UniProtKB - Q15041 (AR6P1_HUMAN)
Protein
ADP-ribosylation factor-like protein 6-interacting protein 1
Gene
ARL6IP1
Organism
Homo sapiens (Human)
Status
Functioni
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).1 PublicationBy similarity2 Publications
GO - Molecular functioni
- identical protein binding Source: IntAct
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cotranslational protein targeting to membrane Source: GO_Central
- endoplasmic reticulum tubular network formation Source: UniProtKB
- endoplasmic reticulum tubular network membrane organization Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- positive regulation of L-glutamate import across plasma membrane Source: UniProtKB
- regulation of endoplasmic reticulum tubular network organization Source: CACAO
Keywordsi
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | Q15041 |
Names & Taxonomyi
Protein namesi | Recommended name: ADP-ribosylation factor-like protein 6-interacting protein 1Short name: ARL-6-interacting protein 1 Short name: Aip-1 Alternative name(s): Apoptotic regulator in the membrane of the endoplasmic reticulum1 Publication |
Gene namesi | Name:ARL6IP1 Synonyms:ARL6IP, ARMER1 Publication, KIAA0069 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:697, ARL6IP1 |
MIMi | 607669, gene |
neXtProti | NX_Q15041 |
VEuPathDBi | HostDB:ENSG00000170540.14 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 3 Publications; Multi-pass membrane protein 1 Publication
- Endoplasmic reticulum By similarity
Other locations
- Endomembrane system 1 Publication; Multi-pass membrane protein 1 Publication
Note: Predominantly localized to intracytoplasmic membranes. Preferentially localizes at the ER tubules and the edge of the ER sheets, both of which are characterized by a high membrane curvature.1 Publication
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
- integral component of endoplasmic reticulum membrane Source: UniProtKB
- Sec61 translocon complex Source: GO_Central
Other locations
- integral component of membrane Source: GO_Central
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 41 | CytoplasmicSequence analysisAdd BLAST | 41 | |
Transmembranei | 42 – 62 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 63 – 65 | LumenalSequence analysis | 3 | |
Transmembranei | 66 – 86 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 87 – 133 | CytoplasmicSequence analysisAdd BLAST | 47 | |
Transmembranei | 134 – 175 | HelicalSequence analysisAdd BLAST | 42 | |
Topological domaini | 176 – 203 | LumenalSequence analysisAdd BLAST | 28 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Spastic paraplegia 61, autosomal recessive (SPG61)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA complicated form of spastic paraplegia with polysensory and motor neuropathy. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082139 | 38 – 203 | Missing in SPG61; unknown pathological significance. 1 PublicationAdd BLAST | 166 |
Keywords - Diseasei
Disease variant, Hereditary spastic paraplegia, NeurodegenerationOrganism-specific databases
DisGeNETi | 23204 |
MalaCardsi | ARL6IP1 |
MIMi | 615685, phenotype |
OpenTargetsi | ENSG00000170540 |
Orphaneti | 401780, Autosomal recessive spastic paraplegia type 61 |
PharmGKBi | PA162376894 |
Miscellaneous databases
Pharosi | Q15041, Tbio |
Genetic variation databases
BioMutai | ARL6IP1 |
DMDMi | 14424435 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000064655 | 1 – 203 | ADP-ribosylation factor-like protein 6-interacting protein 1Add BLAST | 203 |
Proteomic databases
EPDi | Q15041 |
jPOSTi | Q15041 |
MassIVEi | Q15041 |
MaxQBi | Q15041 |
PaxDbi | Q15041 |
PeptideAtlasi | Q15041 |
PRIDEi | Q15041 |
ProteomicsDBi | 24482 60389 [Q15041-1] |
PTM databases
iPTMneti | Q15041 |
PhosphoSitePlusi | Q15041 |
SwissPalmi | Q15041 |
Expressioni
Tissue specificityi
Expressed in all hematopoietic cell lineages, but the highest level of expression is found in early myeloid progenitor cells. Expressed in brain, bone marrow, thymus and lung. Expressed at low level in liver, kidney and spleen. Not detected in heart.1 Publication
Developmental stagei
Down-regulated during myeloid differentiation.
Inductioni
Down-regulated by apoptotic stimuli.1 Publication
Gene expression databases
Bgeei | ENSG00000170540, Expressed in pigmented layer of retina and 247 other tissues |
ExpressionAtlasi | Q15041, baseline and differential |
Genevisiblei | Q15041, HS |
Organism-specific databases
HPAi | ENSG00000170540, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q15041
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 116812, 102 interactors |
IntActi | Q15041, 83 interactors |
MINTi | Q15041 |
STRINGi | 9606.ENSP00000306788 |
Miscellaneous databases
RNActi | Q15041, protein |
Family & Domainsi
Domaini
The transmembrane domains are required for its ability to shape the endoplasmic reticulum membrane into tubules.1 Publication
Sequence similaritiesi
Belongs to the ARL6ip family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QTTI, Eukaryota |
GeneTreei | ENSGT00940000154937 |
HOGENOMi | CLU_100749_0_0_1 |
InParanoidi | Q15041 |
OMAi | NWDGDQE |
PhylomeDBi | Q15041 |
TreeFami | TF105477 |
Family and domain databases
InterProi | View protein in InterPro IPR033301, ARL6IP |
PANTHERi | PTHR20952:SF3, PTHR20952:SF3, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q15041-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAEGDNRSTN LLAAETASLE EQLQGWGEVM LMADKVLRWE RAWFPPAIMG
60 70 80 90 100
VVSLVFLIIY YLDPSVLSGV SCFVMFLCLA DYLVPILAPR IFGSNKWTTE
110 120 130 140 150
QQQRFHEICS NLVKTRRRAV GWWKRLFTLK EEKPKMYFMT MIVSLAAVAW
160 170 180 190 200
VGQQVHNLLL TYLIVTSLLL LPGLNQHGII LKYIGMAKRE INKLLKQKEK
KNE
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BTX6 | H3BTX6_HUMAN | ADP-ribosylation factor-like protei... | ARL6IP1 | 88 | Annotation score: | ||
H3BS91 | H3BS91_HUMAN | ADP-ribosylation factor-like protei... | ARL6IP1 | 99 | Annotation score: | ||
H3BPJ2 | H3BPJ2_HUMAN | ADP-ribosylation factor-like protei... | ARL6IP1 | 101 | Annotation score: |
Sequence cautioni
The sequence BAA06683 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 110 | S → I in BAH13527 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082139 | 38 – 203 | Missing in SPG61; unknown pathological significance. 1 PublicationAdd BLAST | 166 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057297 | 1 – 29 | Missing in isoform 2. 1 PublicationAdd BLAST | 29 | |
Alternative sequenceiVSP_057298 | 105 – 156 | Missing in isoform 3. 1 PublicationAdd BLAST | 52 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D31885 mRNA Translation: BAA06683.1 Different initiation. AK300869 mRNA Translation: BAH13361.1 AK301636 mRNA Translation: BAH13527.1 AC138811 Genomic DNA No translation available. BC010281 mRNA Translation: AAH10281.1 |
CCDSi | CCDS10572.1 [Q15041-1] CCDS81951.1 [Q15041-2] |
RefSeqi | NP_001300787.1, NM_001313858.1 [Q15041-2] NP_055976.1, NM_015161.2 [Q15041-1] |
Genome annotation databases
Ensembli | ENST00000304414; ENSP00000306788; ENSG00000170540 [Q15041-1] ENST00000546206; ENSP00000440048; ENSG00000170540 [Q15041-2] |
GeneIDi | 23204 |
KEGGi | hsa:23204 |
UCSCi | uc002dfl.2, human [Q15041-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D31885 mRNA Translation: BAA06683.1 Different initiation. AK300869 mRNA Translation: BAH13361.1 AK301636 mRNA Translation: BAH13527.1 AC138811 Genomic DNA No translation available. BC010281 mRNA Translation: AAH10281.1 |
CCDSi | CCDS10572.1 [Q15041-1] CCDS81951.1 [Q15041-2] |
RefSeqi | NP_001300787.1, NM_001313858.1 [Q15041-2] NP_055976.1, NM_015161.2 [Q15041-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 116812, 102 interactors |
IntActi | Q15041, 83 interactors |
MINTi | Q15041 |
STRINGi | 9606.ENSP00000306788 |
PTM databases
iPTMneti | Q15041 |
PhosphoSitePlusi | Q15041 |
SwissPalmi | Q15041 |
Genetic variation databases
BioMutai | ARL6IP1 |
DMDMi | 14424435 |
Proteomic databases
EPDi | Q15041 |
jPOSTi | Q15041 |
MassIVEi | Q15041 |
MaxQBi | Q15041 |
PaxDbi | Q15041 |
PeptideAtlasi | Q15041 |
PRIDEi | Q15041 |
ProteomicsDBi | 24482 60389 [Q15041-1] |
Protocols and materials databases
Antibodypediai | 11964, 276 antibodies |
DNASUi | 23204 |
Genome annotation databases
Ensembli | ENST00000304414; ENSP00000306788; ENSG00000170540 [Q15041-1] ENST00000546206; ENSP00000440048; ENSG00000170540 [Q15041-2] |
GeneIDi | 23204 |
KEGGi | hsa:23204 |
UCSCi | uc002dfl.2, human [Q15041-1] |
Organism-specific databases
CTDi | 23204 |
DisGeNETi | 23204 |
GeneCardsi | ARL6IP1 |
HGNCi | HGNC:697, ARL6IP1 |
HPAi | ENSG00000170540, Low tissue specificity |
MalaCardsi | ARL6IP1 |
MIMi | 607669, gene 615685, phenotype |
neXtProti | NX_Q15041 |
OpenTargetsi | ENSG00000170540 |
Orphaneti | 401780, Autosomal recessive spastic paraplegia type 61 |
PharmGKBi | PA162376894 |
VEuPathDBi | HostDB:ENSG00000170540.14 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QTTI, Eukaryota |
GeneTreei | ENSGT00940000154937 |
HOGENOMi | CLU_100749_0_0_1 |
InParanoidi | Q15041 |
OMAi | NWDGDQE |
PhylomeDBi | Q15041 |
TreeFami | TF105477 |
Enzyme and pathway databases
PathwayCommonsi | Q15041 |
Miscellaneous databases
BioGRID-ORCSi | 23204, 13 hits in 994 CRISPR screens |
ChiTaRSi | ARL6IP1, human |
GeneWikii | ARL6IP1 |
GenomeRNAii | 23204 |
Pharosi | Q15041, Tbio |
PROi | PR:Q15041 |
RNActi | Q15041, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000170540, Expressed in pigmented layer of retina and 247 other tissues |
ExpressionAtlasi | Q15041, baseline and differential |
Genevisiblei | Q15041, HS |
Family and domain databases
InterProi | View protein in InterPro IPR033301, ARL6IP |
PANTHERi | PTHR20952:SF3, PTHR20952:SF3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | AR6P1_HUMAN | |
Accessioni | Q15041Primary (citable) accession number: Q15041 Secondary accession number(s): B7Z6S5, B7Z791, F5GXP4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | June 20, 2001 | |
Last modified: | April 7, 2021 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families