SODM_HUMAN
ID SODM_HUMAN Reviewed; 222 AA.
AC P04179; B2R7R1; B3KUK2; B4DL20; B4E3K9; E1P5A9; P78434; Q16792; Q5TCM1;
AC Q96EE6; Q9P2Z3;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 3.
DT 03-AUG-2022, entry version 249.
DE RecName: Full=Superoxide dismutase [Mn], mitochondrial;
DE EC=1.15.1.1 {ECO:0000269|PubMed:10334867, ECO:0000269|PubMed:10852710, ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:8605177, ECO:0000269|PubMed:9537987, ECO:0000269|PubMed:9537988};
DE Flags: Precursor;
GN Name=SOD2;
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).
RX PubMed=2462451; DOI=10.1016/0167-4838(89)90058-7;
RA Wispe J.R., Clark J.C., Burhans M.S., Kropp K.E., Korfhagen T.R.,
RA Whitsett J.A.;
RT "Synthesis and processing of the precursor for human mangano-superoxide
RT dismutase.";
RL Biochim. Biophys. Acta 994:30-36(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3684581; DOI=10.1093/nar/15.21.9076;
RA Beck Y., Oren R., Amit B., Levanon A., Gorecki M., Hartman J.R.;
RT "Human Mn superoxide dismutase cDNA sequence.";
RL Nucleic Acids Res. 15:9076-9076(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3399391; DOI=10.1093/nar/16.13.6224;
RA Heckl K.;
RT "Isolation of cDNAs encoding human manganese superoxide dismutase.";
RL Nucleic Acids Res. 16:6224-6224(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=2831093; DOI=10.1016/0014-5793(88)81136-0;
RA Ho Y.-S., Crapo J.D.;
RT "Isolation and characterization of complementary DNAs encoding human
RT manganese-containing superoxide dismutase.";
RL FEBS Lett. 229:256-260(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1699607; DOI=10.1016/0167-4781(90)90213-l;
RA Church S.L.;
RT "Manganese superoxide dismutase: nucleotide and deduced amino acid sequence
RT of a cDNA encoding a new human transcript.";
RL Biochim. Biophys. Acta 1087:250-252(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=1988135;
RA St Clair D.K., Holland J.C.;
RT "Complementary DNA encoding human colon cancer manganese superoxide
RT dismutase and the expression of its gene in human cells.";
RL Cancer Res. 51:939-943(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7702755; DOI=10.1089/dna.1994.13.1127;
RA Wan X.S., Devalaraja M.N., St Clair D.K.;
RT "Molecular structure and organization of the human manganese superoxide
RT dismutase gene.";
RL DNA Cell Biol. 13:1127-1136(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-10; VAL-66 AND TRP-156.
RG NIEHS SNPs program;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Hippocampus, Testis, Tongue, and Uterus;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [13]
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 [14]
RP PROTEIN SEQUENCE OF 25-222.
RX PubMed=6386798; DOI=10.1016/s0021-9258(18)90788-x;
RA Barra D., Schinina M.E., Simmaco M., Bannister J.V., Bannister W.H.,
RA Rotilio G., Bossa F.;
RT "The primary structure of human liver manganese superoxide dismutase.";
RL J. Biol. Chem. 259:12595-12601(1984).
RN [15]
RP PROTEIN SEQUENCE OF 25-39.
RC TISSUE=Heart;
RX PubMed=7895732; DOI=10.1002/elps.11501501209;
RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.;
RT "The human myocardial two-dimensional gel protein database: update 1994.";
RL Electrophoresis 15:1459-1465(1994).
RN [16]
RP PROTEIN SEQUENCE OF 25-39.
RC TISSUE=Heart;
RX PubMed=7498159; DOI=10.1002/elps.11501601192;
RA Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A.,
RA Ershova E.S., Egorov T.A., Musalyamov A.K.;
RT "The major protein expression profile and two-dimensional protein database
RT of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [17]
RP PROTEIN SEQUENCE OF 25-39.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J.,
RA Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed lineage
RT kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, NITRATION AT TYR-58, AND MUTAGENESIS OF
RP TYR-58.
RX PubMed=10334867; DOI=10.1006/abbi.1999.1202;
RA MacMillan-Crow L.A., Thompson J.A.;
RT "Tyrosine modifications and inactivation of active site manganese
RT superoxide dismutase mutant (Y34F) by peroxynitrite.";
RL Arch. Biochem. Biophys. 366:82-88(1999).
RN [19]
RP NITRATION AT TYR-58.
RX PubMed=16399855; DOI=10.1152/ajpheart.01293.2005;
RA Xu S., Ying J., Jiang B., Guo W., Adachi T., Sharov V., Lazar H.,
RA Menzoian J., Knyushko T.V., Bigelow D., Schoeneich C., Cohen R.A.;
RT "Detection of sequence-specific tyrosine nitration of manganese SOD and
RT SERCA in cardiovascular disease and aging.";
RL Am. J. Physiol. 290:H2220-H2227(2006).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-68 AND LYS-130, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP INDUCTION.
RX PubMed=20668652; DOI=10.1371/journal.pone.0011786;
RA Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P.,
RA Retta S.F.;
RT "KRIT1 regulates the homeostasis of intracellular reactive oxygen
RT species.";
RL PLoS ONE 5:E11786-E11786(2010).
RN [22]
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 [23]
RP UBIQUITINATION, AND DEUBIQUITINATION BY USP36.
RX PubMed=21268071; DOI=10.1002/jcb.22940;
RA Kim M.S., Ramakrishna S., Lim K.H., Kim J.H., Baek K.H.;
RT "Protein stability of mitochondrial superoxide dismutase SOD2 is regulated
RT by USP36.";
RL J. Cell. Biochem. 112:498-508(2011).
RN [24]
RP IDENTIFICATION BY 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 [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [26] {ECO:0007744|PDB:1N0J}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-222 IN COMPLEX WITH MANGANESE.
RX PubMed=1394426; DOI=10.1016/0092-8674(92)90270-m;
RA Borgstahl G.E.O., Parge H.E., Hickey M.J., Beyer W.F. Jr., Hallewell R.A.,
RA Tainer J.A.;
RT "The structure of human mitochondrial manganese superoxide dismutase
RT reveals a novel tetrameric interface of two 4-helix bundles.";
RL Cell 71:107-118(1992).
RN [27] {ECO:0007744|PDB:1VAR}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)OF 25-222 AND OF VARIANT THR-82, AND
RP CATALYTIC ACTIVITY.
RX PubMed=8605177; DOI=10.1021/bi951892w;
RA Borgstahl G.E.O., Parge H.E., Hickey M.J., Johnson M.J., Boissinot M.,
RA Hallewell R.A., Lepock J.R., Cabelli D.E., Tainer J.A.;
RT "Human mitochondrial manganese superoxide dismutase polymorphic variant
RT Ile58Thr reduces activity by destabilizing the tetrameric interface.";
RL Biochemistry 35:4287-4297(1996).
RN [28] {ECO:0007744|PDB:1QNM}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 25-222 AND OF MUTANT ASN-167 IN
RP COMPLEX WITH MANGANESE, AND CATALYTIC ACTIVITY.
RX PubMed=9537988; DOI=10.1021/bi972395d;
RA Hsieh Y., Guan Y., Tu C., Bratt P.J., Angerhofer A., Lepock J.R.,
RA Hickey M.J., Tainer J.A., Nick H.S., Silverman D.N.;
RT "Probing the active site of human manganese superoxide dismutase: the role
RT of glutamine 143.";
RL Biochemistry 37:4731-4739(1998).
RN [29] {ECO:0007744|PDB:1AP5, ECO:0007744|PDB:1AP6}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 25-222 AND OF MUTANT TYR-58 IN
RP COMPLEX WITH MANGANESE, AND CATALYTIC ACTIVITY.
RX PubMed=9537987; DOI=10.1021/bi972394l;
RA Guan Y., Hickey M.J., Borgstahl G.E.O., Hallewell R.A., Lepock J.R.,
RA O'Connor D., Hsieh Y., Nick H.S., Silverman D.N., Tainer J.A.;
RT "Crystal structure of Y34F mutant human mitochondrial manganese superoxide
RT dismutase and the functional role of tyrosine 34.";
RL Biochemistry 37:4722-4730(1998).
RN [30] {ECO:0007744|PDB:1EM1}
RP X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS) OF 25-222 AND OF MUTANT ALA-167 IN
RP COMPLEX WITH MANGANESE, AND CATALYTIC ACTIVITY.
RX PubMed=10852710; DOI=10.1021/bi9929958;
RA Leveque V.J.-P., Stroupe M.E., Lepock J.R., Cabelli D.E., Tainer J.A.,
RA Nick H.S., Silverman D.N.;
RT "Multiple replacements of glutamine 143 in human manganese superoxide
RT dismutase: effects on structure, stability, and catalysis.";
RL Biochemistry 39:7131-7137(2000).
RN [31] {ECO:0007744|PDB:1JA8}
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 25-222 AND MUTANT ALA-185 IN
RP COMPLEX WITH MANGANESE, AND CATALYTIC ACTIVITY.
RX PubMed=11580280; DOI=10.1021/bi011047f;
RA Hearn A.S., Stroupe M.E., Cabelli D.E., Lepock J.R., Tainer J.A.,
RA Nick H.S., Silverman D.N.;
RT "Kinetic analysis of product inhibition in human manganese superoxide
RT dismutase.";
RL Biochemistry 40:12051-12058(2001).
RN [32] {ECO:0007744|PDB:1ZSP, ECO:0007744|PDB:1ZTE, ECO:0007744|PDB:1ZUQ, ECO:0007744|PDB:2P4K}
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 25-222 AND OF MUTANTS
RP ALA/ASN/HIS/VAL-58 IN COMPLEX WITH MANGANESE, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=19265433; DOI=10.1021/bi8023288;
RA Perry J.J., Hearn A.S., Cabelli D.E., Nick H.S., Tainer J.A.,
RA Silverman D.N.;
RT "Contribution of human manganese superoxide dismutase tyrosine 34 to
RT structure and catalysis.";
RL Biochemistry 48:3417-3424(2009).
RN [33]
RP VARIANT ALA-16, AND INVOLVEMENT IN SUSCEPTIBILITY TO MVCD6.
RX PubMed=12624725; DOI=10.1007/s100380300021;
RA Nomiyama T., Tanaka Y., Piao L., Nagasaka K., Sakai K., Ogihara T.,
RA Nakajima K., Watada H., Kawamori R.;
RT "The polymorphism of manganese superoxide dismutase is associated with
RT diabetic nephropathy in Japanese type 2 diabetic patients.";
RL J. Hum. Genet. 48:138-141(2003).
RN [34]
RP VARIANT ALA-16, AND INVOLVEMENT IN SUSCEPTIBILITY TO MVCD6.
RX PubMed=18989629; DOI=10.1007/s11010-008-9943-x;
RA Liu L., Zheng T., Wang N., Wang F., Li M., Jiang J., Zhao R., Li L.,
RA Zhao W., Zhu Q., Jia W.;
RT "The manganese superoxide dismutase Val16Ala polymorphism is associated
RT with decreased risk of diabetic nephropathy in Chinese patients with type 2
RT diabetes.";
RL Mol. Cell. Biochem. 322:87-91(2009).
CC -!- FUNCTION: Destroys superoxide anion radicals which are normally
CC produced within the cells and which are toxic to biological systems.
CC {ECO:0000269|PubMed:10334867}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 superoxide = H2O2 + O2; Xref=Rhea:RHEA:20696,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:18421; EC=1.15.1.1;
CC Evidence={ECO:0000269|PubMed:10334867, ECO:0000269|PubMed:10852710,
CC ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:19265433,
CC ECO:0000269|PubMed:8605177, ECO:0000269|PubMed:9537987,
CC ECO:0000269|PubMed:9537988};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10852710, ECO:0000269|PubMed:11580280,
CC ECO:0000269|PubMed:1394426, ECO:0000269|PubMed:19265433,
CC ECO:0000269|PubMed:9537987, ECO:0000269|PubMed:9537988};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000269|PubMed:10852710,
CC ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:1394426,
CC ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:9537987,
CC ECO:0000269|PubMed:9537988};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:19265433}.
CC -!- INTERACTION:
CC P04179; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-716989, EBI-739624;
CC P04179; P04179: SOD2; NbExp=2; IntAct=EBI-716989, EBI-716989;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P04179-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04179-2; Sequence=VSP_042558;
CC Name=3;
CC IsoId=P04179-3; Sequence=VSP_053762;
CC Name=4;
CC IsoId=P04179-4; Sequence=VSP_053761;
CC -!- INDUCTION: Expression is regulated by KRIT1.
CC {ECO:0000269|PubMed:20668652}.
CC -!- PTM: Nitrated under oxidative stress. Nitration coupled with oxidation
CC inhibits the catalytic activity. {ECO:0000269|PubMed:10334867,
CC ECO:0000269|PubMed:16399855}.
CC -!- PTM: Acetylation at Lys-122 decreases enzymatic activity. Deacetylated
CC by SIRT3 upon exposure to ionizing radiations or after long fasting (By
CC similarity). {ECO:0000250|UniProtKB:P09671}.
CC -!- PTM: Polyubiquitinated; leading to proteasomal degradation.
CC Deubiquitinated by USP36 which increases protein stability.
CC {ECO:0000269|PubMed:21268071}.
CC -!- DISEASE: Microvascular complications of diabetes 6 (MVCD6)
CC [MIM:612634]: Pathological conditions that develop in numerous tissues
CC and organs as a consequence of diabetes mellitus. They include diabetic
CC retinopathy, diabetic nephropathy leading to end-stage renal disease,
CC and diabetic neuropathy. Diabetic retinopathy remains the major cause
CC of new-onset blindness among diabetic adults. It is characterized by
CC vascular permeability and increased tissue ischemia and angiogenesis.
CC {ECO:0000269|PubMed:12624725, ECO:0000269|PubMed:18989629}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the iron/manganese superoxide dismutase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/sod2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Superoxide dismutase entry;
CC URL="https://en.wikipedia.org/wiki/Superoxide_dismutase";
CC ---------------------------------------------------------------------------
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DR EMBL; X59445; CAA42066.1; -; mRNA.
DR EMBL; Y00472; CAA68533.1; -; mRNA.
DR EMBL; Y00985; CAA68791.1; -; mRNA.
DR EMBL; X07834; CAA30687.1; -; mRNA.
DR EMBL; M36693; AAA36622.1; -; mRNA.
DR EMBL; X15132; CAA33228.1; -; mRNA.
DR EMBL; X14322; CAA32502.1; -; mRNA.
DR EMBL; S77127; AAD14248.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BT006967; AAP35613.1; -; mRNA.
DR EMBL; AY267901; AAP03428.1; -; Genomic_DNA.
DR EMBL; AK097395; BAG53464.1; -; mRNA.
DR EMBL; AK296809; BAG59382.1; -; mRNA.
DR EMBL; AK304766; BAG65521.1; -; mRNA.
DR EMBL; AK313082; BAG35908.1; -; mRNA.
DR EMBL; AL135914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47630.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47631.1; -; Genomic_DNA.
DR EMBL; BC012423; AAH12423.1; -; mRNA.
DR CCDS; CCDS34564.1; -. [P04179-2]
DR CCDS; CCDS5265.1; -. [P04179-1]
DR CCDS; CCDS83141.1; -. [P04179-4]
DR CCDS; CCDS83143.1; -. [P04179-3]
DR PIR; S13162; DSHUN.
DR RefSeq; NP_000627.2; NM_000636.3. [P04179-1]
DR RefSeq; NP_001019636.1; NM_001024465.2. [P04179-1]
DR RefSeq; NP_001019637.1; NM_001024466.2. [P04179-2]
DR RefSeq; NP_001309743.1; NM_001322814.1. [P04179-2]
DR RefSeq; NP_001309744.1; NM_001322815.1. [P04179-3]
DR RefSeq; NP_001309746.1; NM_001322817.1. [P04179-4]
DR RefSeq; NP_001309748.1; NM_001322819.1. [P04179-4]
DR RefSeq; NP_001309749.1; NM_001322820.1. [P04179-4]
DR PDB; 1AP5; X-ray; 2.20 A; A/B=25-222.
DR PDB; 1AP6; X-ray; 1.90 A; A/B=25-222.
DR PDB; 1EM1; X-ray; 2.13 A; A/B=25-222.
DR PDB; 1JA8; X-ray; 2.12 A; A/B=25-222.
DR PDB; 1LUV; X-ray; 1.85 A; A/B=25-222.
DR PDB; 1LUW; X-ray; 2.30 A; A/B=25-222.
DR PDB; 1MSD; X-ray; 3.20 A; A/B=25-222.
DR PDB; 1N0J; X-ray; 2.20 A; A/B=25-222.
DR PDB; 1N0N; X-ray; 1.82 A; A/B=25-222.
DR PDB; 1PL4; X-ray; 1.47 A; A/B/C/D=25-222.
DR PDB; 1PM9; X-ray; 1.70 A; A/B=25-222.
DR PDB; 1QNM; X-ray; 2.30 A; A/B=25-222.
DR PDB; 1SZX; X-ray; 1.95 A; A/B=25-222.
DR PDB; 1VAR; X-ray; 2.50 A; A/B=25-222.
DR PDB; 1XDC; X-ray; 1.85 A; A/B=25-222.
DR PDB; 1XIL; X-ray; 1.53 A; A/B=25-222.
DR PDB; 1ZSP; X-ray; 1.90 A; A/B=25-222.
DR PDB; 1ZTE; X-ray; 1.85 A; A/B/C/D=25-222.
DR PDB; 1ZUQ; X-ray; 2.00 A; A/B=25-222.
DR PDB; 2ADP; X-ray; 2.40 A; A=25-222.
DR PDB; 2ADQ; X-ray; 2.40 A; B=25-222.
DR PDB; 2GDS; X-ray; 2.30 A; A/B/C/D=25-222.
DR PDB; 2P4K; X-ray; 1.48 A; A/B/C/D=25-222.
DR PDB; 2QKA; X-ray; 2.20 A; A/C=25-220.
DR PDB; 2QKC; X-ray; 2.30 A; A/C=25-220.
DR PDB; 3C3S; X-ray; 2.50 A; A/B=25-222.
DR PDB; 3C3T; X-ray; 2.20 A; A/B=25-222.
DR PDB; 5GXO; X-ray; 2.30 A; A/B=25-222.
DR PDB; 5T30; X-ray; 1.77 A; A/B=24-222.
DR PDB; 5VF9; X-ray; 1.82 A; A/B=24-222.
DR PDB; 7KKS; Neutron; 2.20 A; A/B=24-222.
DR PDB; 7KKU; X-ray; 2.02 A; A/B=24-222.
DR PDB; 7KKW; Neutron; 2.30 A; A/B=24-222.
DR PDB; 7KLB; X-ray; 2.16 A; A/B=24-222.
DR PDBsum; 1AP5; -.
DR PDBsum; 1AP6; -.
DR PDBsum; 1EM1; -.
DR PDBsum; 1JA8; -.
DR PDBsum; 1LUV; -.
DR PDBsum; 1LUW; -.
DR PDBsum; 1MSD; -.
DR PDBsum; 1N0J; -.
DR PDBsum; 1N0N; -.
DR PDBsum; 1PL4; -.
DR PDBsum; 1PM9; -.
DR PDBsum; 1QNM; -.
DR PDBsum; 1SZX; -.
DR PDBsum; 1VAR; -.
DR PDBsum; 1XDC; -.
DR PDBsum; 1XIL; -.
DR PDBsum; 1ZSP; -.
DR PDBsum; 1ZTE; -.
DR PDBsum; 1ZUQ; -.
DR PDBsum; 2ADP; -.
DR PDBsum; 2ADQ; -.
DR PDBsum; 2GDS; -.
DR PDBsum; 2P4K; -.
DR PDBsum; 2QKA; -.
DR PDBsum; 2QKC; -.
DR PDBsum; 3C3S; -.
DR PDBsum; 3C3T; -.
DR PDBsum; 5GXO; -.
DR PDBsum; 5T30; -.
DR PDBsum; 5VF9; -.
DR PDBsum; 7KKS; -.
DR PDBsum; 7KKU; -.
DR PDBsum; 7KKW; -.
DR PDBsum; 7KLB; -.
DR AlphaFoldDB; P04179; -.
DR SMR; P04179; -.
DR BioGRID; 112531; 77.
DR IntAct; P04179; 28.
DR MINT; P04179; -.
DR STRING; 9606.ENSP00000446252; -.
DR ChEMBL; CHEMBL4105776; -.
DR DrugBank; DB04436; 3-Fluoro-L-tyrosine.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB03297; Benzylsulfonic acid.
DR DrugBank; DB06796; Mangafodipir.
DR DrugBank; DB09221; Polaprezinc.
DR DrugBank; DB11590; Thimerosal.
DR DrugCentral; P04179; -.
DR Allergome; 784; Hom s MnSOD.
DR GlyGen; P04179; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P04179; -.
DR PhosphoSitePlus; P04179; -.
DR SwissPalm; P04179; -.
DR BioMuta; SOD2; -.
DR DMDM; 134665; -.
DR DOSAC-COBS-2DPAGE; P04179; -.
DR OGP; P04179; -.
DR SWISS-2DPAGE; P04179; -.
DR UCD-2DPAGE; P04179; -.
DR EPD; P04179; -.
DR jPOST; P04179; -.
DR MassIVE; P04179; -.
DR MaxQB; P04179; -.
DR PaxDb; P04179; -.
DR PeptideAtlas; P04179; -.
DR PRIDE; P04179; -.
DR ProteomicsDB; 3715; -.
DR ProteomicsDB; 51669; -. [P04179-1]
DR ProteomicsDB; 51670; -. [P04179-2]
DR ProteomicsDB; 5907; -.
DR TopDownProteomics; P04179-1; -. [P04179-1]
DR TopDownProteomics; P04179-2; -. [P04179-2]
DR Antibodypedia; 785; 1089 antibodies from 48 providers.
DR DNASU; 6648; -.
DR Ensembl; ENST00000337404.8; ENSP00000337127.4; ENSG00000112096.19. [P04179-2]
DR Ensembl; ENST00000367054.6; ENSP00000356021.2; ENSG00000112096.19. [P04179-2]
DR Ensembl; ENST00000367055.8; ENSP00000356022.4; ENSG00000112096.19. [P04179-1]
DR Ensembl; ENST00000444946.6; ENSP00000404804.2; ENSG00000112096.19. [P04179-3]
DR Ensembl; ENST00000538183.7; ENSP00000446252.1; ENSG00000112096.19. [P04179-1]
DR Ensembl; ENST00000546087.5; ENSP00000442920.1; ENSG00000112096.19. [P04179-4]
DR GeneID; 6648; -.
DR KEGG; hsa:6648; -.
DR MANE-Select; ENST00000538183.7; ENSP00000446252.1; NM_000636.4; NP_000627.2.
DR UCSC; uc003qsf.6; human. [P04179-1]
DR CTD; 6648; -.
DR DisGeNET; 6648; -.
DR GeneCards; SOD2; -.
DR HGNC; HGNC:11180; SOD2.
DR HPA; ENSG00000112096; Group enriched (bone marrow, skeletal muscle).
DR MalaCards; SOD2; -.
DR MIM; 147460; gene.
DR MIM; 612634; phenotype.
DR neXtProt; NX_P04179; -.
DR OpenTargets; ENSG00000112096; -.
DR PharmGKB; PA36017; -.
DR VEuPathDB; HostDB:ENSG00000112096; -.
DR eggNOG; KOG0876; Eukaryota.
DR GeneTree; ENSGT00390000011877; -.
DR HOGENOM; CLU_031625_2_0_1; -.
DR InParanoid; P04179; -.
DR OMA; KWGSFDK; -.
DR OrthoDB; 1353361at2759; -.
DR PhylomeDB; P04179; -.
DR TreeFam; TF105132; -.
DR BioCyc; MetaCyc:HS03515-MON; -.
DR BRENDA; 1.15.1.1; 2681.
DR PathwayCommons; P04179; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR SABIO-RK; P04179; -.
DR SignaLink; P04179; -.
DR SIGNOR; P04179; -.
DR BioGRID-ORCS; 6648; 522 hits in 1077 CRISPR screens.
DR ChiTaRS; SOD2; human.
DR EvolutionaryTrace; P04179; -.
DR GeneWiki; SOD2; -.
DR GenomeRNAi; 6648; -.
DR Pharos; P04179; Tbio.
DR PRO; PR:P04179; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P04179; protein.
DR Bgee; ENSG00000112096; Expressed in gastrocnemius and 202 other tissues.
DR ExpressionAtlas; P04179; baseline and differential.
DR Genevisible; P04179; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0042645; C:mitochondrial nucleoid; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0019825; F:oxygen binding; IEA:Ensembl.
DR GO; GO:0004784; F:superoxide dismutase activity; IDA:UniProtKB.
DR GO; GO:0003069; P:acetylcholine-mediated vasodilation involved in regulation of systemic arterial blood pressure; ISS:BHF-UCL.
DR GO; GO:0001315; P:age-dependent response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0003032; P:detection of oxygen; IEA:Ensembl.
DR GO; GO:0048773; P:erythrophore differentiation; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl.
DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:1902631; P:negative regulation of membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IGI:BHF-UCL.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0032364; P:oxygen homeostasis; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0010729; P:positive regulation of hydrogen peroxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:1905932; P:positive regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching; IDA:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:BHF-UCL.
DR GO; GO:0050790; P:regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:BHF-UCL.
DR GO; GO:0019430; P:removal of superoxide radicals; IMP:BHF-UCL.
DR GO; GO:0022904; P:respiratory electron transport chain; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0035900; P:response to isolation stress; IEA:Ensembl.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071000; P:response to magnetism; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR GO; GO:0034021; P:response to silicon dioxide; IEA:Ensembl.
DR GO; GO:0000303; P:response to superoxide; IMP:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0042554; P:superoxide anion generation; IEA:Ensembl.
DR GO; GO:0006801; P:superoxide metabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.287.990; -; 1.
DR Gene3D; 3.55.40.20; -; 1.
DR InterPro; IPR001189; Mn/Fe_SOD.
DR InterPro; IPR019833; Mn/Fe_SOD_BS.
DR InterPro; IPR019832; Mn/Fe_SOD_C.
DR InterPro; IPR019831; Mn/Fe_SOD_N.
DR InterPro; IPR036324; Mn/Fe_SOD_N_sf.
DR InterPro; IPR036314; SOD_C_sf.
DR Pfam; PF02777; Sod_Fe_C; 1.
DR Pfam; PF00081; Sod_Fe_N; 1.
DR PIRSF; PIRSF000349; SODismutase; 1.
DR PRINTS; PR01703; MNSODISMTASE.
DR SUPFAM; SSF46609; SSF46609; 1.
DR SUPFAM; SSF54719; SSF54719; 1.
DR PROSITE; PS00088; SOD_MN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW Manganese; Metal-binding; Mitochondrion; Nitration; Oxidoreductase;
KW Reference proteome; Transit peptide; Ubl conjugation.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:6386798,
FT ECO:0000269|PubMed:7498159, ECO:0000269|PubMed:7895732,
FT ECO:0000269|PubMed:9150946"
FT CHAIN 25..222
FT /note="Superoxide dismutase [Mn], mitochondrial"
FT /id="PRO_0000032869"
FT BINDING 50
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:10852710,
FT ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:1394426,
FT ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:9537987,
FT ECO:0000269|PubMed:9537988, ECO:0000312|PDB:1JA8,
FT ECO:0007744|PDB:1AP5, ECO:0007744|PDB:1AP6,
FT ECO:0007744|PDB:1EM1, ECO:0007744|PDB:1N0J,
FT ECO:0007744|PDB:1QNM, ECO:0007744|PDB:1ZSP,
FT ECO:0007744|PDB:1ZTE, ECO:0007744|PDB:1ZUQ,
FT ECO:0007744|PDB:2P4K"
FT BINDING 98
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:10852710,
FT ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:1394426,
FT ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:9537987,
FT ECO:0000269|PubMed:9537988, ECO:0000312|PDB:1JA8,
FT ECO:0007744|PDB:1AP5, ECO:0007744|PDB:1AP6,
FT ECO:0007744|PDB:1EM1, ECO:0007744|PDB:1N0J,
FT ECO:0007744|PDB:1QNM, ECO:0007744|PDB:1ZSP,
FT ECO:0007744|PDB:1ZTE, ECO:0007744|PDB:1ZUQ,
FT ECO:0007744|PDB:2P4K"
FT BINDING 183
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:10852710,
FT ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:1394426,
FT ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:9537987,
FT ECO:0000269|PubMed:9537988, ECO:0000312|PDB:1JA8,
FT ECO:0007744|PDB:1AP5, ECO:0007744|PDB:1AP6,
FT ECO:0007744|PDB:1EM1, ECO:0007744|PDB:1N0J,
FT ECO:0007744|PDB:1QNM, ECO:0007744|PDB:1ZSP,
FT ECO:0007744|PDB:1ZTE, ECO:0007744|PDB:1ZUQ,
FT ECO:0007744|PDB:2P4K"
FT BINDING 187
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:10852710,
FT ECO:0000269|PubMed:11580280, ECO:0000269|PubMed:1394426,
FT ECO:0000269|PubMed:19265433, ECO:0000269|PubMed:9537987,
FT ECO:0000269|PubMed:9537988, ECO:0000312|PDB:1JA8,
FT ECO:0007744|PDB:1AP5, ECO:0007744|PDB:1AP6,
FT ECO:0007744|PDB:1EM1, ECO:0007744|PDB:1N0J,
FT ECO:0007744|PDB:1QNM, ECO:0007744|PDB:1ZSP,
FT ECO:0007744|PDB:1ZTE, ECO:0007744|PDB:1ZUQ,
FT ECO:0007744|PDB:2P4K"
FT MOD_RES 58
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:10334867,
FT ECO:0000269|PubMed:16399855"
FT MOD_RES 68
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 68
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 75
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 75
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 114
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 122
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 122
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 130
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 130
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT MOD_RES 202
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P09671"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053761"
FT VAR_SEQ 75..113
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042558"
FT VAR_SEQ 115..174
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053762"
FT VARIANT 10
FT /note="S -> I (in dbSNP:rs5746096)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_019363"
FT VARIANT 16
FT /note="V -> A (associated with a decreased susceptibility
FT to diabetic nephropathy in Japanese and Chinese patients
FT with type 2 diabetes; dbSNP:rs4880)"
FT /evidence="ECO:0000269|PubMed:12624725,
FT ECO:0000269|PubMed:18989629"
FT /id="VAR_016183"
FT VARIANT 66
FT /note="E -> V (in dbSNP:rs5746097)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_019364"
FT VARIANT 76
FT /note="G -> R (in dbSNP:rs4987023)"
FT /id="VAR_025898"
FT VARIANT 82
FT /note="I -> T (in dbSNP:rs1141718)"
FT /evidence="ECO:0000269|PubMed:8605177"
FT /id="VAR_007165"
FT VARIANT 156
FT /note="R -> W (in dbSNP:rs5746129)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_019365"
FT MUTAGEN 58
FT /note="Y->A,H,N,V,F: Reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10334867"
FT MUTAGEN 58
FT /note="Y->F: Loss of nitration. Enhanced dityrosine
FT formation on peroxynitrite treatment."
FT /evidence="ECO:0000269|PubMed:10334867"
FT CONFLICT 14
FT /note="A -> P (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="T -> N (in Ref. 5; CAA42066/CAA33228)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="E -> Q (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="E -> Q (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="R -> L (in Ref. 3; CAA30687)"
FT /evidence="ECO:0000305"
FT CONFLICT 133
FT /note="E -> Q (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 148..149
FT /note="Missing (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="E -> Q (in Ref. 2; CAA68533 and 6)"
FT /evidence="ECO:0000305"
FT TURN 35..41
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 44..52
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 54..74
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 85..103
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 115..125
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 128..140
FT /evidence="ECO:0007829|PDB:1PL4"
FT STRAND 144..153
FT /evidence="ECO:0007829|PDB:1PL4"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:1PL4"
FT STRAND 158..165
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 170..174
FT /evidence="ECO:0007829|PDB:1PL4"
FT STRAND 177..183
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 197..204
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:1PL4"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:1PL4"
SQ SEQUENCE 222 AA; 24750 MW; CA047D7900AE5905 CRC64;
MLSRAVCGTS RQLAPVLGYL GSRQKHSLPD LPYDYGALEP HINAQIMQLH HSKHHAAYVN
NLNVTEEKYQ EALAKGDVTA QIALQPALKF NGGGHINHSI FWTNLSPNGG GEPKGELLEA
IKRDFGSFDK FKEKLTAASV GVQGSGWGWL GFNKERGHLQ IAACPNQDPL QGTTGLIPLL
GIDVWEHAYY LQYKNVRPDY LKAIWNVINW ENVTERYMAC KK
