SAG

Protein identityUniProt · HPA

UniProt accession

P10523

Gene

SAG

Ensembl

ENSG00000130561

Chromosome

2

Canonical length

405 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Quaternary structure

Homotetramer

OverviewNCBI Gene

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

405 residues, UniProt reviewed canonical sequence.

>P10523|SAG
     1  MAASGKTSKS EPNHVIFKKI SRDKSVTIYL GNRDYIDHVS QVQPVDGVVL VDPDLVKGKK
    61  VYVTLTCAFR YGQEDIDVIG LTFRRDLYFS RVQVYPPVGA ASTPTKLQES LLKKLGSNTY
   121  PFLLTFPDYL PCSVMLQPAP QDSGKSCGVD FEVKAFATDS TDAEEDKIPK KSSVRLLIRK
   181  VQHAPLEMGP QPRAEAAWQF FMSDKPLHLA VSLNKEIYFH GEPIPVTVTV TNNTEKTVKK
   241  IKAFVEQVAN VVLYSSDYYV KPVAMEEAQE KVPPNSTLTK TLTLLPLLAN NRERRGIALD
   301  GKIKHEDTNL ASSTIIKEGI DRTVLGILVS YQIKVKLTVS GFLGELTSSE VATEVPFRLM
   361  HPQPEDPAKE SYQDANLVFE EFARHNLKDA GEAEEGKRDK NDVDE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SAG can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

1,360 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SAG.

Disease | AllUniProt

Conditions SAG is implicated in, by any mechanism.

• Night blindness, congenital stationary, Oguchi type 1 (CSNBO1) MIM:258100
• Retinitis pigmentosa 47 (RP47) MIM:613758
• Retinitis pigmentosa 96 (RP96) MIM:620228

Disease | GeneticClinVar

40 pathogenic / likely-pathogenic of 499 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Oguchi disease-1
• Retinitis pigmentosa 47
• Oguchi disease
• Retinal dystrophy
• Retinitis pigmentosa 96

Disease | ImmuneIEDB

Conditions an epitope on SAG was assayed in.

• autoimmune uveitis B and T cell
• Behcet's disease T cell
• chorioretinitis T cell
• Vogt-Koyanagi-Harada disease T cell
• sarcoidosis T cell
• autoimmune disease of eyes T cell
• multiple sclerosis B cell

ReferencesPubMed · IEDB

Publications for SAG from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.44

gnomAD pLI

0

gnomAD missense Z

0.68

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• G protein-coupled opsin signaling pathway
• G protein-coupled receptor internalization
• sensory perception

Molecular functions

• G protein-coupled receptor binding
• opsin binding
• phosphoprotein binding
• protein phosphatase inhibitor activity
• spectrin binding

Cellular components

• cytosol
• membrane
• photoreceptor inner segment
• photoreceptor outer segment

Protein domainsUniProt · Pfam · InterPro

• Arrestin
• Arrestin-like, N-terminal
• Arrestin-like, C-terminal domain
• Arrestin-like, C-terminal domain superfamily
• Arrestin, N-terminal
• Immunoglobulin E-set
• Arrestin, conserved site
• Arrestin (or S-antigen), N-terminal domain
• Arrestin (or S-antigen), C-terminal domain

KeywordsUniProt

• Cell projection
• Congenital stationary night blindness
• Membrane
• Phosphoprotein
• Retinitis pigmentosa

InteractionsUniProt · HPA

Protein binding partners of SAG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RHO