E3 SUMO-protein ligase

roduced by alternative splicing.

Protein type: EC 6.3.2.-; SUMO ligase; Transcription, coactivator/corepressor

Chromosomal Location of Human Ortholog: 17q25.3

Cellular Component: nucleoplasm; nucleus; PcG protein complex

Molecular Function: enzyme binding; protein binding; SUMO binding; SUMO ligase activity; transcription corepressor activity

Biological Process: negative regulation of apoptosis; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; protein sumoylation

s also known as Charcot- Marie-Tooth disease type 4E (CMT4E). CHN is characterized clinically by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities. Defects in EGR2 are a cause of Charcot-Marie-Tooth disease type 1D (CMT1D). CMT1D is a form of Charcot- Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. Defects in EGR2 are a cause of Dejerine-Sottas syndrome (DSS); also known as Dejerine-Sottas neuropathy (DSN) or hereditary motor and sensory neuropathy III (HMSN3). DSS is a severe degenerating neuropathy of the demyelinating Charcot-Marie- Tooth disease category, with onset by age 2 years. DSS is characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome. Belongs to the EGR C2H2-type zinc-finger protein family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: C2H2-type zinc finger protein; DNA-binding; EC 6.3.2.-

Chromosomal Location of Human Ortholog: 10q21.1

Cellular Component: cytoplasm; nucleus

Molecular Function: chromatin binding; protein binding; transcription factor activity; ubiquitin protein ligase binding

Biological Process: brain development; fat cell differentiation; peripheral nervous system development; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; protein export from nucleus; transcription from RNA polymerase II promoter

Disease: Charcot-marie-tooth Disease, Demyelinating, Type 1d; Hypertrophic Neuropathy Of Dejerine-sottas; Neuropathy, Congenital Hypomyelinating Or Amyelinating, Autosomal Recessive

promoting mus-101 sumoylation (PubMed:15654100).

telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). Acts as a E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TRAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, and maybe the cohesin components RAD21 and STAG2. Required for recruitment of telomeres to PML nuclear bodies. SUMO protein-ligase activity is required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair, and for formation of APBs in ALT cell lines. Required for sister chromatid cohesion during prometaphase and mitotic progression. Belongs to the NSE2 family.

Protein type: EC 6.-.-.-; EC 6.3.2.-; Ligase; SUMO conjugating system; Ubiquitin ligase

Chromosomal Location of Human Ortholog: 8q24.13

Cellular Component: chromosome, telomeric region; nucleoplasm; nucleus; PML body

Molecular Function: protein binding; SUMO ligase activity

Biological Process: double-strand break repair via homologous recombination; double-strand break repair via nonhomologous end joining; positive regulation of maintenance of mitotic sister chromatid cohesion; positive regulation of mitotic metaphase/anaphase transition; protein sumoylation; telomere maintenance via recombination

regulation in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. In vitro, binds A/T-rich DNA. The effects of this transcriptional coregulation, transactivation or silencing, may vary depending upon the biological context. Together with PRMT1, may repress STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. Interacts with NCOA2 and AR. Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with DDX21, CSRP2, AXIN1, JUN, UBE2I, SUMO1, SATB2, PLAG1, TP53 and STAT1 (dimer), following IFNA1-stimulation. Interacts with SP3 (preferentially when SUMO-modified). Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase. Interacts with STAT1. Interacts with CHUK/IKKA; this interaction induces PIAS1 phosphorylation. Interacts with PTK2/FAK1; the interaction promotes its sumoylation. Interacts with DDX5. Expressed in numerous tissues with highest level in testis. Belongs to the PIAS family.

Protein type: EC 6.3.2.-; Nuclear receptor co-regulator; SUMO conjugating system; Transcription, coactivator/corepressor

Chromosomal Location of Human Ortholog: 15q

Cellular Component: nucleoplasm; nucleus; PML body

Molecular Function: enzyme binding; protein binding; SUMO ligase activity; transcription corepressor activity

Biological Process: JAK-STAT cascade; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of protein sumoylation; protein sumoylation; regulation of cell proliferation

ortant roles in many cellular processes by mediating the sumoylation of target proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Isoforms of the encoded protein enhance the sumoylation of specific target proteins including the p53 tumor suppressor protein, c-Jun, and the androgen receptor. A pseudogene of this gene is located on the short arm of chromosome 4. The symbol MIZ1 has also been associated with ZBTB17 which is a different gene located on chromosome 1. [provided by RefSeq, Aug 2011]

uding the STAT pathway and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Monomer. Binds SUMO1 and UBE2I. Interacts with BCL11A, HMGA2, IRF1, MITF and NCOA2. Interacts with STAT5; the interaction occurs on stimulation by PRL. Interacts with GFI1; the interaction relieves the inhibitory effect of PIAS3 on STAT3- mediated transcriptional activity. Interacts with AR, PLAG1 and ZFHX3. Interacts with STAT3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. By dihydrotestosterone (DHT) in prostate cancer cells. Isoform 1 is expressed in most tissues except thymus and small intestine. Isoform 3 is expressed only in brain, heart, thymus, muscle, lung, testis, lactating breast and embryonic stem cells. Belongs to the PIAS family.

Protein type: EC 6.3.2.-; Nuclear receptor co-regulator; SUMO conjugating system

Cellular Component: cytoplasm; dendrite; nucleus; synapse

Molecular Function: enzyme binding; potassium channel regulator activity; protein binding; protein C-terminus binding; protein N-terminus binding; SUMO ligase activity

Biological Process: negative regulation of protein sumoylation; positive regulation of membrane potential; positive regulation of protein sumoylation; protein sumoylation; response to hormone stimulus

us cellular pathways, including the STAT pathway, the p53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Promotes PARK7 sumoylation. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Interacts with AR, AXIN1, GATA2, LEF1, TP53 and STAT1 (IFNG-induced). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs). Interacts with TICAM1. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase. Highly expressed in testis and, at lower levels, in spleen, prostate, ovary, colon and peripheral blood leukocytes. Belongs to the PIAS family.

Protein type: EC 6.3.2.-; Nuclear receptor co-regulator; SUMO conjugating system; Transcription, coactivator/corepressor

Cellular Component: cytoplasm; nuclear matrix; nucleoplasm; nucleus

Molecular Function: DNA binding; protein binding; protein C-terminus binding; SUMO ligase activity; transcription corepressor activity; ubiquitin protein ligase binding

Biological Process: inhibition of NF-kappaB transcription factor; JAK-STAT cascade; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; positive regulation of protein sumoylation; protein sumoylation

omponent of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1. Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (). Binds single-stranded RNA (in vitro).

al Process: negative regulation of transforming growth factor beta receptor signaling pathway; protein sumoylation