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Protein

E3 ubiquitin-protein ligase synoviolin

Gene

SYVN1

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

Functioni

Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation (PubMed:17141218). Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702). Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (By similarity).By similarity11 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.6 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri291 – 330RING-type; atypicalPROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase activity involved in ERAD pathway Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • endoplasmic reticulum mannose trimming Source: Reactome
  • endoplasmic reticulum unfolded protein response Source: GO_Central
  • ERAD pathway Source: ParkinsonsUK-UCL
  • IRE1-mediated unfolded protein response Source: Reactome
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • protein K48-linked ubiquitination Source: ParkinsonsUK-UCL
  • protein N-linked glycosylation via asparagine Source: UniProtKB
  • protein stabilization Source: ParkinsonsUK-UCL
  • protein ubiquitination Source: ParkinsonsUK-UCL
  • retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
  • ubiquitin-dependent ERAD pathway Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionTransferase
Biological processStress response, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-901032 ER Quality Control Compartment (ERQC)
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase synoviolin (EC:2.3.2.27)
Alternative name(s):
RING-type E3 ubiquitin transferase synoviolinCurated
Synovial apoptosis inhibitor 1
Gene namesi
Name:SYVN1
Synonyms:HRD1, KIAA1810
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000162298.16
HGNCiHGNC:20738 SYVN1
MIMi608046 gene
neXtProtiNX_Q86TM6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 41LumenalSequence analysisAdd BLAST19
Transmembranei42 – 62HelicalSequence analysisAdd BLAST21
Topological domaini63 – 98CytoplasmicSequence analysisAdd BLAST36
Transmembranei99 – 119HelicalSequence analysisAdd BLAST21
Topological domaini120 – 140LumenalSequence analysisAdd BLAST21
Transmembranei141 – 161HelicalSequence analysisAdd BLAST21
Topological domaini162 – 169CytoplasmicSequence analysis8
Transmembranei170 – 190HelicalSequence analysisAdd BLAST21
Topological domaini191 – 224LumenalSequence analysisAdd BLAST34
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 617CytoplasmicSequence analysisAdd BLAST372

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi329C → S: Abolishes E3 ligase activity. 1 Publication1

Organism-specific databases

DisGeNETi84447
OpenTargetsiENSG00000162298
PharmGKBiPA128394735

Polymorphism and mutation databases

BioMutaiSYVN1
DMDMi134035039

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000028054823 – 617E3 ubiquitin-protein ligase synoviolinAdd BLAST595

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei613PhosphoserineCombined sources1

Post-translational modificationi

Not N-glycosylated.
Auto-ubiquitinated.3 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ86TM6
MaxQBiQ86TM6
PaxDbiQ86TM6
PeptideAtlasiQ86TM6
PRIDEiQ86TM6

PTM databases

iPTMnetiQ86TM6
PhosphoSitePlusiQ86TM6

Expressioni

Tissue specificityi

Ubiquitously expressed, with highest levels in liver and kidney (at protein level). Up-regulated in synovial tissues from patients with rheumatoid arthritis (at protein level).3 Publications

Inductioni

By endoplasmic reticulum stress-inducing agents such as thapsigargin, tunicamycin or brefeldin A, but not by heat shock.2 Publications

Gene expression databases

BgeeiENSG00000162298
CleanExiHS_SYVN1
ExpressionAtlasiQ86TM6 baseline and differential
GenevisibleiQ86TM6 HS

Organism-specific databases

HPAiCAB037030
HPA005480
HPA024300

Interactioni

Subunit structurei

Homodimer. Interacts with p53/TP53 and HTT. Interacts with VCP, HERPUD1 and DERL1. Part of a complex containing SYVN1, HERPUD1, VIMP and DERL1; which probably transfer misfolded proteins from the ER to VCP. Part of a complex containing SYVN1, SEL1L and DERL2. Interacts with UBXN6. Interacts (via N-terminal loop) with SEL1L; recruits ERLEC1 and OS9. May form a complex with ERLEC1; HSPA5; OS9 AND SEL1L (PubMed:16186509, PubMed:16186510, PubMed:16289116, PubMed:17141218, PubMed:17170702, PubMed:18264092, PubMed:18502753, PubMed:18656546, PubMed:26471130). Interacts with BAG6 (PubMed:21636303). Interacts with NFE2L1 (By similarity).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • chaperone binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi124085, 99 interactors
CORUMiQ86TM6
DIPiDIP-43982N
IntActiQ86TM6, 21 interactors
MINTiQ86TM6
STRINGi9606.ENSP00000366395

Structurei

3D structure databases

ProteinModelPortaliQ86TM6
SMRiQ86TM6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni21 – 42Interaction with SEL1LBy similarityAdd BLAST22
Regioni236 – 270Interaction with p53/TP531 PublicationAdd BLAST35

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi339 – 478Pro-richAdd BLAST140

Domaini

The RING-type zinc finger is required for E3 ligase activity.

Sequence similaritiesi

Belongs to the HRD1 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri291 – 330RING-type; atypicalPROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0802 Eukaryota
COG5243 LUCA
GeneTreeiENSGT00530000062938
HOGENOMiHOG000294196
HOVERGENiHBG094015
InParanoidiQ86TM6
KOiK10601
OMAiFPFPPPW
OrthoDBiEOG091G13IJ
PhylomeDBiQ86TM6
TreeFamiTF318635

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR032832 E3_lig_synoviolin/Hrd1
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR44251 PTHR44251, 1 hit
PfamiView protein in Pfam
PF13639 zf-RING_2, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q86TM6-1) [UniParc]FASTAAdd to basket
Also known as: b, long

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
MFRTAVMMAA SLALTGAVVA HAYYLKHQFY PTVVYLTKSS PSMAVLYIQA
60 70 80 90 100
FVLVFLLGKV MGKVFFGQLR AAEMEHLLER SWYAVTETCL AFTVFRDDFS
110 120 130 140 150
PRFVALFTLL LFLKCFHWLA EDRVDFMERS PNISWLFHCR IVSLMFLLGI
160 170 180 190 200
LDFLFVSHAY HSILTRGASV QLVFGFEYAI LMTMVLTIFI KYVLHSVDLQ
210 220 230 240 250
SENPWDNKAV YMLYTELFTG FIKVLLYMAF MTIMIKVHTF PLFAIRPMYL
260 270 280 290 300
AMRQFKKAVT DAIMSRRAIR NMNTLYPDAT PEELQAMDNV CIICREEMVT
310 320 330 340 350
GAKRLPCNHI FHTSCLRSWF QRQQTCPTCR MDVLRASLPA QSPPPPEPAD
360 370 380 390 400
QGPPPAPHPP PLLPQPPNFP QGLLPPFPPG MFPLWPPMGP FPPVPPPPSS
410 420 430 440 450
GEAVAPPSTS AAALSRPSGA ATTTAAGTSA TAASATASGP GSGSAPEAGP
460 470 480 490 500
APGFPFPPPW MGMPLPPPFA FPPMPVPPAG FAGLTPEELR ALEGHERQHL
510 520 530 540 550
EARLQSLRNI HTLLDAAMLQ INQYLTVLAS LGPPRPATSV NSTEETATTV
560 570 580 590 600
VAAASSTSIP SSEATTPTPG ASPPAPEMER PPAPESVGTE EMPEDGEPDA
610
AELRRRRLQK LESPVAH
Length:617
Mass (Da):67,685
Last modified:March 20, 2007 - v2
Checksum:iB8A6BACBAF9673C1
GO
Isoform 2 (identifier: Q86TM6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-177: Missing.
     411-411: Missing.

Show »
Length:565
Mass (Da):61,732
Checksum:i8C2226662D099D15
GO
Isoform 3 (identifier: Q86TM6-3) [UniParc]FASTAAdd to basket
Also known as: a, short

The sequence of this isoform differs from the canonical sequence as follows:
     411-411: Missing.

Show »
Length:616
Mass (Da):67,614
Checksum:i3D035485BDF67376
GO

Sequence cautioni

The sequence BAB47439 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti145M → I in BAC24801 (PubMed:12459480).Curated1
Sequence conflicti145M → I in AAL26903 (PubMed:14593114).Curated1
Sequence conflicti545E → G in BAC57449 (PubMed:12975321).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023777127 – 177Missing in isoform 2. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_023778411Missing in isoform 2 and isoform 3. 4 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB085847 mRNA Translation: BAC24801.1
AB024690 mRNA Translation: BAC57449.1
AF317634 mRNA Translation: AAL26903.1
AB058713 mRNA Translation: BAB47439.1 Different initiation.
AL834262 mRNA Translation: CAD38937.1
BC030530 mRNA Translation: AAH30530.1
CCDSiCCDS31605.1 [Q86TM6-1]
CCDS8097.1 [Q86TM6-3]
RefSeqiNP_115807.1, NM_032431.2 [Q86TM6-3]
NP_757385.1, NM_172230.2 [Q86TM6-1]
XP_011543605.1, XM_011545303.2 [Q86TM6-1]
UniGeneiHs.75859

Genome annotation databases

EnsembliENST00000294256; ENSP00000294256; ENSG00000162298 [Q86TM6-3]
ENST00000307289; ENSP00000302035; ENSG00000162298 [Q86TM6-2]
ENST00000377190; ENSP00000366395; ENSG00000162298 [Q86TM6-1]
ENST00000526060; ENSP00000436984; ENSG00000162298 [Q86TM6-3]
GeneIDi84447
KEGGihsa:84447
UCSCiuc001odb.4 human [Q86TM6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSYVN1_HUMAN
AccessioniPrimary (citable) accession number: Q86TM6
Secondary accession number(s): Q8N3K3
, Q8N6E8, Q96JL5, Q96PK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: April 25, 2018
This is version 149 of the entry and version 2 of the sequence. See 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health