ID   RFXK_HUMAN              Reviewed;         260 AA.
AC   O14593; O95839; Q6FGA8;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   25-JAN-2012, entry version 112.
DE   RecName: Full=DNA-binding protein RFXANK;
DE   AltName: Full=Ankyrin repeat family A protein 1;
DE   AltName: Full=Regulatory factor X subunit B;
DE            Short=RFX-B;
DE   AltName: Full=Regulatory factor X-associated ankyrin-containing protein;
GN   Name=RFXANK; Synonyms=ANKRA1, RFXB;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MASS SPECTROMETRY, AND
RP   INVOLVEMENT IN BLS2.
RC   TISSUE=B-cell;
RX   MEDLINE=99021383; PubMed=9806546; DOI=10.1038/3081;
RA   Masternak K., Barras E., Zufferey M., Conrad B., Corthals G.,
RA   Aebersold R., Sanchez J.-C., Hochstrasser D.F., Mach B., Reith W.;
RT   "A gene encoding a novel RFX-associated transactivator is mutated in
RT   the majority of MHC class II deficiency patients.";
RL   Nat. Genet. 20:273-277(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF
RP   79-95; 180-198; 100-210 AND 238-248, AND INVOLVEMENT IN BLS2.
RC   TISSUE=Lymphoblast;
RX   MEDLINE=99170284; PubMed=10072068; DOI=10.1016/S1074-7613(00)80016-3;
RA   Nagarajan U.M., Louis-Plence P., DeSandro A., Nilsen R., Bushey A.,
RA   Boss J.M.;
RT   "RFX-B is the gene responsible for the most common cause of the bare
RT   lymphocyte syndrome, an MHC class II immunodeficiency.";
RL   Immunity 10:153-162(1999).
RN   [3]
RP   ERRATUM.
RA   Nagarajan U.M., Louis-Plence P., DeSandro A., Nilsen R., Bushey A.,
RA   Boss J.M.;
RL   Immunity 10:399-399(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Umbilical cord blood;
RX   MEDLINE=20499367; PubMed=11042152; DOI=10.1101/gr.140200;
RA   Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA   Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA   Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT   "Cloning and functional analysis of cDNAs with open reading frames for
RT   300 previously undefined genes expressed in CD34+ hematopoietic
RT   stem/progenitor cells.";
RL   Genome Res. 10:1546-1560(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   SUBUNIT.
RX   PubMed=20732328; DOI=10.1016/j.jmb.2010.08.025;
RA   Laird K.M., Briggs L.L., Boss J.M., Summers M.F., Garvie C.W.;
RT   "Solution structure of the heterotrimeric complex between the
RT   interaction domains of RFX5 and RFXAP from the RFX gene regulatory
RT   complex.";
RL   J. Mol. Biol. 403:40-51(2010).
RN   [10]
RP   VARIANT BLS2 PRO-195.
RX   MEDLINE=20192025; PubMed=10725724;
RA   Nagarajan U.M., Peijnenburg A., Gobin S.J., Boss J.M.,
RA   van den Elsen P.J.;
RT   "Novel mutations within the RFX-B gene and partial rescue of MHC and
RT   related genes through exogenous class II transactivator in RFX-B-
RT   deficient cells.";
RL   J. Immunol. 164:3666-3674(2000).
CC   -!- FUNCTION: Activates transcription from class II MHC promoters.
CC       Activation requires the activity of the MHC class II
CC       transactivator (MHC2TA). May regulate other genes in the cell. RFX
CC       binds the X1 box of MHC-II promoters. Isoform RFX-B-delta5 is not
CC       involved in the positive regulation of MHC class II genes.
CC   -!- SUBUNIT: The RFX heterotetrameric complex consists of 2 molecules
CC       of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit
CC       representing a separate complementation group. RFX forms
CC       cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX
CC       associates with MHC2TA to form an active transcriptional complex.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Long;
CC         IsoId=O14593-1; Sequence=Displayed;
CC       Name=2; Synonyms=RFX-B-delta5;
CC         IsoId=O14593-2; Sequence=VSP_000283, VSP_000284;
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- DOMAIN: The third ankyrin repeat is required for association with
CC       the two other RFX subunits; RFX5 and RFXAP.
CC   -!- DISEASE: Defects in RFXANK are a cause of bare lymphocyte syndrome
CC       type 2 (BLS2) [MIM:209920]; also known as hereditary MHC class II
CC       deficiency or HLA class II-deficient combined immunodeficiency.
CC       BLS2 is a severe combined immunodeficiency disease with early
CC       onset. It is characterized by a profound defect in constitutive
CC       and interferon-gamma induced MHC II expression, absence of
CC       cellular and humoral T-cell response to antigen challenge,
CC       hypogammaglobulinemia and impaired antibody production. The
CC       consequence include extreme susceptibility to viral, bacterial and
CC       fungal infections.
CC   -!- SIMILARITY: Contains 5 ANK repeats.
CC   -!- WEB RESOURCE: Name=RFXANKbase; Note=RFXANK mutation db;
CC       URL="http://bioinf.uta.fi/RFXANKbase/";
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; AF094760; AAC69883.1; -; mRNA.
DR   EMBL; AF105427; AAD17972.1; -; mRNA.
DR   EMBL; AF105428; AAD17973.1; -; mRNA.
DR   EMBL; AF077196; AAD26991.1; -; mRNA.
DR   EMBL; CR542199; CAG46996.1; -; mRNA.
DR   EMBL; AC003110; AAB86654.1; -; Genomic_DNA.
DR   EMBL; CH471106; EAW84795.1; -; Genomic_DNA.
DR   EMBL; BC114563; AAI14564.1; -; mRNA.
DR   IPI; IPI00022520; -.
DR   IPI; IPI00939590; -.
DR   RefSeq; NP_003712.1; NM_003721.2.
DR   RefSeq; NP_604389.1; NM_134440.1.
DR   UniGene; Hs.153629; -.
DR   UniGene; Hs.296776; -.
DR   ProteinModelPortal; O14593; -.
DR   SMR; O14593; 24-254.
DR   STRING; O14593; -.
DR   PRIDE; O14593; -.
DR   Ensembl; ENST00000303088; ENSP00000305071; ENSG00000064490.
DR   Ensembl; ENST00000407360; ENSP00000384572; ENSG00000064490.
DR   GeneID; 8625; -.
DR   KEGG; hsa:8625; -.
DR   UCSC; uc002nls.1; human.
DR   UCSC; uc002nlt.1; human.
DR   CTD; 8625; -.
DR   GeneCards; GC19P019303; -.
DR   H-InvDB; HIX0014935; -.
DR   HGNC; HGNC:9987; RFXANK.
DR   MIM; 209920; phenotype.
DR   MIM; 603200; gene.
DR   neXtProt; NX_O14593; -.
DR   Orphanet; 572; Immunodeficiency by defective expression of HLA class 2.
DR   PharmGKB; PA34357; -.
DR   eggNOG; prNOG12074; -.
DR   HOGENOM; HBG445385; -.
DR   HOVERGEN; HBG017718; -.
DR   InParanoid; O14593; -.
DR   OMA; LFPCTPE; -.
DR   PhylomeDB; O14593; -.
DR   Pathway_Interaction_DB; hdac_classii_pathway; Signaling events mediated by HDAC Class II.
DR   NextBio; 32333; -.
DR   ArrayExpress; O14593; -.
DR   Bgee; O14593; -.
DR   CleanEx; HS_RFXANK; -.
DR   Genevestigator; O14593; -.
DR   GermOnline; ENSG00000064490; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc.
DR   GO; GO:0003712; F:transcription cofactor activity; TAS:ProtInc.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR017362; DNA-bd_RFXANK.
DR   Gene3D; G3DSA:1.25.40.20; ANK; 1.
DR   KO; K08062; -.
DR   Pfam; PF00023; Ank; 2.
DR   PIRSF; PIRSF038034; DNA-binding_RFXANK; 1.
DR   SMART; SM00248; ANK; 4.
DR   SUPFAM; SSF48403; ANK; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 3.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; ANK repeat; Complete proteome;
KW   Direct protein sequencing; Disease mutation; DNA-binding; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome; Repeat; SCID;
KW   Transcription; Transcription regulation.
FT   CHAIN         1    260       DNA-binding protein RFXANK.
FT                                /FTId=PRO_0000067049.
FT   REPEAT       89    118       ANK 1.
FT   REPEAT      123    152       ANK 2.
FT   REPEAT      156    185       ANK 3.
FT   REPEAT      189    218       ANK 4.
FT   REPEAT      222    251       ANK 5.
FT   VAR_SEQ      63     63       Missing (in isoform 2).
FT                                /FTId=VSP_000283.
FT   VAR_SEQ      91    113       SLSIHQLAAQGELDQLKEHLRKG -> C (in isoform
FT                                2).
FT                                /FTId=VSP_000284.
FT   VARIANT      48     48       E -> D (in dbSNP:rs34282046).
FT                                /FTId=VAR_048311.
FT   VARIANT     195    195       L -> P (in BLS2).
FT                                /FTId=VAR_009941.
FT   VARIANT     251    251       Q -> E (in dbSNP:rs1802498).
FT                                /FTId=VAR_014472.
SQ   SEQUENCE   260 AA;  28102 MW;  6280B490F54816D2 CRC64;
     MELTQPAEDL IQTQQTPASE LGDPEDPGEE AADGSDTVVL SLFPCTPEPV NPEPDASVSS
     PQAGSSLKHS TTLTNRQRGN EVSALPATLD SLSIHQLAAQ GELDQLKEHL RKGDNLVNKP
     DERGFTPLIW ASAFGEIETV RFLLEWGADP HILAKERESA LSLASTGGYT DIVGLLLERD
     VDINIYDWNG GTPLLYAVRG NHVKCVEALL ARGADLTTEA DSGYTPMDLA VALGYRKVQQ
     VIENHILKLF QSNLVPADPE
//