Seroatlas · Human Serome Atlas

ICA1

Islet cell autoantigen 1

Also known as: ICA69, ICA69_HUMAN, ICAp69

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q05084
Gene: ICA1
Ensembl: ENSG00000003147
Chromosome: 7
Canonical length: 483 aa
Protein class: Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Vesicles,Cytosol

OverviewNCBI Gene

This gene encodes a protein with an arfaptin homology domain that is found both in the cytosol and as membrane-bound form on the Golgi complex and immature secretory granules. This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

Canonical amino-acid sequenceUniProt

483 residues, UniProt reviewed canonical sequence.

>Q05084|ICA1
     1  MSGHKCSYPW DLQDRYAQDK SVVNKMQQKY WETKQAFIKA TGKKEDEHVV ASDADLDAKL
    61  ELFHSIQRTC LDLSKAIVLY QKRICFLSQE ENELGKFLRS QGFQDKTRAG KMMQATGKAL
   121  CFSSQQRLAL RNPLCRFHQE VETFRHRAIS DTWLTVNRME QCRTEYRGAL LWMKDVSQEL
   181  DPDLYKQMEK FRKVQTQVRL AKKNFDKLKM DVCQKVDLLG ASRCNLLSHM LATYQTTLLH
   241  FWEKTSHTMA AIHESFKGYQ PYEFTTLKSL QDPMKKLVEK EEKKKINQQE STDAAVQEPS
   301  QLISLEEENQ RKESSSFKTE DGKSILSALD KGSTHTACSG PIDELLDMKS EEGACLGPVA
   361  GTPEPEGADK DDLLLLSEIF NASSLEEGEF SKEWAAVFGD GQVKEPVPTM ALGEPDPKAQ
   421  TGSGFLPSQL LDQNMKDLQA SLQEPAKAAS DLTAWFSLFA DLDPLSNPDA VGKTDKEHEL
   481  LNA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ICA1 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: Other membrane
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.47
Highest tissue expression: 59 nTPM

Expression across tissuesHPA

Tissue

pancreas: 59 nTPM
heart muscle: 42 nTPM
salivary gland: 35 nTPM
stomach: 29 nTPM
cerebellum: 27 nTPM
cerebral cortex: 23 nTPM

Single-cell type

late spermatids: 1,438 nCPM
early spermatids: 863 nCPM
distal convoluted tubule cells: 582 nCPM
adrenal medulla cells: 521 nCPM
cardiomyocytes: 352 nCPM
prostatic glandular cells: 267 nCPM

Immune cell

T-reg: 30 nTPM
memory CD4 T-cell: 5.4 nTPM
neutrophil: 3.4 nTPM
classical monocyte: 2.4 nTPM
myeloid DC: 2.4 nTPM
total PBMC: 1.3 nTPM

Brain region

cerebral cortex: 49 nTPM
cerebellum: 49 nTPM
basal ganglia: 38 nTPM
white matter: 35 nTPM
thalamus: 33 nTPM
amygdala: 27 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ICA1.

Disease | ImmuneIEDB

Conditions an epitope on ICA1 was assayed in.

type 1 diabetes mellitus T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against ICA1 are reported. Each links to that disease's full target list.

Diabetes Mellitus, Type 1 5

ReferencesPubMed · IEDB

Publications for ICA1 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.

Reference: AutoantibodyPubMed

6 publications

Autoantibodies to the islet antigen ICA69 occur in IDDM and in rheumatoid arthritis.
1995 · Diabetologia · RCR 1.3 · 54 citations
Sera from patients with IDDM and healthy individuals have antibodies to ICA69 on western blots but do not immunoprecipitate liquid phase antigen.
1994 · J Autoimmun · RCR 0.8 · 27 citations
Anti-BSA antibodies do not cross-react with the 69-kDa islet cell autoantigen ICA69.
1998 · J Autoimmun · RCR 0.3 · 10 citations
Reduced thymic expression of islet antigen contributes to loss of self-tolerance.
2003 · Ann N Y Acad Sci · RCR 0.2 · 14 citations
ICA69 autoantibodies in primary Sjögren's syndrome.
2004 · Lupus · RCR 0.2 · 9 citations

Show 1 more

Production of the islet cell antigen ICA69 (p69) with baculovirus expression system: analysis with a solid-phase time-resolved fluorescence method of sera from patients with IDDM and rheumatoid arthritis.
1999 · Autoimmunity · RCR 0.1 · 4 citations

Reference: T cellIEDB

1 publication

Persistent T cell anergy in human type 1 diabetes.
1999 · J Immunol · RCR 0.8 · 41 citations

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): 0.58
gnomAD pLI: 0
gnomAD missense Z: 0.49
DepMap mean gene effect: -0.04
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ICA1 as an antibody target. Whether an autoantibody or antibody against ICA1 could matter depends on whether native ICA1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ICA1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

This protein is believed to be an autoantigen in insulin-dependent diabetes mellitus and primary Sjogren's syndrome.

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