MTNB_HUMAN
ID MTNB_HUMAN Reviewed; 242 AA.
AC Q96GX9; A8K9D3; Q6PJX6; Q8WVU2; Q96HK2; Q9Y318;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Methylthioribulose-1-phosphate dehydratase {ECO:0000255|HAMAP-Rule:MF_03116};
DE Short=MTRu-1-P dehydratase {ECO:0000255|HAMAP-Rule:MF_03116};
DE EC=4.2.1.109 {ECO:0000255|HAMAP-Rule:MF_03116, ECO:0000269|PubMed:24367089};
DE AltName: Full=APAF1-interacting protein {ECO:0000255|HAMAP-Rule:MF_03116};
DE Short=hAPIP;
GN Name=APIP {ECO:0000255|HAMAP-Rule:MF_03116}; ORFNames=CGI-29;
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 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TRP-7 AND
RP TYR-76.
RC TISSUE=Thymus;
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=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TRP-7;
RP ARG-23; TYR-76 AND VAL-181.
RC TISSUE=Bone marrow, Colon, and Eye;
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, INTERACTION WITH APAF1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=15262985; DOI=10.1074/jbc.m405747200;
RA Cho D.-H., Hong Y.-M., Lee H.-J., Woo H.-N., Pyo J.-O., Mak T.W.,
RA Jung Y.-K.;
RT "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-
RT interacting protein.";
RL J. Biol. Chem. 279:39942-39950(2004).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-87, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP FUNCTION, PATHWAY, ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-84; SER-87; SER-89; HIS-115;
RP HIS-117 AND HIS-195.
RX PubMed=23285211; DOI=10.1371/journal.pone.0052877;
RA Mary C., Duek P., Salleron L., Tienz P., Bumann D., Bairoch A., Lane L.;
RT "Functional identification of APIP as human mtnB, a key enzyme in the
RT methionine salvage pathway.";
RL PLoS ONE 7:E52877-E52877(2012).
RN [9]
RP FUNCTION, INTERACTION WITH CASP1, AND MUTAGENESIS OF CYS-97 AND HIS-115.
RX PubMed=22837397; DOI=10.1073/pnas.1206701109;
RA Ko D.C., Gamazon E.R., Shukla K.P., Pfuetzner R.A., Whittington D.,
RA Holden T.D., Brittnacher M.J., Fong C., Radey M., Ogohara C., Stark A.L.,
RA Akey J.M., Dolan M.E., Wurfel M.M., Miller S.I.;
RT "Functional genetic screen of human diversity reveals that a methionine
RT salvage enzyme regulates inflammatory cell death.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E2343-E2352(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-87, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 20-242 IN COMPLEX WITH ZINC,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, FUNCTION,
RP PATHWAY, ACTIVE SITE, SUBUNIT, AND MUTAGENESIS OF GLN-96; CYS-97; HIS-115
RP AND GLU-139.
RX PubMed=24367089; DOI=10.1073/pnas.1308768111;
RA Kang W., Hong S.H., Lee H.M., Kim N.Y., Lim Y.C., Le le T.M., Lim B.,
RA Kim H.C., Kim T.Y., Ashida H., Yokota A., Hah S.S., Chun K.H., Jung Y.K.,
RA Yang J.K.;
RT "Structural and biochemical basis for the inhibition of cell death by APIP,
RT a methionine salvage enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E54-E61(2014).
CC -!- FUNCTION: Catalyzes the dehydration of methylthioribulose-1-phosphate
CC (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P).
CC Functions in the methionine salvage pathway, which plays a key role in
CC cancer, apoptosis, microbial proliferation and inflammation. May
CC inhibit the CASP1-related inflammatory response (pyroptosis), the
CC CASP9-dependent apoptotic pathway and the cytochrome c-dependent and
CC APAF1-mediated cell death. {ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:22837397,
CC ECO:0000269|PubMed:23285211, ECO:0000269|PubMed:24367089}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-methyl-5-thio-D-ribulose 1-phosphate = 5-methylsulfanyl-2,3-
CC dioxopentyl phosphate + H2O; Xref=Rhea:RHEA:15549, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:58548, ChEBI:CHEBI:58828; EC=4.2.1.109;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:24367089};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:24367089};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:24367089};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.3 uM for S-methyl-5-thio-D-ribulose 1-phosphate;
CC Vmax=1.39 umol/min/mg enzyme;
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via salvage
CC pathway; L-methionine from S-methyl-5-thio-alpha-D-ribose 1-phosphate:
CC step 2/6. {ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:23285211, ECO:0000269|PubMed:24367089}.
CC -!- SUBUNIT: Homotetramer (PubMed:24367089). Interacts with APAF1
CC (PubMed:15262985). May interact with CASP1 (PubMed:22837397).
CC {ECO:0000255|HAMAP-Rule:MF_03116, ECO:0000269|PubMed:15262985,
CC ECO:0000269|PubMed:22837397, ECO:0000269|PubMed:24367089}.
CC -!- INTERACTION:
CC Q96GX9; Q96GX9: APIP; NbExp=12; IntAct=EBI-359248, EBI-359248;
CC Q96GX9; A0A0A0MR97: BAZ2B; NbExp=3; IntAct=EBI-359248, EBI-11985607;
CC Q96GX9; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-359248, EBI-749051;
CC Q96GX9; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-359248, EBI-739467;
CC Q96GX9; P12268: IMPDH2; NbExp=3; IntAct=EBI-359248, EBI-353389;
CC Q96GX9; Q8TBB1: LNX1; NbExp=11; IntAct=EBI-359248, EBI-739832;
CC Q96GX9; Q96HA8: NTAQ1; NbExp=5; IntAct=EBI-359248, EBI-741158;
CC Q96GX9; Q6ZVK8: NUDT18; NbExp=4; IntAct=EBI-359248, EBI-740486;
CC Q96GX9; Q17RL8: PDZD4; NbExp=4; IntAct=EBI-359248, EBI-10239064;
CC Q96GX9; P25786: PSMA1; NbExp=3; IntAct=EBI-359248, EBI-359352;
CC Q96GX9; O00560: SDCBP; NbExp=5; IntAct=EBI-359248, EBI-727004;
CC Q96GX9; P63208: SKP1; NbExp=3; IntAct=EBI-359248, EBI-307486;
CC Q96GX9; Q16637: SMN2; NbExp=3; IntAct=EBI-359248, EBI-395421;
CC Q96GX9; O14787: TNPO2; NbExp=4; IntAct=EBI-359248, EBI-431907;
CC Q96GX9; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-359248, EBI-739485;
CC Q96GX9; P24278: ZBTB25; NbExp=3; IntAct=EBI-359248, EBI-739899;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03116,
CC ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:23285211}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q96GX9-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q96GX9-3; Sequence=VSP_044403;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed. Isoform 2 is
CC expressed at lower levels and detected in heart, brain, pancreas,
CC liver, placenta, skeletal muscle and kidney.
CC {ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:23285211}.
CC -!- SIMILARITY: Belongs to the aldolase class II family. MtnB subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03116}.
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DR EMBL; AF132963; AAD27738.1; -; mRNA.
DR EMBL; AK292648; BAF85337.1; -; mRNA.
DR EMBL; AC107928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008440; AAH08440.1; -; mRNA.
DR EMBL; BC009077; AAH09077.1; -; mRNA.
DR EMBL; BC017594; AAH17594.1; -; mRNA.
DR CCDS; CCDS7895.1; -. [Q96GX9-1]
DR RefSeq; NP_057041.2; NM_015957.3. [Q96GX9-1]
DR PDB; 4M6R; X-ray; 2.00 A; A/B/C/D=20-242.
DR PDBsum; 4M6R; -.
DR AlphaFoldDB; Q96GX9; -.
DR SMR; Q96GX9; -.
DR BioGRID; 119265; 51.
DR IntAct; Q96GX9; 39.
DR STRING; 9606.ENSP00000379133; -.
DR GlyGen; Q96GX9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96GX9; -.
DR PhosphoSitePlus; Q96GX9; -.
DR BioMuta; APIP; -.
DR DMDM; 74731866; -.
DR EPD; Q96GX9; -.
DR jPOST; Q96GX9; -.
DR MassIVE; Q96GX9; -.
DR MaxQB; Q96GX9; -.
DR PaxDb; Q96GX9; -.
DR PeptideAtlas; Q96GX9; -.
DR PRIDE; Q96GX9; -.
DR ProteomicsDB; 76681; -. [Q96GX9-1]
DR Antibodypedia; 25889; 337 antibodies from 31 providers.
DR DNASU; 51074; -.
DR Ensembl; ENST00000395787.4; ENSP00000379133.3; ENSG00000149089.13. [Q96GX9-1]
DR GeneID; 51074; -.
DR KEGG; hsa:51074; -.
DR MANE-Select; ENST00000395787.4; ENSP00000379133.3; NM_015957.4; NP_057041.2.
DR UCSC; uc001mvs.4; human. [Q96GX9-1]
DR CTD; 51074; -.
DR DisGeNET; 51074; -.
DR GeneCards; APIP; -.
DR HGNC; HGNC:17581; APIP.
DR HPA; ENSG00000149089; Low tissue specificity.
DR MalaCards; APIP; -.
DR MIM; 612491; gene.
DR neXtProt; NX_Q96GX9; -.
DR OpenTargets; ENSG00000149089; -.
DR PharmGKB; PA142672601; -.
DR VEuPathDB; HostDB:ENSG00000149089; -.
DR eggNOG; KOG2631; Eukaryota.
DR GeneTree; ENSGT00390000001680; -.
DR HOGENOM; CLU_006033_4_0_1; -.
DR InParanoid; Q96GX9; -.
DR OMA; IRGHGLY; -.
DR OrthoDB; 1062330at2759; -.
DR PhylomeDB; Q96GX9; -.
DR TreeFam; TF105632; -.
DR BRENDA; 4.2.1.109; 2681.
DR PathwayCommons; Q96GX9; -.
DR Reactome; R-HSA-111458; Formation of apoptosome.
DR Reactome; R-HSA-1237112; Methionine salvage pathway.
DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity.
DR SignaLink; Q96GX9; -.
DR SIGNOR; Q96GX9; -.
DR UniPathway; UPA00904; UER00875.
DR BioGRID-ORCS; 51074; 65 hits in 1045 CRISPR screens.
DR ChiTaRS; APIP; human.
DR GeneWiki; APIP; -.
DR GenomeRNAi; 51074; -.
DR Pharos; Q96GX9; Tbio.
DR PRO; PR:Q96GX9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96GX9; protein.
DR Bgee; ENSG00000149089; Expressed in C1 segment of cervical spinal cord and 101 other tissues.
DR ExpressionAtlas; Q96GX9; baseline and differential.
DR Genevisible; Q96GX9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046570; F:methylthioribulose 1-phosphate dehydratase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0019509; P:L-methionine salvage from methylthioadenosine; IMP:UniProtKB.
DR GO; GO:0019284; P:L-methionine salvage from S-adenosylmethionine; IEA:UniProtKB-UniRule.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IMP:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR Gene3D; 3.40.225.10; -; 1.
DR HAMAP; MF_03116; Salvage_MtnB_euk; 1.
DR InterPro; IPR001303; Aldolase_II/adducin_N.
DR InterPro; IPR036409; Aldolase_II/adducin_N_sf.
DR InterPro; IPR017714; MethylthioRu-1-P_deHdtase_MtnB.
DR InterPro; IPR027514; Salvage_MtnB_euk.
DR PANTHER; PTHR10640; PTHR10640; 1.
DR Pfam; PF00596; Aldolase_II; 1.
DR SMART; SM01007; Aldolase_II; 1.
DR SUPFAM; SSF53639; SSF53639; 1.
DR TIGRFAMs; TIGR03328; salvage_mtnB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amino-acid biosynthesis; Apoptosis;
KW Cytoplasm; Lyase; Metal-binding; Methionine biosynthesis; Phosphoprotein;
KW Reference proteome; Zinc.
FT CHAIN 1..242
FT /note="Methylthioribulose-1-phosphate dehydratase"
FT /id="PRO_0000239022"
FT ACT_SITE 139
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03116,
FT ECO:0000269|PubMed:24367089"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03116,
FT ECO:0000305|PubMed:24367089"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03116,
FT ECO:0000305|PubMed:24367089, ECO:0007744|PDB:4M6R"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03116,
FT ECO:0000305|PubMed:24367089, ECO:0007744|PDB:4M6R"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03116,
FT ECO:0000305|PubMed:24367089, ECO:0007744|PDB:4M6R"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..53
FT /note="MSGCDAREGDCCSRRCGAQDKEHPRYLIPELCKQFYHLGWVTGTGGGISLKH
FT G -> MLGRETVVPGDAARS (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044403"
FT VARIANT 7
FT /note="R -> W (in dbSNP:rs2956114)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_026575"
FT VARIANT 23
FT /note="H -> R (in dbSNP:rs17850326)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026576"
FT VARIANT 76
FT /note="C -> Y (in dbSNP:rs1977420)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_026577"
FT VARIANT 181
FT /note="M -> V (in dbSNP:rs17850327)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026578"
FT MUTAGEN 84
FT /note="S->A,D: Does not affect ability of cells to grow in
FT media where methionine is replaced by 5-
FT methylthioadenosine; when associated with A,D-87 and A,D-
FT 89."
FT /evidence="ECO:0000269|PubMed:23285211"
FT MUTAGEN 87
FT /note="S->A,D: Does not affect ability of cells to grow in
FT media where methionine is replaced by 5-
FT methylthioadenosine; when associated with A,D-84 and A,D-
FT 89."
FT /evidence="ECO:0000269|PubMed:23285211"
FT MUTAGEN 89
FT /note="S->A,D: Does not affect ability of cells to grow in
FT media where methionine is replaced by 5-
FT methylthioadenosine; when associated with A,D-84 and A,D-
FT 87."
FT /evidence="ECO:0000269|PubMed:23285211"
FT MUTAGEN 96
FT /note="Q->A: Mildly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:24367089"
FT MUTAGEN 97
FT /note="C->A: Acts as a dominant negative mutant; unable to
FT use 5'-methylthioadenosine as source of methionine. Does
FT not affect the ability to bind CASP1 and to inhibit cell
FT death induced by CASP9 overexpression."
FT /evidence="ECO:0000269|PubMed:22837397"
FT MUTAGEN 97
FT /note="C->A: Almost complete loss of enzyme activity.
FT Abolishes protection against pyroptosis. No effect on anti-
FT apoptotic activity."
FT /evidence="ECO:0000269|PubMed:24367089"
FT MUTAGEN 115
FT /note="H->A: Almost complete loss of enzyme activity.
FT Abolishes protection against pyroptosis. No effect on anti-
FT apoptotic activity."
FT /evidence="ECO:0000269|PubMed:24367089"
FT MUTAGEN 115
FT /note="H->A: Impaired ability of cells to grow in media
FT where methionine is replaced by 5-methylthioadenosine; when
FT associated with A-117 and A-195. Unable to inhibit both
FT CASP1 and CASP9 mediated cell death."
FT /evidence="ECO:0000269|PubMed:22837397,
FT ECO:0000269|PubMed:23285211"
FT MUTAGEN 117
FT /note="H->A: Impaired ability of cells to grow in media
FT where methionine is replaced by 5-methylthioadenosine; when
FT associated with A-115 and A-195."
FT /evidence="ECO:0000269|PubMed:23285211"
FT MUTAGEN 139
FT /note="E->A: Almost complete loss of enzyme activity.
FT Abolishes protection against pyroptosis. No effect on anti-
FT apoptotic activity."
FT /evidence="ECO:0000269|PubMed:24367089"
FT MUTAGEN 195
FT /note="H->A: Impaired ability of cells to grow in media
FT where methionine is replaced by 5-methylthioadenosine; when
FT associated with 87-A--A-89."
FT /evidence="ECO:0000269|PubMed:23285211"
FT CONFLICT 7
FT /note="R -> G (in Ref. 1; AAD27738)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="D -> T (in Ref. 1; AAD27738)"
FT /evidence="ECO:0000305"
FT HELIX 24..37
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 98..108
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 130..137
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:4M6R"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 170..183
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:4M6R"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:4M6R"
FT STRAND 196..203
FT /evidence="ECO:0007829|PDB:4M6R"
FT HELIX 204..226
FT /evidence="ECO:0007829|PDB:4M6R"
SQ SEQUENCE 242 AA; 27125 MW; 9B8D5D1435D6775A CRC64;
MSGCDAREGD CCSRRCGAQD KEHPRYLIPE LCKQFYHLGW VTGTGGGISL KHGDEIYIAP
SGVQKERIQP EDMFVCDINE KDISGPSPSK KLKKSQCTPL FMNAYTMRGA GAVIHTHSKA
AVMATLLFPG REFKITHQEM IKGIKKCTSG GYYRYDDMLV VPIIENTPEE KDLKDRMAHA
MNEYPDSCAV LVRRHGVYVW GETWEKAKTM CECYDYLFDI AVSMKKVGLD PSQLPVGENG
IV
