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Database: UniProt/SWISS-PROT
Entry: SODM_HUMAN
LinkDB: SODM_HUMAN
Original site: SODM_HUMAN 
ID   SODM_HUMAN              Reviewed;         222 AA.
AC   P04179; B2R7R1; B3KUK2; B4DL20; B4E3K9; E1P5A9; P78434; Q16792;
AC   Q5TCM1; Q96EE6; Q9P2Z3;
DT   20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2017, sequence version 3.
DT   12-SEP-2018, entry version 224.
DE   RecName: Full=Superoxide dismutase [Mn], mitochondrial;
DE            EC=1.15.1.1;
DE   Flags: Precursor;
GN   Name=SOD2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=2462451;
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-
RT   superoxide 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
RT   sequence 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
RT   superoxide 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
RT   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
RP   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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA   Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA   Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA   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.,
RA   Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA   Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA   Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA   Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA   Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA   Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA   Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA   Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA   McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA   Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA   Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA   Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA   Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA   Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA   Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA   Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA   Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA   Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [14]
RP   PROTEIN SEQUENCE OF 25-222.
RX   PubMed=6386798;
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
RT   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
RT   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
RT   database 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.,
RA   Simpson R.J., 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
RT   lineage kinase MLK2.";
RL   Electrophoresis 18:588-598(1997).
RN   [18]
RP   NITRATION AT TYR-58, FUNCTION, AND MUTAGENESIS OF 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
RT   and 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.,
RA   Walther T.C., 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.,
RA   Buerckstuemmer T., 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
RT   regulated 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver 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.,
RA   Ayoub D., 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]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
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.,
RA   Hallewell R.A., 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]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF VARIANT THR-82.
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
RT   variant Ile58Thr reduces activity by destabilizing the tetrameric
RT   interface.";
RL   Biochemistry 35:4287-4297(1996).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-167.
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
RT   role of glutamine 143.";
RL   Biochemistry 37:4731-4739(1998).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT TYR-58.
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
RT   superoxide dismutase and the functional role of tyrosine 34.";
RL   Biochemistry 37:4722-4730(1998).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS) OF MUTANT ALA-167.
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]
RP   X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF MUTANT ALA-185.
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]
RP   X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF MUTANTS ALA/ASN/HIS/VAL-58
RP   IN COMPLEX WITH MANGANESE IONS, AND 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
RT   associated with decreased risk of diabetic nephropathy in Chinese
RT   patients with type 2 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
CC       systems. {ECO:0000269|PubMed:10334867}.
CC   -!- CATALYTIC ACTIVITY: 2 superoxide + 2 H(+) = O(2) + H(2)O(2).
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC       Note=Binds 1 Mn(2+) ion per subunit.;
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:19265433}.
CC   -!- INTERACTION:
CC       Self; 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         Note=No experimental confirmation available.;
CC       Name=3;
CC         IsoId=P04179-3; Sequence=VSP_053762;
CC         Note=No experimental confirmation available.;
CC       Name=4;
CC         IsoId=P04179-4; Sequence=VSP_053761;
CC         Note=No experimental confirmation available.;
CC   -!- INDUCTION: Expression is regulated by KRIT1.
CC       {ECO:0000269|PubMed:20668652}.
CC   -!- PTM: Nitrated under oxidative stress. Nitration coupled with
CC       oxidation inhibits the catalytic activity.
CC       {ECO:0000269|PubMed:10334867, ECO:0000269|PubMed:16399855}.
CC   -!- PTM: Acetylation at Lys-122 decreases enzymatic activity.
CC       Deacetylated by SIRT3 upon exposure to ionizing radiations or
CC       after long fasting (By similarity).
CC       {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
CC       tissues and organs as a consequence of diabetes mellitus. They
CC       include diabetic retinopathy, diabetic nephropathy leading to end-
CC       stage renal disease, and diabetic neuropathy. Diabetic retinopathy
CC       remains the major cause of new-onset blindness among diabetic
CC       adults. It is characterized by vascular permeability and increased
CC       tissue ischemia and angiogenesis. {ECO:0000269|PubMed:12624725,
CC       ECO:0000269|PubMed:18989629}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the iron/manganese superoxide dismutase
CC       family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/sod2/";
CC   -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC       polymorphism database;
CC       URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=SOD2";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Superoxide dismutase entry;
CC       URL="https://en.wikipedia.org/wiki/Superoxide_dismutase";
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   UniGene; Hs.487046; -.
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   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   ProteinModelPortal; P04179; -.
DR   SMR; P04179; -.
DR   BioGrid; 112531; 41.
DR   IntAct; P04179; 21.
DR   MINT; P04179; -.
DR   STRING; 9606.ENSP00000356022; -.
DR   DrugBank; DB04436; 3-Fluorotyrosine.
DR   DrugBank; DB03297; Benzylsulfinic Acid.
DR   Allergome; 784; Hom s MnSOD.
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   MaxQB; P04179; -.
DR   PaxDb; P04179; -.
DR   PeptideAtlas; P04179; -.
DR   PRIDE; P04179; -.
DR   ProteomicsDB; 51669; -.
DR   ProteomicsDB; 51670; -. [P04179-2]
DR   TopDownProteomics; P04179-1; -. [P04179-1]
DR   TopDownProteomics; P04179-2; -. [P04179-2]
DR   DNASU; 6648; -.
DR   Ensembl; ENST00000337404; ENSP00000337127; ENSG00000112096. [P04179-2]
DR   Ensembl; ENST00000367054; ENSP00000356021; ENSG00000112096. [P04179-2]
DR   Ensembl; ENST00000367055; ENSP00000356022; ENSG00000112096. [P04179-1]
DR   Ensembl; ENST00000444946; ENSP00000404804; ENSG00000112096. [P04179-3]
DR   Ensembl; ENST00000538183; ENSP00000446252; ENSG00000112096. [P04179-1]
DR   GeneID; 6648; -.
DR   KEGG; hsa:6648; -.
DR   UCSC; uc003qsf.6; human. [P04179-1]
DR   CTD; 6648; -.
DR   DisGeNET; 6648; -.
DR   EuPathDB; HostDB:ENSG00000112096.16; -.
DR   GeneCards; SOD2; -.
DR   GeneCards; SOD2-OT1; -.
DR   HGNC; HGNC:11180; SOD2.
DR   HPA; CAB002013; -.
DR   HPA; HPA001814; -.
DR   MalaCards; SOD2; -.
DR   MIM; 147460; gene.
DR   MIM; 612634; phenotype.
DR   neXtProt; NX_P04179; -.
DR   OpenTargets; ENSG00000112096; -.
DR   PharmGKB; PA36017; -.
DR   eggNOG; KOG0876; Eukaryota.
DR   eggNOG; COG0605; LUCA.
DR   GeneTree; ENSGT00390000011877; -.
DR   HOGENOM; HOG000013583; -.
DR   HOVERGEN; HBG004451; -.
DR   InParanoid; P04179; -.
DR   KO; K04564; -.
DR   PhylomeDB; P04179; -.
DR   TreeFam; TF105132; -.
DR   BioCyc; MetaCyc:HS03515-MONOMER; -.
DR   BRENDA; 1.15.1.1; 2681.
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   SIGNOR; P04179; -.
DR   ChiTaRS; SOD2; human.
DR   EvolutionaryTrace; P04179; -.
DR   GeneWiki; SOD2; -.
DR   GenomeRNAi; 6648; -.
DR   PRO; PR:P04179; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   Bgee; ENSG00000112096; Expressed in 229 organ(s), highest expression level in gastrocnemius.
DR   CleanEx; HS_SOD2; -.
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:0005739; C:mitochondrion; IDA:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
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:0034599; P:cellular response to oxidative stress; TAS:Reactome.
DR   GO; GO:0035722; P:interleukin-12-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; IMP:BHF-UCL.
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 smooth muscle cell proliferation; IDA:BHF-UCL.
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:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; IDA:BHF-UCL.
DR   GO; GO:1905932; P:positive regulation of vascular smooth muscle cell differentiation involved in phenotypic switching; IDA:BHF-UCL.
DR   GO; GO:0051289; P:protein homotetramerization; IPI:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; ISS:BHF-UCL.
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:0000303; P:response to superoxide; IMP:BHF-UCL.
DR   GO; GO:0006801; P:superoxide metabolic process; IDA:UniProtKB.
DR   Gene3D; 1.10.287.990; -; 1.
DR   Gene3D; 2.40.500.20; -; 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; Complete proteome;
KW   Direct protein sequencing; Manganese; Metal-binding; Mitochondrion;
KW   Nitration; Oxidoreductase; Polymorphism; Reference proteome;
KW   Transit peptide; Ubl conjugation.
FT   TRANSIT       1     24       Mitochondrion.
FT                                {ECO:0000269|PubMed:6386798,
FT                                ECO:0000269|PubMed:7498159,
FT                                ECO:0000269|PubMed:7895732,
FT                                ECO:0000269|PubMed:9150946}.
FT   CHAIN        25    222       Superoxide dismutase [Mn], mitochondrial.
FT                                /FTId=PRO_0000032869.
FT   METAL        50     50       Manganese.
FT   METAL        98     98       Manganese.
FT   METAL       183    183       Manganese.
FT   METAL       187    187       Manganese.
FT   MOD_RES      58     58       Nitrated tyrosine.
FT                                {ECO:0000269|PubMed:10334867,
FT                                ECO:0000269|PubMed:16399855}.
FT   MOD_RES      68     68       N6-acetyllysine; alternate.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES      68     68       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES      75     75       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES      75     75       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES     114    114       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES     122    122       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES     122    122       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES     130    130       N6-acetyllysine; alternate.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     130    130       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   MOD_RES     202    202       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P09671}.
FT   VAR_SEQ       1     46       Missing (in isoform 4).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_053761.
FT   VAR_SEQ      75    113       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_042558.
FT   VAR_SEQ     115    174       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_053762.
FT   VARIANT      10     10       S -> I (in dbSNP:rs5746096).
FT                                {ECO:0000269|Ref.9}.
FT                                /FTId=VAR_019363.
FT   VARIANT      16     16       V -> A (frequent polymorphism; associated
FT                                with a decreased susceptibility to
FT                                diabetic nephropathy in Japanese and
FT                                Chinese patients with type 2 diabetes;
FT                                dbSNP:rs4880).
FT                                {ECO:0000269|PubMed:12624725,
FT                                ECO:0000269|PubMed:18989629}.
FT                                /FTId=VAR_016183.
FT   VARIANT      66     66       E -> V (in dbSNP:rs5746097).
FT                                {ECO:0000269|Ref.9}.
FT                                /FTId=VAR_019364.
FT   VARIANT      76     76       G -> R (in dbSNP:rs4987023).
FT                                /FTId=VAR_025898.
FT   VARIANT      82     82       I -> T (in dbSNP:rs1141718).
FT                                {ECO:0000269|PubMed:8605177}.
FT                                /FTId=VAR_007165.
FT   VARIANT     156    156       R -> W (in dbSNP:rs5746129).
FT                                {ECO:0000269|Ref.9}.
FT                                /FTId=VAR_019365.
FT   MUTAGEN      58     58       Y->A,H,N,V,F: Reduced enzyme activity.
FT                                {ECO:0000269|PubMed:10334867}.
FT   MUTAGEN      58     58       Y->F: Loss of nitration. Enhanced
FT                                dityrosine formation on peroxynitrite
FT                                treatment. {ECO:0000269|PubMed:10334867}.
FT   CONFLICT     14     14       A -> P (in Ref. 3). {ECO:0000305}.
FT   CONFLICT     65     65       T -> N (in Ref. 5; CAA42066/CAA33228).
FT                                {ECO:0000305}.
FT   CONFLICT     66     66       E -> Q (in Ref. 6). {ECO:0000305}.
FT   CONFLICT    112    112       E -> Q (in Ref. 6). {ECO:0000305}.
FT   CONFLICT    123    123       R -> L (in Ref. 3; CAA30687).
FT                                {ECO:0000305}.
FT   CONFLICT    133    133       E -> Q (in Ref. 6). {ECO:0000305}.
FT   CONFLICT    148    149       Missing (in Ref. 6). {ECO:0000305}.
FT   CONFLICT    155    155       E -> Q (in Ref. 2; CAA68533 and 6).
FT                                {ECO:0000305}.
FT   TURN         35     41       {ECO:0000244|PDB:1PL4}.
FT   HELIX        44     52       {ECO:0000244|PDB:1PL4}.
FT   HELIX        54     74       {ECO:0000244|PDB:1PL4}.
FT   HELIX        78     83       {ECO:0000244|PDB:1PL4}.
FT   HELIX        85    103       {ECO:0000244|PDB:1PL4}.
FT   HELIX       115    125       {ECO:0000244|PDB:1PL4}.
FT   HELIX       128    140       {ECO:0000244|PDB:1PL4}.
FT   STRAND      144    153       {ECO:0000244|PDB:1PL4}.
FT   TURN        154    157       {ECO:0000244|PDB:1PL4}.
FT   STRAND      158    165       {ECO:0000244|PDB:1PL4}.
FT   HELIX       170    174       {ECO:0000244|PDB:1PL4}.
FT   STRAND      177    183       {ECO:0000244|PDB:1PL4}.
FT   HELIX       186    188       {ECO:0000244|PDB:1PL4}.
FT   HELIX       190    193       {ECO:0000244|PDB:1PL4}.
FT   HELIX       197    204       {ECO:0000244|PDB:1PL4}.
FT   HELIX       205    207       {ECO:0000244|PDB:1PL4}.
FT   HELIX       210    219       {ECO:0000244|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
//
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