ID TMLH_HUMAN Reviewed; 421 AA. AC Q9NVH6; A8K6M9; B4E3R3; Q5TZB5; Q6IA90; Q8TBT0; DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 29-APR-2015, entry version 124. DE RecName: Full=Trimethyllysine dioxygenase, mitochondrial; DE EC=1.14.11.8; DE AltName: Full=Epsilon-trimethyllysine 2-oxoglutarate dioxygenase; DE AltName: Full=Epsilon-trimethyllysine hydroxylase; DE AltName: Full=TML hydroxylase; DE AltName: Full=TML-alpha-ketoglutarate dioxygenase; DE Short=TML dioxygenase; DE Short=TMLD; DE Flags: Precursor; GN Name=TMLHE; Synonyms=TMLH; 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] (ISOFORM 1). RX PubMed=11431483; DOI=10.1074/jbc.M105929200; RA Vaz F.M., Ofman R., Westinga K., Back J.W., Wanders R.J.A.; RT "Molecular and biochemical characterization of rat epsilon-N- RT trimethyllysine hydroxylase, the first enzyme of carnitine RT biosynthesis."; RL J. Biol. Chem. 276:33512-33517(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 66-332 (ISOFORM 3). RC TISSUE=Placenta, Teratocarcinoma, Thymus, and Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RA Bechtel S., Schupp I., Duda A., Wellenreuther R., Mehrle A., RA Ruschke V., Poustka A., Wiemann S.; RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Pancreas; 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 [7] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE RP SITE, MUTAGENESIS OF HIS-389, AND ALTERNATIVE SPLICING (ISOFORMS 1 AND RP 2). RX PubMed=15754339; DOI=10.1002/jcp.20332; RA Monfregola J., Cevenini A., Terracciano A., van Vlies N., Arbucci S., RA Wanders R.J., D'Urso M., Vaz F.M., Ursini M.V.; RT "Functional analysis of TMLH variants and definition of domains RT required for catalytic activity and mitochondrial targeting."; RL J. Cell. Physiol. 204:839-847(2005). RN [8] RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=17408883; DOI=10.1016/j.gene.2007.02.012; RA Monfregola J., Napolitano G., Conte I., Cevenini A., Migliaccio C., RA D'Urso M., Ursini M.V.; RT "Functional characterization of the TMLH gene: promoter analysis, in RT situ hybridization, identification and mapping of alternative splicing RT variants."; RL Gene 395:86-97(2007). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-236, AND IDENTIFICATION BY RP 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 [10] RP INVOLVEMENT IN TMLHED. RX PubMed=21865298; DOI=10.1093/hmg/ddr363; RA Celestino-Soper P.B., Shaw C.A., Sanders S.J., Li J., Murtha M.T., RA Ercan-Sencicek A.G., Davis L., Thomson S., Gambin T., Chinault A.C., RA Ou Z., German J.R., Milosavljevic A., Sutcliffe J.S., Cook E.H. Jr., RA Stankiewicz P., State M.W., Beaudet A.L.; RT "Use of array CGH to detect exonic copy number variants throughout the RT genome in autism families detects a novel deletion in TMLHE."; RL Hum. Mol. Genet. 20:4360-4370(2011). CC -!- FUNCTION: Converts trimethyllysine (TML) into CC hydroxytrimethyllysine (HTML). CC -!- CATALYTIC ACTIVITY: N(6),N(6),N(6)-trimethyl-L-lysine + 2- CC oxoglutarate + O(2) = 3-hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine CC + succinate + CO(2). CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC -!- PATHWAY: Amine and polyamine biosynthesis; carnitine biosynthesis. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:15754339}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=8; CC Name=1; Synonyms=TMLHa, TMLH1a; CC IsoId=Q9NVH6-1; Sequence=Displayed; CC Name=2; Synonyms=TMLHb; CC IsoId=Q9NVH6-3; Sequence=VSP_042278; CC Note=Produced by alternative splicing. Lacks enzymatic CC activity.; CC Name=3; Synonyms=TMLHc; CC IsoId=Q9NVH6-4; Sequence=VSP_042279; CC Note=Produced by alternative splicing. Lacks enzymatic CC activity.; CC Name=4; Synonyms=TMLHd; CC IsoId=Q9NVH6-2; Sequence=VSP_021579; CC Note=Produced by alternative splicing. Lacks enzymatic CC activity.; CC Name=5; Synonyms=TMLHe; CC IsoId=Q9NVH6-5; Sequence=VSP_042280, VSP_042281; CC Note=Produced by alternative splicing. Lacks enzymatic CC activity.; CC Name=6; Synonyms=TMLHf; CC IsoId=Q9NVH6-6; Sequence=VSP_042277; CC Note=Produced by alternative splicing. Lacks the mitochondrial CC transit signal.; CC Name=7; Synonyms=TMLHg; CC IsoId=Q9NVH6-7; Sequence=VSP_042275; CC Note=Produced by alternative splicing.; CC Name=8; Synonyms=TMLH1b; CC IsoId=Q9NVH6-8; Sequence=VSP_042276; CC Note=Produced by alternative promoter usage. Although the CC expression of the alternative 5' exon has been detected by PCR CC in heart and skeletal muscle, the identification of the CC alternative promoter leading to this form remains elusive CC (PubMed:17408883). {ECO:0000305|PubMed:17408883}; CC -!- TISSUE SPECIFICITY: All isoforms, but isoform 8, are widely CC expressed in adult and fetal tissues. Isoform 8 is restricted to CC heart and skeletal muscle. {ECO:0000269|PubMed:15754339, CC ECO:0000269|PubMed:17408883}. CC -!- DISEASE: Epsilon-trimethyllysine hydroxylase deficiency (TMLHED) CC [MIM:300872]: An inborn error of carnitine biosynthesis associated CC with an increased risk for developing autistic behavior. Autism is CC a complex multifactorial, pervasive developmental disorder CC characterized by impairments in reciprocal social interaction and CC communication, restricted and stereotyped patterns of interests CC and activities, and the presence of developmental abnormalities by CC 3 years of age. Most individuals with autism also manifest CC moderate mental retardation. {ECO:0000269|PubMed:21865298}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the gamma-BBH/TMLD family. {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; AF373407; AAL01871.1; -; mRNA. DR EMBL; AK001589; BAA91775.1; -; mRNA. DR EMBL; AK291694; BAF84383.1; -; mRNA. DR EMBL; AK304830; BAG65575.1; -; mRNA. DR EMBL; AK310667; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CR457265; CAG33546.1; -; mRNA. DR EMBL; AM393196; CAL38074.1; -; mRNA. DR EMBL; BX276110; CAH71441.1; -; Genomic_DNA. DR EMBL; BX276110; CAH71442.1; -; Genomic_DNA. DR EMBL; BC025269; AAH25269.1; -; mRNA. DR CCDS; CCDS14768.1; -. [Q9NVH6-1] DR CCDS; CCDS55547.1; -. [Q9NVH6-2] DR RefSeq; NP_001171726.1; NM_001184797.1. [Q9NVH6-2] DR RefSeq; NP_060666.1; NM_018196.3. [Q9NVH6-1] DR UniGene; Hs.133321; -. DR ProteinModelPortal; Q9NVH6; -. DR SMR; Q9NVH6; 74-417. DR BioGrid; 120513; 4. DR IntAct; Q9NVH6; 6. DR MINT; MINT-3074990; -. DR STRING; 9606.ENSP00000335261; -. DR DrugBank; DB00139; Succinic acid. DR DrugBank; DB00126; Vitamin C. DR PhosphoSite; Q9NVH6; -. DR BioMuta; TMLHE; -. DR DMDM; 21542295; -. DR MaxQB; Q9NVH6; -. DR PaxDb; Q9NVH6; -. DR PRIDE; Q9NVH6; -. DR DNASU; 55217; -. DR Ensembl; ENST00000334398; ENSP00000335261; ENSG00000185973. [Q9NVH6-1] DR Ensembl; ENST00000369439; ENSP00000358447; ENSG00000185973. [Q9NVH6-2] DR GeneID; 55217; -. DR KEGG; hsa:55217; -. DR UCSC; uc004fnn.3; human. [Q9NVH6-1] DR UCSC; uc004fnp.4; human. [Q9NVH6-2] DR CTD; 55217; -. DR GeneCards; GC0XM154719; -. DR HGNC; HGNC:18308; TMLHE. DR HPA; HPA034589; -. DR HPA; HPA040331; -. DR MIM; 300777; gene. DR MIM; 300872; phenotype. DR neXtProt; NX_Q9NVH6; -. DR Orphanet; 106; Autism. DR PharmGKB; PA38311; -. DR eggNOG; COG2175; -. DR GeneTree; ENSGT00530000063582; -. DR HOGENOM; HOG000210004; -. DR HOVERGEN; HBG035650; -. DR InParanoid; Q9NVH6; -. DR KO; K00474; -. DR OMA; HPRILWN; -. DR OrthoDB; EOG7XPZ5P; -. DR PhylomeDB; Q9NVH6; -. DR TreeFam; TF313805; -. DR BioCyc; MetaCyc:HS08089-MONOMER; -. DR BRENDA; 1.14.11.8; 2681. DR Reactome; REACT_2125; Carnitine synthesis. DR UniPathway; UPA00118; -. DR GeneWiki; TMLHE; -. DR GenomeRNAi; 55217; -. DR NextBio; 59184; -. DR PRO; PR:Q9NVH6; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q9NVH6; -. DR CleanEx; HS_TMLHE; -. DR Genevestigator; Q9NVH6; -. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:InterPro. DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:Ensembl. DR GO; GO:0050353; F:trimethyllysine dioxygenase activity; IDA:BHF-UCL. DR GO; GO:0045329; P:carnitine biosynthetic process; IDA:BHF-UCL. DR GO; GO:0034641; P:cellular nitrogen compound metabolic process; TAS:Reactome. DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:BHF-UCL. DR GO; GO:0055114; P:oxidation-reduction process; IDA:GOC. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR InterPro; IPR010376; DUF971. DR InterPro; IPR003819; Taurine_dOase. DR InterPro; IPR012776; Trimethyllysine_dOase. DR Pfam; PF06155; DUF971; 1. DR Pfam; PF02668; TauD; 1. DR TIGRFAMs; TIGR02410; carnitine_TMLD; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative promoter usage; Alternative splicing; KW Carnitine biosynthesis; Complete proteome; Dioxygenase; Iron; KW Metal-binding; Mitochondrion; Oxidoreductase; Reference proteome; KW Transit peptide. FT TRANSIT 1 15 Mitochondrion. FT {ECO:0000269|PubMed:15754339}. FT CHAIN 16 421 Trimethyllysine dioxygenase, FT mitochondrial. FT /FTId=PRO_0000002795. FT METAL 242 242 Iron; catalytic. {ECO:0000250}. FT METAL 244 244 Iron; catalytic. {ECO:0000250}. FT METAL 389 389 Iron; catalytic. {ECO:0000250}. FT MOD_RES 179 179 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q91ZE0}. FT MOD_RES 236 236 N6-acetyllysine. FT {ECO:0000269|PubMed:19608861}. FT VAR_SEQ 1 68 Missing (in isoform 7). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042275. FT VAR_SEQ 1 1 M -> MKIDSFLPILRM (in isoform 8). FT {ECO:0000305}. FT /FTId=VSP_042276. FT VAR_SEQ 61 120 ELKYANTVMRFDYVWLRDHCRSASCYNSKTHQRSLDTASVD FT LCIKPKTIRLDETTLFFTW -> G (in isoform 6). FT {ECO:0000305}. FT /FTId=VSP_042277. FT VAR_SEQ 333 421 YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVK FT LKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTA FT RLLGLQA -> VLRSWCSTRTIEATSKEIKLYIVCRYSYFG FT ETLFPRSKETVTSLPHMCAYKAAATNRPWLSGVFYTI (in FT isoform 2). {ECO:0000305}. FT /FTId=VSP_042278. FT VAR_SEQ 333 421 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042279. FT VAR_SEQ 333 421 YNNYDRAVINTVPYDVVHRWYTAHRTLTIELRRPENEFWVK FT LKPGRVLFIDNWRVLHGRECFTGYRQLCGCYLTRDDVLNTA FT RLLGLQA -> LFKEKQNTVNRQWNSSLQCDIPERILTYRH FT FVSGTSIEHRGSLI (in isoform 4). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.4}. FT /FTId=VSP_021579. FT VAR_SEQ 380 383 LFID -> GPN (in isoform 5). FT {ECO:0000305}. FT /FTId=VSP_042280. FT VAR_SEQ 384 421 Missing (in isoform 5). {ECO:0000305}. FT /FTId=VSP_042281. FT MUTAGEN 389 389 H->L: No catalytic activity. FT {ECO:0000269|PubMed:15754339}. FT CONFLICT 66 66 N -> D (in Ref. 3; CAG33546). FT {ECO:0000305}. FT CONFLICT 170 170 F -> S (in Ref. 2; BAF84383). FT {ECO:0000305}. SQ SEQUENCE 421 AA; 49518 MW; 4E55DF349B866B43 CRC64; MWYHRLSHLH SRLQDLLKGG VIYPALPQPN FKSLLPLAVH WHHTASKSLT CAWQQHEDHF ELKYANTVMR FDYVWLRDHC RSASCYNSKT HQRSLDTASV DLCIKPKTIR LDETTLFFTW PDGHVTKYDL NWLVKNSYEG QKQKVIQPRI LWNAEIYQQA QVPSVDCQSF LETNEGLKKF LQNFLLYGIA FVENVPPTQE HTEKLAERIS LIRETIYGRM WYFTSDFSRG DTAYTKLALD RHTDTTYFQE PCGIQVFHCL KHEGTGGRTL LVDGFYAAEQ VLQKAPEEFE LLSKVPLKHE YIEDVGECHN HMIGIGPVLN IYPWNKELYL IRYNNYDRAV INTVPYDVVH RWYTAHRTLT IELRRPENEF WVKLKPGRVL FIDNWRVLHG RECFTGYRQL CGCYLTRDDV LNTARLLGLQ A //