STUB1 STIP1 homology and U-box containing protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: STUB1provided by HGNC
Official Full Name: STIP1 homology and U-box containing protein 1provided by HGNC
Primary source: HGNC:HGNC:11427
See related: Ensembl:ENSG00000103266 MIM:607207
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CHIP; SCA48; UBOX1; SCAR16; HSPABP2; NY-CO-7; SDCCAG7
Summary: This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. [provided by RefSeq, Jun 2014]
Expression: Ubiquitous expression in fat (RPKM 42.9), kidney (RPKM 39.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 16p13.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	16	NC_000016.10 (680410..682801)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (730115..732768)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and beta-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates.
Title: Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer.
We report a heterozygous STUB1 pathogenic genetic variant causing dominant cerebellar ataxia
Title: Heterozygous <i>STUB1</i> mutation causes familial ataxia with cognitive affective syndrome (SCA48).
IRS4, as a new substrate of CHIP, is negatively regulated by CK1gamma2 at the posttranslational level.
Title: Phosphorylation of IRS4 by CK1γ2 promotes its degradation by CHIP through the ubiquitin/lysosome pathway.
The existence of a multiprotein complex containing UBXN2A, CHIP, and mot-2 suggests a synergistic tumor suppressor activity of UBXN2A and CHIP in mot-2-enriched tumors.
Title: UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2 in cancer cells.
CHIP depletion inhibited cell growth, migration and invasion potential of colorectal cancer cells, accompanied by downregulation of MAPK and AKT signaling activities and upregulation of E-cadherin.
Title: CHIP functions as an oncogene by promoting colorectal cancer metastasis via activation of MAPK and AKT signaling and suppression of E-cadherin.
CHIP negatively regulates cathepsin B protein/cathepsin L protein expression in ErbB2(+) and other breast cancer cell lines. cathepsin B protein inhibition abrogates invasion and matrix degradation in vitro and halts ErbB2(+) breast cancer cell line xenograft growth.
Title: Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program.
the present study demonstrates that covalent ISG15 conjugation produces a novel CHIP regulatory mode that enhances the tumor-suppressive activity of CHIP.
Title: Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon.
Our results provide the first evidence for a mediator function of cIAP1 and collaborative activity of cIAP1 and CHIP, suggesting that maintaining balanced levels of these E3 ligases might be beneficial for normal cell growth.
Title: A novel function of cIAP1 as a mediator of CHIP-driven eIF4E regulation.
K6-linked ubiquitylation of FADD by CHIP is a crucial checkpoint in cytokine-dependent extrinsic apoptosis.
Title: K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death.
ORP150 and CHIP demonstrate antagonism under normal and stress conditions wherein they inversely regulate each other thus affecting BACE1 level.
Title: ORP150-CHIP chaperone antagonism control BACE1-mediated amyloid processing.

Submit: New GeneRIF Correction See all GeneRIFs (160)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
SPINOCEREBELLAR ATAXIA 48 MedGen: C4748158 OMIM: 618093 GeneReviews: Not available	Compare labs
Spinocerebellar ataxia, autosomal recessive 16 MedGen: C4014261 OMIM: 615768 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif is identified to have a physical interaction with STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase (STUB1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Adaptive Immune System, organism-specific biosystem (from REACTOME)
Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
Alpha-synuclein signaling, organism-specific biosystem (from Pathway Interaction Database)
Alpha-synuclein signaling, organism-specific biosystem
Alpha-synuclein signaling
Androgen receptor signaling pathway, organism-specific biosystem (from WikiPathways)
Androgen receptor signaling pathway, organism-specific biosystemAndrogens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biolo...
Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystem (from REACTOME)
Antigen processing: Ubiquitination & Proteasome degradation, organism-specific biosystemIntracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T ...
Class I MHC mediated antigen processing & presentation, organism-specific biosystem (from REACTOME)
Class I MHC mediated antigen processing & presentation, organism-specific biosystemMajor histocompatibility complex (MHC) class I molecules play an important role in cell mediated immunity by reporting on intracellular events such as viral infection, the presence of intracellular b...
Downregulation of ERBB2 signaling, organism-specific biosystem (from REACTOME)
Downregulation of ERBB2 signaling, organism-specific biosystemSignaling by ERBB2 can be downregulated by ubiquitination and subsequent proteasome-dependent degradation of ERBB2 or activated ERBB2 heterodimers. In addition, protein tyrosine phosphatases that dep...
Downregulation of TGF-beta receptor signaling, organism-specific biosystem (from REACTOME)
Downregulation of TGF-beta receptor signaling, organism-specific biosystemTGF-beta receptor signaling is downregulated by proteasome and lysosome-mediated degradation of ubiquitinated TGFBR1, SMAD2 and SMAD3, as well as by dephosphorylation of TGFBR1, SMAD2 and SMAD3. In t...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystem (from WikiPathways)
Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystemThis pathway describes the Parkin-Ubiquitin proteasome degradation system.
Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by ERBB2, organism-specific biosystem (from REACTOME)
Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
TGF-beta receptor signaling activates SMADs, organism-specific biosystem (from REACTOME)
TGF-beta receptor signaling activates SMADs, organism-specific biosystemBinding of transforming growth factor beta 1 (TGF beta 1, i.e. TGFB1) to TGF beta receptor type 2 (TGFBR2) activates TGF beta receptor signaling cascade. TGFB1 is posttranslationally processed by fur...
Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

IB740 (e-PCR)
- UniSTS:35213

RH15604 (e-PCR)
- UniSTS:86698

Homology

Homologs of the STUB1 gene: The STUB1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 263 organisms have orthologs with human gene STUB1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G protein-coupled receptor binding	IPI Inferred from Physical Interaction more info	PubMed
Hsp70 protein binding	IDA Inferred from Direct Assay more info	PubMed
Hsp70 protein binding	IPI Inferred from Physical Interaction more info	PubMed
Hsp90 protein binding	IDA Inferred from Direct Assay more info	PubMed
SMAD binding	IDA Inferred from Direct Assay more info	PubMed
SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
TPR domain binding	IDA Inferred from Direct Assay more info	PubMed
chaperone binding	IPI Inferred from Physical Interaction more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
heat shock protein binding	IPI Inferred from Physical Interaction more info	PubMed
kinase binding	IPI Inferred from Physical Interaction more info	PubMed
misfolded protein binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding, bridging	TAS Traceable Author Statement more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
tau protein binding	NAS Non-traceable Author Statement more info	PubMed
ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
ubiquitin protein ligase activity	IGI Inferred from Genetic Interaction more info	PubMed
ubiquitin protein ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
ubiquitin protein ligase activity	TAS Traceable Author Statement more info
ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
ubiquitin-protein transferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
ubiquitin-protein transferase activity	TAS Traceable Author Statement more info	PubMed
ubiquitin-ubiquitin ligase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
DNA repair	IEA Inferred from Electronic Annotation more info
ERBB2 signaling pathway	TAS Traceable Author Statement more info
cellular response to heat	ISS Inferred from Sequence or Structural Similarity more info
cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
cellular response to misfolded protein	IDA Inferred from Direct Assay more info	PubMed
chaperone-mediated autophagy	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum unfolded protein response	IEA Inferred from Electronic Annotation more info
negative regulation of protein binding	IEA Inferred from Electronic Annotation more info
negative regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transforming growth factor beta receptor signaling pathway	TAS Traceable Author Statement more info
positive regulation of chaperone-mediated protein complex assembly	IDA Inferred from Direct Assay more info	PubMed
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
positive regulation of ubiquitin-protein transferase activity	IEA Inferred from Electronic Annotation more info
proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
proteasome-mediated ubiquitin-dependent protein catabolic process	TAS Traceable Author Statement more info	PubMed
protein K63-linked ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein maturation	TAS Traceable Author Statement more info	PubMed
protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein polyubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
protein quality control for misfolded or incompletely synthesized proteins	IDA Inferred from Direct Assay more info	PubMed
protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of glucocorticoid metabolic process	IDA Inferred from Direct Assay more info	PubMed
regulation of protein stability	IDA Inferred from Direct Assay more info	PubMed
response to ischemia	ISS Inferred from Sequence or Structural Similarity more info
ubiquitin-dependent ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
ubiquitin-dependent SMAD protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
ubiquitin-dependent protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
Z disc	IEA Inferred from Electronic Annotation more info
chaperone complex	IPI Inferred from Physical Interaction more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
nuclear inclusion body	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	ISS Inferred from Sequence or Structural Similarity more info
ubiquitin conjugating enzyme complex	TAS Traceable Author Statement more info	PubMed
ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: E3 ubiquitin-protein ligase CHIP

Names: CLL-associated antigen KW-8; RING-type E3 ubiquitin transferase CHIP; STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase; antigen NY-CO-7; carboxy terminus of Hsp70-interacting protein; heat shock protein A binding protein 2 (c-terminal); serologically defined colon cancer antigen 7

NP_001280126.1

EC 2.3.2.27

NP_005852.2

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_034141.1 RefSeqGene

Range

5300..7691

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001293197.2 → NP_001280126.1 E3 ubiquitin-protein ligase CHIP isoform b

See identical proteins and their annotated locations for NP_001280126.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus than isoform a.

Source sequence(s)

AF217968, BC017178, Z92544

Consensus CDS

CCDS76797.1

UniProtKB/Swiss-Prot

Q9UNE7

Related

ENSP00000457228.1, ENST00000565677.5

Conserved Domains (3) summary

sd00006
Location:21 → 51

TPR; TPR repeat [structural motif]

cd16654
Location:155 → 221

RING-Ubox_CHIP; U-box domain, a modified RING finger, found in carboxyl terminus of HSP70-interacting protein (CHIP) and similar proteins

pfam12895
Location:1 → 48

ANAPC3; Anaphase-promoting complex, cyclosome, subunit 3
NM_005861.4 → NP_005852.2 E3 ubiquitin-protein ligase CHIP isoform a

See identical proteins and their annotated locations for NP_005852.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the longer isoform (a).

Source sequence(s)

AF217968, BC017178, Z92544

Consensus CDS

CCDS10419.1

UniProtKB/Swiss-Prot

Q9UNE7

Related

ENSP00000219548.4, ENST00000219548.9

Conserved Domains (3) summary

sd00006
Location:26 → 54

TPR; TPR repeat [structural motif]

cd16654
Location:227 → 293

RING-Ubox_CHIP; U-box domain, a modified RING finger, found in carboxyl terminus of HSP70-interacting protein (CHIP) and similar proteins

cl26005
Location:26 → 126

PLN03088; SGT1, suppressor of G2 allele of SKP1; Provisional