P17735 (ATTY_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine aminotransferase
Short name=TAT
EC=2.6.1.5

Alternative name(s):
L-tyrosine:2-oxoglutarate aminotransferase

Gene names

Name:

TAT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	454 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has no transaminase activity towards phenylalanine. Ref.3 Ref.6
Catalytic activity	L-tyrosine + 2-oxoglutarate = 4-hydroxyphenylpyruvate + L-glutamate. Ref.3 Ref.6
Cofactor	Pyridoxal phosphate.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 2/6.
Subunit structure	Homodimer Probable.
Involvement in disease	Defects in TAT are the cause of tyrosinemia type 2 (TYRO2) [MIM:276600]; also known as Richner-Hanhart syndrome. TYRO2 is an inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and mental retardation. Ref.8
Sequence similarities	Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.

Ontologies

Keywords
Biological process	Phenylalanine catabolism Tyrosine catabolism
Coding sequence diversity	Polymorphism
Disease	Disease mutation Mental retardation Palmoplantar keratoderma
Ligand	Pyridoxal phosphate
Molecular function	Aminotransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	2-oxoglutarate metabolic process Inferred from direct assay Ref.3. Source: UniProtKB L-phenylalanine catabolic process Non-traceable author statement. Source: UniProtKB glutamate metabolic process Inferred from direct assay Ref.3. Source: UniProtKB tyrosine catabolic process Inferred from direct assay Ref.3. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	1-aminocyclopropane-1-carboxylate synthase activity Inferred from electronic annotation. Source: InterPro L-phenylalanine:2-oxoglutarate aminotransferase activity Inferred from electronic annotation. Source: EC L-tyrosine:2-oxoglutarate aminotransferase activity Inferred from direct assay Ref.3. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 454

454

Tyrosine aminotransferase

PRO_0000123887

Amino acid modifications

Modified residue

280

1

N6-(pyridoxal phosphate)lysine

Natural variations

Natural variant

70

1

N → D.
Corresponds to variant rs16973344 [ dbSNP | Ensembl ].

VAR_048226

Natural variant

362

1

G → V in TYRO2. Ref.8
Corresponds to variant rs28934277 [ dbSNP | Ensembl ].

VAR_000560

Experimental info

Mutagenesis

294

1

I → A: Reduced catalytic activity. Ref.6

Secondary structure

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454

Helix Strand Turn

Details...

Helix

91 – 102

12

Helix

116 – 126

11

Helix

135 – 137

3

Helix

145 – 155

11

Beta strand

161 – 166

6

Helix

171 – 178

8

Beta strand

182 – 188

7

Helix

190 – 192

3

Helix

198 – 202

5

Beta strand

209 – 217

9

Helix

227 – 239

13

Beta strand

244 – 247

4

Helix

263 – 266

4

Beta strand

272 – 275

4

Turn

279 – 281

3

Beta strand

292 – 295

4

Turn

304 – 306

3

Helix

310 – 316

7

Turn

321 – 323

3

Helix

327 – 333

7

Helix

338 – 353

16

Turn

357 – 359

3

Beta strand

373 – 376

4

Helix

380 – 382

3

Helix

389 – 400

12

Helix

407 – 410

4

Beta strand

416 – 420

5

Helix

424 – 441

18

Sequences

	Sequence		Length	Mass (Da)
	P17735 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 82B5B24F3B2CE489	FASTA	454	50,399
	10 20 30 40 50 60 MDPYMIQMSS KGNLPSILDV HVNVGGRSSV PGKMKGRKAR WSVRPSDMAK KTFNPIRAIV 70 80 90 100 110 120 DNMKVKPNPN KTMISLSIGD PTVFGNLPTD PEVTQAMKDA LDSGKYNGYA PSIGFLSSRE 130 140 150 160 170 180 EIASYYHCPE APLEAKDVIL TSGCSQAIDL CLAVLANPGQ NILVPRPGFS LYKTLAESMG 190 200 210 220 230 240 IEVKLYNLLP EKSWEIDLKQ LEYLIDEKTA CLIVNNPSNP CGSVFSKRHL QKILAVAARQ 250 260 270 280 290 300 CVPILADEIY GDMVFSDCKY EPLATLSTDV PILSCGGLAK RWLVPGWRLG WILIHDRRDI 310 320 330 340 350 360 FGNEIRDGLV KLSQRILGPC TIVQGALKSI LCRTPGEFYH NTLSFLKSNA DLCYGALAAI 370 380 390 400 410 420 PGLRPVRPSG AMYLMVGIEM EHFPEFENDV EFTERLVAEQ SVHCLPATCF EYPNFIRVVI 430 440 450 TVPEVMMLEA CSRIQEFCEQ HYHCAEGSQE ECDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the human tyrosine aminotransferase gene." Rettenmeier R., Natt E., Zentgraf H., Scherer G. Nucleic Acids Res. 18:3853-3861(1990) [PubMed: 1973834] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence of the human tyrosine aminotransferase gene." Zelenin S.M., Mertvetsov N.P. Bioorg. Khim. 20:196-204(1994) [PubMed: 7908801] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning and expression of human tyrosine aminotransferase cDNA." Seralini G.E., Luu-The V., Labrie F. Biochim. Biophys. Acta 1260:97-101(1995) [PubMed: 7999802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY. Tissue: Liver.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II." Sivaraman S., Kirsch J.F. FEBS J. 273:1920-1929(2006) [PubMed: 16640556] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-294.
[7]	"Human tyrosine aminotransferase." Structural genomics consortium (SGC) Submitted (AUG-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 38-444 IN COMPLEX WITH PYRIDOXAL PHOSPHATE.
[8]	"Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II." Natt E., Kida K., Odievre M., di Rocco M., Scherer G. Proc. Natl. Acad. Sci. U.S.A. 89:9297-9301(1992) [PubMed: 1357662] [Abstract] Cited for: VARIANT TYRO2 VAL-362.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52520 mRNA. Translation: CAA36750.1.
X52509 , X52510, X52511, X52512, X52513, X52514, X52515, X52516, X52517, X52518, X52519 Genomic DNA. Translation: CAA36749.1.
X55675 mRNA. Translation: CAA39210.1.
AK313380 mRNA. Translation: BAG36178.1.
CH471166 Genomic DNA. Translation: EAW59230.1.
CH471166 Genomic DNA. Translation: EAW59231.1.

IPI

IPI00016764.

PIR

S10887.

RefSeq

NP_000344.1. NM_000353.2.

UniGene

Hs.161640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DYD	X-ray	2.30	A/B	41-444	[»]

ProteinModelPortal

P17735.

SMR

P17735. Positions 41-444.

ModBase

Search...

Protein-protein interaction databases

STRING

P17735.

PTM databases

PhosphoSite

P17735.

Polymorphism databases

DMDM

114713.

Proteomic databases

PRIDE

P17735.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355962; ENSP00000348234; ENSG00000198650.

GeneID

6898.

KEGG

hsa:6898.

UCSC

uc002fap.2. human.

Organism-specific databases

CTD

6898.

GeneCards

GC16M071599.

H-InvDB

HIX0038602.

HGNC

HGNC:11573. TAT.

HPA

HPA029316.

MIM

276600. phenotype.
613018. gene.

neXtProt

NX_P17735.

Orphanet

28378. Tyrosinemia type 2.

PharmGKB

PA36338.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00530000063107.

HOGENOM

HBG525477.

HOVERGEN

HBG004318.

InParanoid

P17735.

OMA

LLPEKSW.

OrthoDB

EOG4SQWWR.

PhylomeDB

P17735.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-12018.

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P17735.

Bgee

P17735.

CleanEx

HS_TAT.

Genevestigator

P17735.

GermOnline

ENSG00000198650. Homo sapiens.

Family and domain databases

InterPro

IPR001176. ACC_synthase.
IPR004839. Aminotransferase_I/II.
IPR004838. NHTrfase_class1_PyrdxlP-BS.
IPR015424. PyrdxlP-dep_Trfase_major_dom.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
IPR011715. Tyr_aminoTrfase_ubiquitination.
IPR005958. TyrNic_aminoTrfase.
IPR005957. Tyrosine_aminoTrfase.
IPR021178. Tyrosine_transaminase.
[Graphical view]

Gene3D

G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.
G3DSA:3.90.1150.10. PyrdxlP-dep_Trfase_major_sub2. 1 hit.

KO

K00815.

Pfam

PF00155. Aminotran_1_2. 1 hit.
PF07706. TAT_ubiq. 1 hit.
[Graphical view]

PIRSF

PIRSF000517. Tyr_transaminase. 1 hit.

PRINTS

PR00753. ACCSYNTHASE.

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

TIGRFAMs

TIGR01264. Tyr_amTase_E. 1 hit.
TIGR01265. Tyr_nico_aTase. 1 hit.

PROSITE

PS00105. AA_TRANSFER_CLASS_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00142. L-Glutamic Acid.
DB00120. L-Phenylalanine.
DB00135. L-Tyrosine.
DB00114. Pyridoxal Phosphate.

NextBio

26963.

SOURCE

Search...

Entry information

Entry name

ATTY_HUMAN

Accession

Primary (citable) accession number: P17735
Secondary accession number(s): B2R8I1, D3DWS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	January 25, 2012
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.