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Q8IUQ4 (SIAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processApoptosis
Cell cycle
Differentiation
Spermatogenesis
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionDevelopmental protein
Ligase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.2. Source: ProtInc

apoptotic process

Traceable author statement Ref.2. Source: ProtInc

axon guidance

Traceable author statement. Source: Reactome

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

nervous system development

Traceable author statement Ref.7. Source: ProtInc

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

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein catabolic process

Inferred from direct assay Ref.13. Source: UniProtKB

protein destabilization

Inferred from electronic annotation. Source: Ensembl

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

proteolysis

Traceable author statement Ref.7. Source: ProtInc

spermatogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 23001567. Source: MGI

   Cellular_componentbeta-catenin destruction complex

Inferred from direct assay Ref.31. Source: UniProtKB

cytoplasm

Traceable author statement Ref.7. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

early endosome

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein C-terminus binding

Inferred from physical interaction Ref.13. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.31. Source: UniProtKB

ubiquitin-protein transferase 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

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282E3 ubiquitin-protein ligase SIAH1
PRO_0000056163

Regions

Zinc finger41 – 7636RING-type
Zinc finger93 – 15361SIAH-type
Region90 – 282193SBD

Sites

Metal binding981Zinc 1 By similarity
Metal binding1051Zinc 1 By similarity
Metal binding1171Zinc 1 By similarity
Metal binding1211Zinc 1 By similarity
Metal binding1281Zinc 2
Metal binding1351Zinc 2
Metal binding1471Zinc 2
Metal binding1521Zinc 2

Amino acid modifications

Modified residue191Phosphoserine; by ATM and ATR Ref.26

Natural variations

Alternative sequence11M → MTGKATPPSLYSWRGVLFTC LPAARTRKRKEM in isoform 2.
VSP_010166
Alternative sequence193 – 1953LEK → DLS in isoform 3.
VSP_029210
Alternative sequence196 – 28287Missing in isoform 3.
VSP_029211

Experimental info

Mutagenesis191S → A: Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. Ref.26
Mutagenesis191S → D: Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. Ref.26
Mutagenesis401E → R: Loss of function. Ref.9
Mutagenesis411C → S: Loss of function; when associated with S-44. Ref.9
Mutagenesis441C → S: Loss of function. Ref.9 Ref.26
Mutagenesis551C → A: Loss of function; when associated with A-59 and S-72. Ref.9 Ref.25
Mutagenesis551C → S: Loss of function; when associated with Y-59. Ref.9 Ref.25
Mutagenesis591H → A: Loss of function; when associated with A-55 and S-72. Ref.9 Ref.25
Mutagenesis591H → Y: Loss of function. Ref.9 Ref.25
Mutagenesis661R → L: Decreased activity; when associated with T-68. Ref.9
Mutagenesis681K → T: Decreased activity; when associated with L-66. Ref.9
Mutagenesis721C → S: Loss of function; when associated with A-55 and A-59. Ref.25
Mutagenesis761R → E: Decreased activity. Ref.9
Mutagenesis1241R → 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.
Mutagenesis1421D → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.
Mutagenesis1511Q → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142.
Mutagenesis1521H → Y: Abolishes ability to degrade DCC. Ref.9
Mutagenesis161 – 1622ED → 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.
Mutagenesis198 – 2003KYD → GDG: Impairs CTNNB1 degradation. Ref.31
Mutagenesis2021H → Y: No effect. Ref.9
Mutagenesis2111L → R: Abolishes ability to degrade DCC. Ref.9
Mutagenesis214 – 2152TR → 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.
Mutagenesis2241R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
Mutagenesis2261E → 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.
Mutagenesis231 – 2322RR → 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.
Mutagenesis2331R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
Mutagenesis2371E → 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.
Mutagenesis2521M → D or K: Impairs CTNNB1 degradation. Ref.31
Mutagenesis2531N → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265.
Mutagenesis2651Q → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253.
Sequence conflict1731P → S in CAE46191. Ref.5
Sequence conflict2451E → G in CAE46191. Ref.5

Secondary structure

................................... 282
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 26, 2004. Version 2.
Checksum: FA0698D0DC1B0A15

FASTA28231,123
        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 

« Hide

Isoform 2 [UniParc].

Checksum: BE3085493B0ABEC1
Show »

FASTA31334,628
Isoform 3 (Siah-1S) [UniParc].

Checksum: B5AB8D4079A7C723
Show »

FASTA19521,215

References

« Hide '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. expand/collapse author list , 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.
CCDSCCDS10735.1. [Q8IUQ4-1]
CCDS32444.1. [Q8IUQ4-2]
RefSeqNP_001006611.1. NM_001006610.1. [Q8IUQ4-2]
NP_003022.3. NM_003031.3. [Q8IUQ4-1]
XP_006721309.1. XM_006721246.1. [Q8IUQ4-1]
UniGeneHs.706828.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A25X-ray2.20A90-282[»]
4C9ZX-ray1.95A/B91-282[»]
4CA1X-ray1.58A/B91-282[»]
4I7BX-ray3.00A/C90-282[»]
4I7CX-ray2.80A/C90-282[»]
4I7DX-ray2.40A/C90-282[»]
ProteinModelPortalQ8IUQ4.
SMRQ8IUQ4. Positions 35-81, 95-282.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112372. 85 interactions.
IntActQ8IUQ4. 40 interactions.
MINTMINT-156060.
STRING9606.ENSP00000349156.

PTM databases

PhosphoSiteQ8IUQ4.

Polymorphism databases

DMDM46577493.

Proteomic databases

MaxQBQ8IUQ4.
PaxDbQ8IUQ4.
PRIDEQ8IUQ4.

Protocols and materials databases

DNASU6477.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356721; ENSP00000349156; ENSG00000196470. [Q8IUQ4-2]
ENST00000380006; ENSP00000369343; ENSG00000196470. [Q8IUQ4-1]
ENST00000394725; ENSP00000378214; ENSG00000196470. [Q8IUQ4-1]
ENST00000568007; ENSP00000456421; ENSG00000196470. [Q8IUQ4-1]
GeneID6477.
KEGGhsa:6477.
UCSCuc002efn.1. human. [Q8IUQ4-2]
uc002efo.1. human. [Q8IUQ4-1]

Organism-specific databases

CTD6477.
GeneCardsGC16M048443.
HGNCHGNC:10857. SIAH1.
HPACAB018724.
MIM602212. gene.
neXtProtNX_Q8IUQ4.
PharmGKBPA35759.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG264215.
HOGENOMHOG000231487.
HOVERGENHBG055701.
KOK04506.
OMAHEETCEF.
OrthoDBEOG7JT6XC.
PhylomeDBQ8IUQ4.
TreeFamTF312976.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ8IUQ4.
BgeeQ8IUQ4.
CleanExHS_SIAH1.
GenevestigatorQ8IUQ4.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProIPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR004162. SINA_like.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]
PANTHERPTHR10315. PTHR10315. 1 hit.
PfamPF03145. Sina. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
PROSITEPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8IUQ4.
GeneWikiSIAH1.
GenomeRNAi6477.
NextBio25161.
PROQ8IUQ4.
SOURCESearch...

Entry information

Entry nameSIAH1_HUMAN
AccessionPrimary (citable) accession number: Q8IUQ4
Secondary accession number(s): A0FKF3 expand/collapse secondary AC list , O43269, Q49A58, Q92880
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 9, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM