Stub1 STIP1 homology and U-box containing protein 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Stub1provided by RGD
Official Full Name: STIP1 homology and U-box containing protein 1provided by RGD
Primary source: RGD:1306167
See related: EnsemblRapid:ENSRNOG00000019798 AllianceGenome:RGD:1306167
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Chip
Summary: Enables ubiquitin protein ligase activity. Involved in several processes, including positive regulation of mitophagy; regulation of muscle system process; and regulation of smooth muscle cell apoptotic process. Located in mitochondrion and nucleus. Human ortholog(s) of this gene implicated in autosomal recessive spinocerebellar ataxia 16 and cerebellar ataxia type 48. Orthologous to human STUB1 (STIP1 homology and U-box containing protein 1). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Heart (RPKM 564.6), Brain (RPKM 441.7) and 9 other tissues See more
Orthologs: human mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 10q12

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (15355278..15357559, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (14850765..14853046, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (15197754..15200035, complement)

Chromosome 10 - NC_086028.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats.
Title: Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats.
Silencing of STUB1 relieves osteoarthritis via inducing NRF2-mediated M2 macrophage polarization.
Title: Silencing of STUB1 relieves osteoarthritis via inducing NRF2-mediated M2 macrophage polarization.
CHIP attenuates LPS-induced cardiac hypertrophy.
Title: CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and apoptosis by promoting NFATc3 proteasomal degradation.
In forebrain neuron cultures, C terminus of HSC70-Interacting Protein (CHIP) is critical for neuronal responses to stress. CHIP upregulation and localization to mitochondria is required for mitochondrial autophagy (mitophagy).
Title: Neuronal Preconditioning Requires the Mitophagic Activity of C-terminus of HSC70-Interacting Protein.
Study using two rodent models demonstrated that T246M mutation (described in autosomal recessive spinocerebellar ataxia-16 patients) results in structural disorganization and misfolding of the CHIP U-box domain, promoting oligomerization, and increased proteasome-dependent turnover. CHIP-T246M has no ligase activity but maintains interactions with chaperones and chaperone-related functions.
Title: Disrupted structure and aberrant function of CHIP mediates the loss of motor and cognitive function in preclinical models of SCAR16.
upon CHIP knockdown, the expression of Bax and caspase-3 mRNAs increased even further, and the expression of Bcl-2 mRNA was further suppressed. The expression of the phosphorylated p65 and p38 proteins (p-p65 and p-p38) was also further enhanced. Thus, CHIP is a potent cardioprotective molecule.
Title: The carboxyl terminus of heat shock protein 70-interacting protein (CHIP) participates in high glucose-induced cardiac injury.
The carboxyl terminus of Hsc70-interacting protein (CHIP) overexpression leads to inhibition of tendon-derived stem cells (TDSCs) differentiation into osteogenic and adipogenic lineages.
Title: Enhanced tenogenic differentiation and tendon-like tissue formation by CHIP overexpression in tendon-derived stem cells.
Hsp70 and CHIP mediates the ubiquitination and proteasomal degradation of Nox4 as part of the antioxidative effect of Losartan in spontaneous hypertensive rats.
Title: Heat Shock Protein 70 and CHIP Promote Nox4 Ubiquitination and Degradation within the Losartan Antioxidative Effect in Proximal Tubule Cells.
CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of BACE1.
Title: CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of β-secretase.
C terminus of Hsc70-interacting protein
Title: Direct visualization of CHIP-mediated degradation of alpha-synuclein in vivo: implications for PD therapeutics.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

AA957388 (e-PCR)
- UniSTS:248125

RH137115 (e-PCR)
- UniSTS:219203

RH137204 (e-PCR)
- UniSTS:219292

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables G protein-coupled receptor binding	ISO Inferred from Sequence Orthology more info
enables Hsp70 protein binding	ISO Inferred from Sequence Orthology more info
enables Hsp90 protein binding	ISO Inferred from Sequence Orthology more info
enables R-SMAD binding	ISO Inferred from Sequence Orthology more info
enables SMAD binding	ISO Inferred from Sequence Orthology more info
enables TPR domain binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables heat shock protein binding	ISO Inferred from Sequence Orthology more info
enables kinase binding	ISO Inferred from Sequence Orthology more info
enables misfolded protein binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-folding chaperone binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin-ubiquitin ligase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in ERAD pathway	ISO Inferred from Sequence Orthology more info
involved_in MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to misfolded protein	ISO Inferred from Sequence Orthology more info
involved_in endoplasmic reticulum unfolded protein response	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac muscle hypertrophy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of peroxisome proliferator activated receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of smooth muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smooth muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of smooth muscle cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular associated smooth muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ERAD pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chaperone-mediated protein complex assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of mitophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of proteolysis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein autoubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein monoubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein polyubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein polyubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein quality control for misfolded or incompletely synthesized proteins	ISO Inferred from Sequence Orthology more info
involved_in protein stabilization	ISO Inferred from Sequence Orthology more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in regulation of glucocorticoid metabolic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein stability	ISO Inferred from Sequence Orthology more info
involved_in ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Z disc	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear inclusion body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein folding chaperone complex	ISO Inferred from Sequence Orthology more info
part_of ubiquitin ligase complex	ISO Inferred from Sequence Orthology more info

General protein information

Go to the top of the page Help

Preferred Names: E3 ubiquitin-protein ligase CHIP

Names: RING-type E3 ubiquitin transferase CHIP; STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase; carboxy terminus of Hsp70-interacting protein

NP_001020796.2

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

mRNA and Protein(s)

NM_001025625.2 → NP_001020796.2 E3 ubiquitin-protein ligase CHIP

See identical proteins and their annotated locations for NP_001020796.2

Status: VALIDATED

Source sequence(s)

CB326459, CB568781, JAXUCZ010000010

UniProtKB/Swiss-Prot

A6HD62, D4A4T0

UniProtKB/TrEMBL

A0A8I5ZPA4

Related

ENSRNOP00000026921.4, ENSRNOT00000026921.8

Conserved Domains (4) summary

pfam04564
Location:228 → 300

U-box; U-box domain

sd00006
Location:27 → 55

TPR; TPR repeat [structural motif]

pfam00515
Location:61 → 91

TPR_1; Tetratricopeptide repeat

pfam13414
Location:26 → 91

TPR_11; TPR repeat