ID   ALAT1_HUMAN             Reviewed;         496 AA.
AC   P24298; B0YJ18; D3DWM7; P78398; Q93076;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   02-SEP-2026, entry version 224.
DE   RecName: Full=Alanine aminotransferase 1 {ECO:0000305|PubMed:11863375};
DE            Short=ALT1 {ECO:0000303|PubMed:11863375};
DE            EC=2.6.1.2 {ECO:0000269|PubMed:11863375};
DE   AltName: Full=Glutamate pyruvate transaminase {ECO:0000303|PubMed:9119391};
DE   AltName: Full=Glutamate pyruvate transaminase 1;
DE            Short=GPT-1 {ECO:0000303|PubMed:9119391};
DE   AltName: Full=Glutamic--alanine transaminase 1;
DE   AltName: Full=Glutamic--pyruvic transaminase 1;
GN   Name=GPT {ECO:0000303|PubMed:9119391, ECO:0000312|HGNC:HGNC:4552};
GN   Synonyms=AAT1, GPT1;
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 [GENOMIC DNA], AND VARIANT ASN-14.
RX   PubMed=9119391; DOI=10.1006/geno.1996.4604;
RA   Sohocki M.M., Sullivan L.S., Harrison W.R., Sodergren E.J., Elder F.F.B.,
RA   Weinstock G., Tanase S., Daiger S.P.;
RT   "Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA
RT   and genomic sequences, and polymorphic sites.";
RL   Genomics 40:247-252(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-14.
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PROTEIN SEQUENCE OF 2-496, SUBUNIT, SUBCELLULAR LOCATION, CLEAVAGE OF
RP   INITIATOR METHIONINE, AND ACETYLATION AT ALA-2.
RC   TISSUE=Liver;
RX   PubMed=1931970; DOI=10.1021/bi00107a013;
RA   Ishiguro M., Takio K., Suzuki M., Oyama R., Matsuzawa T., Titani K.;
RT   "Complete amino acid sequence of human liver cytosolic alanine
RT   aminotransferase (GPT) determined by a combination of conventional and mass
RT   spectral methods.";
RL   Biochemistry 30:10451-10457(1991).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-496.
RC   TISSUE=Liver;
RA   Funatsu M., Tanase S., Nakao J., Hamada F., Oka T., Morino Y.;
RT   "Human mRNA for alanine aminotransferase.";
RL   Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RX   PubMed=11863375; DOI=10.1006/geno.2002.6722;
RA   Yang R.-Z., Blaileanu G., Hansen B.C., Shuldiner A.R., Gong D.-W.;
RT   "cDNA cloning, genomic structure, chromosomal mapping, and functional
RT   expression of a novel human alanine aminotransferase.";
RL   Genomics 79:445-450(2002).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22, 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   [10]
RP   VARIANTS GLN-430 AND LEU-452.
RX   PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009;
RG   Care4Rare Canada Consortium;
RA   Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H.,
RA   Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A.,
RA   Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B.,
RA   Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C.,
RA   Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M.,
RA   Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K.,
RA   Shalev S., Michaud J.L.;
RT   "Joubert Syndrome in French Canadians and Identification of Mutations in
RT   CEP104.";
RL   Am. J. Hum. Genet. 97:744-753(2015).
CC   -!- FUNCTION: Pyridoxal enzyme tha catalyzes the reversible transamination
CC       between alanine and 2-oxoglutarate to form pyruvate and glutamate
CC       (PubMed:11863375). By mediating the conversion of these four major
CC       intermediate metabolites, plays an important role in gluconeogenesis
CC       and amino acid metabolism (PubMed:11863375).
CC       {ECO:0000269|PubMed:11863375}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-alanine + 2-oxoglutarate = pyruvate + L-glutamate;
CC         Xref=Rhea:RHEA:19453, ChEBI:CHEBI:15361, ChEBI:CHEBI:16810,
CC         ChEBI:CHEBI:29985, ChEBI:CHEBI:57972; EC=2.6.1.2;
CC         Evidence={ECO:0000269|PubMed:11863375};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000250|UniProtKB:Q8TD30};
CC   -!- PATHWAY: Amino-acid degradation; L-alanine degradation via transaminase
CC       pathway; pyruvate from L-alanine: step 1/1.
CC       {ECO:0000269|PubMed:11863375}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:1931970}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:1931970}.
CC   -!- TISSUE SPECIFICITY: Liver, kidney, heart, and skeletal muscles.
CC       Expressed at moderate levels in the adipose tissue.
CC       {ECO:0000269|PubMed:11863375}.
CC   -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC       aminotransferase family. Alanine aminotransferase subfamily.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Alanine transaminase entry;
CC       URL="https://en.wikipedia.org/wiki/Alanine_transaminase";
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DR   EMBL; U70732; AAC51155.1; -; Genomic_DNA.
DR   EMBL; BT006992; AAP35638.1; -; mRNA.
DR   EMBL; EF444981; ACA05996.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82077.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82078.1; -; Genomic_DNA.
DR   EMBL; BC018207; AAH18207.1; -; mRNA.
DR   EMBL; D10355; BAA01186.1; -; mRNA.
DR   CCDS; CCDS6430.1; -.
DR   PIR; A40465; A40465.
DR   RefSeq; NP_001369593.1; NM_001382664.1.
DR   RefSeq; NP_001369594.1; NM_001382665.1.
DR   RefSeq; NP_005300.1; NM_005309.3.
DR   AlphaFoldDB; P24298; -.
DR   SMR; P24298; -.
DR   BioGRID; 109133; 16.
DR   FunCoup; P24298; 765.
DR   IntAct; P24298; 9.
DR   NDEx; IQUERY-CP-GPT; 6 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000378408; -.
DR   ChEMBL; CHEMBL5929; -.
DR   DrugBank; DB00160; Alanine.
DR   DrugBank; DB00142; Glutamic acid.
DR   DrugBank; DB00780; Phenelzine.
DR   DrugBank; DB00114; Pyridoxal phosphate.
DR   GlyGen; P24298; 1 site.
DR   iPTMnet; P24298; -.
DR   PhosphoSitePlus; P24298; -.
DR   BioMuta; GPT; -.
DR   DMDM; 46577683; -.
DR   jPOST; P24298; -.
DR   MassIVE; P24298; -.
DR   PaxDb; 9606-ENSP00000378408; -.
DR   PeptideAtlas; P24298; -.
DR   ProteomicsDB; 54194; -.
DR   Antibodypedia; 14920; 413 antibodies from 32 providers.
DR   DNASU; 2875; -.
DR   Ensembl; ENST00000394955.3; ENSP00000378408.2; ENSG00000167701.15.
DR   Ensembl; ENST00000528431.5; ENSP00000433586.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894967.1; ENSP00000565026.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894968.1; ENSP00000565027.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894969.1; ENSP00000565028.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894970.1; ENSP00000565029.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894972.1; ENSP00000565031.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894973.1; ENSP00000565032.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894974.1; ENSP00000565033.1; ENSG00000167701.15.
DR   Ensembl; ENST00000894975.1; ENSP00000565034.1; ENSG00000167701.15.
DR   GeneID; 2875; -.
DR   KEGG; hsa:2875; -.
DR   MANE-Select; ENST00000394955.3; ENSP00000378408.2; NM_005309.3; NP_005300.1.
DR   UCSC; uc003zdh.5; human.
DR   AGR; HGNC:4552; -.
DR   ClinPGx; PA28947; -.
DR   CTD; 2875; -.
DR   DisGeNET; 2875; -.
DR   GeneCards; GPT; -.
DR   HGNC; HGNC:4552; GPT.
DR   HPA; ENSG00000167701; Tissue enhanced (liver).
DR   MIM; 138200; gene.
DR   OpenTargets; ENSG00000167701; -.
DR   VEuPathDB; HostDB:ENSG00000167701; -.
DR   eggNOG; KOG0258; Eukaryota.
DR   GeneTree; ENSGT00940000155265; -.
DR   HOGENOM; CLU_014254_3_1_1; -.
DR   InParanoid; P24298; -.
DR   OMA; GTQHFRV; -.
DR   OrthoDB; 1732682at2759; -.
DR   PAN-GO; P24298; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; P24298; -.
DR   BioCyc; MetaCyc:HS09610-MONOMER; -.
DR   BRENDA; 2.6.1.2; 2681.
DR   BRENDA; 2.6.1.4; 2681.
DR   PathwayCommons; P24298; -.
DR   Reactome; R-HSA-70268; Pyruvate metabolism.
DR   Reactome; R-HSA-8964540; Alanine metabolism.
DR   SignaLink; P24298; -.
DR   UniPathway; UPA00528; UER00586.
DR   Agora; ENSG00000167701; -.
DR   BioGRID-ORCS; 2875; 12 hits in 1146 CRISPR screens.
DR   GenomeRNAi; 2875; -.
DR   Pharos; P24298; Tbio.
DR   PRO; PR:P24298; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; P24298; protein.
DR   Bgee; ENSG00000167701; Expressed in right lobe of liver and 110 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0004021; F:L-alanine:2-oxoglutarate transaminase activity; IDA:UniProtKB.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0042853; P:L-alanine catabolic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00609; AAT_like; 1.
DR   FunFam; 1.10.287.1970:FF:000001; Alanine aminotransferase 2; 1.
DR   FunFam; 3.40.640.10:FF:000236; Alanine aminotransferase 2; 1.
DR   FunFam; 3.90.1150.10:FF:000345; Alanine aminotransferase 2; 1.
DR   Gene3D; 1.10.287.1970; -; 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; IPR045088; ALAT1/2-like.
DR   InterPro; IPR004839; Aminotransferase_I/II_large.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR   PANTHER; PTHR11751; ALANINE AMINOTRANSFERASE; 1.
DR   PANTHER; PTHR11751:SF308; ALANINE AMINOTRANSFERASE 1; 1.
DR   Pfam; PF00155; Aminotran_1_2; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Aminotransferase; Cytoplasm; Direct protein sequencing;
KW   Phosphoprotein; Proteomics identification; Pyridoxal phosphate;
KW   Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:1931970"
FT   CHAIN           2..496
FT                   /note="Alanine aminotransferase 1"
FT                   /id="PRO_0000123933"
FT   BINDING         160
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   BINDING         161
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   BINDING         189
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   BINDING         244
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   BINDING         311
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   BINDING         323
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TD30"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|PubMed:1931970"
FT   MOD_RES         22
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         314
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P13191"
FT   VARIANT         14
FT                   /note="H -> N (in allele GPT*2; dbSNP:rs1063739)"
FT                   /evidence="ECO:0000269|PubMed:9119391, ECO:0000269|Ref.4"
FT                   /id="VAR_000561"
FT   VARIANT         430
FT                   /note="E -> Q (found in patient with Joubert syndrome;
FT                   uncertain significance; dbSNP:rs141505249)"
FT                   /evidence="ECO:0000269|PubMed:26477546"
FT                   /id="VAR_075711"
FT   VARIANT         452
FT                   /note="V -> L (found in patient with Joubert syndrome;
FT                   uncertain significance; dbSNP:rs147998249)"
FT                   /evidence="ECO:0000269|PubMed:26477546"
FT                   /id="VAR_075712"
FT   CONFLICT        4..7
FT                   /note="STGD -> RRGN (in Ref. 7; BAA01186)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        39
FT                   /note="G -> S (in Ref. 7; BAA01186)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        222
FT                   /note="H -> A (in Ref. 6; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   496 AA;  54637 MW;  23705E7A3A4283B6 CRC64;
     MASSTGDRSQ AVRHGLRAKV LTLDGMNPRV RRVEYAVRGP IVQRALELEQ ELRQGVKKPF
     TEVIRANIGD AQAMGQRPIT FLRQVLALCV NPDLLSSPNF PDDAKKRAER ILQACGGHSL
     GAYSVSSGIQ LIREDVARYI ERRDGGIPAD PNNVFLSTGA SDAIVTVLKL LVAGEGHTRT
     GVLIPIPQYP LYSATLAELG AVQVDYYLDE ERAWALDVAE LHRALGQARD HCRPRALCVI
     NPGNPTGQVQ TRECIEAVIR FAFEERLFLL ADEVYQDNVY AAGSQFHSFK KVLMEMGPPY
     AGQQELASFH STSKGYMGEC GFRGGYVEVV NMDAAVQQQM LKLMSVRLCP PVPGQALLDL
     VVSPPAPTDP SFAQFQAEKQ AVLAELAAKA KLTEQVFNEA PGISCNPVQG AMYSFPRVQL
     PPRAVERAQE LGLAPDMFFC LRLLEETGIC VVPGSGFGQR EGTYHFRMTI LPPLEKLRLL
     LEKLSRFHAK FTLEYS
//