Q920M9 (SIAH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase SIAH1
EC=6.3.2.-

Alternative name(s):
Seven in absentia homolog 1
Short name=Siah-1
Siah-1a

Gene names

Name:	Siah1
Synonyms:	Siah1a

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	282 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 (MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3 By similarity. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. Ref.1 Ref.5
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homodimer. Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity. Interacts with PEG3 and HIPK2 By similarity. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with SNCAIP. Interacts with GAPDH; leading to stabilize SIAH1. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Partially nuclear. Ref.1 Ref.5 Ref.6
Domain	The RING-type zinc finger domain is essential for ubiquitin ligase activity By similarity. The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family By similarity.
Post-translational modification	Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 By similarity.
Sequence similarities	Belongs to the SINA (Seven in absentia) family. Contains 1 RING-type zinc finger. Contains 1 SIAH-type zinc finger.
Sequence caution	The sequence BAB70753.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Differentiation Spermatogenesis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein Ligase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW neuron apoptosis Inferred from mutant phenotype Ref.5. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein destabilization Inferred from mutant phenotype. Source: RGD protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.5. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	beta-catenin destruction complex Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from direct assay Ref.5. Source: UniProtKB early endosome Inferred from direct assay Ref.1. Source: RGD membrane fraction Inferred from direct assay Ref.1. Source: RGD nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	protein C-terminus binding Inferred from physical interaction Ref.1. Source: RGD ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sh3rf1	Q71F54	2	EBI-957514,EBI-957526

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 282	282	E3 ubiquitin-protein ligase SIAH1		PRO_0000056166
Regions
	Zinc finger	41 – 76	36	RING-type
	Zinc finger	93 – 153	61	SIAH-type
	Region	90 – 282	193	SBD
Sites
	Metal binding	98	1	Zinc 1 By similarity
	Metal binding	105	1	Zinc 1 By similarity
	Metal binding	117	1	Zinc 1 By similarity
	Metal binding	121	1	Zinc 1 By similarity
	Metal binding	128	1	Zinc 2 By similarity
	Metal binding	135	1	Zinc 2 By similarity
	Metal binding	147	1	Zinc 2 By similarity
	Metal binding	152	1	Zinc 2 By similarity
Amino acid modifications
	Modified residue	19	1	Phosphoserine; by ATM and ATR By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q920M9 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: 852EADC5DD4A4FFA	FASTA	282	31,137
	10 20 30 40 50 60 MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL 70 80 90 100 110 120 VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKAEHEEL 130 140 150 160 170 180 CEFRPYSCPC PGASCKWQGS LDAVMPHLMH QHKSITTLQG EDIVFLATDI NLPGAVDWVM 190 200 210 220 230 240 MQSCFGFHFM LVLEKQEKYD GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP 250 260 270 280 RSIHEGIATA IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC

References

[1]	"Regulation of synaptophysin degradation by mammalian homologues of Seven in Absentia." Wheeler T.C., Chin L.-S., Li Y., Roudabush F.L., Li L. J. Biol. Chem. 277:10273-10282(2002) [PubMed: 11786535] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN DEGRADATION OF SYP, SUBCELLULAR LOCATION, INTERACTION WITH UBE2E2. Strain: Sprague-Dawley.
[2]	"Rat Siah1A." Yamaguchi A., Hori O., Tohyama M. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors." Ishikawa K., Nash S.R., Nishimune A., Neki A., Kaneko S., Nakanishi S. Genes Cells 4:381-390(1999) [PubMed: 10469171] [Abstract] Cited for: INTERACTION WITH GRM1 AND GRM5.
[4]	"Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease." Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D., Bornemann A., Riess O., Ross C.A., Rott R., Engelender S. Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004) [PubMed: 15064394] [Abstract] Cited for: INTERACTION WITH SNCAIP.
[5]	"S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding." Hara M.R., Agrawal N., Kim S.F., Cascio M.B., Fujimuro M., Ozeki Y., Takahashi M., Cheah J.H., Tankou S.K., Hester L.D., Ferris C.D., Hayward S.D., Snyder S.H., Sawa A. Nat. Cell Biol. 7:665-674(2005) [PubMed: 15951807] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GAPDH.
[6]	"Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation." Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H., Engelender S. J. Biol. Chem. 284:11706-11716(2009) [PubMed: 19224863] [Abstract] Cited for: INTERACTION WITH SNCAIP, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF389476 mRNA. Translation: AAL91362.1. AB067814 mRNA. Translation: BAB70753.1. Different initiation.
IPI	IPI00200708.
RefSeq	NP_543181.2. NM_080905.2.
UniGene	Rn.73937.
3D structure databases
ProteinModelPortal	Q920M9.
SMR	Q920M9. Positions 33-282.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q920M9. 1 interaction.
STRING	Q920M9.
Proteomic databases
PRIDE	Q920M9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000020329; ENSRNOP00000020329; ENSRNOG00000015143.
GeneID	140941.
KEGG	rno:140941.
UCSC	NM_080905. rat.
Organism-specific databases
CTD	20437.
RGD	620449. Siah1a.
Phylogenomic databases
eggNOG	maNOG15709.
GeneTree	ENSGT00390000005434.
HOVERGEN	HBG055701.
InParanoid	Q920M9.
OMA	PLGNIRN.
OrthoDB	EOG4F7NKB.
PhylomeDB	Q920M9.
Gene expression databases
ArrayExpress	Q920M9.
Genevestigator	Q920M9.
GermOnline	ENSRNOG00000015143. Rattus norvegicus.
Family and domain databases
InterPro	IPR004162. 7-in-absentia-prot. IPR018121. 7-in-absentia-prot_TRAF-dom. IPR013323. SIAH-type. IPR008974. TRAF-like. IPR013322. TRAF-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR013010. Znf_SIAH. [Graphical view]
Gene3D	G3DSA:3.90.890.10. SIAH-type. 1 hit. G3DSA:2.60.210.10. TRAF-type. 1 hit. G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K04506.
PANTHER	PTHR10315. Sina. 1 hit.
Pfam	PF03145. Sina. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF49599. Traf_like. 1 hit.
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. PS51081. ZF_SIAH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	620838.

Entry information

Entry name

SIAH1_RAT

Accession

Primary (citable) accession number: Q920M9
Secondary accession number(s): Q06984

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	November 16, 2011
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program