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Protein

Ubiquilin-4

Gene

UBQLN4

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

Functioni

Plays a role in the regulation of protein degradation via the ubiquitin-proteasome system (UPS). 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:15280365). Plays a role in the regulation of the proteasomal degradation of non-ubiquitinated GJA1 (By similarity). Acts as an adapter protein that recruits UBQLN1 to the autophagy machinery. Mediates the association of UBQLN1 with autophagosomes and the autophagy-related protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:23459205).By similarity2 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • polyubiquitin modification-dependent protein binding Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • negative regulation of autophagosome maturation Source: UniProtKB
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Biological processAutophagy

Protein family/group databases

TCDBi8.A.52.1.1. the ubiquitin-related protein degradation (upd) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquilin-4
Alternative name(s):
Ataxin-1 interacting ubiquitin-like protein
Short name:
A1Up
Ataxin-1 ubiquitin-like-interacting protein A1U
Connexin43-interacting protein of 75 kDa
Short name:
CIP75
Gene namesi
Name:UBQLN4
Synonyms:C1orf6, CIP75, UBIN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000160803.7.
HGNCiHGNC:1237. UBQLN4.

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, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi55I → A: Loss of interaction with UBQLN1. 1

Organism-specific databases

DisGeNETi56893.
OpenTargetsiENSG00000160803.
PharmGKBiPA25619.

Polymorphism and mutation databases

BioMutaiUBQLN4.
DMDMi45476982.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002110151 – 601Ubiquilin-4Add BLAST601

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki23Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki62Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei98PhosphoserineCombined sources1
Modified residuei287PhosphothreonineCombined sources1

Post-translational modificationi

Ubiquitinated; this does not lead to proteasomal degradation. May undergo both 'Lys-48'- and 'Lys-63'-linked polyubiquitination.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NRR5.
MaxQBiQ9NRR5.
PaxDbiQ9NRR5.
PeptideAtlasiQ9NRR5.
PRIDEiQ9NRR5.
TopDownProteomicsiQ9NRR5-2. [Q9NRR5-2]

PTM databases

iPTMnetiQ9NRR5.
PhosphoSitePlusiQ9NRR5.

Expressioni

Tissue specificityi

Highly expressed in pancreas, kidney, skeletal muscle, heart and throughout the brain, and at lower levels in placenta, lung and liver.1 Publication

Gene expression databases

BgeeiENSG00000160803.
CleanExiHS_UBQLN4.
GenevisibleiQ9NRR5. HS.

Organism-specific databases

HPAiHPA061797.

Interactioni

Subunit structurei

Homooligomer (PubMed:15280365). Binds signal sequences of proteins that are targeted to the endoplasmic reticulum. Interacts (via UBA domain) with GJA1 (not ubiquitinated) and with ubiquitin; both compete for the same binding site. Interacts (via UBA domain) with ubiquitin and with polyubiquitin chains. Interacts with PSMD2 (By similarity). Interacts (via ubiquitin-like domain) with PSMD4, a regulatory subunit of the 26S proteasome. Interacts with ATXN1/SCA1. Interaction with ATXN1 inhibits polyubiquitination of UBQLN4 and interferes with PSMD4 binding. Interacts with HERPUD1. Interacts (via ubiquitin-like domain) with UBQLN1 (via UBA domain). Interacts (via STI1 1 and 2 domains) with MAP1LC3A/B/C. Interacts with UBQLN2.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • polyubiquitin modification-dependent protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121223. 191 interactors.
IntActiQ9NRR5. 159 interactors.
MINTiMINT-1373057.
STRINGi9606.ENSP00000357292.

Structurei

3D structure databases

ProteinModelPortaliQ9NRR5.
SMRiQ9NRR5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 87Ubiquitin-likePROSITE-ProRule annotationAdd BLAST75
Domaini192 – 229STI1 1Sequence analysisAdd BLAST38
Domaini230 – 261STI1 2Sequence analysisAdd BLAST32
Domaini393 – 440STI1 3Sequence analysisAdd BLAST48
Domaini444 – 476STI1 4Sequence analysisAdd BLAST33
Domaini553 – 598UBAPROSITE-ProRule annotationAdd BLAST46

Phylogenomic databases

eggNOGiKOG0010. Eukaryota.
COG5272. LUCA.
GeneTreeiENSGT00390000005720.
HOVERGENiHBG064537.
InParanoidiQ9NRR5.
KOiK04523.
OMAiMISAPYM.
OrthoDBiEOG091G08WB.
PhylomeDBiQ9NRR5.
TreeFamiTF314412.

Family and domain databases

InterProiView protein in InterPro
IPR006636. STI1_HS-bd.
IPR015940. UBA.
IPR009060. UBA-like_sf.
IPR015496. Ubiquilin.
IPR029071. Ubiquitin-like_domsf.
IPR000626. Ubiquitin_dom.
PANTHERiPTHR10677. PTHR10677. 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.
SSF54236. SSF54236. 1 hit.
PROSITEiView protein in PROSITE
PS50030. UBA. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRR5-1) [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
MAEPSGAETR PPIRVTVKTP KDKEEIVICD RASVKEFKEE ISRRFKAQQD
60 70 80 90 100
QLVLIFAGKI LKDGDTLNQH GIKDGLTVHL VIKTPQKAQD PAAATASSPS
110 120 130 140 150
TPDPASAPST TPASPATPAQ PSTSGSASSD AGSGSRRSSG GGPSPGAGEG
160 170 180 190 200
SPSATASILS GFGGILGLGS LGLGSANFME LQQQMQRQLM SNPEMLSQIM
210 220 230 240 250
ENPLVQDMMS NPDLMRHMIM ANPQMQQLME RNPEISHMLN NPELMRQTME
260 270 280 290 300
LARNPAMMQE MMRNQDRALS NLESIPGGYN ALRRMYTDIQ EPMFSAAREQ
310 320 330 340 350
FGNNPFSSLA GNSDSSSSQP LRTENREPLP NPWSPSPPTS QAPGSGGEGT
360 370 380 390 400
GGSGTSQVHP TVSNPFGINA ASLGSGMFNS PEMQALLQQI SENPQLMQNV
410 420 430 440 450
ISAPYMRSMM QTLAQNPDFA AQMMVNVPLF AGNPQLQEQL RLQLPVFLQQ
460 470 480 490 500
MQNPESLSIL TNPRAMQALL QIQQGLQTLQ TEAPGLVPSL GSFGISRTPA
510 520 530 540 550
PSAGSNAGST PEAPTSSPAT PATSSPTGAS SAQQQLMQQM IQLLAGSGNS
560 570 580 590 600
QVQTPEVRFQ QQLEQLNSMG FINREANLQA LIATGGDINA AIERLLGSQL

S
Length:601
Mass (Da):63,853
Last modified:March 15, 2004 - v2
Checksum:iE57B9FFEF90793FE
GO
Isoform 2 (identifier: Q9NRR5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     93-226: AATASSPSTP...HMIMANPQMQ → PPAAPSLPAA...AAQLHGLHQS
     227-601: Missing.

Note: No experimental confirmation available.
Show »
Length:226
Mass (Da):24,527
Checksum:i69101551F1551A93
GO

Sequence cautioni

The sequence AAF19084 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH06410 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti188 – 189QL → HV in AAF80171 (PubMed:11001934).Curated2
Sequence conflicti298R → Q in AAF80171 (PubMed:11001934).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052685495I → M2 PublicationsCorresponds to variant dbSNP:rs2297792Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04118793 – 226AATAS…NPQMQ → PPAAPSLPAADAEPRVTLHP YQSPSHAGIAADPAGTTDLA DRGPWAGTQPWLLWDIPDPS TLSRQQRRVYARGPHFLTSH ASHIFSNRGFQRPAATHAAD DPAFGWKWKLTGADARSEIS AAAGAAQLHGLHQS in isoform 2. 1 PublicationAdd BLAST134
Alternative sequenceiVSP_041188227 – 601Missing in isoform 2. 1 PublicationAdd BLAST375

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF188240 mRNA. Translation: AAF80171.1.
AK098368 mRNA. No translation available.
AK314413 mRNA. Translation: BAG37034.1.
AL355388 Genomic DNA. Translation: CAH72633.1.
AL355388 Genomic DNA. Translation: CAH72634.1.
BC006410 mRNA. Translation: AAH06410.1. Different initiation.
BC018403 mRNA. Translation: AAH18403.1.
BC063841 mRNA. Translation: AAH63841.1.
AF113544 mRNA. Translation: AAF19084.1. Different initiation.
CCDSiCCDS1127.1. [Q9NRR5-1]
RefSeqiNP_001291271.1. NM_001304342.1.
NP_064516.2. NM_020131.4. [Q9NRR5-1]
UniGeneiHs.283739.

Genome annotation databases

EnsembliENST00000368309; ENSP00000357292; ENSG00000160803. [Q9NRR5-1]
GeneIDi56893.
KEGGihsa:56893.
UCSCiuc001fna.4. human. [Q9NRR5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBQL4_HUMAN
AccessioniPrimary (citable) accession number: Q9NRR5
Secondary accession number(s): A6ND44
, B2RAY7, Q5VYA0, Q5VYA1, Q9BR98, Q9UHX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: March 15, 2004
Last modified: November 22, 2017
This is version 150 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

Documents

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