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Protein

E3 ubiquitin-protein ligase RNF19A

Gene

RNF19A

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

Functioni

E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR. Specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation and to neuronal protection.5 Publications

Catalytic activityi

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

Pathwayi: 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)DescriptionActionsGraphical viewLength
Active sitei316By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri132 – 179RING-type 1PROSITE-ProRule annotationAdd BLAST48
Zinc fingeri199 – 264IBR-typeAdd BLAST66
Zinc fingeri301 – 332RING-type 2PROSITE-ProRule annotationAdd BLAST32

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF19A (EC:2.3.2.31By similarity)
Alternative name(s):
Double ring-finger protein
Short name:
Dorfin
RING finger protein 19A
p38
Gene namesi
Name:RNF19A
Synonyms:RNF19
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000034677.11
HGNCiHGNC:13432 RNF19A
MIMi607119 gene
neXtProtiNX_Q9NV58

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
Transmembranei368 – 388HelicalSequence analysisAdd BLAST21
Transmembranei424 – 444HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132C → S: Abolishes interaction with VCP and E3 ligase activity toward mutant SOD1; when associated with S-135. 1 Publication1
Mutagenesisi135C → S: Abolishes interaction with VCP and E3 ligase activity toward mutant SOD1; when associated with S-132. 1 Publication1

Organism-specific databases

DisGeNETi25897
OpenTargetsiENSG00000034677
PharmGKBiPA162401601

Polymorphism and mutation databases

DMDMi116242764

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000560611 – 838E3 ubiquitin-protein ligase RNF19AAdd BLAST838

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei631PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NV58
PaxDbiQ9NV58
PeptideAtlasiQ9NV58
PRIDEiQ9NV58
ProteomicsDBi82747
82748 [Q9NV58-2]
82749 [Q9NV58-3]

PTM databases

iPTMnetiQ9NV58
PhosphoSitePlusiQ9NV58

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart. Ubiquitously expressed in the central nervous system.1 Publication

Gene expression databases

BgeeiENSG00000034677
CleanExiHS_RNF19A
ExpressionAtlasiQ9NV58 baseline and differential
GenevisibleiQ9NV58 HS

Organism-specific databases

HPAiCAB011455
HPA023652

Interactioni

Subunit structurei

Interacts with UBE2L3 and UBE2L6. Interacts with transcription factor Sp1. Interacts with VCP, CASR, SNCAIP and with some SOD1 variants which cause amyotrophic lateral sclerosis, but not with wild-type SOD1.6 Publications

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: GO_Central

Protein-protein interaction databases

BioGridi117405, 13 interactors
IntActiQ9NV58, 7 interactors
MINTiQ9NV58
STRINGi9606.ENSP00000342667

Structurei

3D structure databases

ProteinModelPortaliQ9NV58
SMRiQ9NV58
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni660 – 838Interaction with CASR1 PublicationAdd BLAST179

Domaini

Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.By similarity

Sequence similaritiesi

Belongs to the RBR family. RNF19 subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri132 – 179RING-type 1PROSITE-ProRule annotationAdd BLAST48
Zinc fingeri199 – 264IBR-typeAdd BLAST66
Zinc fingeri301 – 332RING-type 2PROSITE-ProRule annotationAdd BLAST32

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG1815 Eukaryota
ENOG410XP9Y LUCA
GeneTreeiENSGT00840000129738
HOVERGENiHBG052073
InParanoidiQ9NV58
KOiK11972
OMAiSNMKINE
OrthoDBiEOG091G0503
PhylomeDBiQ9NV58
TreeFamiTF324777

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR031127 E3_UB_ligase_RBR
IPR002867 IBR_dom
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR11685 PTHR11685, 1 hit
PfamiView protein in Pfam
PF01485 IBR, 2 hits
SMARTiView protein in SMART
SM00647 IBR, 2 hits
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS50089 ZF_RING_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9NV58-1) [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
MQEQEIGFIS KYNEGLCVNT DPVSILTSIL DMSLHRQMGS DRDLQSSASS
60 70 80 90 100
VSLPSVKKAP KKRRISIGSL FRRKKDNKRK SRELNGGVDG IASIESIHSE
110 120 130 140 150
MCTDKNSIFS TNTSSDNGLT SISKQIGDFI ECPLCLLRHS KDRFPDIMTC
160 170 180 190 200
HHRSCVDCLR QYLRIEISES RVNISCPECT ERFNPHDIRL ILSDDVLMEK
210 220 230 240 250
YEEFMLRRWL VADPDCRWCP APDCGYAVIA FGCASCPKLT CGREGCGTEF
260 270 280 290 300
CYHCKQIWHP NQTCDAARQE RAQSLRLRTI RSSSISYSQE SGAAADDIKP
310 320 330 340 350
CPRCAAYIIK MNDGSCNHMT CAVCGCEFCW LCMKEISDLH YLSPSGCTFW
360 370 380 390 400
GKKPWSRKKK ILWQLGTLVG APVGIALIAG IAIPAMIIGI PVYVGRKIHN
410 420 430 440 450
RYEGKDVSKH KRNLAIAGGV TLSVIVSPVV AAVTVGIGVP IMLAYVYGVV
460 470 480 490 500
PISLCRSGGC GVSAGNGKGV RIEFDDENDI NVGGTNTAVD TTSVAEARHN
510 520 530 540 550
PSIGEGSVGG LTGSLSASGS HMDRIGAIRD NLSETASTMA LAGASITGSL
560 570 580 590 600
SGSAMVNCFN RLEVQADVQK ERYSLSGESG TVSLGTVSDN ASTKAMAGSI
610 620 630 640 650
LNSYIPLDKE GNSMEVQVDI ESKPSKFRHN SGSSSVDDGS ATRSHAGGSS
660 670 680 690 700
SGLPEGKSSA TKWSKEATAG KKSKSGKLRK KGNMKINETR EDMDAQLLEQ
710 720 730 740 750
QSTNSSEFEA PSLSDSMPSV ADSHSSHFSE FSCSDLESMK TSCSHGSSDY
760 770 780 790 800
HTRFATVNIL PEVENDRLEN SPHQCSISVV TQTASCSEVS QLNHIAEEHG
810 820 830
NNGIKPNVDL YFGDALKETN NNHSHQTMEL KVAIQTEI
Length:838
Mass (Da):90,696
Last modified:October 17, 2006 - v3
Checksum:i00A7DED5023FDC06
GO
Isoform 2 (identifier: Q9NV58-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     572-604: RYSLSGESGTVSLGTVSDNASTKAMAGSILNSY → AAVAAAGRWAYSPATLRCRRSEELKNIHDSS
     605-838: Missing.

Note: No experimental confirmation available.
Show »
Length:602
Mass (Da):65,416
Checksum:i0B210220B7C0F623
GO
Isoform 3 (identifier: Q9NV58-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Show »
Length:807
Mass (Da):87,256
Checksum:iF50D47C3EA851842
GO

Sequence cautioni

The sequence BAB14581 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB15647 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti645H → Y in BAB39353 (PubMed:11237715).Curated1
Sequence conflicti744S → R in CAB53700 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028045835Q → H. Corresponds to variant dbSNP:rs9642785Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0286311 – 31Missing in isoform 3. 1 PublicationAdd BLAST31
Alternative sequenceiVSP_021010572 – 604RYSLS…ILNSY → AAVAAAGRWAYSPATLRCRR SEELKNIHDSS in isoform 2. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_021011605 – 838Missing in isoform 2. 1 PublicationAdd BLAST234

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029316 mRNA Translation: BAB39353.1
BC093938 mRNA Translation: AAH93938.1
BC093940 mRNA Translation: AAH93940.1
AB271914 mRNA Translation: BAF48117.1
AK001774 mRNA Translation: BAA91900.1
AK023455 mRNA Translation: BAB14581.1 Different initiation.
AK027070 mRNA Translation: BAB15647.1 Different initiation.
AJ242975 mRNA Translation: CAB45132.1
AL110253 mRNA Translation: CAB53700.1
AL122096 mRNA Translation: CAB59264.1
CCDSiCCDS6286.1 [Q9NV58-1]
PIRiT34528
RefSeqiNP_001267468.1, NM_001280539.1 [Q9NV58-1]
NP_056250.3, NM_015435.4 [Q9NV58-1]
NP_904355.1, NM_183419.3 [Q9NV58-1]
XP_005250910.1, XM_005250853.3
XP_016868791.1, XM_017013302.1 [Q9NV58-1]
XP_016868792.1, XM_017013303.1 [Q9NV58-1]
UniGeneiHs.292882

Genome annotation databases

EnsembliENST00000341084; ENSP00000342667; ENSG00000034677 [Q9NV58-1]
ENST00000519449; ENSP00000428968; ENSG00000034677 [Q9NV58-1]
GeneIDi25897
KEGGihsa:25897
UCSCiuc003yjj.3 human [Q9NV58-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRN19A_HUMAN
AccessioniPrimary (citable) accession number: Q9NV58
Secondary accession number(s): A3KCU9
, Q52LG1, Q9H5H9, Q9H8M8, Q9UFG0, Q9UFX6, Q9Y4Y1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 162 of the entry and version 3 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

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