ALAT2_HUMAN
ID ALAT2_HUMAN Reviewed; 523 AA.
AC Q8TD30; Q8N9E2;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Alanine aminotransferase 2;
DE Short=ALT2;
DE EC=2.6.1.2;
DE AltName: Full=Glutamate pyruvate transaminase 2;
DE Short=GPT 2;
DE AltName: Full=Glutamic--alanine transaminase 2;
DE AltName: Full=Glutamic--pyruvic transaminase 2;
GN Name=GPT2; Synonyms=AAT2, ALT2;
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Adipose tissue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hippocampus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP INVOLVEMENT IN NEDSPM, VARIANT NEDSPM ARG-153, AND CHARACTERIZATION OF
RP VARIANT NEDSPM ARG-153.
RX PubMed=25758935; DOI=10.1007/s10545-015-9824-x;
RA Celis K., Shuldiner S., Haverfield E.V., Cappell J., Yang R., Gong D.W.,
RA Chung W.K.;
RT "Loss of function mutation in glutamic pyruvate transaminase 2 (GPT2)
RT causes developmental encephalopathy.";
RL J. Inherit. Metab. Dis. 38:941-948(2015).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 49-523 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE, AND COFACTOR.
RG Structural genomics consortium (SGC);
RT "Human glutamate pyruvate transaminase 2.";
RL Submitted (AUG-2009) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the reversible transamination between alanine and
CC 2-oxoglutarate to form pyruvate and glutamate.
CC {ECO:0000269|PubMed:11863375}.
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 Evidence={ECO:0000269|PubMed:11863375};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|Ref.7};
CC -!- PATHWAY: Amino-acid degradation; L-alanine degradation via transaminase
CC pathway; pyruvate from L-alanine: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TD30-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TD30-2; Sequence=VSP_020008;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in muscle, adipose tissue,
CC kidney and brain and at lower levels in the liver and breast.
CC {ECO:0000269|PubMed:11863375}.
CC -!- DISEASE: Neurodevelopmental disorder with spastic paraplegia and
CC microcephaly (NEDSPM) [MIM:616281]: An autosomal recessive syndrome
CC characterized by severe psychomotor developmental delay, dysarthria,
CC walking difficulties, moderately to severely impaired intellectual
CC development, poor or absent speech, and progressive microcephaly.
CC {ECO:0000269|PubMed:25758935}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-I pyridoxal-phosphate-dependent
CC aminotransferase family. Alanine aminotransferase subfamily.
CC {ECO:0000305}.
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DR EMBL; AY029173; AAK31794.2; -; mRNA.
DR EMBL; AK094971; BAC04465.1; -; mRNA.
DR EMBL; AC018845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062555; AAH62555.1; -; mRNA.
DR CCDS; CCDS10725.1; -. [Q8TD30-1]
DR CCDS; CCDS45478.1; -. [Q8TD30-2]
DR RefSeq; NP_001135938.1; NM_001142466.2. [Q8TD30-2]
DR RefSeq; NP_597700.1; NM_133443.3. [Q8TD30-1]
DR PDB; 3IHJ; X-ray; 2.30 A; A=49-523.
DR PDBsum; 3IHJ; -.
DR AlphaFoldDB; Q8TD30; -.
DR SMR; Q8TD30; -.
DR BioGRID; 124217; 31.
DR IntAct; Q8TD30; 11.
DR MINT; Q8TD30; -.
DR STRING; 9606.ENSP00000345282; -.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00780; Phenelzine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR GlyGen; Q8TD30; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TD30; -.
DR PhosphoSitePlus; Q8TD30; -.
DR BioMuta; GPT2; -.
DR DMDM; 74730602; -.
DR EPD; Q8TD30; -.
DR jPOST; Q8TD30; -.
DR MassIVE; Q8TD30; -.
DR MaxQB; Q8TD30; -.
DR PaxDb; Q8TD30; -.
DR PeptideAtlas; Q8TD30; -.
DR PRIDE; Q8TD30; -.
DR ProteomicsDB; 74226; -. [Q8TD30-1]
DR ProteomicsDB; 74227; -. [Q8TD30-2]
DR Antibodypedia; 28066; 240 antibodies from 29 providers.
DR DNASU; 84706; -.
DR Ensembl; ENST00000340124.9; ENSP00000345282.4; ENSG00000166123.14. [Q8TD30-1]
DR Ensembl; ENST00000440783.2; ENSP00000413804.2; ENSG00000166123.14. [Q8TD30-2]
DR GeneID; 84706; -.
DR KEGG; hsa:84706; -.
DR MANE-Select; ENST00000340124.9; ENSP00000345282.4; NM_133443.4; NP_597700.1.
DR UCSC; uc002eel.4; human. [Q8TD30-1]
DR CTD; 84706; -.
DR DisGeNET; 84706; -.
DR GeneCards; GPT2; -.
DR HGNC; HGNC:18062; GPT2.
DR HPA; ENSG00000166123; Tissue enhanced (pancreas, skeletal muscle, tongue).
DR MalaCards; GPT2; -.
DR MIM; 138210; gene.
DR MIM; 616281; phenotype.
DR neXtProt; NX_Q8TD30; -.
DR OpenTargets; ENSG00000166123; -.
DR Orphanet; 477673; Postnatal microcephaly-infantile hypotonia-spastic diplegia-dysarthria-intellectual disability syndrome.
DR PharmGKB; PA28948; -.
DR VEuPathDB; HostDB:ENSG00000166123; -.
DR eggNOG; KOG0258; Eukaryota.
DR GeneTree; ENSGT00940000159061; -.
DR HOGENOM; CLU_014254_3_1_1; -.
DR InParanoid; Q8TD30; -.
DR OMA; AKEHQMA; -.
DR OrthoDB; 477122at2759; -.
DR PhylomeDB; Q8TD30; -.
DR TreeFam; TF300839; -.
DR BioCyc; MetaCyc:HS09332-MON; -.
DR PathwayCommons; Q8TD30; -.
DR Reactome; R-HSA-8964540; Alanine metabolism. [Q8TD30-1]
DR SignaLink; Q8TD30; -.
DR SIGNOR; Q8TD30; -.
DR UniPathway; UPA00528; UER00586.
DR BioGRID-ORCS; 84706; 14 hits in 1029 CRISPR screens.
DR ChiTaRS; GPT2; human.
DR EvolutionaryTrace; Q8TD30; -.
DR GenomeRNAi; 84706; -.
DR Pharos; Q8TD30; Tbio.
DR PRO; PR:Q8TD30; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8TD30; protein.
DR Bgee; ENSG00000166123; Expressed in lower esophagus mucosa and 168 other tissues.
DR ExpressionAtlas; Q8TD30; baseline and differential.
DR Genevisible; Q8TD30; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0004021; F:L-alanine: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:0042853; P:L-alanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042851; P:L-alanine metabolic process; IDA:UniProtKB.
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 3D-structure; Acetylation; Alternative splicing; Aminotransferase;
KW Disease variant; Intellectual disability; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT CHAIN 1..523
FT /note="Alanine aminotransferase 2"
FT /id="PRO_0000247532"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 341
FT /note="N6-(pyridoxal phosphate)lysine"
FT MOD_RES 415
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGT5"
FT MOD_RES 505
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGT5"
FT MOD_RES 512
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGT5"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020008"
FT VARIANT 153
FT /note="S -> R (in NEDSPM; loss of function mutation;
FT dbSNP:rs786203999)"
FT /evidence="ECO:0000269|PubMed:25758935"
FT /id="VAR_073379"
FT CONFLICT 284
FT /note="D -> G (in Ref. 4; BAC04465)"
FT /evidence="ECO:0000305"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:3IHJ"
FT TURN 53..56
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 67..80
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 107..117
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 129..141
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 157..170
FT /evidence="ECO:0007829|PDB:3IHJ"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 187..198
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 206..214
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 218..225
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:3IHJ"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 259..269
FT /evidence="ECO:0007829|PDB:3IHJ"
FT TURN 271..273
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 279..292
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:3IHJ"
FT TURN 301..304
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 316..322
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 333..342
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 352..358
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 361..373
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 379..388
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 399..425
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 437..441
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 449..457
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 462..474
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:3IHJ"
FT STRAND 492..496
FT /evidence="ECO:0007829|PDB:3IHJ"
FT HELIX 501..521
FT /evidence="ECO:0007829|PDB:3IHJ"
SQ SEQUENCE 523 AA; 57904 MW; 4DD87814C62C7DEA CRC64;
MQRAAALVRR GCGPRTPSSW GRSQSSAAAE ASAVLKVRPE RSRRERILTL ESMNPQVKAV
EYAVRGPIVL KAGEIELELQ RGIKKPFTEV IRANIGDAQA MGQQPITFLR QVMALCTYPN
LLDSPSFPED AKKRARRILQ ACGGNSLGSY SASQGVNCIR EDVAAYITRR DGGVPADPDN
IYLTTGASDG ISTILKILVS GGGKSRTGVM IPIPQYPLYS AVISELDAIQ VNYYLDEENC
WALNVNELRR AVQEAKDHCD PKVLCIINPG NPTGQVQSRK CIEDVIHFAW EEKLFLLADE
VYQDNVYSPD CRFHSFKKVL YEMGPEYSSN VELASFHSTS KGYMGECGYR GGYMEVINLH
PEIKGQLVKL LSVRLCPPVS GQAAMDIVVN PPVAGEESFE QFSREKESVL GNLAKKAKLT
EDLFNQVPGI HCNPLQGAMY AFPRIFIPAK AVEAAQAHQM APDMFYCMKL LEETGICVVP
GSGFGQREGT YHFRMTILPP VEKLKTVLQK VKDFHINFLE KYA
