Q6EEV6 (SUMO4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Small ubiquitin-related modifier 4
Short name=SUMO-4

Alternative name(s):
Small ubiquitin-like protein 4

Gene names

Name:	SUMO4
Synonyms:	SMT3H4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	95 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may modulate protein subcellular localization, stability or activity. Upon oxidative stress, conjugates to various anti-oxidant enzymes, chaperones, and stress defense proteins. May also conjugate to NFKBIA, TFAP2A and FOS, negatively regulating their transcriptional activity, and to NR3C1, positively regulating its transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I. Ref.1 Ref.2 Ref.9
Subunit structure	Interacts with SAE2. Covalently attached to a number of proteins Probable.
Tissue specificity	Expressed mainly in adult and embryonic kidney. Expressed at various levels in immune tissues, with the highest expression in the lymph node and spleen. Ref.1 Ref.2
Post-translational modification	In contrast to SUMO1, SUMO2 and SUMO3, seems to be insensitive to sentrin-specific proteases due to the presence of Pro-90. This may impair processing to mature form and conjugation to substrates.
Polymorphism	Variant Val-55 could be associated with insulin-dependent diabetes mellitus 5 (IDDM5) [MIM:600320].
Sequence similarities	Belongs to the ubiquitin family. SUMO subfamily. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Polymorphism
PTM	Isopeptide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein sumoylation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular_function	SUMO ligase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 93	93	Small ubiquitin-related modifier 4		PRO_0000042710
	Propeptide	94 – 95	2	By similarity		PRO_0000042711
Regions
	Domain	17 – 95	79	Ubiquitin-like
Amino acid modifications
	Cross-link	93		Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)
Natural variations
	Natural variant	55	1	M → V May be associated with susceptibility to type 1 diabetes; greater NFKB1 transcriptional activity and IL12B expression. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Ref.7 Ref.10 Ref.12 Ref.13 Corresponds to variant rs237025 [ dbSNP | Ensembl ].		VAR_023740

Sequences

	Sequence		Length	Mass (Da)
	Q6EEV6 [UniParc]. Last modified November 8, 2005. Version 2. Checksum: 9012CAEE734ED223	FASTA	95	10,685
	10 20 30 40 50 60 MANEKPTEEV KTENNNHINL KVAGQDGSVV QFKIKRQTPL SKLMKAYCEP RGLSMKQIRF 70 80 90 RFGGQPISGT DKPAQLEMED EDTIDVFQQP TGGVY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus." Bohren K.M., Nadkarni V., Song J.H., Gabbay K.H., Owerbach D. J. Biol. Chem. 279:27233-27238(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANT VAL-55, CHARACTERIZATION OF VARIANT VAL-55.
[2]	"A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes." Guo D., Li M., Zhang Y., Yang P., Eckenrode S., Hopkins D., Zheng W., Purohit S., Podolsky R.H., Muir A., Wang J., Dong Z., Brusko T., Atkinson M., Pozzilli P., Zeidler A., Raffel L.J., Jacob C.O. , Park Y., Serrano-Rios M., Martinez Larrad M.T., Zhang Z., Garchon H.-J., Bach J.-F., Rotter J.I., She J.-X., Wang C.-Y. Nat. Genet. 36:837-841(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, VARIANT VAL-55, CHARACTERIZATION OF VARIANT VAL-55.
[3]	Erratum Guo D., Li M., Zhang Y., Yang P., Eckenrode S., Hopkins D., Zheng W., Purohit S., Podolsky R.H., Muir A., Wang J., Dong Z., Brusko T., Atkinson M., Pozzilli P., Zeidler A., Raffel L.J., Jacob C.O. , Park Y., Serrano-Rios M., Martinez Larrad M.T., Zhang Z., Garchon H.-J., Bach J.-F., Rotter J.I., She J.-X., Wang C.-Y. Nat. Genet. 36:1024-1024(2004)
[4]	"SUMO4." Noso S. Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-55.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-55.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-55.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-55.
[8]	"A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation." Owerbach D., McKay E.M., Yeh E.T.H., Gabbay K.H., Bohren K.M. Biochem. Biophys. Res. Commun. 337:517-520(2005) [PubMed] [Europe PMC] [Abstract] Cited for: LACK OF PROTEOLYTIC CLEAVAGE.
[9]	"Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress." Guo D., Han J., Adam B.-L., Colburn N.H., Wang M.-H., Dong Z., Eizirik D.L., She J.-X., Wang C.-Y. Biochem. Biophys. Res. Commun. 337:1308-1318(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes." Smyth D.J., Howson J.M.M., Lowe C.E., Walker N.M., Lam A.C., Nutland S., Hutchings J., Tuomilehto-Wolf E., Tuomilehto J., Guja C., Ionescu-Tirgoviste C., Undlien D.E., Roenningen K.S., Savage D., Dunger D.B., Twells R.C.J., McArdle W.L., Strachan D.P., Todd J.A. Nat. Genet. 37:110-111(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF VARIANT VAL-55 WITH INSULIN-DEPENDENT DIABETES MELLITUS.
[11]	Erratum Smyth D.J., Howson J.M.M., Lowe C.E., Walker N.M., Lam A.C., Nutland S., Hutchings J., Tuomilehto-Wolf E., Tuomilehto J., Guja C., Ionescu-Tirgoviste C., Undlien D.E., Roenningen K.S., Savage D., Dunger D.B., Twells R.C.J., McArdle W.L., Strachan D.P., Todd J.A. Nat. Genet. 37:328-328(2004)
[12]	"Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes." Qu H., Bharaj B., Liu X.Q., Curtis J.A., Newhook L.A., Paterson A.D., Hudson T.J., Polychronakos C. Nat. Genet. 37:111-112(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF VARIANT VAL-55 WITH INSULIN-DEPENDENT DIABETES MELLITUS.
[13]	"Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes." Park Y., Park S., Kang J., Yang S., Kim D. Nat. Genet. 37:112-112(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION OF VARIANT VAL-55 WITH INSULIN-DEPENDENT DIABETES MELLITUS.
+	Additional computationally mapped references.

Web resources

Wikipedia

SUMO protein entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY340238 mRNA. Translation: AAR04484.1. AB205057 Genomic DNA. Translation: BAH05006.1. AL031133 Genomic DNA. Translation: CAA20019.1. CH471051 Genomic DNA. Translation: EAW47808.1. BC130305 mRNA. Translation: AAI30306.1.
IPI	IPI00434968.
RefSeq	NP_001002255.1. NM_001002255.1.
UniGene	Hs.657168.
3D structure databases
ProteinModelPortal	Q6EEV6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000318635.
PTM databases
PhosphoSite	Q6EEV6.
Polymorphism databases
DMDM	81175019.
Proteomic databases
PaxDb	Q6EEV6.
PRIDE	Q6EEV6.
Protocols and materials databases
DNASU	387082.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000326669; ENSP00000318635; ENSG00000177688.
GeneID	387082.
KEGG	hsa:387082.
UCSC	uc003qml.3. human.
Organism-specific databases
CTD	387082.
GeneCards	GC06P149763.
HGNC	HGNC:21181. SUMO4.
MIM	600320. phenotype. 608829. gene.
neXtProt	NX_Q6EEV6.
PharmGKB	PA134979206.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5227.
HOGENOM	HOG000207495.
HOVERGEN	HBG053025.
InParanoid	Q6EEV6.
KO	K12160.
OrthoDB	EOG46HGC8.
Gene expression databases
Bgee	Q6EEV6.
CleanEx	HS_SUMO4.
Genevestigator	Q6EEV6.
GermOnline	ENSG00000177688. Homo sapiens.
Family and domain databases
InterPro	IPR022617. SUMO. IPR027218. SUMO_chordates. IPR000626. Ubiquitin. IPR019955. Ubiquitin_supergroup. [Graphical view]
PANTHER	PTHR10562:SF10. PTHR10562:SF10. 1 hit.
Pfam	PF11976. Rad60-SLD. 1 hit. [Graphical view]
SMART	SM00213. UBQ. 1 hit. [Graphical view]
PROSITE	PS50053. UBIQUITIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	387082.
NextBio	101180.
SOURCE	Search...

Entry information

Entry name

SUMO4_HUMAN

Accession

Primary (citable) accession number: Q6EEV6
Secondary accession number(s): A1L3W5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	November 8, 2005
Last modified:	May 1, 2013
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.