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UniProtKB - Q9UHD9 (UBQL2_HUMAN)

Protein

Ubiquilin-2

Gene

UBQLN2

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

Functioni

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:10983987). Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:24215460, PubMed:18307982). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957). Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits (CCPs) (PubMed:18199683).6 Publications

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processAutophagy

Enzyme and pathway databases

ReactomeiR-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis

Protein family/group databases

MoonDBiQ9UHD9 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquilin-2
Alternative name(s):
Chap1
DSK2 homolog
Protein linking IAP with cytoskeleton 2
Short name:
PLIC-2
Short name:
hPLIC-2
Ubiquitin-like product Chap1/Dsk2
Gene namesi
Name:UBQLN2
Synonyms:N4BP4, PLIC2
ORF Names:HRIHFB2157
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000188021.8
HGNCiHGNC:12509 UBQLN2
MIMi300264 gene
neXtProtiNX_Q9UHD9

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

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (ALS15)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia.
See also OMIM:300857
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068892155S → N in ALS15; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs374522677Ensembl.1
Natural variantiVAR_068893189P → T in ALS15; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1490021329Ensembl.1
Natural variantiVAR_068895283A → T in ALS15. 1 PublicationCorresponds to variant dbSNP:rs749463696Ensembl.1
Natural variantiVAR_068896425Q → R in ALS15. 1 PublicationCorresponds to variant dbSNP:rs1243726473Ensembl.1
Natural variantiVAR_068897487T → I in ALS15. 1 Publication1
Natural variantiVAR_066562497P → H in ALS15; leads to defective ubiquitin-mediated proteasomal degradation; reduces binding to HNRNPA1 and FAF2; increases translocation of HNRNPA1 to the cytoplasm; adversely affects ERAD. 3 PublicationsCorresponds to variant dbSNP:rs387906709EnsemblClinVar.1
Natural variantiVAR_066563497P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906710EnsemblClinVar.1
Natural variantiVAR_066564506P → T in ALS15; leads to defective ubiquitin-mediated proteasomal degradation; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906711EnsemblClinVar.1
Natural variantiVAR_066565509P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906712EnsemblClinVar.1
Natural variantiVAR_066566525P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs369947678EnsemblClinVar.1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi29978
GeneReviewsiUBQLN2
MalaCardsiUBQLN2
MIMi300857 phenotype
OpenTargetsiENSG00000188021
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA37156

Polymorphism and mutation databases

BioMutaiUBQLN2
DMDMi124056593

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002110112 – 624Ubiquilin-2Add BLAST623

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Post-translational modificationi

Degraded during macroautophagy.1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UHD9
MaxQBiQ9UHD9
PaxDbiQ9UHD9
PeptideAtlasiQ9UHD9
PRIDEiQ9UHD9
ProteomicsDBi84333

PTM databases

iPTMnetiQ9UHD9
PhosphoSitePlusiQ9UHD9

Expressioni

Inductioni

Highly expressed in mitotic cells from metaphase to telophase. Expression in non-mitotic cells is very low.

Gene expression databases

BgeeiENSG00000188021 Expressed in 245 organ(s), highest expression level in cerebellar vermis
CleanExiHS_UBQLN2
GenevisibleiQ9UHD9 HS

Organism-specific databases

HPAiCAB013481
HPA006431

Interactioni

Subunit structurei

Homodimer. Forms heterodimer with UBQLN1. Binds UBE3A and BTRC. Interacts with the 19S proteasome subunit. Interacts with C9orf72. Interacts with HNRNPA1 and HNRNPU. Found in a complex with UBQLN1 and MAP1LC3A/B/C. Interacts with EPS15, EPN1 and EPN2. Interacts with HERPUD1. Interacts with RAD23A. Interacts with TARDBP. Interacts (via C-terminus) with FAF2 (via N-terminus). Interacts with UBQLN4. Binds CD47 (By similarity).By similarity12 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi119006, 89 interactors
CORUMiQ9UHD9
DIPiDIP-42116N
IntActiQ9UHD9, 252 interactors
MINTiQ9UHD9
STRINGi9606.ENSP00000345195

Structurei

Secondary structure

1624
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UHD9
SMRiQ9UHD9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UHD9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 107Ubiquitin-likePROSITE-ProRule annotationAdd BLAST75
Domaini178 – 206STI1 1Sequence analysisAdd BLAST29
Domaini208 – 247STI1 2Sequence analysisAdd BLAST40
Domaini379 – 426STI1 3Sequence analysisAdd BLAST48
Domaini430 – 462STI1 4Sequence analysisAdd BLAST33
Repeati491 – 49313
Repeati494 – 49623
Repeati497 – 49933
Repeati500 – 50243
Repeati503 – 50553
Repeati506 – 50863
Repeati509 – 51173
Repeati512 – 51483
Repeati515 – 51793
Repeati518 – 520103
Repeati521 – 523113
Repeati524 – 526123
Domaini581 – 621UBAPROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni491 – 52612 X 3 AA tandem repeats of P-X-XAdd BLAST36

Domaini

The ubiquitin-like domain is essential for its inhibitory effect on GPCR endocytosis. Mediates its association with the subunits of the proteasome.1 Publication1 Publication
The UBA domain is essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3). Mediates its association with ubiquitinated substrates.1 Publication1 Publication
Dimerization is dependent upon the central region of the protein containing the STI1 domains and is independent of its ubiquitin-like and UBA domains.1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0010 Eukaryota
COG5272 LUCA
GeneTreeiENSGT00390000005720
HOGENOMiHOG000234878
HOVERGENiHBG064537
InParanoidiQ9UHD9
KOiK04523
OMAiPQQGTEN
OrthoDBiEOG091G08WB
PhylomeDBiQ9UHD9
TreeFamiTF314412

Family and domain databases

InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR006636 STI1_HS-bd
IPR015940 UBA
IPR009060 UBA-like_sf
IPR015496 Ubiquilin
IPR028430 Ubiquilin-2
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR10677 PTHR10677, 1 hit
PTHR10677:SF5 PTHR10677:SF5, 1 hit
PfamiView protein in Pfam
PF00627 UBA, 1 hit
PF00240 ubiquitin, 1 hit
SMARTiView protein in SMART
SM00727 STI1, 4 hits
SM00165 UBA, 1 hit
SM00213 UBQ, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF48371 SSF48371, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50030 UBA, 1 hit
PS50053 UBIQUITIN_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9UHD9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAENGESSGP PRPSRGPAAA QGSAAAPAEP KIIKVTVKTP KEKEEFAVPE 
        60         70         80         90        100
NSSVQQFKEA ISKRFKSQTD QLVLIFAGKI LKDQDTLIQH GIHDGLTVHL 
       110        120        130        140        150
VIKSQNRPQG QSTQPSNAAG TNTTSASTPR SNSTPISTNS NPFGLGSLGG 
       160        170        180        190        200
LAGLSSLGLS STNFSELQSQ MQQQLMASPE MMIQIMENPF VQSMLSNPDL 
       210        220        230        240        250
MRQLIMANPQ MQQLIQRNPE ISHLLNNPDI MRQTLEIARN PAMMQEMMRN 
       260        270        280        290        300
QDLALSNLES IPGGYNALRR MYTDIQEPML NAAQEQFGGN PFASVGSSSS 
       310        320        330        340        350
SGEGTQPSRT ENRDPLPNPW APPPATQSSA TTSTTTSTGS GSGNSSSNAT 
       360        370        380        390        400
GNTVAAANYV ASIFSTPGMQ SLLQQITENP QLIQNMLSAP YMRSMMQSLS 
       410        420        430        440        450
QNPDLAAQMM LNSPLFTANP QLQEQMRPQL PAFLQQMQNP DTLSAMSNPR 
       460        470        480        490        500
AMQALMQIQQ GLQTLATEAP GLIPSFTPGV GVGVLGTAIG PVGPVTPIGP 
       510        520        530        540        550
IGPIVPFTPI GPIGPIGPTG PAAPPGSTGS GGPTGPTVSS AAPSETTSPT 
       560        570        580        590        600
SESGPNQQFI QQMVQALAGA NAPQLPNPEV RFQQQLEQLN AMGFLNREAN 
       610        620 
LQALIATGGD INAAIERLLG SQPS
Length:624
Mass (Da):65,696
Last modified:January 23, 2007 - v2
Checksum:iDF7DF8C4D7B71AC3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti544S → R in AAF17237 (PubMed:10675567).Curated1
Sequence conflicti544S → R in BAA34801 (PubMed:9853615).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068892155S → N in ALS15; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs374522677Ensembl.1
Natural variantiVAR_068893189P → T in ALS15; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1490021329Ensembl.1
Natural variantiVAR_052680235L → H. Corresponds to variant dbSNP:rs17002693Ensembl.1
Natural variantiVAR_068894282A → V Probable disease-associated mutation found in a patient with frontotemporal dementia. 1 PublicationCorresponds to variant dbSNP:rs1001930696Ensembl.1
Natural variantiVAR_068895283A → T in ALS15. 1 PublicationCorresponds to variant dbSNP:rs749463696Ensembl.1
Natural variantiVAR_068896425Q → R in ALS15. 1 PublicationCorresponds to variant dbSNP:rs1243726473Ensembl.1
Natural variantiVAR_068897487T → I in ALS15. 1 Publication1
Natural variantiVAR_066562497P → H in ALS15; leads to defective ubiquitin-mediated proteasomal degradation; reduces binding to HNRNPA1 and FAF2; increases translocation of HNRNPA1 to the cytoplasm; adversely affects ERAD. 3 PublicationsCorresponds to variant dbSNP:rs387906709EnsemblClinVar.1
Natural variantiVAR_066563497P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906710EnsemblClinVar.1
Natural variantiVAR_066564506P → T in ALS15; leads to defective ubiquitin-mediated proteasomal degradation; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906711EnsemblClinVar.1
Natural variantiVAR_066565509P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs387906712EnsemblClinVar.1
Natural variantiVAR_066566525P → S in ALS15; reduces binding to HNRNPA1; increases translocation of HNRNPA1 to the cytoplasm. 2 PublicationsCorresponds to variant dbSNP:rs369947678EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF189009 mRNA Translation: AAF17237.1
AF293385 mRNA Translation: AAG02474.1
AL354793 Genomic DNA No translation available.
CH471154 Genomic DNA Translation: EAW93233.1
BC069237 mRNA Translation: AAH69237.1
AL442081 mRNA Translation: CAC09446.1
AB015344 mRNA Translation: BAA34801.1
CCDSiCCDS14374.1
RefSeqiNP_038472.2, NM_013444.3
UniGeneiHs.179309

Genome annotation databases

EnsembliENST00000338222; ENSP00000345195; ENSG00000188021
GeneIDi29978
KEGGihsa:29978
UCSCiuc004dus.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF189009 mRNA Translation: AAF17237.1
AF293385 mRNA Translation: AAG02474.1
AL354793 Genomic DNA No translation available.
CH471154 Genomic DNA Translation: EAW93233.1
BC069237 mRNA Translation: AAH69237.1
AL442081 mRNA Translation: CAC09446.1
AB015344 mRNA Translation: BAA34801.1
CCDSiCCDS14374.1
RefSeqiNP_038472.2, NM_013444.3
UniGeneiHs.179309

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J8CNMR-A1-103[»]
2NBVNMR-B26-103[»]
ProteinModelPortaliQ9UHD9
SMRiQ9UHD9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119006, 89 interactors
CORUMiQ9UHD9
DIPiDIP-42116N
IntActiQ9UHD9, 252 interactors
MINTiQ9UHD9
STRINGi9606.ENSP00000345195

Protein family/group databases

MoonDBiQ9UHD9 Predicted

PTM databases

iPTMnetiQ9UHD9
PhosphoSitePlusiQ9UHD9

Polymorphism and mutation databases

BioMutaiUBQLN2
DMDMi124056593

Proteomic databases

EPDiQ9UHD9
MaxQBiQ9UHD9
PaxDbiQ9UHD9
PeptideAtlasiQ9UHD9
PRIDEiQ9UHD9
ProteomicsDBi84333

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338222; ENSP00000345195; ENSG00000188021
GeneIDi29978
KEGGihsa:29978
UCSCiuc004dus.4 human

Organism-specific databases

CTDi29978
DisGeNETi29978
EuPathDBiHostDB:ENSG00000188021.8
GeneCardsiUBQLN2
GeneReviewsiUBQLN2
HGNCiHGNC:12509 UBQLN2
HPAiCAB013481
HPA006431
MalaCardsiUBQLN2
MIMi300264 gene
300857 phenotype
neXtProtiNX_Q9UHD9
OpenTargetsiENSG00000188021
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA37156
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0010 Eukaryota
COG5272 LUCA
GeneTreeiENSGT00390000005720
HOGENOMiHOG000234878
HOVERGENiHBG064537
InParanoidiQ9UHD9
KOiK04523
OMAiPQQGTEN
OrthoDBiEOG091G08WB
PhylomeDBiQ9UHD9
TreeFamiTF314412

Enzyme and pathway databases

ReactomeiR-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis

Miscellaneous databases

ChiTaRSiUBQLN2 human
EvolutionaryTraceiQ9UHD9
GeneWikiiUBQLN2
GenomeRNAii29978
PROiPR:Q9UHD9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000188021 Expressed in 245 organ(s), highest expression level in cerebellar vermis
CleanExiHS_UBQLN2
GenevisibleiQ9UHD9 HS

Family and domain databases

InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR006636 STI1_HS-bd
IPR015940 UBA
IPR009060 UBA-like_sf
IPR015496 Ubiquilin
IPR028430 Ubiquilin-2
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR10677 PTHR10677, 1 hit
PTHR10677:SF5 PTHR10677:SF5, 1 hit
PfamiView protein in Pfam
PF00627 UBA, 1 hit
PF00240 ubiquitin, 1 hit
SMARTiView protein in SMART
SM00727 STI1, 4 hits
SM00165 UBA, 1 hit
SM00213 UBQ, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF48371 SSF48371, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50030 UBA, 1 hit
PS50053 UBIQUITIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBQL2_HUMAN
AccessioniPrimary (citable) accession number: Q9UHD9
Secondary accession number(s): O94798
, Q5D027, Q9H3W6, Q9HAZ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 161 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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