 404 420 FT HELIX 424 426 FT STRAND 427 431 FT HELIX 434 436 FT STRAND 442 451 FT STRAND 454 462 FT HELIX 467 476 FT STRAND 482 484 FT HELIX 501 507 FT HELIX 512 519 FT HELIX 524 535 FT STRAND 541 544 FT STRAND 547 550 FT STRAND 552 554 FT STRAND 562 564 FT TURN 565 567 FT STRAND 568 570 FT STRAND 573 580 FT HELIX 581 592 FT STRAND 593 595 FT STRAND 597 600 FT STRAND 603 605 FT TURN 609 611 FT STRAND 615 621 FT TURN 625 627 FT HELIX 628 640 FT STRAND 645 647 FT STRAND 650 652 FT HELIX 654 663 FT STRAND 668 672 FT HELIX 674 677 FT STRAND 679 681 FT STRAND 683 688 FT TURN 689 691 FT STRAND 694 698 FT TURN 699 701 FT HELIX 702 710 FT STRAND 712 714 FT HELIX 716 722 SQ SEQUENCE 739 AA; 83166 MW; E4C001CEBF985C59 CRC64; MPSPRPVLLR GARAALLLLL PPRLLARPSL LLRRSLSAAS CPPISLPAAA SRSSMDGAGA EEVLAPLRLA VRQQGDLVRK LKEDKAPQVD VDKAVAELKA RKRVLEAKEL ALQPKDDIVD RAKMEDTLKR RFFYDQAFAI YGGVSGLYDF GPVGCALKNN IIQTWRQHFI QEEQILEIDC TMLTPEPVLK TSGHVDKFAD FMVKDVKNGE CFRADHLLKA HLQKLMSDKK CSVEKKSEME SVLAQLDNYG QQELADLFVN YNVKSPITGN DLSPPVSFNL MFKTFIGPGG NMPGYLRPET AQGIFLNFKR LLEFNQGKLP FAAAQIGNSF RNEISPRSGL IRVREFTMAE IEHFVDPSEK DHPKFQNVAD LHLYLYSAKA QVSGQSARKM RLGDAVEQGV INNTVLGYFI GRIYLYLTKV GISPDKLRFR QHMENEMAHY ACDCWDAESK TSYGWIEIVG CADRSCYDLS CHARATKVPL VAEKPLKEPK TVNVVQFEPS KGAIGKAYKK DAKLVMEYLA ICDECYITEM EMLLNEKGEF TIETEGKTFQ LTKDMINVKR FQKTLYVEEV VPNVIEPSFG LGRIMYTVFE HTFHVREGDE QRTFFSFPAV VAPFKCSVLP LSQNQEFMPF VKELSEALTR HGVSHKVDDS SGSIGRRYAR TDEIGVAFGV TIDFDTVNKT PHTATLRDRD SMRQIRAEIS ELPSIVQDLA NGNITWADVE ARYPLFEGQE TGKKETIEE //