ALAT1_HUMAN
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 03-AUG-2022, entry version 206.
DE RecName: Full=Alanine aminotransferase 1;
DE Short=ALT1;
DE EC=2.6.1.2;
DE AltName: Full=Glutamate pyruvate transaminase 1;
DE Short=GPT 1;
DE AltName: Full=Glutamic--alanine transaminase 1;
DE AltName: Full=Glutamic--pyruvic transaminase 1;
GN Name=GPT; 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, CLEAVAGE OF INITIATOR METHIONINE, AND
RP 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 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: Catalyzes the reversible transamination between alanine and
CC 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular
CC nitrogen metabolism and also in liver gluconeogenesis starting with
CC precursors transported from skeletal muscles (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-alanine = L-glutamate + pyruvate;
CC Xref=Rhea:RHEA:19453, ChEBI:CHEBI:15361, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:57972; EC=2.6.1.2;
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC -!- PATHWAY: Amino-acid degradation; L-alanine degradation via transaminase
CC pathway; pyruvate from L-alanine: step 1/1.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Liver, kidney, heart, and skeletal muscles.
CC Expressed at moderate levels in the adipose tissue.
CC {ECO:0000269|PubMed:11863375}.
CC -!- INDUCTION: By glucocorticoids.
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_005300.1; NM_005309.2.
DR RefSeq; XP_011515295.1; XM_011516993.2.
DR AlphaFoldDB; P24298; -.
DR SMR; P24298; -.
DR BioGRID; 109133; 16.
DR IntAct; P24298; 3.
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 iPTMnet; P24298; -.
DR PhosphoSitePlus; P24298; -.
DR BioMuta; GPT; -.
DR DMDM; 46577683; -.
DR EPD; P24298; -.
DR jPOST; P24298; -.
DR MassIVE; P24298; -.
DR MaxQB; P24298; -.
DR PaxDb; P24298; -.
DR PeptideAtlas; P24298; -.
DR PRIDE; P24298; -.
DR ProteomicsDB; 54194; -.
DR Antibodypedia; 14920; 409 antibodies from 31 providers.
DR DNASU; 2875; -.
DR Ensembl; ENST00000394955.3; ENSP00000378408.2; ENSG00000167701.14.
DR Ensembl; ENST00000528431.5; ENSP00000433586.1; ENSG00000167701.14.
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 CTD; 2875; -.
DR DisGeNET; 2875; -.
DR GeneCards; GPT; -.
DR HGNC; HGNC:4552; GPT.
DR HPA; ENSG00000167701; Group enriched (liver, skeletal muscle).
DR MIM; 138200; gene.
DR neXtProt; NX_P24298; -.
DR OpenTargets; ENSG00000167701; -.
DR PharmGKB; PA28947; -.
DR VEuPathDB; HostDB:ENSG00000167701; -.
DR eggNOG; KOG0258; Eukaryota.
DR GeneTree; ENSGT00940000155265; -.
DR HOGENOM; CLU_014254_3_1_1; -.
DR InParanoid; P24298; -.
DR OMA; LDEEHAW; -.
DR OrthoDB; 477122at2759; -.
DR PhylomeDB; P24298; -.
DR TreeFam; TF300839; -.
DR BioCyc; MetaCyc:HS09610-MON; -.
DR BRENDA; 2.6.1.2; 2681.
DR BRENDA; 2.6.1.4; 2681.
DR PathwayCommons; P24298; -.
DR Reactome; R-HSA-8964540; Alanine metabolism.
DR SignaLink; P24298; -.
DR UniPathway; UPA00528; UER00586.
DR BioGRID-ORCS; 2875; 10 hits in 1066 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 109 other tissues.
DR Genevisible; P24298; HS.
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 aminotransferase activity; NAS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0042853; P:L-alanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR045088; ALAT1/2-like.
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 PANTHER; PTHR11751; PTHR11751; 1.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminotransferase; Cytoplasm; Direct protein sequencing;
KW Phosphoprotein; Pyridoxal phosphate; 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 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"
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 unknown pathological 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 unknown pathological 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
