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Protein

E3 ubiquitin-protein ligase SIAH1

Gene

SIAH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.19 Publications

Enzyme regulationi

Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.1 Publication

Pathway: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi98 – 981Zinc 1By similarity
Metal bindingi105 – 1051Zinc 1By similarity
Metal bindingi117 – 1171Zinc 1By similarity
Metal bindingi121 – 1211Zinc 1By similarity
Metal bindingi128 – 1281Zinc 2
Metal bindingi135 – 1351Zinc 2
Metal bindingi147 – 1471Zinc 2
Metal bindingi152 – 1521Zinc 2

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • ligase activity Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • anatomical structure morphogenesis Source: ProtInc
  • apoptotic process Source: ProtInc
  • axon guidance Source: Reactome
  • cell cycle Source: UniProtKB-KW
  • nervous system development Source: ProtInc
  • neuron apoptotic process Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein catabolic process Source: UniProtKB
  • protein destabilization Source: Ensembl
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • spermatogenesis Source: UniProtKB-KW
  • ubiquitin-dependent protein catabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Ligase

Keywords - Biological processi

Apoptosis, Cell cycle, Differentiation, Spermatogenesis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiREACT_22237. Netrin-1 signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SIAH1
Synonyms:HUMSIAH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:10857. SIAH1.

Subcellular locationi

GO - Cellular componenti

  • beta-catenin destruction complex Source: UniProtKB
  • cytoplasm Source: ProtInc
  • cytosol Source: Reactome
  • early endosome Source: Ensembl
  • nucleus Source: UniProtKB
  • plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi19 – 191S → A: Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. 1 Publication
Mutagenesisi19 – 191S → D: Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation. 1 Publication
Mutagenesisi40 – 401E → R: Loss of function. 1 Publication
Mutagenesisi41 – 411C → S: Loss of function; when associated with S-44. 1 Publication
Mutagenesisi44 – 441C → S: Loss of function. 2 Publications
Mutagenesisi55 – 551C → A: Loss of function; when associated with A-59 and S-72. 2 Publications
Mutagenesisi55 – 551C → S: Loss of function; when associated with Y-59. 2 Publications
Mutagenesisi59 – 591H → A: Loss of function; when associated with A-55 and S-72. 2 Publications
Mutagenesisi59 – 591H → Y: Loss of function. 2 Publications
Mutagenesisi66 – 661R → L: Decreased activity; when associated with T-68. 1 Publication
Mutagenesisi68 – 681K → T: Decreased activity; when associated with L-66. 1 Publication
Mutagenesisi72 – 721C → S: Loss of function; when associated with A-55 and A-59. 1 Publication
Mutagenesisi76 – 761R → E: Decreased activity. 1 Publication
Mutagenesisi124 – 1241R → 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.
Mutagenesisi142 – 1421D → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.
Mutagenesisi151 – 1511Q → A in E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142.
Mutagenesisi152 – 1521H → Y: Abolishes ability to degrade DCC. 1 Publication
Mutagenesisi161 – 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.
Mutagenesisi198 – 2003KYD → GDG: Impairs CTNNB1 degradation. 1 Publication
Mutagenesisi202 – 2021H → Y: No effect. 1 Publication
Mutagenesisi211 – 2111L → R: Abolishes ability to degrade DCC. 1 Publication
Mutagenesisi214 – 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.
Mutagenesisi224 – 2241R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
Mutagenesisi226 – 2261E → 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.
Mutagenesisi231 – 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.
Mutagenesisi233 – 2331R → A in C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
Mutagenesisi237 – 2371E → 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.
Mutagenesisi252 – 2521M → D or K: Impairs CTNNB1 degradation. 1 Publication
Mutagenesisi253 – 2531N → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265.
Mutagenesisi265 – 2651Q → A in B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253.

Organism-specific databases

PharmGKBiPA35759.

Polymorphism and mutation databases

BioMutaiSIAH1.
DMDMi46577493.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282E3 ubiquitin-protein ligase SIAH1PRO_0000056163Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Phosphoserine; by ATM and ATR1 Publication

Post-translational modificationi

Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8IUQ4.
PaxDbiQ8IUQ4.
PRIDEiQ8IUQ4.

PTM databases

PhosphoSiteiQ8IUQ4.

Expressioni

Tissue specificityi

Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.2 Publications

Inductioni

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.

Gene expression databases

BgeeiQ8IUQ4.
CleanExiHS_SIAH1.
ExpressionAtlasiQ8IUQ4. baseline and differential.
GenevisibleiQ8IUQ4. HS.

Organism-specific databases

HPAiCAB018724.

Interactioni

Subunit structurei

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.By similarity11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-747107,EBI-747107
Q59GP63EBI-747107,EBI-10243413
AASDHPPTQ9NRN73EBI-747107,EBI-740884
AFF4Q9UHB75EBI-747107,EBI-395282
AFF4Q9UHB7-25EBI-747107,EBI-10261324
AQP1P299723EBI-747107,EBI-745213
ARMC9Q7Z3E5-23EBI-747107,EBI-10256990
ATXN7O152652EBI-747107,EBI-708350
BCL6P411823EBI-747107,EBI-765407
C14orf105Q17R993EBI-747107,EBI-10238351
CAPGP401213EBI-747107,EBI-4291044
CDC23Q9UJX23EBI-747107,EBI-396137
CDC34P494273EBI-747107,EBI-975634
CDK5R1Q8N6193EBI-747107,EBI-10266998
CDK5R1Q8TAM43EBI-747107,EBI-10271838
DDX41Q9UJV93EBI-747107,EBI-1046350
DNAJC15Q9Y5T43EBI-747107,EBI-10329228
DNALI1O146453EBI-747107,EBI-395638
EEF1DP296924EBI-747107,EBI-358607
EXOC3-AS1Q8N2X63EBI-747107,EBI-749333
FAM90A1Q86YD73EBI-747107,EBI-6658203
FLI1Q015433EBI-747107,EBI-2271018
FZD9Q8TAN23EBI-747107,EBI-741016
GDPD5Q8WTR43EBI-747107,EBI-2833203
HIST2H4BP628053EBI-747107,EBI-302023
INHAP051113EBI-747107,EBI-10194422
KATNAL1Q9BW623EBI-747107,EBI-743591
KCNJ10P785083EBI-747107,EBI-9117877
KIAA0319LQ8IZA03EBI-747107,EBI-5240269
KIAA1217Q5T5P2-63EBI-747107,EBI-10188326
KIAA1683Q9H0B33EBI-747107,EBI-745878
KIF1BO603333EBI-747107,EBI-465633
KIFC3Q9BVG83EBI-747107,EBI-2125614
LACTB2Q53H823EBI-747107,EBI-3943430
MAB21L1Q133943EBI-747107,EBI-10229059
MAPK12P537783EBI-747107,EBI-602406
MAPKBP1O603363EBI-747107,EBI-947402
MOB3CQ70IA83EBI-747107,EBI-9679267
MTIF3Q9H2K03EBI-747107,EBI-3923617
MX1P205913EBI-747107,EBI-929476
MYD88Q998363EBI-747107,EBI-447677
NELFAQ9H3P23EBI-747107,EBI-5461341
NOL6Q9H6R4-43EBI-747107,EBI-10307896
OPRM1P353724EBI-747107,EBI-2624570
OTUB2Q96DC93EBI-747107,EBI-746259
PEG10Q86TG73EBI-747107,EBI-2858265
PFKMP082373EBI-747107,EBI-514788
PHC2Q8IXK05EBI-747107,EBI-713786
POU2AF1Q166332EBI-747107,EBI-943588
Pou2af1Q646935EBI-747107,EBI-943530From a different organism.
PRPF31F1T0A53EBI-747107,EBI-10177194
PRR20CP864795EBI-747107,EBI-10172814
PTPMT1Q8WUK03EBI-747107,EBI-7199479
PUF60Q9UHX17EBI-747107,EBI-1053259
PVRL2Q926923EBI-747107,EBI-718419
PYGBP112163EBI-747107,EBI-1047231
QRICH1Q2TAL83EBI-747107,EBI-2798044
RAB33AQ140883EBI-747107,EBI-744685
RAD51AP1Q96B013EBI-747107,EBI-1178724
RAD51AP1Q96B01-23EBI-747107,EBI-1178743
RAD54L2Q9Y4B43EBI-747107,EBI-948156
RPS19BP1Q86WX33EBI-747107,EBI-4479407
SDCBPO005603EBI-747107,EBI-727004
SEPT4O43236-62EBI-747107,EBI-4372019
Sh3rf1Q69ZI15EBI-747107,EBI-957380From a different organism.
SPATA4Q8NEY33EBI-747107,EBI-7067221
SPATC1LQ9H0A93EBI-747107,EBI-372911
SYT7O435813EBI-747107,EBI-10184345
TBC1D22BQ9NU193EBI-747107,EBI-8787464
TMEM43Q9BTV43EBI-747107,EBI-721293
TOLLIPQ6FIE93EBI-747107,EBI-10249783
TP53BP2Q13625-33EBI-747107,EBI-10175039
TRIM23P364063EBI-747107,EBI-740098
TRIM27P143733EBI-747107,EBI-719493
TRIM7Q9C0293EBI-747107,EBI-2813981
UBE2KP610864EBI-747107,EBI-473850
UPP2O950453EBI-747107,EBI-10191025
UXTQ9UBK93EBI-747107,EBI-357355
WDYHV1Q96HA83EBI-747107,EBI-741158
XP697134EBI-747107,EBI-7088789From a different organism.
XIAPP981703EBI-747107,EBI-517127
ZBP1A2RRL93EBI-747107,EBI-10173066
ZCCHC10Q8TBK63EBI-747107,EBI-597063
ZCCHC13Q8WW363EBI-747107,EBI-954111
ZFYVE21Q9BQ243EBI-747107,EBI-2849569
ZMAT3Q9HA383EBI-747107,EBI-2548480
ZNF148Q9UQR13EBI-747107,EBI-2688184
ZNF512BQ96KM63EBI-747107,EBI-1049952

Protein-protein interaction databases

BioGridi112372. 161 interactions.
IntActiQ8IUQ4. 113 interactions.
MINTiMINT-156060.
STRINGi9606.ENSP00000349156.

Structurei

Secondary structure

1
282
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi95 – 973Combined sources
Helixi101 – 1033Combined sources
Beta strandi108 – 1103Combined sources
Helixi111 – 12010Combined sources
Beta strandi122 – 1243Combined sources
Beta strandi130 – 1345Combined sources
Helixi141 – 1433Combined sources
Helixi144 – 1518Combined sources
Beta strandi156 – 16712Combined sources
Beta strandi172 – 18413Combined sources
Beta strandi187 – 19711Combined sources
Beta strandi203 – 21311Combined sources
Helixi215 – 2184Combined sources
Beta strandi221 – 2299Combined sources
Beta strandi232 – 2387Combined sources
Turni243 – 2453Combined sources
Helixi248 – 2525Combined sources
Beta strandi256 – 2605Combined sources
Helixi261 – 2677Combined sources
Beta strandi272 – 28110Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4X3GX-ray2.34A/B91-282[»]
ProteinModelPortaliQ8IUQ4.
SMRiQ8IUQ4. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IUQ4.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni90 – 282193SBDAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the SINA (Seven in absentia) family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SIAH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG264215.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ8IUQ4.
KOiK04506.
OMAiFDTNIAQ.
OrthoDBiEOG7JT6XC.
PhylomeDBiQ8IUQ4.
TreeFamiTF312976.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 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]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IUQ4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP
60 70 80 90 100
PILQCQSGHL VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY
110 120 130 140 150
ASSGCEITLP HTEKADHEEL CEFRPYSCPC PGASCKWQGS LDAVMPHLMH
160 170 180 190 200
QHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGFHFM LVLEKQEKYD
210 220 230 240 250
GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP RSIHEGIATA
260 270 280
IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC
Length:282
Mass (Da):31,123
Last modified:April 26, 2004 - v2
Checksum:iFA0698D0DC1B0A15
GO
Isoform 2 (identifier: Q8IUQ4-2) [UniParc]FASTAAdd to basket

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

Show »
Length:313
Mass (Da):34,628
Checksum:iBE3085493B0ABEC1
GO
Isoform 3 (identifier: Q8IUQ4-3) [UniParc]FASTAAdd to basket

Also known as: Siah-1S

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

Show »
Length:195
Mass (Da):21,215
Checksum:iB5AB8D4079A7C723
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti173 – 1731P → S in CAE46191 (PubMed:17974005).Curated
Sequence conflicti245 – 2451E → G in CAE46191 (PubMed:17974005).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MTGKATPPSLYSWRGVLFTC LPAARTRKRKEM in isoform 2. 2 PublicationsVSP_010166
Alternative sequencei193 – 1953LEK → DLS in isoform 3. 1 PublicationVSP_029210
Alternative sequencei196 – 28287Missing in isoform 3. 1 PublicationVSP_029211Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10735.1. [Q8IUQ4-1]
CCDS32444.1. [Q8IUQ4-2]
RefSeqiNP_001006611.1. NM_001006610.1. [Q8IUQ4-2]
NP_003022.3. NM_003031.3. [Q8IUQ4-1]
XP_006721309.1. XM_006721246.1. [Q8IUQ4-1]
UniGeneiHs.706828.

Genome annotation databases

EnsembliENST00000356721; ENSP00000349156; ENSG00000196470. [Q8IUQ4-2]
ENST00000380006; ENSP00000369343; ENSG00000196470. [Q8IUQ4-1]
ENST00000394725; ENSP00000378214; ENSG00000196470. [Q8IUQ4-1]
ENST00000568007; ENSP00000456421; ENSG00000196470. [Q8IUQ4-1]
GeneIDi6477.
KEGGihsa:6477.
UCSCiuc002efn.1. human. [Q8IUQ4-2]
uc002efo.1. human. [Q8IUQ4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10735.1. [Q8IUQ4-1]
CCDS32444.1. [Q8IUQ4-2]
RefSeqiNP_001006611.1. NM_001006610.1. [Q8IUQ4-2]
NP_003022.3. NM_003031.3. [Q8IUQ4-1]
XP_006721309.1. XM_006721246.1. [Q8IUQ4-1]
UniGeneiHs.706828.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4X3GX-ray2.34A/B91-282[»]
ProteinModelPortaliQ8IUQ4.
SMRiQ8IUQ4. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112372. 161 interactions.
IntActiQ8IUQ4. 113 interactions.
MINTiMINT-156060.
STRINGi9606.ENSP00000349156.

PTM databases

PhosphoSiteiQ8IUQ4.

Polymorphism and mutation databases

BioMutaiSIAH1.
DMDMi46577493.

Proteomic databases

MaxQBiQ8IUQ4.
PaxDbiQ8IUQ4.
PRIDEiQ8IUQ4.

Protocols and materials databases

DNASUi6477.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356721; ENSP00000349156; ENSG00000196470. [Q8IUQ4-2]
ENST00000380006; ENSP00000369343; ENSG00000196470. [Q8IUQ4-1]
ENST00000394725; ENSP00000378214; ENSG00000196470. [Q8IUQ4-1]
ENST00000568007; ENSP00000456421; ENSG00000196470. [Q8IUQ4-1]
GeneIDi6477.
KEGGihsa:6477.
UCSCiuc002efn.1. human. [Q8IUQ4-2]
uc002efo.1. human. [Q8IUQ4-1]

Organism-specific databases

CTDi6477.
GeneCardsiGC16M048391.
HGNCiHGNC:10857. SIAH1.
HPAiCAB018724.
MIMi602212. gene.
neXtProtiNX_Q8IUQ4.
PharmGKBiPA35759.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG264215.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ8IUQ4.
KOiK04506.
OMAiFDTNIAQ.
OrthoDBiEOG7JT6XC.
PhylomeDBiQ8IUQ4.
TreeFamiTF312976.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 2681.
ReactomeiREACT_22237. Netrin-1 signaling.

Miscellaneous databases

ChiTaRSiSIAH1. human.
EvolutionaryTraceiQ8IUQ4.
GeneWikiiSIAH1.
GenomeRNAii6477.
NextBioi25161.
PROiQ8IUQ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IUQ4.
CleanExiHS_SIAH1.
ExpressionAtlasiQ8IUQ4. baseline and differential.
GenevisibleiQ8IUQ4. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 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]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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. 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. 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. 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. 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.

Entry informationi

Entry nameiSIAH1_HUMAN
AccessioniPrimary (citable) accession number: Q8IUQ4
Secondary accession number(s): A0FKF3
, O43269, Q49A58, Q92880
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: June 24, 2015
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.