Q8IUQ4 (SIAH1_HUMAN) 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:	HUMSIAH

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	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 (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the 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 regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. 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.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31
Enzyme regulation	Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10. Ref.28
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with PEG3. Interacts with GAPDH; leading to stabilize SIAH1 By similarity. 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 KHDRBS3. Interacts with SNCAIP and HIPK2. Ref.7 Ref.8 Ref.10 Ref.12 Ref.19 Ref.22 Ref.23 Ref.25 Ref.26 Ref.28 Ref.31
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Partially nuclear. Ref.2 Ref.7 Ref.8 Ref.9 Ref.14 Ref.18 Ref.25
Tissue specificity	Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas. Ref.2 Ref.20
Induction	May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response. The relevance of such activity in vivo is however unclear and may not exist. Ref.28
Domain	The RING-type zinc finger domain is essential for ubiquitin ligase activity. 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. Ref.26
Sequence similarities	Belongs to the SINA (Seven in absentia) family. Contains 1 RING-type zinc finger. Contains 1 SIAH-type zinc finger.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Differentiation Spermatogenesis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome cell cycle Inferred from electronic annotation. Source: UniProtKB-KW neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from direct assay PubMed 21185211. Source: UniProtKB positive regulation of intrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 21185211. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein destabilization Inferred from electronic annotation. Source: Compara protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	beta-catenin destruction complex Inferred from direct assay Ref.31. Source: UniProtKB cytosol Traceable author statement. Source: Reactome early endosome Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ubiquitin-protein ligase activity Inferred from mutant phenotype PubMed 21185211. Source: UniProtKB zinc ion binding Inferred from direct assay PubMed 11863358Ref.31. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATXN7	O15265	2	EBI-747107,EBI-708350
MYD88	Q99836	3	EBI-747107,EBI-447677
SEPT4	O43236-6	2	EBI-747107,EBI-4372019
Sh3rf1	Q69ZI1	5	EBI-747107,EBI-957380	From a different organism.
XIAP	P98170	3	EBI-747107,EBI-517127

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IUQ4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8IUQ4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MTGKATPPSLYSWRGVLFTCLPAARTRKRKEM

Isoform 3 (identifier: Q8IUQ4-3)

Also known as: Siah-1S;

The sequence of this isoform differs from the canonical sequence as follows:
     193-195: LEK → DLS
     196-282: Missing.

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_0000056163

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

Metal binding

135

1

Zinc 2

Metal binding

147

1

Zinc 2

Metal binding

152

1

Zinc 2

Amino acid modifications

Modified residue

19

1

Phosphoserine; by ATM and ATR Ref.26

Natural variations

Alternative sequence

1

1

M → MTGKATPPSLYSWRGVLFTC LPAARTRKRKEM in isoform 2.

VSP_010166

Alternative sequence

193 – 195

3

LEK → DLS in isoform 3.

VSP_029210

Alternative sequence

196 – 282

87

Missing in isoform 3.

VSP_029211

Experimental info

Mutagenesis

19

1

S → A: Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. Ref.26

Mutagenesis

19

1

S → D: Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. Ref.26

Mutagenesis

40

1

E → R: Loss of function. Ref.9

Mutagenesis

41

1

C → S: Loss of function; when associated with S-44. Ref.9

Mutagenesis

44

1

C → S: Loss of function. Ref.9 Ref.26

Mutagenesis

55

1

C → A: Loss of function; when associated with A-59 and S-72. Ref.9 Ref.25

Mutagenesis

55

1

C → S: Loss of function; when associated with Y-59. Ref.9 Ref.25

Mutagenesis

59

1

H → A: Loss of function; when associated with A-55 and S-72. Ref.9 Ref.25

Mutagenesis

59

1

H → Y: Loss of function. Ref.9 Ref.25

Mutagenesis

66

1

R → L: Decreased activity; when associated with T-68. Ref.9

Mutagenesis

68

1

K → T: Decreased activity; when associated with L-66. Ref.9

Mutagenesis

72

1

C → S: Loss of function; when associated with A-55 and A-59. Ref.25

Mutagenesis

76

1

R → E: Decreased activity. Ref.9

Mutagenesis

124

1

R → A in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-214; A-215; A-231 and A-232.

Mutagenesis

142

1

D → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.

Mutagenesis

151

1

Q → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142.

Mutagenesis

152

1

H → Y: Abolishes ability to degrade DCC. Ref.9

Mutagenesis

161 – 162

2

ED → AA in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-226 and A-237.

Mutagenesis

198 – 200

3

KYD → GDG: Impairs CTNNB1 degradation. Ref.31

Mutagenesis

202

1

H → Y: No effect. Ref.9

Mutagenesis

211

1

L → R: Abolishes ability to degrade DCC. Ref.9

Mutagenesis

214 – 215

2

TR → AA in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-231 and A-232.

Mutagenesis

224

1

R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.

Mutagenesis

226

1

E → A in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-237.

Mutagenesis

231 – 232

2

RR → AA in D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-214 and A-215.

Mutagenesis

233

1

R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.

Mutagenesis

237

1

E → A in A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-226.

Mutagenesis

252

1

M → D or K: Impairs CTNNB1 degradation. Ref.31

Mutagenesis

253

1

N → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265.

Mutagenesis

265

1

Q → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253.

Sequence conflict

173

1

P → S in CAE46191. Ref.5

Sequence conflict

245

1

E → G in CAE46191. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

282

Helix Strand Turn

Details...

Helix

144 – 151

8

Beta strand

157 – 168

12

Beta strand

177 – 184

8

Beta strand

187 – 195

9

Beta strand

204 – 213

10

Helix

215 – 218

4

Beta strand

221 – 229

9

Beta strand

232 – 238

7

Turn

243 – 245

3

Helix

248 – 252

5

Beta strand

256 – 260

5

Helix

261 – 267

7

Beta strand

269 – 281

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: FA0698D0DC1B0A15	FASTA	282	31,123
	10 20 30 40 50 60 MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL 70 80 90 100 110 120 VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKADHEEL 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
	Isoform 2 [UniParc]. Checksum: BE3085493B0ABEC1	FASTA	313	34,628
	10 20 30 40 50 60 MTGKATPPSL YSWRGVLFTC LPAARTRKRK EMSRQTATAL PTGTSKCPPS QRVPALTGTT 70 80 90 100 110 120 ASNNDLASLF ECPVCFDYVL PPILQCQSGH LVCSNCRPKL TCCPTCRGPL GSIRNLAMEK 130 140 150 160 170 180 VANSVLFPCK YASSGCEITL PHTEKADHEE LCEFRPYSCP CPGASCKWQG SLDAVMPHLM 190 200 210 220 230 240 HQHKSITTLQ GEDIVFLATD INLPGAVDWV MMQSCFGFHF MLVLEKQEKY DGHQQFFAIV 250 260 270 280 290 300 QLIGTRKQAE NFAYRLELNG HRRRLTWEAT PRSIHEGIAT AIMNSDCLVF DTSIAQLFAE 310 NGNLGINVTI SMC
	Isoform 3 (Siah-1S) [UniParc]. Checksum: B5AB8D4079A7C723	FASTA	195	21,215
	10 20 30 40 50 60 MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL 70 80 90 100 110 120 VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKADHEEL 130 140 150 160 170 180 CEFRPYSCPC PGASCKWQGS LDAVMPHLMH QHKSITTLQG EDIVFLATDI NLPGAVDWVM 190 MQSCFGFHFM LVDLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression." Nemani M., Linares-Cruz G., Bruzzoni-Giovanelli H., Roperch J.-P., Tuynder M., Bougueleret L., Cherif D., Medhioub M., Pasturaud P., Alvaro V., Der Sarkissan H., Cazes L., Le Paslier D., Le Gall I., Israeli D., Dausset J., Sigaux F., Chumakov I. , Oren M., Calvo F., Amson R.B., Cohen D., Telerman A. Proc. Natl. Acad. Sci. U.S.A. 93:9039-9042(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Intestinal epithelium.
[2]	"Characterization of human homologs of the Drosophila seven in absentia (sina) gene." Hu G., Chung Y.-L., Glover T., Valentine V., Look A.T., Fearon E.R. Genomics 46:103-111(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Fetal brain.
[3]	"Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene." Medhioub M., Vaury C., Hamelin R., Thomas G. Int. J. Cancer 87:794-797(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Siah-1S, a novel splice variant of Siah-1 (seven in absentia homolog), counteracts Siah-1-mediated downregulation of beta-catenin." Mei Y., Xie C., Xie W., Wu Z., Wu M. Oncogene 26:6319-6331(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Retina.
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Brain, Pancreas and Testis.
[7]	"Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway." Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R. Genes Dev. 11:2701-2714(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF DCC, SUBCELLULAR LOCATION, INTERACTION WITH UBE2I.
[8]	"p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1." Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C. EMBO J. 17:2736-2747(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BAG1, SUBCELLULAR LOCATION.
[9]	"Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins." Hu G., Fearon E.R. Mol. Cell. Biol. 19:724-732(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-40; CYS-41; CYS-44; CYS-55; HIS-59; ARG-66; LYS-68; ARG-76; HIS-152; HIS-202 AND LEU-211.
[10]	"SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis." Germani A., Bruzzoni-Giovanelli H., Fellous A., Gisselbrecht S., Varin-Blank N., Calvo F. Oncogene 19:5997-6006(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF KIF22, INTERACTION WITH ALPHA-TUBULIN.
[11]	"p53 suppresses the c-Myb-induced activation of heat shock transcription factor 3." Tanikawa J., Ichikawa-Iwata E., Kanei-Ishii C., Nakai A., Matsuzawa S., Reed J.C., Ishii S. J. Biol. Chem. 275:15578-15585(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF MYB.
[12]	"Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses." Matsuzawa S., Reed J.C. Mol. Cell 7:915-926(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF CTNNB1, SUBUNIT OF A COMPLEX WITH UBE2D1; CACYBP; SKP1; APC AND TBL1X.
[13]	"Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein." Liu J., Stevens J., Rote C.A., Yost H.J., Hu Y., Neufeld K.L., White R.L., Matsunami N. Mol. Cell 7:927-936(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF CTNNB1.
[14]	"The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1." Tiedt R., Bartholdy B.A., Matthias G., Newell J.W., Matthias P. EMBO J. 20:4143-4152(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF POU2AF1, SUBCELLULAR LOCATION.
[15]	"Regulation of BOB.1/OBF.1 stability by SIAH." Boehm J., He Y., Greiner A., Staudt L., Wirth T. EMBO J. 20:4153-4162(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF POU2AF1.
[16]	"Siah-1 binds and regulates the function of Numb." Susini L., Passer B.J., Amzallag-Elbaz N., Juven-Gershon T., Prieur S., Privat N., Tuynder M., Gendron M.-C., Israeel A., Amson R., Oren M., Telerman A. Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF NUMB.
[17]	"Modulation of transforming growth factor beta (TGFbeta)/Smad transcriptional responses through targeted degradation of TGFbeta-inducible early gene-1 by human seven in absentia homologue." Johnsen S.A., Subramaniam M., Monroe D.G., Janknecht R., Spelsberg T.C. J. Biol. Chem. 277:30754-30759(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF KLF10.
[18]	"Siah-1 facilitates ubiquitination and degradation of synphilin-1." Nagano Y., Yamashita H., Takahashi T., Kishida S., Nakamura T., Iseki E., Hattori N., Mizuno Y., Kikuchi A., Matsumoto M. J. Biol. Chem. 278:51504-51514(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF SNCAIP, SUBCELLULAR LOCATION.
[19]	"Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1." Okabe H., Satoh S., Furukawa Y., Kato T., Hasegawa S., Nakajima Y., Yamaoka Y., Nakamura Y. Cancer Res. 63:3043-3048(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PEG10.
[20]	"SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas." Matsuo K., Satoh S., Okabe H., Nomura A., Maeda T., Yamaoka Y., Ikai I. Genes Chromosomes Cancer 36:283-291(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[21]	"SIAH-1 interacts with CtIP and promotes its degradation by the proteasome pathway." Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A., Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F., Bruzzoni-Giovanelli H. Oncogene 22:8845-8851(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF RBBP8.
[22]	"Structural analysis of Siah1 and its interactions with Siah-interacting protein (SIP)." Matsuzawa S., Li C., Ni C.-Z., Takayama S., Reed J.C., Ely K.R. J. Biol. Chem. 278:1837-1840(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CACYBP, MUTANTS A; B; C; D AND E.
[23]	"SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome." Venables J.P., Dalgliesh C., Paronetto M.P., Skitt L., Thornton J.K., Saunders P.T., Sette C., Jones K.T., Elliott D.J. Hum. Mol. Genet. 13:1525-1534(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KHDRBS3.
[24]	"The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome." Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S., Lazar M.A., Pelicci P.G., Minucci S. J. Biol. Chem. 279:5374-5379(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DEGRADATION OF PML, MUTANTS A AND D.
[25]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNCAIP AND SNCA, MUTAGENESIS OF CYS-55; HIS-59 AND CYS-72.
[26]	"Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR." Winter M., Sombroek D., Dauth I., Moehlenbrink J., Scheuermann K., Crone J., Hofmann T.G. Nat. Cell Biol. 10:812-824(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-19 AND CYS-44, INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-19 BY ATM AND ATR.
[27]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[28]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNCAIP, ENZYME REGULATION, FUNCTION.
[29]	"Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for proteasomal degradation." Buchwald M., Pietschmann K., Muller J.P., Bohmer F.D., Heinzel T., Kramer O.H. Leukemia 24:1412-1421(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF FLT3.
[30]	"The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription." Liu M., Hsu J., Chan C., Li Z., Zhou Q. Mol. Cell 46:325-334(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[31]	"Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex." Santelli E., Leone M., Li C., Fukushima T., Preece N.E., Olson A.J., Ely K.R., Reed J.C., Pellecchia M., Liddington R.C., Matsuzawa S. J. Biol. Chem. 280:34278-34287(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 90-282 IN COMPLEX WITH ZINC IONS AND CACYBP, FUNCTION, MUTAGENESIS OF 198-LYS--ASP-200 AND MET-252, INTERACTION WITH CACYBP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U63295 mRNA. Translation: AAC12950.1.
U76247 mRNA. Translation: AAC51907.1.
AJ400626 Genomic DNA. Translation: CAC35542.1.
EF026094 mRNA. Translation: ABK15529.1.
BX647064 mRNA. Translation: CAE46191.1.
BC035562 mRNA. Translation: AAH35562.1.
BC042550 mRNA. Translation: AAH42550.1.
BC044920 mRNA. Translation: AAH44920.1.

IPI

IPI00328242.
IPI00396517.
IPI00872574.

RefSeq

NP_001006611.1. NM_001006610.1.
NP_003022.3. NM_003031.3.

UniGene

Hs.706828.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A25	X-ray	2.20	A	90-282	[»]

ProteinModelPortal

Q8IUQ4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8IUQ4. 30 interactions.

MINT

MINT-156060.

STRING

9606.ENSP00000349156.

PTM databases

PhosphoSite

Q8IUQ4.

Polymorphism databases

DMDM

46577493.

Proteomic databases

PaxDb

Q8IUQ4.

PRIDE

Q8IUQ4.

Protocols and materials databases

DNASU

6477.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356721; ENSP00000349156; ENSG00000196470.
ENST00000380006; ENSP00000369343; ENSG00000196470.
ENST00000394725; ENSP00000378214; ENSG00000196470.
ENST00000568007; ENSP00000456421; ENSG00000196470.

GeneID

6477.

KEGG

hsa:6477.

UCSC

uc002efn.1. human.
uc002efo.1. human.

Organism-specific databases

CTD

6477.

GeneCards

GC16M048443.

HGNC

HGNC:10857. SIAH1.

HPA

CAB018724.

MIM

602212. gene.

neXtProt

NX_Q8IUQ4.

PharmGKB

PA35759.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG264215.

HOGENOM

HOG000231487.

HOVERGEN

HBG055701.

KO

K04506.

OMA

HEETCEF.

OrthoDB

EOG4F7NKB.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q8IUQ4.

Bgee

Q8IUQ4.

CleanEx

HS_SIAH1.

Genevestigator

Q8IUQ4.

GermOnline

ENSG00000196470. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.
3.90.890.10. 1 hit.

InterPro

IPR004162. 7-in-absentia-prot.
IPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]

PANTHER

PTHR10315. PTHR10315. 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

EvolutionaryTrace

Q8IUQ4.

GenomeRNAi

6477.

NextBio

25161.

SOURCE

Search...

Entry information

Entry name

SIAH1_HUMAN

Accession

Primary (citable) accession number: Q8IUQ4
Secondary accession number(s): A0FKF3 , O43269, Q49A58, Q92880

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	May 1, 2013
This is version 113 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.