ID ATTY_HUMAN Reviewed; 454 AA. AC P17735; B2R8I1; D3DWS2; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 24-JAN-2024, entry version 211. DE RecName: Full=Tyrosine aminotransferase; DE Short=TAT; DE EC=2.6.1.5; DE AltName: Full=L-tyrosine:2-oxoglutarate aminotransferase; GN Name=TAT; 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]. RX PubMed=1973834; DOI=10.1093/nar/18.13.3853; RA Rettenmeier R., Natt E., Zentgraf H., Scherer G.; RT "Isolation and characterization of the human tyrosine aminotransferase RT gene."; RL Nucleic Acids Res. 18:3853-3861(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7908801; RA Zelenin S.M., Mertvetsov N.P.; RT "Nucleotide sequence of the human tyrosine aminotransferase gene."; RL Bioorg. Khim. 20:196-204(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=7999802; DOI=10.1016/0167-4781(94)00191-5; RA Seralini G.E., Luu-The V., Labrie F.; RT "Cloning and expression of human tyrosine aminotransferase cDNA."; RL Biochim. Biophys. Acta 1260:97-101(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 [6] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ILE-294. RX PubMed=16640556; DOI=10.1111/j.1742-4658.2006.05202.x; RA Sivaraman S., Kirsch J.F.; RT "The narrow substrate specificity of human tyrosine aminotransferase -- the RT enzyme deficient in tyrosinemia type II."; RL FEBS J. 273:1920-1929(2006). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 38-444 IN COMPLEX WITH PYRIDOXAL RP PHOSPHATE. RG Structural genomics consortium (SGC); RT "Human tyrosine aminotransferase."; RL Submitted (AUG-2008) to the PDB data bank. RN [9] RP VARIANT TYRSN2 VAL-362. RX PubMed=1357662; DOI=10.1073/pnas.89.19.9297; RA Natt E., Kida K., Odievre M., di Rocco M., Scherer G.; RT "Point mutations in the tyrosine aminotransferase gene in tyrosinemia type RT II."; RL Proc. Natl. Acad. Sci. U.S.A. 89:9297-9301(1992). CC -!- FUNCTION: Transaminase involved in tyrosine breakdown. Converts CC tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, CC using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has CC much lower affinity and transaminase activity towards phenylalanine. CC {ECO:0000269|PubMed:16640556, ECO:0000269|PubMed:7999802}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-tyrosine = 3-(4-hydroxyphenyl)pyruvate + L- CC glutamate; Xref=Rhea:RHEA:15093, ChEBI:CHEBI:16810, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:36242, ChEBI:CHEBI:58315; EC=2.6.1.5; CC Evidence={ECO:0000269|PubMed:16640556, ECO:0000269|PubMed:7999802}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC Evidence={ECO:0000269|Ref.8}; CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation; CC acetoacetate and fumarate from L-phenylalanine: step 2/6. CC -!- SUBUNIT: Homodimer. {ECO:0000305|Ref.8}. CC -!- INTERACTION: CC P17735; P15104: GLUL; NbExp=3; IntAct=EBI-12046643, EBI-746653; CC P17735; P28799: GRN; NbExp=3; IntAct=EBI-12046643, EBI-747754; CC P17735; P28799-2: GRN; NbExp=3; IntAct=EBI-12046643, EBI-25860013; CC P17735; P17735: TAT; NbExp=5; IntAct=EBI-12046643, EBI-12046643; CC P17735; Q05086: UBE3A; NbExp=3; IntAct=EBI-12046643, EBI-954357; CC P17735; Q05086-3: UBE3A; NbExp=11; IntAct=EBI-12046643, EBI-11026619; CC -!- DISEASE: Tyrosinemia 2 (TYRSN2) [MIM:276600]: An inborn error of CC metabolism characterized by elevations of tyrosine in the blood and CC urine, and oculocutaneous manifestations. Typical features include CC palmoplantar keratosis, painful corneal ulcers, and intellectual CC disability. {ECO:0000269|PubMed:1357662}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent CC aminotransferase 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; X52520; CAA36750.1; -; mRNA. DR EMBL; X52509; CAA36749.1; -; Genomic_DNA. DR EMBL; X52510; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52511; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52512; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52513; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52514; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52515; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52516; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52517; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52518; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X52519; CAA36749.1; JOINED; Genomic_DNA. DR EMBL; X55675; CAA39210.1; -; mRNA. DR EMBL; AK313380; BAG36178.1; -; mRNA. DR EMBL; CH471166; EAW59230.1; -; Genomic_DNA. DR EMBL; CH471166; EAW59231.1; -; Genomic_DNA. DR CCDS; CCDS10903.1; -. DR PIR; S10887; S10887. DR RefSeq; NP_000344.1; NM_000353.2. DR PDB; 3DYD; X-ray; 2.30 A; A/B=41-444. DR PDBsum; 3DYD; -. DR AlphaFoldDB; P17735; -. DR SMR; P17735; -. DR BioGRID; 112761; 6. DR IntAct; P17735; 6. DR STRING; 9606.ENSP00000348234; -. DR ChEMBL; CHEMBL3043; -. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB00120; Phenylalanine. DR DrugBank; DB00114; Pyridoxal phosphate. DR DrugBank; DB00135; Tyrosine. DR iPTMnet; P17735; -. DR PhosphoSitePlus; P17735; -. DR BioMuta; TAT; -. DR DMDM; 114713; -. DR MassIVE; P17735; -. DR MaxQB; P17735; -. DR PaxDb; 9606-ENSP00000348234; -. DR PeptideAtlas; P17735; -. DR ProteomicsDB; 53512; -. DR Antibodypedia; 30099; 316 antibodies from 28 providers. DR DNASU; 6898; -. DR Ensembl; ENST00000355962.5; ENSP00000348234.4; ENSG00000198650.11. DR GeneID; 6898; -. DR KEGG; hsa:6898; -. DR MANE-Select; ENST00000355962.5; ENSP00000348234.4; NM_000353.3; NP_000344.1. DR UCSC; uc002fap.3; human. DR AGR; HGNC:11573; -. DR CTD; 6898; -. DR DisGeNET; 6898; -. DR GeneCards; TAT; -. DR HGNC; HGNC:11573; TAT. DR HPA; ENSG00000198650; Tissue enriched (liver). DR MalaCards; TAT; -. DR MIM; 276600; phenotype. DR MIM; 613018; gene. DR neXtProt; NX_P17735; -. DR OpenTargets; ENSG00000198650; -. DR Orphanet; 28378; Tyrosinemia type 2. DR PharmGKB; PA36338; -. DR VEuPathDB; HostDB:ENSG00000198650; -. DR eggNOG; KOG0259; Eukaryota. DR GeneTree; ENSGT00940000156704; -. DR HOGENOM; CLU_017584_4_2_1; -. DR InParanoid; P17735; -. DR OMA; CALDLCI; -. DR OrthoDB; 5474881at2759; -. DR PhylomeDB; P17735; -. DR TreeFam; TF105999; -. DR BioCyc; MetaCyc:HS06761-MONOMER; -. DR PathwayCommons; P17735; -. DR Reactome; R-HSA-8963684; Tyrosine catabolism. DR SignaLink; P17735; -. DR UniPathway; UPA00139; UER00338. DR BioGRID-ORCS; 6898; 9 hits in 1155 CRISPR screens. DR ChiTaRS; TAT; human. DR EvolutionaryTrace; P17735; -. DR GenomeRNAi; 6898; -. DR Pharos; P17735; Tbio. DR PRO; PR:P17735; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P17735; Protein. DR Bgee; ENSG00000198650; Expressed in right lobe of liver and 105 other cell types or tissues. DR ExpressionAtlas; P17735; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004838; F:L-tyrosine:2-oxoglutarate aminotransferase activity; IDA:UniProtKB. DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro. DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:UniProtKB. DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro. DR GO; GO:0006536; P:glutamate metabolic process; IDA:UniProtKB. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central. DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl. DR GO; GO:0046689; P:response to mercury ion; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0006572; P:tyrosine catabolic process; IDA:UniProtKB. DR CDD; cd00609; AAT_like; 1. DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1. DR InterPro; IPR004839; Aminotransferase_I/II. DR InterPro; IPR004838; NHTrfase_class1_PyrdxlP-BS. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small. DR InterPro; IPR011715; Tyr_aminoTrfase_ubiquitination. DR InterPro; IPR005958; TyrNic_aminoTrfase. DR InterPro; IPR005957; Tyrosine_aminoTrfase. DR NCBIfam; TIGR01264; tyr_amTase_E; 1. DR NCBIfam; TIGR01265; tyr_nico_aTase; 1. DR PANTHER; PTHR45744; TYROSINE AMINOTRANSFERASE; 1. DR PANTHER; PTHR45744:SF2; TYROSINE AMINOTRANSFERASE; 1. DR Pfam; PF00155; Aminotran_1_2; 1. DR Pfam; PF07706; TAT_ubiq; 1. DR PIRSF; PIRSF000517; Tyr_transaminase; 1. DR SUPFAM; SSF53383; PLP-dependent transferases; 1. DR PROSITE; PS00105; AA_TRANSFER_CLASS_1; 1. DR Genevisible; P17735; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aminotransferase; Disease variant; KW Intellectual disability; Palmoplantar keratoderma; KW Phenylalanine catabolism; Phosphoprotein; Pyridoxal phosphate; KW Reference proteome; Transferase; Tyrosine catabolism. FT CHAIN 1..454 FT /note="Tyrosine aminotransferase" FT /id="PRO_0000123887" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P04694" FT MOD_RES 280 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:3DYD" FT MOD_RES 448 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VARIANT 70 FT /note="N -> D (in dbSNP:rs16973344)" FT /id="VAR_048226" FT VARIANT 362 FT /note="G -> V (in TYRSN2; dbSNP:rs587776511)" FT /evidence="ECO:0000269|PubMed:1357662" FT /id="VAR_000560" FT MUTAGEN 294 FT /note="I->A: Reduced catalytic activity." FT /evidence="ECO:0000269|PubMed:16640556" FT TURN 81..84 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 91..103 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 116..126 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 135..137 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 138..143 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 144..155 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 171..178 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 182..188 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 198..202 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 209..217 FT /evidence="ECO:0007829|PDB:3DYD" FT TURN 219..221 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 227..239 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 244..247 FT /evidence="ECO:0007829|PDB:3DYD" FT TURN 249..252 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 263..266 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 272..278 FT /evidence="ECO:0007829|PDB:3DYD" FT TURN 279..281 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 285..287 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 290..295 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 302..316 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 321..333 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 336..359 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 363..366 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 373..378 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 380..382 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 389..400 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 407..410 FT /evidence="ECO:0007829|PDB:3DYD" FT STRAND 415..420 FT /evidence="ECO:0007829|PDB:3DYD" FT HELIX 424..441 FT /evidence="ECO:0007829|PDB:3DYD" SQ SEQUENCE 454 AA; 50399 MW; 82B5B24F3B2CE489 CRC64; MDPYMIQMSS KGNLPSILDV HVNVGGRSSV PGKMKGRKAR WSVRPSDMAK KTFNPIRAIV DNMKVKPNPN KTMISLSIGD PTVFGNLPTD PEVTQAMKDA LDSGKYNGYA PSIGFLSSRE EIASYYHCPE APLEAKDVIL TSGCSQAIDL CLAVLANPGQ NILVPRPGFS LYKTLAESMG IEVKLYNLLP EKSWEIDLKQ LEYLIDEKTA CLIVNNPSNP CGSVFSKRHL QKILAVAARQ CVPILADEIY GDMVFSDCKY EPLATLSTDV PILSCGGLAK RWLVPGWRLG WILIHDRRDI FGNEIRDGLV KLSQRILGPC TIVQGALKSI LCRTPGEFYH NTLSFLKSNA DLCYGALAAI PGLRPVRPSG AMYLMVGIEM EHFPEFENDV EFTERLVAEQ SVHCLPATCF EYPNFIRVVI TVPEVMMLEA CSRIQEFCEQ HYHCAEGSQE ECDK //