ATTY_HUMAN
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 03-AUG-2022, entry version 203.
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}.
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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; P17735; -.
DR PeptideAtlas; P17735; -.
DR PRIDE; P17735; -.
DR ProteomicsDB; 53512; -.
DR Antibodypedia; 30099; 281 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 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; WRMGWII; -.
DR OrthoDB; 734452at2759; -.
DR PhylomeDB; P17735; -.
DR TreeFam; TF105999; -.
DR BioCyc; MetaCyc:HS06761-MON; -.
DR PathwayCommons; P17735; -.
DR Reactome; R-HSA-8963684; Tyrosine catabolism.
DR SignaLink; P17735; -.
DR UniPathway; UPA00139; UER00338.
DR BioGRID-ORCS; 6898; 9 hits in 1072 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 104 other tissues.
DR ExpressionAtlas; P17735; baseline and differential.
DR Genevisible; P17735; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
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 Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 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 Pfam; PF00155; Aminotran_1_2; 1.
DR Pfam; PF07706; TAT_ubiq; 1.
DR PIRSF; PIRSF000517; Tyr_transaminase; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR01264; tyr_amTase_E; 1.
DR TIGRFAMs; TIGR01265; tyr_nico_aTase; 1.
DR PROSITE; PS00105; AA_TRANSFER_CLASS_1; 1.
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
