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onsdag 3 oktober 2018

Geeni CTLA-4 (2q33.2) . Geenimutaatioista monta kansantautia.

Tämä geeni ei olekaan niin yksiseliteinen kuin edellinen PD-1, sillä se voi pleissautua  varianteiksi jotka koodaavat  eri isoformeja. lisäksi sillä voi olla kalvoonsitoutunut (TM domaanin omaava ) muoto , joka toimii dimeerinä sekä   sellainen isoformi, josta puuttuu TM jakso ja se on liukoinen, joka toimii monomeerina. sCTLA-4, ( CTLA-4delTM).
Tieto tästä geenistä. Huomaa, miten moniin yleisiin kansantauteihin  se assosioituu, jos siinä on mutaatioita.
 

Geeni CTLA4 , (2q33.2)

Sytotoksiseen T–imusoluun liittyvä proteiini 4 , CTLA4.
Suositeltu nimi
cytotoxic T-lymphocyte protein 4
Nimet
CD152 isoform
celiac disease 3
cytotoxic T lymphocyte associated antigen 4 short spliced form
cytotoxic T-lymphocyte-associated serine esterase-4
insulin-dependent diabetes mellitus 12
ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4
Synonyyminimien merkinnät : tälle geenille ovat:
CD; GSE; GRD4; ALPS5; CD152; CTLA-4; IDDM12; CELIAC3

Suomennosta yhteenvedosta. Tämä geeni on immunoglobuliinien superperheen jäsen ja se koodaa erästä proteiinia, joka välittää T-soluihin estäviä signaaleita. Proteiinissa on V-domeeni, transmembraaninen domeeni ja sytoplasminen pääty. On luonnehdittu myös vaihtoehtoisesti pleissautuneita variantteja, jotka koodaavat eri isoformeja. Kalvoonsitoutunut isoformi toimii homodimeerinä, jonka osat ovat liittyneet toisiinsa rikkisillalla. Liukoinen isoformi toimii monomeerinä. Tämän geenin mutaatiot ovat assosioituneet insuliinsita riippuvaan diabetekseen, Graven tautiin, Hashimoton tyreoidiittiin, keliakiaan, systeemiseen lupus erytematosukseen, kilpirauhaseen assosioituvaan orbitopatiaan ja muihin autoimmuunitauteihin. Geeniä ilmenee imusolmukkeissa, umpilisäkkeessä ja 8 muussa kudoksessa.

CTLA4 cytotoxic T-lymphocyte associated protein 4 [ Homo sapiens (human) ]
Gene ID: 1493, updated on 23-Sep-2018
Official Symbol
CTLA4provided by HGNC
Official Full Name
cytotoxic T-lymphocyte associated protein 4provided by HGNC
Also known as
CD; GSE; GRD4; ALPS5; CD152; CTLA-4; IDDM12; CELIAC3
Summary
This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]
Expression
Biased expression in lymph node (RPKM 10.3), appendix (RPKM 9.7) and 8 other tissues See more
Related articles in PubMed
  1. CTLA-4 polymorphisms: influence on transplant-related mortality and survival in children undergoing allogeneic hematopoietic stem cell transplantation. Hammrich J, et al. J Cancer Res Clin Oncol, 2018 Mar. PMID 29335768
See all (1058) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene
GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
  1. the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor

Sequence:
sCTLA-4delTM (soluble isoform)
( variantti joka on liukoinen ja jossa ei ole transmembraania osaa)
Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform CTLA-4delTM (also known as sCTLA4) is soluble and lacks the transmembrane domain, compared to isoform a. The exon skip represented in this variant is based on human U90273.1, and is consistent with mouse U90270.1 and the data published in PMID:10831323 and PMID:10556814.

CTLA-4TM precursor
(Citate)
cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor [Homo sapiens]
NCBI Reference Sequence: NP_005205.2
Identical Proteins FASTA Graphics
LOCUS       NP_005205                223 aa            linear   PRI 30-SEP-2018
DEFINITION  cytotoxic T-lymphocyte protein 4 isoform CTLA4-TM precursor [Homo
            sapiens].
ACCESSION   NP_005205 XP_001129541 XP_001129550 XP_001129561
VERSION     NP_005205.2
DBSOURCE    REFSEQ: accession NM_005214.5
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 223)
  AUTHORS   Zurawek M, Dzikiewicz-Krawczyk A, Izykowska K, Ziolkowska-Suchanek
            I, Skowronska B, Czainska M, Podralska M, Fichna P, Przybylski G,
            Fichna M and Nowak J.
  TITLE     miR-487a-3p upregulated in type 1 diabetes targets CTLA4 and FOXO3
  JOURNAL   Diabetes Res. Clin. Pract. 142, 146-153 (2018)
   PUBMED   29859273
  REMARK    GeneRIF: Study suggests that miR-487a-3p might repress CTLA4 and
            FOXO3 by binding to their 3'UTRs and contribute to the development
            of T1D.
REFERENCE   2  (residues 1 to 223)
  AUTHORS   Su J, Li Y, Su G, Wang J, Qiu T, Ma R and Zhao L.
  TITLE     Genetic association of CTLA4 gene with polycystic ovary syndrome in
            the Chinese Han population
  JOURNAL   Medicine (Baltimore) 97 (29), e11422 (2018)
   PUBMED   30024513
  REMARK    GeneRIF: CTLA4 gene is suggested to correlated with polycyctic
            ovary syndrome, and influence polycycstic ovary syndrome through
            regulating obesity and the homeostatic model assessment for insulin
            resistance in a novel way.
REFERENCE   3  (residues 1 to 223)
  AUTHORS   Zheng Y, Wang H, Luo L, Liao L, You L, Wang J and Li Q.
  TITLE     A meta-analysis of the association between CTLA-4 genetic
            polymorphism and susceptibility of asthma
  JOURNAL   Medicine (Baltimore) 97 (28), e11380 (2018)
   PUBMED   29995780
  REMARK    GeneRIF: Our meta-analysis suggested that the +49 A/G polymorphism
            in CTLA4 might be a risk factor for asthma susceptibility,
            especially in Asian individuals, children, and patients with atopy
            Review article
REFERENCE   4  (residues 1 to 223)
  AUTHORS   Fang M, Huang W, Mo D, Zhao W and Huang R.
  TITLE     Association of Five Snps in Cytotoxic T-Lymphocyte Antigen 4 and
            Cancer Susceptibility: Evidence from 67 Studies
  JOURNAL   Cell. Physiol. Biochem. 47 (1), 414-427 (2018)
   PUBMED   29794444
  REMARK    GeneRIF: rs231775, rs4553808 and rs5742909 but not rs3087243 and
            rs733618 were significantly related to cancer risk. In analyses
            stratified by ethnicity, both rs231775 and rs4553808 were
            significant susceptibility polymorphisms in an Asian population but
            not in a Caucasian population.
REFERENCE   5  (residues 1 to 223)
  AUTHORS   Oaks MK, Hallett KM, Penwell RT, Stauber EC, Warren SJ and Tector
            AJ.
  TITLE     A native soluble form of CTLA-4
  JOURNAL   Cell. Immunol. 201 (2), 144-153 (2000)
   PUBMED   10831323
REFERENCE   6  (residues 1 to 223)
  AUTHORS   Magistrelli G, Jeannin P, Herbault N, Benoit De Coignac A, Gauchat
            JF, Bonnefoy JY and Delneste Y.
  TITLE     A soluble form of CTLA-4 generated by alternative splicing is
            expressed by nonstimulated human T cells
  JOURNAL   Eur. J. Immunol. 29 (11), 3596-3602 (1999)
   PUBMED   10556814
REFERENCE   7  (residues 1 to 223)
  AUTHORS   Chen C, Gault A, Shen L and Nabavi N.
  TITLE     Molecular cloning and expression of early T cell costimulatory
            molecule-1 and its characterization as B7-2 molecule
  JOURNAL   J. Immunol. 152 (10), 4929-4936 (1994)
   PUBMED   7513726
REFERENCE   8  (residues 1 to 223)
  AUTHORS   Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK and Ledbetter
            JA.
  TITLE     CTLA-4 is a second receptor for the B cell activation antigen B7
  JOURNAL   J. Exp. Med. 174 (3), 561-569 (1991)
   PUBMED   1714933
REFERENCE   9  (residues 1 to 223)
  AUTHORS   Harper K, Balzano C, Rouvier E, Mattei MG, Luciani MF and Golstein
            P.
  TITLE     CTLA-4 and CD28 activated lymphocyte molecules are closely related
            in both mouse and human as to sequence, message expression, gene
            structure, and chromosomal location
  JOURNAL   J. Immunol. 147 (3), 1037-1044 (1991)
   PUBMED   1713603
REFERENCE   10 (residues 1 to 223)
  AUTHORS   Dariavach P, Mattei MG, Golstein P and Lefranc MP.
  TITLE     Human Ig superfamily CTLA-4 gene: chromosomal localization and
            identity of protein sequence between murine and human CTLA-4
            cytoplasmic domains
  JOURNAL   Eur. J. Immunol. 18 (12), 1901-1905 (1988)
   PUBMED   3220103
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC010138.6, AF414120.1 and
            AI733018.1.
            This sequence is a reference standard in the RefSeqGene project.
            On or before Sep 20, 2006 this sequence version replaced
            XP_001129561.1, XP_001129550.1, XP_001129541.1, NP_005205.1.
            
            Summary: This gene is a member of the immunoglobulin superfamily
            and encodes a protein which transmits an inhibitory signal to T
            cells. The protein contains a V domain, a transmembrane domain, and
            a cytoplasmic tail. Alternate transcriptional splice variants,
            encoding different isoforms, have been characterized. The
            membrane-bound isoform functions as a homodimer interconnected by a
            disulfide bond, while the soluble isoform functions as a monomer.
            Mutations in this gene have been associated with insulin-dependent
            diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac
            disease, systemic lupus erythematosus, thyroid-associated
            orbitopathy, and other autoimmune diseases. [provided by RefSeq,
            Jul 2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer membrane-bound isoform CTLA4-TM.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF414120.1, BC069566.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..223
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q33.2"
     Protein         1..223
                     /product="cytotoxic T-lymphocyte protein 4 isoform
                     CTLA4-TM precursor"
                     /note="celiac disease 3; cytotoxic T-lymphocyte-associated
                     serine esterase-4; ligand and transmembrane spliced
                     cytotoxic T lymphocyte associated antigen 4;
                     insulin-dependent diabetes mellitus 12; CD152 isoform;
                     cytotoxic T lymphocyte associated antigen 4 short spliced
                     form"
                     /calculated_mol_wt=20573
     sig_peptide     1..35
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="{ECO:0000255}; propagated from UniProtKB/Swiss-Prot
                     (P16410.3)"
                     /calculated_mol_wt=4101
     mat_peptide     36..223
                     /product="Cytotoxic T-lymphocyte protein 4"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P16410.3)"
                     /calculated_mol_wt=20573
     Region          39..152
                     /region_name="IgV_CTLA-4"
                     /note="Immunoglobulin (Ig) domain of cytotoxic T
                     lymphocyte-associated antigen 4 (CTLA-4); cd05721"
                     /db_xref="CDD:143198"
     Region          46..50
                     /region_name="Homodimerization.
                     {ECO:0000269|PubMed:21156796}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P16410.3)"
     Site            order(51,53,59,106,117)
                     /site_type="other"
                     /note="homodimer interface [polypeptide binding]"
                     /db_xref="CDD:143198"
     Region          134..139
                     /region_name="Important for interaction with CD80 and
                     CD86. {ECO:0000269|PubMed:28484017}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P16410.3)"
     Site            order(134..135,138..139)
                     /site_type="other"
                     /note="antigen binding site [polypeptide binding]"
                     /db_xref="CDD:143198"
     Region          150..155
                     /region_name="Homodimerization.
                     {ECO:0000269|PubMed:21156796,
                     ECO:0000269|PubMed:28484017}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P16410.3)"
     Site            162..182
                     /site_type="transmembrane region"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P16410.3)"
     Site            201
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphotyrosine, by TXK and JAK2.
                     {ECO:0000269|PubMed:10842319, ECO:0000269|PubMed:9175836,
                     ECO:0000269|PubMed:9813138}; propagated from
                     UniProtKB/Swiss-Prot (P16410.3)"
     CDS             1..223
                     /gene="CTLA4"
                     /gene_synonym="ALPS5; CD; CD152; CELIAC3; CTLA-4; GRD4;
                     GSE; IDDM12"
                     /coded_by="NM_005214.5:173..844"
                     /note="isoform CTLA4-TM precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS2362.1"
                     /db_xref="GeneID:1493"
                     /db_xref="HGNC:HGNC:2505"
                     /db_xref="MIM:123890"
ORIGIN      
        1 maclgfqrhk aqlnlatrtw pctllffllf ipvfckamhv aqpavvlass rgiasfvcey
       61 aspgkatevr vtvlrqadsq vtevcaatym mgneltfldd sictgtssgn qvnltiqglr
      121 amdtglyick velmypppyy lgigngtqiy vidpepcpds dfllwilaav ssglffysfl
      181 ltavslskml kkrsplttgv yvkmpptepe cekqfqpyfi pin
//




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