GADL1_HUMAN
ID GADL1_HUMAN Reviewed; 521 AA.
AC Q6ZQY3;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 4.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Acidic amino acid decarboxylase GADL1;
DE AltName: Full=Aspartate 1-decarboxylase;
DE Short=ADC;
DE Short=HuADC;
DE EC=4.1.1.11 {ECO:0000269|PubMed:23038267};
DE AltName: Full=Cysteine sulfinic acid decarboxylase;
DE Short=CSADC;
DE Short=HuCSADC;
DE EC=4.1.1.29 {ECO:0000269|PubMed:23038267};
DE AltName: Full=Glutamate decarboxylase-like protein 1;
GN Name=GADL1;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 176-521 (ISOFORM 1).
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 178-521 (ISOFORM 1).
RC TISSUE=Cerebellum;
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 FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, COFACTOR, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23038267; DOI=10.1074/jbc.m112.393728;
RA Liu P., Ge X., Ding H., Jiang H., Christensen B.M., Li J.;
RT "Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine
RT biosynthesis.";
RL J. Biol. Chem. 287:40898-40906(2012).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=26327310; DOI=10.1016/j.neuint.2015.08.013;
RA Winge I., Teigen K., Fossbakk A., Mahootchi E., Kleppe R., Skoeldberg F.,
RA Kaempe O., Haavik J.;
RT "Mammalian CSAD and GADL1 have distinct biochemical properties and patterns
RT of brain expression.";
RL Neurochem. Int. 90:173-184(2015).
CC -!- FUNCTION: May catalyze the decarboxylation of L-aspartate, 3-sulfino-L-
CC alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine,
CC hypotaurine and taurine, respectively. Does not exhibit any
CC decarboxylation activity toward glutamate.
CC {ECO:0000269|PubMed:23038267}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-aspartate = beta-alanine + CO2; Xref=Rhea:RHEA:19497,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:29991,
CC ChEBI:CHEBI:57966; EC=4.1.1.11;
CC Evidence={ECO:0000269|PubMed:23038267};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-sulfino-L-alanine + H(+) = CO2 + hypotaurine;
CC Xref=Rhea:RHEA:16877, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57853, ChEBI:CHEBI:61085; EC=4.1.1.29;
CC Evidence={ECO:0000269|PubMed:23038267};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-cysteate = CO2 + taurine; Xref=Rhea:RHEA:25221,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:58090,
CC ChEBI:CHEBI:507393; EC=4.1.1.29;
CC Evidence={ECO:0000250|UniProtKB:Q80WP8};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:23038267};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.72 mM for L-aspartate {ECO:0000269|PubMed:23038267};
CC KM=1.14 mM for 3-sulfino-L-alanine (cysteine sulfinic acid)
CC {ECO:0000269|PubMed:23038267};
CC Vmax=1.56 umol/min/mg enzyme toward L-aspartate
CC {ECO:0000269|PubMed:23038267};
CC Vmax=2.31 umol/min/mg enzyme toward 3-sulfino-L-alanine (cysteine
CC sulfinic acid) {ECO:0000269|PubMed:23038267};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q80WP8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ZQY3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZQY3-3; Sequence=VSP_036227;
CC -!- TISSUE SPECIFICITY: Expressed very weakly in neurons and not detected
CC in astrocytes, brain or liver. {ECO:0000269|PubMed:26327310}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH93701.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI11987.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC87546.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL832766; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC095029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK128643; BAC87546.1; ALT_INIT; mRNA.
DR EMBL; BC093701; AAH93701.1; ALT_INIT; mRNA.
DR EMBL; BC111986; AAI11987.1; ALT_INIT; mRNA.
DR CCDS; CCDS2649.2; -. [Q6ZQY3-1]
DR RefSeq; NP_997242.2; NM_207359.2. [Q6ZQY3-1]
DR AlphaFoldDB; Q6ZQY3; -.
DR SMR; Q6ZQY3; -.
DR BioGRID; 130959; 9.
DR STRING; 9606.ENSP00000282538; -.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR iPTMnet; Q6ZQY3; -.
DR PhosphoSitePlus; Q6ZQY3; -.
DR BioMuta; GADL1; -.
DR DMDM; 269849753; -.
DR MassIVE; Q6ZQY3; -.
DR PaxDb; Q6ZQY3; -.
DR PeptideAtlas; Q6ZQY3; -.
DR PRIDE; Q6ZQY3; -.
DR ProteomicsDB; 68102; -. [Q6ZQY3-1]
DR ProteomicsDB; 68103; -. [Q6ZQY3-3]
DR Antibodypedia; 45281; 111 antibodies from 22 providers.
DR DNASU; 339896; -.
DR Ensembl; ENST00000282538.10; ENSP00000282538.5; ENSG00000144644.15. [Q6ZQY3-1]
DR Ensembl; ENST00000454381.3; ENSP00000427059.1; ENSG00000144644.15. [Q6ZQY3-3]
DR GeneID; 339896; -.
DR KEGG; hsa:339896; -.
DR MANE-Select; ENST00000282538.10; ENSP00000282538.5; NM_207359.3; NP_997242.2.
DR UCSC; uc003cep.3; human. [Q6ZQY3-1]
DR CTD; 339896; -.
DR DisGeNET; 339896; -.
DR GeneCards; GADL1; -.
DR HGNC; HGNC:27949; GADL1.
DR HPA; ENSG00000144644; Group enriched (skeletal muscle, tongue).
DR MalaCards; GADL1; -.
DR MIM; 615601; gene.
DR neXtProt; NX_Q6ZQY3; -.
DR OpenTargets; ENSG00000144644; -.
DR PharmGKB; PA134944477; -.
DR VEuPathDB; HostDB:ENSG00000144644; -.
DR eggNOG; KOG0629; Eukaryota.
DR GeneTree; ENSGT00940000158391; -.
DR HOGENOM; CLU_011856_0_0_1; -.
DR InParanoid; Q6ZQY3; -.
DR OMA; DESDMLY; -.
DR OrthoDB; 810772at2759; -.
DR PhylomeDB; Q6ZQY3; -.
DR TreeFam; TF314688; -.
DR PathwayCommons; Q6ZQY3; -.
DR Reactome; R-HSA-1614558; Degradation of cysteine and homocysteine.
DR Reactome; R-HSA-8963693; Aspartate and asparagine metabolism.
DR SABIO-RK; Q6ZQY3; -.
DR SignaLink; Q6ZQY3; -.
DR SIGNOR; Q6ZQY3; -.
DR BioGRID-ORCS; 339896; 5 hits in 1071 CRISPR screens.
DR ChiTaRS; GADL1; human.
DR GenomeRNAi; 339896; -.
DR Pharos; Q6ZQY3; Tbio.
DR PRO; PR:Q6ZQY3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q6ZQY3; protein.
DR Bgee; ENSG00000144644; Expressed in buccal mucosa cell and 55 other tissues.
DR Genevisible; Q6ZQY3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004068; F:aspartate 1-decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0016831; F:carboxy-lyase activity; IBA:GO_Central.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004782; F:sulfinoalanine decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
DR Gene3D; 3.40.640.10; -; 1.
DR InterPro; IPR039025; GADL1.
DR InterPro; IPR002129; PyrdxlP-dep_de-COase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR021115; Pyridoxal-P_BS.
DR PANTHER; PTHR45677:SF1; PTHR45677:SF1; 1.
DR Pfam; PF00282; Pyridoxal_deC; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00392; DDC_GAD_HDC_YDC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Decarboxylase; Lyase; Pyridoxal phosphate;
KW Reference proteome.
FT CHAIN 1..521
FT /note="Acidic amino acid decarboxylase GADL1"
FT /id="PRO_0000312224"
FT MOD_RES 333
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:Q80WP8"
FT VAR_SEQ 419..521
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_036227"
FT CONFLICT 66
FT /note="D -> G (in Ref. 1; AL832766)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 59246 MW; 8D11C50E7F25053B CRC64;
MSSDSDRQCP VDGDIDQQEM IPSKKNAVLV DGVVLNGPTT DAKAGEKFVE EACRLIMEEV
VLKATDVNEK VCEWRPPEQL KQLLDLEMRD SGEPPHKLLE LCRDVIHYSV KTNHPRFFNQ
LYAGLDYYSL VARFMTEALN PSVYTYEVSP VFLLVEEAVL KKMIEFIGWK EGDGIFNPGG
SVSNMYAMNL ARYKYCPDIK EKGLSGSPRL ILFTSAECHY SMKKAASFLG IGTENVCFVE
TDGRGKMIPE ELEKQVWQAR KEGAAPFLVC ATSGTTVLGA FDPLDEIADI CERHSLWLHV
DASWGGSALM SRKHRKLLHG IHRADSVAWN PHKMLMAGIQ CCALLVKDKS DLLKKCYSAK
ASYLFQQDKF YDVSYDTGDK SIQCSRRPDA FKFWMTWKAL GTLGLEERVN RALALSRYLV
DEIKKREGFK LLMEPEYANI CFWYIPPSLR EMEEGPEFWA KLNLVAPAIK ERMMKKGSLM
LGYQPHRGKV NFFRQVVISP QVSREDMDFL LDEIDLLGKD M
