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MICA (MHC class I polypeptide-related sequence A)

Written2014-07Zain Ahmed, Medhat Askar
Cleveland Clinic/, Cleveland, OH; askarm@ccf.org

Abstract Human Major Histocompatibility Complex (MHC) Class I Chain-Related gene A (MICA) is located 46 Kb centromeric to the HLA-B locus on the short arm of human chromosome 6 and encodes for a 62-kda cell surface glycoprotein. It is expressed on endothelial cells, dendritic cells, fibroblasts, epithelial cells, and many tumours and serves as target for both cellular and humoral immune responses in transformed cells. MICA protein at normal states has a low level of expression in epithelial tissues but is upregulated in response to various stimuli of cellular stress. MICA also functions as a ligand recognized by the activating receptor NKG2D that is expressed on the surface of NK, NKT, CD8+ and TCRγδ+ T cells. Allelic variants of MICA due to a single amino acid substitution at position 129 in the α2 domain have been reported to result in large differences in NKG2D binding. These variable affinities have been suggested to affect thresholds of NK cell triggering and T cell modulation in autoimmune diseases and malignancies. MICA molecules exist also in soluble forms (sMICA) and altered serum levels of sMICA have been reported in multiple states of health and disease.

Keywords MICA, MHC, Malignancy, Autoimmunity, NK cells; Transplantation; Rejection; GVHD

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Identity

Alias_symbol (synonym)PERB11.1
Other aliasMHC (Human Major Histocompatibility Complex)
Class I Chain-Related Gene A,
MHC Class I Chain-related Protein A,
MHC class I-related chain A,
MIC-A,
HGNC (Hugo) MICA
LocusID (NCBI) 100507436
Atlas_Id 41364
Location 6p21.33  [Link to chromosome band 6p21]
Location_base_pair Starts at 31403567 and ends at 31415315 bp from pter ( according to hg19-Feb_2009)  [Mapping MICA.png]
 
  Figure 1: Chromosomal location of MICA genes shown on a map of the MHC on chromosome 6p21.3 (not to scale). Chromosome 6 [Drawing modified from the National Library of Medicine, the National Center for Biotechnology Information public website (2013)]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CSNK2B (6p21.33) / MICA (6p21.33)MICA (6p21.33) / ASXL2 (2p23.3)PLOD3 (7q22.1) / MICA (6p21.33)

DNA/RNA

 
  Figure 2: The MICA gene spans a 11,720-bp stretch of DNA was located 46,445 bp centromeric of the HLA-B locus on the short arm of human chromosome 6 (Mizuki et al., 1997).
Description The MICA gene was described in 1994 among a group of genes within the MHC class I region (Bahram et al., 1994). It is a member of the MIC gene family, which consists of 7 members (MICA-MICG). MICA is classified as a non-classical MHC class I gene as opposed to classical MHC class I genes encoding the commonly known Human Leukocyte Antigen (HLA) proteins. Similar to the HLA genes, the MICA gene is highly polymorphic. One hundred alleles have been reported (according to IMGT Release 3.17.0, 2014-07-14), with new alleles being continuously described and added to the database. As such it is significantly less polymorphic than HLA loci A (2,884 alleles), B (3,589), C (2,375), DRB1 (1,540), DQB1 (664), and DPB1 (422). However, MICA is more polymorphic than HLA loci G (50), DRB3 (58), DRB4 (15), DRB5 (20), DRA (7), DQA1 (52), DPA1 (38), and its closely related MICB gene (40) (Robinson et al., 2013).
MICA gene is organized into 7 exons of which exon 5 encodes the transmembrane (TM) region of the MICA molecule. TM encodes the repeat polymorphism (GCT/Ala) and eight types of repeats have been described as A4, A5, A5.1, A6, A7, A8, A9, and A10 (Gambelunghe et al., 2006; Zou et al., 2006). The combinations of extracellular and TM types facilitates the identification of the MICA alleles and reduces the number of potential ambiguous typings in heterozygous individuals. This combination identifies MICA alleles based on polymorphisms in the TM region as well as elsewhere, e.g., MICA*007:01/A4, MICA*008:01/A5.1, etc.
Transcription MICA gene encodes 383 amino acids polypeptide. MICA is up-regulated on human endothelial cells by the pro-inflammatory cytokine TNFα. This up-regulation is controlled at the transcriptional level by a master regulatory control element positioned 130-base pair (bp) upstream of the MICA transcription start site integrating input from the NF-kB and heat shock pathways (Lin et al., 2012).
Pseudogene Of the MIC gene family, only MICA and MICB are true genes with protein products while the remaining (MICC-MICG) are pseudogenes.

Protein

Note Due to synonymous substitutions being the only differences among some of the MICA alleles, the 100 MICA alleles encode for only 79 distinct proteins. Two of the MICA alleles are null alleles with no expressed protein products. MICA molecules are considered non-classical MHC class I molecules rather than human leukocyte antigens (HLA) since they are not expressed on the surface of human leukocytes. Nevertheless they are expressed on endothelial cells, dendritic cells, fibroblasts, epithelial cells, and many tumors and serve as targets for both cellular and humoral immune responses (Bahram et al., 1994; Zou and Stastny, 2010). MICA protein at normal states has a low level of expression in epithelial tissues but is upregulated in many tumors and under various stimuli of cellular stress including heat shock proteins (Groh et al., 1996). Similar to MHC class I, MICA molecules have 3 extracellular immunoglobulin-like domains, a transmembrane domain and intracellular cytoplasmic tail. However, unlike class I, MICA is not covalently bound a monomorphic β2 microglobulin and its peptide binding groove is empty and does not present peptides (Figure 3).
Allelic variants of MICA based on a single amino acid substitution at position 129 in the α2 domain have been reported to result in large differences in the affinity of binding to the activating natural killer group 2, member D (NKG2D) (Steinle et al., 2001). MICA alleles with a methionine (M) or valine (V) have been classified as having strong or weak binding affinity for NKG2D, respectively. These variable affinities have been suggested to affect thresholds of NK cell triggering and T cell modulation and consequently influencing clinical phenotypes in autoimmune disorders and malignancies (Amroun et al., 2005; Douik et al., 2009).
MICA molecules exist also in soluble forms (sMICA) encompassing three extracellular domains (Salih et al., 2002). ADAM, a disintegrin and metalloproteinase, is reported to mediate sMICA generation by cleavage of the molecule in the α3 domain close to the papain cleavage site (Figure X), however the precise location of the cleavage site is still unknown (Waldhauer et al., 2008). sMICA are not normally detected in sera of healthy donors and tumor cells are the major source of sMICA generation (Holdenrieder et al., 2006). In addition to patients with malignancies, sMICA is detected in the sera of patients with autoimmune diseases, acute bacterial infections, renal insufficiency, and cholestasis (Holdenrieder et al., 2007). Unlike the surface-bound form of MICA that stimulates immune responses, the secreted soluble counterpart, sMICA abates immune responses primarily by down regulating NKG2D expression which impairs the cellular cytotoxicity of T cells and NK cells against tumor cells (Groh et al., 2002). This may partly explain why higher levels of sMICA were observed in the serum of chronically infected individuals compared to healthy controls and HIV-1 controllers (Nolting et al., 2010). Similarly CMV infection triggers shedding of sMICA (Andresen et al., 2009).
 
  Figure 3: Diagram of comparison among HLA-Class I, MICA and sMICA molecules
Description 383 amino acids in length (including the 23 amino acids leader sequence that is lost from the 360 amino acid mature protein), 42,915 Da protein, undergoes N-glycoslation as post-translational modification, although not required to interact with NKG2D. MICA has three external (α1, α2, α3), a transmembrane and an intracytoplasmic domains (figure 4).
 
  Figure 4: The amino acid sequence of the full length MICA molecule. Source: IMGT/HLA online database (Robinson et al., 2013)
Expression Co-dominantly and constitutively expressed on cell membranes of human epithelial, endothelial, fibroblasts cells, keratinocytes, monocytes, dendritic cells, thymic medulla, and gastrointestinal epithelial cells but not on the surface of other healthy cells (Zwirner et al., 1999). Activated CD4+ and CD8+ T cells are shown to express MICA. Nuclear factor (NF)-kB regulates MICA expression on activated T lymphocytes by binding to a specific sequence in the long intron 1 of the MICA gene (Molinero et al., 2004). MICA expression is also up-regulated on stressed cells, tumour cells, and pathogen-infected cells (Mistry and O'Callaghan, 2007). It's noteworthy that in vitro CMV infection strongly induces expression of MICA (Groh et al., 2001). Similarly, respiratory syncytial virus (RSV) infection of epithelial cells up-regulated cell surface expression of MICA and levels of soluble MICA (Zdrenghea et al., 2012). It is also reported that CMV induced expression on the surface of fibroblasts is skewed towards a common form of MICA (A5.1), which has a nucleotide insertion in exon 5 corresponding to the transmembrane region and no cytoplasmic tail and less activation of the NKG2D pathway (Zou et al., 2005).
 
  Figure 5: A phylogram of the genetic distance between HLA class I consensus sequence, MICA and MICB reference alleles. This Phylogram considers only amino acid sequence of the 'Mature Protein' excluding the 23 amino acids leader sequence in MICA and MICB reference sequences and 24 amino acids leader sequence in the Class I consensus sequence due to lack of consensus among leader sequences of loci HLA-A, B, and C
Localisation Cell surface as a single-pass type 1 membrane protein
Function Like other MHC Class I molecules, MICA is a highly polymorphic MHC Class I molecule expressed on the cell surface of cells mentioned above. However, unlike other classical MHC Class I molecules, MICA is not involved in antigen presentation because its peptide-binding groove is too narrow to present antigens and is not associated with β2-microglobulin (Groh et al., 1996). MICA is expressed under cellular stress and is a ligand for NKG2D receptor expressed on surface of NK, NKT, CD8+ and TCRγδ T cells (Bauer et al., 1999). NKG2D binding results in up-regulation of MICA and ultimately cytotoxicity and release of IFN? by NKG2D-expressing cells.
 
  Figure 6: Sequence alignment between MICA (MICA*001) and MICB (MICB*001) reference sequences. This alignment considers the 'Full Length Protein' including the 23 amino acids leader sequence that is lost in the mature protein
Homology Searching the non-redundant protein sequences (nr) database for the protein sequences similar to the MICA reference amino acid sequence (MICA*001) using Blastp (protein-protein BLAST) tool publicly available from the website of The National Center for Biotechnology Information (https://blast.ncbi.nlm.nih.gov/Blast) showed that the closest protein sequences are MICB followed by MHC class I (Wheeler and Bhagwat, 2007). The phylogenetic distance among these 3 sequences as determined by the online ClustalW2 (version CLUSTAL 2.1) Multiple Sequence Alignments tool publicly available at the website of the European Bioinformatics Institute of the European Molecular Biology Laboratory (EMBL-EBI) (http://www.ebi.ac.uk/Tools/msa/clustalw2/) is shown in figure (5) (McWilliam et al., 2013). Aligning MICA *001 and MICB reference amino acid sequence (MICB *001) using the same ClustalW2 tool yields scores of 83.03% sequence identity (Figure 6). Similarly alignment of MICA*001 and HLA class I consensus amino acid sequence yielded an identity score of 26.47% between (Figure 7).
 

Mutations

Note Similar to HLA genes, each allelic variant of MICA is given a distinct name that is officiated by the WHO Nomenclature Committee for Factors of the HLA System. The following are the 100 recognized MICA alleles (according to IMGT Release 3.17.0, 2014-07-14): MICA*001, MICA*002:01, MICA*002:02, MICA*002:03, MICA*002:04, MICA*004, MICA*005, MICA*006, MICA*007:01, MICA*007:02, MICA*007:03, MICA*007:04, MICA*007:05, MICA*007:06, MICA*008:01:01, MICA*008:01:02, MICA*008:02, MICA*008:03, MICA*008:04, MICA*008:05, MICA*009:01, MICA*009:02, MICA*010:01, MICA*010:02, MICA*011, MICA*012:01, MICA*012:02, MICA*012:03, MICA*012:04, MICA*013, MICA*014, MICA*015, MICA*016, MICA*017, MICA*018:01, MICA*018:02, MICA*019, MICA*020, MICA*022, MICA*023, MICA*024, MICA*025, MICA*026, MICA*027, MICA*028, MICA*029, MICA*030, MICA*031, MICA*032, MICA*033, MICA*034, MICA*035, MICA*036, MICA*037, MICA*038, MICA*039, MICA*040, MICA*041, MICA*042, MICA*043, MICA*044, MICA*045, MICA*046, MICA*047, MICA*048, MICA*049, MICA*050, MICA*051, MICA*052, MICA*053, MICA*054, MICA*055, MICA*056, MICA*057, MICA*058, MICA*059, MICA*060, MICA*061, MICA*062, MICA*063N, MICA*064N, MICA*065, MICA*066, MICA*067, MICA*068, MICA*069, MICA*070, MICA*072, MICA*073, MICA*074, MICA*075, MICA*076, MICA*077, MICA*078, MICA*079, MICA*080, MICA*081, MICA*082, MICA*083, MICA*084 (Robinson et al., 2013).

Implicated in

Note
  
Entity Pregnancy
Note MICA genotypes MICA5.0/5.1 were associated with autoimmune type 1 diabetes with onset during pregnancy (Torn et al., 2004). On the other hand sMIC molecules released from the placenta is considered as a possible immune escape mechanism important for fetal survival (Mincheva-Nilsson et al., 2006). sMIC was also reported as a novel blood biomarker of the chances of a viable baby in infertile women undergoing in vitro fertilization (Porcu-Buisson et al., 2007). Consistent with these reports is the finding of reduced production of sMICA by the aged placenta playing a role in parturition (Huang et al., 2011).
  
  
Entity Malignancies
Note MICA 129 M/V dimorphism with variable NKG2D binding affinities has been reported to affect thresholds of NK cell triggering and T cell modulation in malignancies (Douik et al., 2009). In cancer patients, elevated sMICA levels are significantly correlated with cancer stage, differentiation, and metastasis (Holdenrieder et al., 2006). MICA is also expressed in abundance in large granular lymphocyte leukemia cells. Neutrophil counts were inversely correlated with MICA expression and MICA*00801/A5.1 was reported in higher frequency in patients with large granular lymphocyte leukemia (Viny et al., 2010).
  
  
Entity Graft versus host disease (GVHD)
Disease GVHD is an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver, skin, and lungs and results from donor-host disparities in major and minor histocompatibility antigens following solid organs and hematopoietic stem cell transplantation (Ferrara et al., 2009; Sharma et al., 2012).
Prognosis GVHD remains a significant hurdle in overcoming the morbidity and mortality associated with hematopoietic stem cell transplantation (Dhir et al., 2014).
Because of its genomic location between MHC Class I and Class II genes, there is strong linkage disequilibrium between many MICA and HLA-B alleles. MICA could also serve as a genetic marker of recombination between MHC classes I and II in otherwise MHC matched individuals where MICA mismatched individuals would be predicted to have mismatched haplotypes whereas the MICA matched pairs may or may not be haplotype matched. This distinction is biologically relevant since MHC haplotype mismatching in otherwise HLA matched donor/recipient pairs was reported in association with a statistically significantly increased risk of severe acute GvHD (Petersdorf et al., 2007). Donor/recipient MICA mismatches were associated with increased risk of severe acute GVHD and were also reported to have a synergistic effect with HLA-DPB1 mismatches on the risk of severe acute GVHD (Askar et al., 2012). MICA-129 genotype, sMICA, and anti-MICA antibodies were reported as biomarkers of chronic GVHD (Boukouaci et al., 2009).
  
  
Entity Allograft rejection
Disease MICA mismatch is associated with presence of MICA antibodies in serum of solid organ transplant recipient, which in turn is associated with acute rejection. Anti-MICA sera can bind to endothelial cells from MICA A5.1 donors. Thus, MICA A5.1 can potentially serve as an alloantigen and possibly mediate an alloimmune response. Transplant recipients can also develop donor-specific antibodies to MICA. MICA DSA were associated with decreased graft function.
Prognosis Presensitization of kidney-transplant recipients to MICA antigens was reported in association with an increased frequency of graft loss and was suggested to contribute to allograft loss among recipients who are otherwise well matched for HLA (Zou et al., 2007).
Donor MICA A5.1 mismatch is associated with anti-MICA antibody formation and increased proteinuria in kidney recipients. MICA*001,*004, *007, *009, *012, and *018 are more prevalent in patients with impaired renal function than normal function.
  
  
Entity Psoriasis
Disease Psoriasis is a disease of the skin characterized by chronic inflammation leading to scaly plaques.
Prognosis MICA transmembrane (MICA-TM) A9 allele is associated with increased susceptibility to psoriasis in Asian populations (Song et al., 2014).
  
  
Entity Psoriatic arthritis
Disease Psoriastic arthritis is a seronegative inflammatory arthritis that develops in a more than 10% of patients with psoriasis. Like other seronegative spondyloarthropathies, psoriastic arthritis is associated with HLA-B27 allele.
Prognosis Psoriastic arthritis tends not to be as serve as rheumatoid arthritis in joint destruction.
MICA-TM A9 allele is associated with a PsA susceptibility in European populations (Amroun H et. al, 2005).
Since MICA is located 46 kb centromeric to the HLA-B gene cluster, its location may explain its association.
  
  
Entity Ankylosing spondylitis (AS)
Disease Ankylosing spondylitis is a seronegative spondyloarthropathies associated with HLA-B27 allele. AS is characterized by chronic inflammation of joints typically in the axial skeleton, such as spine and sacroiliac joints, leading to destruction of cartilage and ultimately bony ankylosis causing severe joint immobility. AS is also characterized by extraarticular manifestations including uveitis, aortitis, and amyloidosis.
Prognosis MICA alleles are associated with AS in both HLA-B27-positive and B27-negative AS patients. The MICA*007:01 allele is associated with increased susceptibility to AS in Caucasian and Han Chinese populations. The MICA*019 allele increases the risk for AS in Chinese patients. In a small cohort study of of Algerian patients with AS, MICA-129 allele was associated with an early onset of AS (Tong, 2013).
  
  
Entity Systemic lupus erythematosus (SLE)
Prognosis Poor (Susceptibility)
Polymorphisms of MICA TM region have been reported in association with susceptibility to SLE (Yoshida et al., 2011).
  
  
Entity Hepatitis B and C
Note There is an association of MICA rs2596542G/A promoter variant and substitutions MICA-129Met/Val, MICA-251Gln/Arg, MICA-175Gly/Ser with HBV-induced hepatocellular carcinoma and HBV persistence (Kumar V, 2012).
Disease Hepatitis B and C are viral infections that can chronically predispose to hepatocellular carcinoma. MICA genetic variations and soluble MICA levels may serve as predictive biomarker for HBV- and HCV-induced HCC. Expression of MICA may be induced by the stress of viral infection and play a role in tumor immune surveillance (Kumar V, 2012).
Prognosis Poor. HBV-induced HCC patients with the high serum level of sMICA have shown to have worse prognosis than those with low serum level of sMICA (?5 pg/ml).5
A single nucleotide polymorphism of MICA rs2596542 located in MICA promotor region is associated with hepatitis C-induced HCC in a Japanese patients and serum levels of soluble MICA (sMICA).
  

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PMID 21702010
 
RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells
Zdrenghea MT, Telcian AG, Laza-Stanca V, Bellettato CM, Edwards MR, Nikonova A, Khaitov MR, Azimi N, Groh V, Mallia P, Johnston SL, Stanciu LA
Eur Respir J 2012 Mar;39(3):712-20
PMID 21852331
 
Effect of human cytomegalovirus on expression of MHC class I-related chains A
Zou Y, Bresnahan W, Taylor RT, Stastny P
J Immunol 2005 Mar 1;174(5):3098-104
PMID 15728525
 
MICA allele-level typing by sequence-based typing with computerized assignment of polymorphic sites and short tandem repeats within the transmembrane region
Zou Y, Han M, Wang Z, Stastny P
Hum Immunol 2006 Mar;67(3):145-51
PMID 16698436
 
Antibodies against MICA antigens and kidney-transplant rejection
Zou Y, Stastny P, Süsal C, Döhler B, Opelz G
N Engl J Med 2007 Sep 27;357(13):1293-300
PMID 17898098
 
Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes
Zwirner NW, Dole K, Stastny P
Hum Immunol 1999 Apr;60(4):323-30
PMID 10363723
 

Citation

This paper should be referenced as such :
Zain Ahmed, Medhat Askar
MICA (MHC class I polypeptide-related sequence A)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(5):340-348.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MICAID41364ch6p21.html


External links

Nomenclature
HGNC (Hugo)MICA   7090
Cards
AtlasMICAID41364ch6p21
Entrez_Gene (NCBI)MICA  100507436  MHC class I polypeptide-related sequence A
AliasesMIC-A; PERB11.1
GeneCards (Weizmann)MICA
Ensembl hg19 (Hinxton)ENSG00000204520 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000204520 [Gene_View]  chr6:31403567-31415315 [Contig_View]  MICA [Vega]
ICGC DataPortalENSG00000204520
TCGA cBioPortalMICA
AceView (NCBI)MICA
Genatlas (Paris)MICA
WikiGenes100507436
SOURCE (Princeton)MICA
Genetics Home Reference (NIH)MICA
Genomic and cartography
GoldenPath hg38 (UCSC)MICA  -     chr6:31403567-31415315 +  6p21.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MICA  -     6p21.33   [Description]    (hg19-Feb_2009)
EnsemblMICA - 6p21.33 [CytoView hg19]  MICA - 6p21.33 [CytoView hg38]
Mapping of homologs : NCBIMICA [Mapview hg19]  MICA [Mapview hg38]
OMIM600169   
Gene and transcription
Genbank (Entrez)AB506764 AK094237 AK225393 AK299135 AK310028
RefSeq transcript (Entrez)NM_000247 NM_001177519 NM_001289152 NM_001289153 NM_001289154
RefSeq genomic (Entrez)NC_000006 NC_018917 NG_034139 NT_113891 NT_167246 NT_167248 NT_167249
Consensus coding sequences : CCDS (NCBI)MICA
Cluster EST : UnigeneHs.130838 [ NCBI ]
CGAP (NCI)Hs.130838
Alternative Splicing GalleryENSG00000204520
Gene ExpressionMICA [ NCBI-GEO ]   MICA [ EBI - ARRAY_EXPRESS ]   MICA [ SEEK ]   MICA [ MEM ]
Gene Expression Viewer (FireBrowse)MICA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)100507436
GTEX Portal (Tissue expression)MICA
Human Protein AtlasENSG00000204520-MICA [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ29983   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ29983  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ29983
Splice isoforms : SwissVarQ29983
PhosPhoSitePlusQ29983
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
Domains : Interpro (EBI)Ig-like_dom    Ig-like_fold    Ig_C1-set    MHC_I-like_Ag-recog    MHC_I/II-like_Ag-recog   
Domain families : Pfam (Sanger)C1-set (PF07654)    MHC_I (PF00129)   
Domain families : Pfam (NCBI)pfam07654    pfam00129   
Domain families : Smart (EMBL)IGc1 (SM00407)  
Conserved Domain (NCBI)MICA
DMDM Disease mutations100507436
Blocks (Seattle)MICA
PDB (SRS)1B3J    1HYR   
PDB (PDBSum)1B3J    1HYR   
PDB (IMB)1B3J    1HYR   
PDB (RSDB)1B3J    1HYR   
Structural Biology KnowledgeBase1B3J    1HYR   
SCOP (Structural Classification of Proteins)1B3J    1HYR   
CATH (Classification of proteins structures)1B3J    1HYR   
SuperfamilyQ29983
Human Protein Atlas [tissue]ENSG00000204520-MICA [tissue]
Peptide AtlasQ29983
Protein Interaction databases
DIP (DOE-UCLA)Q29983
IntAct (EBI)Q29983
FunCoupENSG00000204520
BioGRIDMICA
STRING (EMBL)MICA
ZODIACMICA
Ontologies - Pathways
QuickGOQ29983
Ontology : AmiGOT cell mediated cytotoxicity  immune response to tumor cell  antigen binding  protein binding  extracellular space  cytoplasm  plasma membrane  integral component of plasma membrane  cellular response to DNA damage stimulus  response to heat  cell surface  cytolysis  antigen processing and presentation  beta-2-microglobulin binding  negative regulation of natural killer cell activation  natural killer cell mediated cytotoxicity  defense response to bacterium  negative regulation of natural killer cell mediated cytotoxicity  gamma-delta T cell activation  natural killer cell lectin-like receptor binding  natural killer cell lectin-like receptor binding  regulation of immune response  defense response to virus  
Ontology : EGO-EBIT cell mediated cytotoxicity  immune response to tumor cell  antigen binding  protein binding  extracellular space  cytoplasm  plasma membrane  integral component of plasma membrane  cellular response to DNA damage stimulus  response to heat  cell surface  cytolysis  antigen processing and presentation  beta-2-microglobulin binding  negative regulation of natural killer cell activation  natural killer cell mediated cytotoxicity  defense response to bacterium  negative regulation of natural killer cell mediated cytotoxicity  gamma-delta T cell activation  natural killer cell lectin-like receptor binding  natural killer cell lectin-like receptor binding  regulation of immune response  defense response to virus  
Pathways : KEGGNatural killer cell mediated cytotoxicity   
NDEx NetworkMICA
Atlas of Cancer Signalling NetworkMICA
Wikipedia pathwaysMICA
Orthology - Evolution
OrthoDB100507436
GeneTree (enSembl)ENSG00000204520
Phylogenetic Trees/Animal Genes : TreeFamMICA
HOVERGENQ29983
HOGENOMQ29983
Homologs : HomoloGeneMICA
Homology/Alignments : Family Browser (UCSC)MICA
Gene fusions - Rearrangements
Tumor Fusion PortalMICA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMICA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MICA
dbVarMICA
ClinVarMICA
1000_GenomesMICA 
Exome Variant ServerMICA
ExAC (Exome Aggregation Consortium)ENSG00000204520
GNOMAD BrowserENSG00000204520
Genetic variants : HAPMAP100507436
Genomic Variants (DGV)MICA [DGVbeta]
DECIPHERMICA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMICA 
Mutations
ICGC Data PortalMICA 
TCGA Data PortalMICA 
Broad Tumor PortalMICA
OASIS PortalMICA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMICA  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMICA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MICA
DgiDB (Drug Gene Interaction Database)MICA
DoCM (Curated mutations)MICA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MICA (select a term)
intoGenMICA
NCG5 (London)MICA
Cancer3DMICA(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600169   
Orphanet
DisGeNETMICA
MedgenMICA
Genetic Testing Registry MICA
NextProtQ29983 [Medical]
TSGene100507436
GENETestsMICA
Target ValidationMICA
Huge Navigator MICA [HugePedia]
snp3D : Map Gene to Disease100507436
BioCentury BCIQMICA
ClinGenMICA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD100507436
Chemical/Pharm GKB GenePA30811
Clinical trialMICA
Miscellaneous
canSAR (ICR)MICA (select the gene name)
Other databasedbMHC Alignment Viewer
Other databasePharmGKB
Probes
Litterature
PubMed451 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMICA
EVEXMICA
GoPubMedMICA
iHOPMICA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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