SUMO4_HUMAN
ID SUMO4_HUMAN Reviewed; 95 AA.
AC Q6EEV6; A1L3W5;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Small ubiquitin-related modifier 4;
DE Short=SUMO-4;
DE AltName: Full=Small ubiquitin-like protein 4;
DE Flags: Precursor;
GN Name=SUMO4; Synonyms=SMT3H4;
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], FUNCTION, TISSUE SPECIFICITY, POSSIBLE
RP INVOLVEMENT IN IDDM5, AND VARIANT MET-55.
RX PubMed=15123604; DOI=10.1074/jbc.m402273200;
RA Bohren K.M., Nadkarni V., Song J.H., Gabbay K.H., Owerbach D.;
RT "A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates
RT heat shock transcription factors and is associated with susceptibility to
RT type I diabetes mellitus.";
RL J. Biol. Chem. 279:27233-27238(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, POSSIBLE
RP INVOLVEMENT IN IDDM5, AND VARIANT MET-55.
RX PubMed=15247916; DOI=10.1038/ng1391;
RA Guo D., Li M., Zhang Y., Yang P., Eckenrode S., Hopkins D., Zheng W.,
RA Purohit S., Podolsky R.H., Muir A., Wang J., Dong Z., Brusko T.,
RA Atkinson M., Pozzilli P., Zeidler A., Raffel L.J., Jacob C.O., Park Y.,
RA Serrano-Rios M., Martinez Larrad M.T., Zhang Z., Garchon H.-J., Bach J.-F.,
RA Rotter J.I., She J.-X., Wang C.-Y.;
RT "A functional variant of SUMO4, a new I kappa B alpha modifier, is
RT associated with type 1 diabetes.";
RL Nat. Genet. 36:837-841(2004).
RN [3]
RP ERRATUM OF PUBMED:15247916.
RA Guo D., Li M., Zhang Y., Yang P., Eckenrode S., Hopkins D., Zheng W.,
RA Purohit S., Podolsky R.H., Muir A., Wang J., Dong Z., Brusko T.,
RA Atkinson M., Pozzilli P., Zeidler A., Raffel L.J., Jacob C.O., Park Y.,
RA Serrano-Rios M., Martinez Larrad M.T., Zhang Z., Garchon H.-J., Bach J.-F.,
RA Rotter J.I., She J.-X., Wang C.-Y.;
RL Nat. Genet. 36:1024-1024(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Noso S.;
RT "SUMO4.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP LACK OF PROTEOLYTIC CLEAVAGE.
RX PubMed=16198310; DOI=10.1016/j.bbrc.2005.09.090;
RA Owerbach D., McKay E.M., Yeh E.T.H., Gabbay K.H., Bohren K.M.;
RT "A proline-90 residue unique to SUMO-4 prevents maturation and
RT sumoylation.";
RL Biochem. Biophys. Res. Commun. 337:517-520(2005).
RN [9]
RP FUNCTION.
RX PubMed=16236267; DOI=10.1016/j.bbrc.2005.09.191;
RA Guo D., Han J., Adam B.-L., Colburn N.H., Wang M.-H., Dong Z.,
RA Eizirik D.L., She J.-X., Wang C.-Y.;
RT "Proteomic analysis of SUMO4 substrates in HEK293 cells under serum
RT starvation-induced stress.";
RL Biochem. Biophys. Res. Commun. 337:1308-1318(2005).
RN [10]
RP POSSIBLE INVOLVEMENT IN IDDM5.
RX PubMed=15678134; DOI=10.1038/ng0205-110;
RA Smyth D.J., Howson J.M.M., Lowe C.E., Walker N.M., Lam A.C., Nutland S.,
RA Hutchings J., Tuomilehto-Wolf E., Tuomilehto J., Guja C.,
RA Ionescu-Tirgoviste C., Undlien D.E., Roenningen K.S., Savage D.,
RA Dunger D.B., Twells R.C.J., McArdle W.L., Strachan D.P., Todd J.A.;
RT "Assessing the validity of the association between the SUMO4 M55V variant
RT and risk of type 1 diabetes.";
RL Nat. Genet. 37:110-111(2005).
RN [11]
RP ERRATUM OF PUBMED:15678134.
RA Smyth D.J., Howson J.M.M., Lowe C.E., Walker N.M., Lam A.C., Nutland S.,
RA Hutchings J., Tuomilehto-Wolf E., Tuomilehto J., Guja C.,
RA Ionescu-Tirgoviste C., Undlien D.E., Roenningen K.S., Savage D.,
RA Dunger D.B., Twells R.C.J., McArdle W.L., Strachan D.P., Todd J.A.;
RL Nat. Genet. 37:328-328(2004).
RN [12]
RP POSSIBLE INVOLVEMENT IN IDDM5.
RX PubMed=15678135; DOI=10.1038/ng0205-111;
RA Qu H., Bharaj B., Liu X.Q., Curtis J.A., Newhook L.A., Paterson A.D.,
RA Hudson T.J., Polychronakos C.;
RT "Assessing the validity of the association between the SUMO4 M55V variant
RT and risk of type 1 diabetes.";
RL Nat. Genet. 37:111-112(2005).
RN [13]
RP POSSIBLE INVOLVEMENT IN IDDM5.
RX PubMed=15678137; DOI=10.1038/ng0205-112a;
RA Park Y., Park S., Kang J., Yang S., Kim D.;
RT "Assessing the validity of the association between the SUMO4 M55V variant
RT and risk of type 1 diabetes.";
RL Nat. Genet. 37:112-112(2005).
CC -!- FUNCTION: Ubiquitin-like protein which can be covalently attached to
CC target lysines as a monomer. Does not seem to be involved in protein
CC degradation and may modulate protein subcellular localization,
CC stability or activity. Upon oxidative stress, conjugates to various
CC anti-oxidant enzymes, chaperones, and stress defense proteins. May also
CC conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their
CC transcriptional activity, and to NR3C1, positively regulating its
CC transcriptional activity. Covalent attachment to its substrates
CC requires prior activation by the E1 complex SAE1-SAE2 and linkage to
CC the E2 enzyme UBE2I. {ECO:0000269|PubMed:15123604,
CC ECO:0000269|PubMed:15247916, ECO:0000269|PubMed:16236267}.
CC -!- SUBUNIT: Interacts with SAE2. Covalently attached to a number of
CC proteins (Probable). {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed mainly in adult and embryonic kidney.
CC Expressed at various levels in immune tissues, with the highest
CC expression in the lymph node and spleen. {ECO:0000269|PubMed:15123604,
CC ECO:0000269|PubMed:15247916}.
CC -!- PTM: In contrast to SUMO1, SUMO2 and SUMO3, seems to be insensitive to
CC sentrin-specific proteases due to the presence of Pro-90. This may
CC impair processing to mature form and conjugation to substrates.
CC -!- DISEASE: Diabetes mellitus, insulin-dependent, 5 (IDDM5) [MIM:600320]:
CC A form of diabetes mellitus, a multifactorial disorder of glucose
CC homeostasis that is characterized by susceptibility to ketoacidosis in
CC the absence of insulin therapy. Clinical features are polydipsia,
CC polyphagia and polyuria which result from hyperglycemia-induced osmotic
CC diuresis and secondary thirst. These derangements result in long-term
CC complications that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:15123604, ECO:0000269|PubMed:15247916,
CC ECO:0000269|PubMed:15678134, ECO:0000269|PubMed:15678135,
CC ECO:0000269|PubMed:15678137}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC Valine at position 55 results in greater NFKB1 transcriptional activity
CC and IL12B expression and may be associated with susceptibility to
CC insulin-dependent diabetes mellitus. {ECO:0000269|PubMed:15123604,
CC ECO:0000269|PubMed:15247916}.
CC -!- SIMILARITY: Belongs to the ubiquitin family. SUMO subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=SUMO protein entry;
CC URL="https://en.wikipedia.org/wiki/SUMO_protein";
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DR EMBL; AY340238; AAR04484.1; -; mRNA.
DR EMBL; AB205057; BAH05006.1; -; Genomic_DNA.
DR EMBL; AL031133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47808.1; -; Genomic_DNA.
DR EMBL; BC130305; AAI30306.1; -; mRNA.
DR CCDS; CCDS34549.1; -.
DR RefSeq; NP_001002255.1; NM_001002255.1.
DR AlphaFoldDB; Q6EEV6; -.
DR BioGRID; 132223; 13.
DR IntAct; Q6EEV6; 3.
DR MINT; Q6EEV6; -.
DR STRING; 9606.ENSP00000318635; -.
DR iPTMnet; Q6EEV6; -.
DR PhosphoSitePlus; Q6EEV6; -.
DR BioMuta; SUMO4; -.
DR DMDM; 81175019; -.
DR EPD; Q6EEV6; -.
DR jPOST; Q6EEV6; -.
DR MassIVE; Q6EEV6; -.
DR MaxQB; Q6EEV6; -.
DR PaxDb; Q6EEV6; -.
DR PeptideAtlas; Q6EEV6; -.
DR PRIDE; Q6EEV6; -.
DR ProteomicsDB; 66280; -.
DR TopDownProteomics; Q6EEV6; -.
DR Antibodypedia; 33266; 282 antibodies from 29 providers.
DR DNASU; 387082; -.
DR Ensembl; ENST00000326669.6; ENSP00000318635.4; ENSG00000177688.7.
DR GeneID; 387082; -.
DR KEGG; hsa:387082; -.
DR MANE-Select; ENST00000326669.6; ENSP00000318635.4; NM_001002255.2; NP_001002255.1.
DR UCSC; uc003qml.4; human.
DR CTD; 387082; -.
DR DisGeNET; 387082; -.
DR GeneCards; SUMO4; -.
DR HGNC; HGNC:21181; SUMO4.
DR HPA; ENSG00000177688; Low tissue specificity.
DR MalaCards; SUMO4; -.
DR MIM; 600320; phenotype.
DR MIM; 608829; gene.
DR neXtProt; NX_Q6EEV6; -.
DR OpenTargets; ENSG00000177688; -.
DR PharmGKB; PA134979206; -.
DR VEuPathDB; HostDB:ENSG00000177688; -.
DR eggNOG; KOG1769; Eukaryota.
DR GeneTree; ENSGT00950000182895; -.
DR HOGENOM; CLU_148322_2_1_1; -.
DR InParanoid; Q6EEV6; -.
DR OrthoDB; 1583700at2759; -.
DR PhylomeDB; Q6EEV6; -.
DR TreeFam; TF315116; -.
DR PathwayCommons; Q6EEV6; -.
DR SignaLink; Q6EEV6; -.
DR BioGRID-ORCS; 387082; 20 hits in 1040 CRISPR screens.
DR GeneWiki; SUMO4; -.
DR GenomeRNAi; 387082; -.
DR Pharos; Q6EEV6; Tbio.
DR PRO; PR:Q6EEV6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6EEV6; protein.
DR Bgee; ENSG00000177688; Expressed in oocyte and 207 other tissues.
DR Genevisible; Q6EEV6; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0106068; C:SUMO ligase complex; IDA:UniProtKB.
DR GO; GO:0031386; F:protein tag; IBA:GO_Central.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IDA:UniProtKB.
DR InterPro; IPR022617; Rad60/SUMO-like_dom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF11976; Rad60-SLD; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW Diabetes mellitus; Isopeptide bond; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..93
FT /note="Small ubiquitin-related modifier 4"
FT /id="PRO_0000042710"
FT PROPEP 94..95
FT /evidence="ECO:0000250"
FT /id="PRO_0000042711"
FT DOMAIN 17..95
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT CROSSLNK 93
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor proteins)"
FT VARIANT 55
FT /note="V -> M (in dbSNP:rs237025)"
FT /evidence="ECO:0000269|PubMed:15123604,
FT ECO:0000269|PubMed:15247916"
FT /id="VAR_023740"
SQ SEQUENCE 95 AA; 10653 MW; 8C7F7C29734ED223 CRC64;
MANEKPTEEV KTENNNHINL KVAGQDGSVV QFKIKRQTPL SKLMKAYCEP RGLSVKQIRF
RFGGQPISGT DKPAQLEMED EDTIDVFQQP TGGVY
