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Identification
HMDB Protein ID HMDBP09308
Secondary Accession Numbers
  • 15140
Name E3 ubiquitin-protein ligase SIAH2
Synonyms
  1. Seven in absentia homolog 2
  2. Siah-2
  3. hSiah2
Gene Name SIAH2
Protein Type Enzyme
Biological Properties
General Function Involved in ubiquitin-dependent protein catabolic process
Specific Function E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 can not. Promotes monoubiquitination of SNCA
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
small conjugating protein ligase activity
transition metal ion binding
zinc ion binding
ligase activity
protein binding
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
ubiquitin-protein ligase activity
Process
metabolic process
multicellular organismal process
macromolecule metabolic process
multicellular organismal development
protein modification by small protein conjugation or removal
protein modification by small protein conjugation
protein ubiquitination
catabolic process
macromolecule catabolic process
cellular macromolecule catabolic process
modification-dependent macromolecule catabolic process
modification-dependent protein catabolic process
ubiquitin-dependent protein catabolic process
macromolecule modification
protein modification process
Cellular Location
  1. Cytoplasm
  2. Nucleus (Probable)
Gene Properties
Chromosome Location Chromosome:3
Locus 3q25
SNPs SIAH2
Gene Sequence
>975 bp
ATGAGCCGCCCGTCCTCCACCGGCCCCAGCGCTAATAAACCCTGCAGCAAGCAGCCGCCG
CCGCAGCCCCAGCACACTCCGTCCCCGGCTGCGCCCCCGGCCGCCGCCACCATCTCGGCT
GCGGGCCCCGGCTCGTCCGCGGTGCCCGCCGCGGCGGCGGTGATCTCGGGCCCCGGCGGC
GGCGGCGGGGCCGGCCCGGTGTCCCCGCAGCACCACGAGCTGACCTCGCTCTTCGAGTGT
CCGGTCTGCTTTGACTATGTCCTGCCTCCTATTCTGCAGTGCCAGGCCGGGCACCTGGTG
TGTAACCAATGCCGCCAGAAGTTGAGCTGCTGCCCGACGTGCAGGGGCGCCCTGACGCCC
AGCATCAGGAACCTGGCTATGGAGAAGGTGGCCTCGGCAGTCCTGTTTCCCTGTAAGTAT
GCCACCACGGGCTGTTCCCTGACCCTGCACCATACGGAGAAACCAGAACATGAAGACATA
TGTGAATACCGTCCCTACTCCTGCCCATGTCCTGGTGCTTCCTGCAAGTGGCAGGGGTCC
CTGGAAGCTGTGATGTCCCATCTCATGCACGCCCACAAGAGCATTACCACCCTTCAGGGA
GAAGACATCGTCTTTCTAGCTACAGACATTAACTTGCCAGGGGCTGTCGACTGGGTGATG
ATGCAGTCATGTTTTGGCCATCACTTCATGCTGGTGCTGGAGAAACAAGAGAAGTACGAA
GGCCACCAGCAGTTTTTTGCCATCGTCCTGCTCATTGGCACCCGCAAGCAAGCCGAGAAC
TTTGCCTACAGACTGGAGTTGAATGGGAACCGGCGGAGATTGACCTGGGAGGCCACGCCC
CGTTCGATTCATGACGGTGTGGCTGCGGCCATCATGAACAGCGACTGCCTTGTTTTCGAC
ACAGCCATAGCACATCTTTTTGCAGATAATGGGAACCTTGGAATCAATGTTACTATTTCT
ACATGTTGTCCATGA
Protein Properties
Number of Residues 324
Molecular Weight 34614.4
Theoretical pI 7.14
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>E3 ubiquitin-protein ligase SIAH2
MSRPSSTGPSANKPCSKQPPPQPQHTPSPAAPPAAATISAAGPGSSAVPAAAAVISGPGG
GGGAGPVSPQHHELTSLFECPVCFDYVLPPILQCQAGHLVCNQCRQKLSCCPTCRGALTP
SIRNLAMEKVASAVLFPCKYATTGCSLTLHHTEKPEHEDICEYRPYSCPCPGASCKWQGS
LEAVMSHLMHAHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGHHFMLVLEKQEKYE
GHQQFFAIVLLIGTRKQAENFAYRLELNGNRRRLTWEATPRSIHDGVAAAIMNSDCLVFD
TAIAHLFADNGNLGINVTISTCCP
GenBank ID Protein 15341820
UniProtKB/Swiss-Prot ID O43255
UniProtKB/Swiss-Prot Entry Name SIAH2_HUMAN
PDB IDs Not Available
GenBank Gene ID BC013082
GeneCard ID SIAH2
GenAtlas ID SIAH2
HGNC ID HGNC:10858
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Matsuzawa SI, Reed JC: Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell. 2001 May;7(5):915-26. [PubMed:11389839 ]
  3. Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER: Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway. Genes Dev. 1997 Oct 15;11(20):2701-14. [PubMed:9334332 ]
  4. Tian YM, Mole DR, Ratcliffe PJ, Gleadle JM: Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation. Biochem J. 2006 Jul 1;397(1):179-86. [PubMed:16509823 ]
  5. Hu G, Chung YL, Glover T, Valentine V, Look AT, Fearon ER: Characterization of human homologs of the Drosophila seven in absentia (sina) gene. Genomics. 1997 Nov 15;46(1):103-11. [PubMed:9403064 ]
  6. Boehm J, He Y, Greiner A, Staudt L, Wirth T: Regulation of BOB.1/OBF.1 stability by SIAH. EMBO J. 2001 Aug 1;20(15):4153-62. [PubMed:11483518 ]
  7. Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y: Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 2003 Jun 15;63(12):3043-8. [PubMed:12810624 ]
  8. Szargel R, Rott R, Eyal A, Haskin J, Shani V, Balan L, Wolosker H, Engelender S: Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation. J Biol Chem. 2009 Apr 24;284(17):11706-16. doi: 10.1074/jbc.M805990200. Epub 2009 Feb 17. [PubMed:19224863 ]
  9. Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N: hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways. Mol Cell Biol. 1999 May;19(5):3798-807. [PubMed:10207103 ]
  10. Habelhah H, Frew IJ, Laine A, Janes PW, Relaix F, Sassoon D, Bowtell DD, Ronai Z: Stress-induced decrease in TRAF2 stability is mediated by Siah2. EMBO J. 2002 Nov 1;21(21):5756-65. [PubMed:12411493 ]