ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1)

The protein contains 203 amino acids for an estimated molecular weight of 23363 Da.

 

Positively regulates SLC1A1/EAAC1-mediated glutamate transport by increasing its affinity for glutamate in a PKC activity-dependent manner. Promotes the catalytic efficiency of SLC1A1/EAAC1 probably by reducing its interaction with ARL6IP5, a negative regulator of SLC1A1/EAAC1-mediated glutamate transport (By similarity). Plays a role in the formation and stabilization of endoplasmic reticulum tubules (PubMed:24262037). Negatively regulates apoptosis, possibly by modulating the activity of caspase-9 (CASP9). Inhibits cleavage of CASP9-dependent substrates and downstream markers of apoptosis but not CASP9 itself (PubMed:12754298). May be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation (PubMed:10995579). (updated: Sept. 12, 2018)

Protein identification was indicated in the following studies:

  1. 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.
  2. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.

This protein is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 46

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The reference OMIM entry for this protein is 607669

Adp-ribosylation-like factor 6-interacting protein 1; arl6ip1
Arl6ip
Kiaa0069

CLONING

Using differential display, Pettersson et al. (2000) identified a mouse gene that was downregulated during myeloid differentiation and encoded a 23-kD protein with 4 transmembrane domains. The protein was found to be identical to mouse Arl6-interacting protein-1, which had been identified by yeast 2-hybrid screening as a protein interacting with mouse ADP-ribosylation-like factor (103180) by Clark et al. (1993). The protein also showed significant homology with human KIAA0069, which had been identified by Nomura et al. (1994). Pettersson et al. (2000) found that the deduced 203-amino acid human protein shares 96% sequence identity with mouse Arl6ip. By Northern blot analysis of mouse tissues, Pettersson et al. (2000) detected high expression of Arl6ip in brain, bone marrow, thymus, and lung; low expression in liver, kidney, and spleen; and no expression in heart. Immunofluorescence microscopy showed that mouse Arl6ip is predominantly localized to intracytoplasmic membranes, suggesting an involvement of the gene in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation.

MAPPING

By FISH, Pettersson et al. (2000) mapped the human ARL6IP gene to chromosome 16p12-p11.2 and the mouse homolog to chromosome 7 in a region of syntenic homology.

MOLECULAR GENETICS

In affected members of a consanguineous family segregating complicated spastic paraplegia with diffuse sensory and motor polyneuropathy (SPG61; 615685), Novarino et al. (2014) identified a homozygous frameshift mutation in the ARL6IP1 gene (607669.0001). ... More on the omim web site

Subscribe to this protein entry history

June 29, 2020: Protein entry updated
Automatic update: OMIM entry 607669 was added.

Feb. 22, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).