ATTY_CAEEL
ID ATTY_CAEEL Reviewed; 464 AA.
AC Q93703;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Tyrosine aminotransferase {ECO:0000255|PIRNR:PIRNR000517};
DE Short=TAT {ECO:0000255|PIRNR:PIRNR000517};
DE EC=2.6.1.5 {ECO:0000255|PIRNR:PIRNR000517, ECO:0000269|PubMed:31043480};
DE AltName: Full=L-tyrosine:2-oxoglutarate aminotransferase {ECO:0000250|UniProtKB:P17735};
GN Name=tatn-1 {ECO:0000312|WormBase:F42D1.2};
GN ORFNames=F42D1.2 {ECO:0000312|WormBase:F42D1.2};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-224.
RX PubMed=18227072; DOI=10.1074/jbc.m708341200;
RA Fisher A.L., Page K.E., Lithgow G.J., Nash L.;
RT "The Caenorhabditis elegans K10C2.4 gene encodes a member of the
RT fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of
RT type I tyrosinemia.";
RL J. Biol. Chem. 283:9127-9135(2008).
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLY-171 AND PRO-224.
RX PubMed=24385923; DOI=10.1371/journal.pgen.1004020;
RA Ferguson A.A., Roy S., Kormanik K.N., Kim Y., Dumas K.J., Ritov V.B.,
RA Matern D., Hu P.J., Fisher A.L.;
RT "TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal
RT that influences developmental decisions and longevity in Caenorhabditis
RT elegans.";
RL PLoS Genet. 9:e1004020-e1004020(2013).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF GLY-171.
RX PubMed=31043480; DOI=10.1074/jbc.ra118.004426;
RA Ipson B.R., Green R.A., Wilson J.T., Watson J.N., Faull K.F., Fisher A.L.;
RT "Tyrosine aminotransferase is involved in the oxidative stress response by
RT metabolizing meta-tyrosine in Caenorhabditis elegans.";
RL J. Biol. Chem. 294:9536-9554(2019).
CC -!- FUNCTION: Transaminase involved in tyrosine breakdown (PubMed:24385923,
CC PubMed:31043480). Converts tyrosine to p-hydroxyphenylpyruvate
CC (PubMed:31043480). Has no transaminase activity towards phenylalanine
CC (PubMed:31043480). Plays protective role against oxidative stress,
CC metabolizing meta-tyrosine and negatively regulating its accumulation
CC (PubMed:31043480). Plays a role in modulating the daf-2/insulin
CC receptor-like transduction pathway through regulating tyrosine levels
CC (PubMed:24385923). Negatively regulates dauer formation
CC (PubMed:24385923). Plays a role in longevity (PubMed:24385923,
CC PubMed:31043480). {ECO:0000269|PubMed:24385923,
CC ECO:0000269|PubMed:31043480}.
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:0000255|PIRNR:PIRNR000517,
CC ECO:0000269|PubMed:31043480};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-hydroxy-L-phenylalanine = 3-(3-
CC hydroxyphenyl)pyruvate + L-glutamate; Xref=Rhea:RHEA:67168,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:29985, ChEBI:CHEBI:78290,
CC ChEBI:CHEBI:167869; Evidence={ECO:0000269|PubMed:31043480};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|PIRNR:PIRNR000517,
CC ECO:0000255|PIRSR:PIRSR000517-1};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.23 mM for tyrosine (para-tyrosine)
CC {ECO:0000269|PubMed:31043480};
CC KM=7.57 mM for meta-tyrosine {ECO:0000269|PubMed:31043480};
CC Note=kcat is 2852 sec(-1) with tyrosine (para-tyrosine) as substrate
CC (PubMed:31043480). kcat is 2520 sec(-1) with meta-tyrosine as
CC substrate (PubMed:31043480). {ECO:0000269|PubMed:31043480};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 2/6.
CC {ECO:0000255|PIRNR:PIRNR000517}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|PIRNR:PIRNR000517}.
CC -!- TISSUE SPECIFICITY: Expressed in the muscle (PubMed:18227072).
CC Expressed in the hypodermis and intestine (PubMed:18227072,
CC PubMed:24385923). {ECO:0000269|PubMed:18227072,
CC ECO:0000269|PubMed:24385923}.
CC -!- INDUCTION: Up-regulated in response to oxidative stress.
CC {ECO:0000269|PubMed:31043480}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown increases lifespan by
CC 17.8%, and reduces tyrosine aminotransferase activity by 75% thus
CC increasing tyrosine levels (PubMed:24385923, PubMed:31043480). RNAi-
CC mediated knockdown delays reproductive adult development in response to
CC oxidative stress induced by the superoxide paraquat (PubMed:31043480).
CC RNAi-mediated knockdown increases dauer formation in eak-4 mg348, eak-3
CC mg344, eak-5 mg337, eak-2 mg433, or eak-7 tm3188 mutant backgrounds at
CC 25 degrees Celsius (PubMed:24385923). RNAi-mediated knockdown increases
CC aak-2 phosphorylation, but does not impair energy production in a eak-4
CC mg348 mutant background (PubMed:24385923). RNAi-mediated knockdown
CC results in a reduced lifespan in an aak-2 gt33 mutant background
CC (PubMed:24385923). RNAi-mediated knockdown results in reduced dauer
CC formation in an eak-4 mg348 and aak-2 gt33 mutant background
CC (PubMed:24385923). RNAi-mediated knockdown extends the lifespan of eak-
CC 7 tm3188 mutants (PubMed:24385923). RNAi-mediated knockdown together
CC with fah-1 RNAi rescues the impaired growth and fertility defects in
CC the single fah-1 RNAi mutant (PubMed:18227072).
CC {ECO:0000269|PubMed:18227072, ECO:0000269|PubMed:24385923,
CC ECO:0000269|PubMed:31043480}.
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000255|PIRNR:PIRNR000517}.
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DR EMBL; BX284606; CAB03090.1; -; Genomic_DNA.
DR PIR; T22087; T22087.
DR RefSeq; NP_510454.1; NM_078053.5.
DR AlphaFoldDB; Q93703; -.
DR SMR; Q93703; -.
DR DIP; DIP-24643N; -.
DR IntAct; Q93703; 2.
DR STRING; 6239.F42D1.2; -.
DR EPD; Q93703; -.
DR PaxDb; Q93703; -.
DR PeptideAtlas; Q93703; -.
DR EnsemblMetazoa; F42D1.2.1; F42D1.2.1; WBGene00009628.
DR GeneID; 181574; -.
DR KEGG; cel:CELE_F42D1.2; -.
DR UCSC; F42D1.2.1; c. elegans.
DR CTD; 181574; -.
DR WormBase; F42D1.2; CE10298; WBGene00009628; tatn-1.
DR eggNOG; KOG0259; Eukaryota.
DR GeneTree; ENSGT00940000156704; -.
DR HOGENOM; CLU_017584_4_2_1; -.
DR InParanoid; Q93703; -.
DR OMA; WRMGWII; -.
DR OrthoDB; 734452at2759; -.
DR PhylomeDB; Q93703; -.
DR Reactome; R-CEL-8963684; Tyrosine catabolism.
DR UniPathway; UPA00139; UER00338.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00009628; Expressed in larva and 3 other tissues.
DR GO; GO:0004838; F:L-tyrosine:2-oxoglutarate aminotransferase activity; IBA:GO_Central.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR GO; GO:0043053; P:dauer entry; IGI:CACAO.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR GO; GO:0006572; P:tyrosine catabolic process; IBA:GO_Central.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR005958; TyrNic_aminoTrfase.
DR InterPro; IPR005957; Tyrosine_aminoTrfase.
DR Pfam; PF00155; Aminotran_1_2; 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; PS00626; RCC1_2; 1.
PE 1: Evidence at protein level;
KW Aminotransferase; Pyridoxal phosphate; Reference proteome; Transferase;
KW Tyrosine catabolism.
FT CHAIN 1..464
FT /note="Tyrosine aminotransferase"
FT /id="PRO_0000453178"
FT MOD_RES 284
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000255|PIRSR:PIRSR000517-1"
FT MUTAGEN 171
FT /note="G->E: In qd182; reduces tyrosine aminotransferase
FT activity by 90% and results in increased tyrosine levels.
FT Delays development, increases embryonic lethality and
FT results in germline defects in response to increased levels
FT of meta-tyrosine, but not in response to increased levels
FT of tyrosine (para-tyrosine). Delays the development to
FT reproductive adults in response to oxidative stress induced
FT by the superoxide paraquat, with only 4.9% developing into
FT fertile adults. Increases dauer formation in an eak-4 mg348
FT mutant background. Reduces dauer formation in an eak-4
FT mg348 and aak-2 gt33 mutant background."
FT /evidence="ECO:0000269|PubMed:24385923,
FT ECO:0000269|PubMed:31043480"
FT MUTAGEN 224
FT /note="P->S: Increases dauer formation in an eak-4 mg348
FT mutant background. Suppresses fah-1 RNAi-mediated
FT toxicity."
FT /evidence="ECO:0000269|PubMed:18227072,
FT ECO:0000269|PubMed:24385923"
SQ SEQUENCE 464 AA; 51031 MW; 5808CB5DE0AB3EA3 CRC64;
MQTLMSHSRI TPLPGAITKE EIKNQLLVHE RRFLSKPNRK DQWNVLPQSA HSKNTVNPVR
KIADACAVPP HPEKKVIKLH LGDPSVGGKL PPSEIAVQAM HESVSSHMFD GYGPAVGALA
AREAIVERYS SADNVFTADD VVLASGCSHA LQMAIEAVAN AGENILVPHP GFPLYSTLCR
PHNIVDKPYK IDMTGEDVRI DLSYMATIID DNTKAIIVNN PGNPTGGVFT KEHLEEILAF
AHQYKLIIIA DEIYGDLVYN GATFYPLASL SPKVPIITCD GIAKRWMVPG WRLGWLIIHN
HFGVLTDVKN GIVALSQKIV GPCSLVQGAL PKILRETPED YFVYTRNVIE TNANIVDSIL
ADVPGMRVVK PKGAMYMMVN ISRTAYGSDV SFCQNLIREE SVFCLPGQAF SAPGYFRVVL
TCGSEDMEEA ALRIREFCYR NFNQHSDSED SSDEGLDLSA MESD
