Deubiquitinating protein VCPIP1 (VCPIP1)

The protein contains 1222 amino acids for an estimated molecular weight of 134321 Da.

 

Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681).(Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients. (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 611745

Vcp/p47 complex-interacting protein 1; vcpip1
Vcp/p47 complex-interacting protein, 135-kd; vcip135
Kiaa1850

CLONING

By sequencing clones obtained from a size-fractionated adult hippocampus cDNA library, Nagase et al. (2001) cloned VCPIP1, which they designated KIAA1850. The deduced protein contains 1,236 amino acids. RT-PCR ELISA detected moderate VCPIP1 expression in all adult and fetal tissues examined.

GENE FUNCTION

Reassembly of the Golgi apparatus from membrane fragments after cell division requires the ATPases NSF (601633) and p97 (VCP; 601023), as well as the cofactor p47 (NSFL1C; 606610) and the receptor syntaxin-5 (STX5A; 603189). Uchiyama et al. (2002) showed that rat Vcip135 was essential for p97/p47-mediated membrane fusion and that Vcip135 bound to the p97/p47/Stx5a complex and dissociated it via p97-catalyzed ATP hydrolysis. Microinjection of antibodies against Vcip135 and p47 in rat kidney cells showed that Vcip135 and p47 were required for Golgi and endoplasmic reticulum assembly. Wang et al. (2004) found that p97/p47-mediated reassembly of Golgi cisternae required ubiquitin. They identified rat Vcip135 as a deubiquitinating enzyme and found that it reversed the ubiquitination event that occurred during mitotic disassembly. Wang et al. (2004) concluded that a cycle of ubiquitination and VCIP135-mediated deubiquitination regulates Golgi membrane dynamics during mitosis.

MAPPING

By radiation hybrid analysis, Nagase et al. (2001) mapped the VCPIP1 gene to chromosome 8. ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611745 was added.