Full text data of BANF1
BANF1
(BAF, BCRG1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Barrier-to-autointegration factor (Breakpoint cluster region protein 1; Barrier-to-autointegration factor, N-terminally processed)
Barrier-to-autointegration factor (Breakpoint cluster region protein 1; Barrier-to-autointegration factor, N-terminally processed)
UniProt
O75531
ID BAF_HUMAN Reviewed; 89 AA.
AC O75531; O60558; Q6FGG7;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Barrier-to-autointegration factor;
DE AltName: Full=Breakpoint cluster region protein 1;
DE Contains:
DE RecName: Full=Barrier-to-autointegration factor, N-terminally processed;
GN Name=BANF1; Synonyms=BAF, BCRG1;
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].
RX PubMed=9465049; DOI=10.1073/pnas.95.4.1528;
RA Lee M.S., Craigie R.;
RT "A previously unidentified host protein protects retroviral DNA from
RT autointegration.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1528-1533(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Uterus;
RX PubMed=9740667; DOI=10.1006/geno.1998.5406;
RA Lynch R.A., Piper M., Bankier A., Bhugra B., Surti U., Liu J.,
RA Buckler A., Dear P.H., Menon A.G.;
RT "Genomic and functional map of the chromosome 14 t(12;14) breakpoint
RT cluster region in uterine leiomyoma.";
RL Genomics 52:17-26(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang J., Liu T., Ye M., Zhang Q., Fu G., Zhou J., Wu J., Shen Y.,
RA Yu M., Chen S., Mao M., Chen Z.;
RT "Human BAF homolog gene.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP FUNCTION IN HIV-1 INTEGRATION, AND MUTAGENESIS OF LYS-6; PRO-14;
RP LYS-18; ILE-26; LYS-41; LEU-50; LYS-53; LYS-54; TRP-62 AND CYS-80.
RX PubMed=11005805; DOI=10.1074/jbc.M002626200;
RA Harris D., Engelman A.;
RT "Both the structure and DNA binding function of the barrier-to-
RT autointegration factor contribute to reconstitution of HIV type 1
RT integration in vitro.";
RL J. Biol. Chem. 275:39671-39677(2000).
RN [7]
RP MULTIMERIZATION.
RX PubMed=10908652; DOI=10.1073/pnas.150240197;
RA Zheng R., Ghirlando R., Lee M.S., Mizuuchi K., Krause M., Craigie R.;
RT "Barrier-to-autointegration factor (BAF) bridges DNA in a discrete,
RT higher-order nucleoprotein complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8997-9002(2000).
RN [8]
RP INTERACTION WITH EMD.
RX PubMed=11792822;
RA Haraguchi T., Koujin T., Segura-Totten M., Lee K.K., Matsuoka Y.,
RA Yoneda Y., Wilson K.L., Hiraoka Y.;
RT "BAF is required for emerin assembly into the reforming nuclear
RT envelope.";
RL J. Cell Sci. 114:4575-4585(2001).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF LYS-6; ASP-9; GLY-25; GLY-27; LEU-46;
RP GLY-47; VAL-51; LYS-53; LYS-54 AND ARG-75.
RX PubMed=12163470; DOI=10.1083/jcb.200202019;
RA Segura-Totten M., Kowalski A.K., Craigie R., Wilson K.L.;
RT "Barrier-to-autointegration factor: major roles in chromatin
RT decondensation and nuclear assembly.";
RL J. Cell Biol. 158:475-485(2002).
RN [10]
RP INTERACTION WITH HIV-1 PRE-INTEGRATION COMPLEX.
RX PubMed=12663813; DOI=10.1128/JVI.77.8.5030-5036.2003;
RA Lin C.W., Engelman A.;
RT "The barrier-to-autointegration factor is a component of functional
RT human immunodeficiency virus type 1 preintegration complexes.";
RL J. Virol. 77:5030-5036(2003).
RN [11]
RP INTERACTION WITH HIV-1 MATRIX PROTEIN.
RX PubMed=14645565; DOI=10.1128/JVI.77.24.13084-13092.2003;
RA Mansharamani M., Graham D.R., Monie D., Lee K.K., Hildreth J.E.,
RA Siliciano R.F., Wilson K.L.;
RT "Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is
RT a host component of human immunodeficiency virus type 1 virions.";
RL J. Virol. 77:13084-13092(2003).
RN [12]
RP INTERACTION WITH LEMD3/MAN1, AND MUTAGENESIS OF LYS-6; ARG-8; ASP-9;
RP PRO-14; GLY-25; ILE-26; ARG-37; LYS-41; LEU-46; GLY-47; LEU-50;
RP VAL-51; LYS-53; LYS-54; TRP-62 AND CYS-80.
RX PubMed=15681850; DOI=10.1074/jbc.M413020200;
RA Mansharamani M., Wilson K.L.;
RT "Direct binding of nuclear membrane protein MAN1 to emerin in vitro
RT and two modes of binding to barrier-to-autointegration factor.";
RL J. Biol. Chem. 280:13863-13870(2005).
RN [13]
RP INTERACTION WITH HISTONE H1/H3, AND MUTAGENESIS OF LYS-6; ARG-8;
RP ASP-9; PRO-14; LYS-18; GLY-25; ILE-26; VAL-29; LYS-32; LYS-33; ARG-37;
RP LYS-41; LEU-46; GLY-47; LEU-50; VAL-51; LYS-53; LYS-54; ARG-60;
RP TRP-62; LYS-64; ARG-75; CYS-80 AND ARG-82.
RX PubMed=16203725; DOI=10.1074/jbc.M509917200;
RA de Oca R.M., Lee K.K., Wilson K.L.;
RT "Binding of barrier to autointegration factor (BAF) to histone H3 and
RT selected linker histones including H1.1.";
RL J. Biol. Chem. 280:42252-42262(2005).
RN [14]
RP PHOSPHORYLATION AT SER-4, AND MUTAGENESIS OF SER-4.
RX PubMed=16371512; DOI=10.1091/mbc.E05-04-0356;
RA Bengtsson L., Wilson K.L.;
RT "Barrier-to-autointegration factor phosphorylation on Ser-4 regulates
RT emerin binding to lamin A in vitro and emerin localization in vivo.";
RL Mol. Biol. Cell 17:1154-1163(2006).
RN [15]
RP INTERACTION WITH BAFL.
RX PubMed=16337940; DOI=10.1016/j.yexcr.2005.11.013;
RA Tifft K.E., Segura-Totten M., Lee K.K., Wilson K.L.;
RT "Barrier-to-autointegration factor-like (BAF-L): a proposed regulator
RT of BAF.";
RL Exp. Cell Res. 312:478-487(2006).
RN [16]
RP PHOSPHORYLATION AT THR-2; THR-3 AND SER-4, AND SUBCELLULAR LOCATION.
RX PubMed=16495336; DOI=10.1091/mbc.E05-12-1179;
RA Nichols R.J., Wiebe M.S., Traktman P.;
RT "The vaccinia-related kinases phosphorylate the N' terminus of BAF,
RT regulating its interaction with DNA and its retention in the
RT nucleus.";
RL Mol. Biol. Cell 17:2451-2464(2006).
RN [17]
RP FUNCTION.
RX PubMed=16680152; DOI=10.1038/nature04682;
RA Jacque J.-M., Stevenson M.;
RT "The inner-nuclear-envelope protein emerin regulates HIV-1
RT infectivity.";
RL Nature 441:641-645(2006).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP PHOSPHORYLATION, DEPHOSPHORYLATION, AND INTERACTION WITH ANKLE2.
RX PubMed=22770216; DOI=10.1016/j.cell.2012.04.043;
RA Asencio C., Davidson I.F., Santarella-Mellwig R., Ly-Hartig T.B.,
RA Mall M., Wallenfang M.R., Mattaj I.W., Gorjanacz M.;
RT "Coordination of kinase and phosphatase activities by Lem4 enables
RT nuclear envelope reassembly during mitosis.";
RL Cell 150:122-135(2012).
RN [23]
RP REVIEW.
RX PubMed=15130582; DOI=10.1016/j.tcb.2004.03.004;
RA Segura-Totten M., Wilson K.L.;
RT "BAF: roles in chromatin, nuclear structure and retrovirus
RT integration.";
RL Trends Cell Biol. 14:261-266(2004).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=9783751; DOI=10.1038/2345;
RA Cai M., Huang Y., Zheng R., Wei S.Q., Ghirlando R., Lee M.S.,
RA Craigie R., Gronenborn A.M., Clore G.M.;
RT "Solution structure of the cellular factor BAF responsible for
RT protecting retroviral DNA from autointegration.";
RL Nat. Struct. Biol. 5:903-909(1998).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF HOMODIMER.
RX PubMed=10924106; DOI=10.1021/bi000572w;
RA Umland T.C., Wei S.-Q., Craigie R., Davies D.R.;
RT "Structural basis of DNA bridging by barrier-to-autointegration
RT factor.";
RL Biochemistry 39:9130-9138(2000).
RN [26]
RP VARIANT NGPS THR-12.
RX PubMed=21549337; DOI=10.1016/j.ajhg.2011.04.010;
RA Puente X.S., Quesada V., Osorio F.G., Cabanillas R., Cadinanos J.,
RA Fraile J.M., Ordonez G.R., Puente D.A., Gutierrez-Fernandez A.,
RA Fanjul-Fernandez M., Levy N., Freije J.M., Lopez-Otin C.;
RT "Exome sequencing and functional analysis identifies BANF1 mutation as
RT the cause of a hereditary progeroid syndrome.";
RL Am. J. Hum. Genet. 88:650-656(2011).
CC -!- FUNCTION: Plays fundamental roles in nuclear assembly, chromatin
CC organization, gene expression and gonad development. May potently
CC compress chromatin structure and be involved in membrane
CC recruitment and chromatin decondensation during nuclear assembly.
CC Contains 2 non-specific dsDNA-binding sites which may promote DNA
CC cross-bridging. Exploited by retroviruses for inhibiting self-
CC destructing autointegration of retroviral DNA, thereby promoting
CC integration of viral DNA into the host chromosome. EMD and BAF are
CC cooperative cofactors of HIV-1 infection. Association of EMD with
CC the viral DNA requires the presence of BAF and viral integrase.
CC The association of viral DNA with chromatin requires the presence
CC of BAF and EMD.
CC -!- SUBUNIT: Homodimer. Heterodimerizes with BAFL. Interacts with
CC ANKLE2/LEM4, leading to decreased phosphorylation by VRK1 and
CC promoting dephosphorylation by protein phosphatase 2A (PP2A).
CC Binds non-specifically to double-stranded DNA, and is found as a
CC hexamer or dodecamer upon DNA binding. Binds to LEM domain-
CC containing nuclear proteins such as LEMD3/MAN1, TMPO/LAP2 and EMD
CC (emerin). Interacts with CRX and LMNA (lamin-A). Binds linker
CC histone H1.1 and core histones H3 with in vitro affinities of 500-
CC 900 and 100-200 nM. Interacts with HIV-1 pre-integration complex
CC in cytoplasm by binding to viral matrix protein and Gag
CC polyprotein.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Chromosome.
CC Note=Significantly enriched at the nuclear inner membrane,
CC diffusely throughout the nucleus during interphase and
CC concentrated at the chromosomes during the M-phase. May be
CC included in HIV-1 virions via its interaction with viral GAG
CC polyprotein. The phosphorylated form (by VRK1) shows a cytoplasmic
CC localization.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in colon, brain,
CC heart, kidney, liver, lung, ovary, pancreas, placenta, prostate,
CC skeletal muscle, small intestine, spleen and testis. Not detected
CC in thymus and peripheral blood leukocytes.
CC -!- DOMAIN: Has a helix-hairpin-helix (HhH) structural motif conserved
CC among proteins that bind non-specifically to DNA.
CC -!- DOMAIN: LEM domain proteins bind centrally on the BAF dimer,
CC whereas DNA binds to the left and right sides.
CC -!- PTM: Ser-4 is the major site of phosphorylation as compared to
CC Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4
CC disrupts its ability to bind DNA and reduces its ability to bind
CC LEM domain-containing proteins. Non phosphorylated BAF seems to
CC enhance binding between EMD and LMNA. Dephosphorylated by protein
CC phosphatase 2A (PP2A) following interaction with ANKLE2/LEM4
CC during mitotic exit, leading to mitotic nuclear envelope
CC reassembly.
CC -!- DISEASE: Nestor-Guillermo progeria syndrome (NGPS) [MIM:614008]:
CC An atypical progeroid syndrome characterized by normal development
CC in the first years of life, later followed by the emergence of
CC generalized lipoatrophy, severe osteoporosis, and marked
CC osteolysis. The atrophic facial subcutaneous fat pad and the
CC marked osteolysis of the maxilla and mandible result in a typical
CC pseudosenile facial appearance with micrognathia, prominent
CC subcutaneous venous patterning, a convex nasal ridge, and
CC proptosis. Cognitive development is completely normal. Patients do
CC not have cardiovascular dysfunction, atherosclerosis, or metabolic
CC anomalies. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the BAF family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC08964.1; Type=Frameshift; Positions=87;
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DR EMBL; AF070447; AAC23575.1; -; mRNA.
DR EMBL; AF044773; AAC08964.1; ALT_FRAME; mRNA.
DR EMBL; AF068235; AAD15901.1; -; mRNA.
DR EMBL; CR542140; CAG46937.1; -; mRNA.
DR EMBL; BC005942; AAH05942.1; -; mRNA.
DR EMBL; BC107702; AAI07703.1; -; mRNA.
DR RefSeq; NP_001137457.1; NM_001143985.1.
DR RefSeq; NP_003851.1; NM_003860.3.
DR UniGene; Hs.433759; -.
DR PDB; 1CI4; X-ray; 1.90 A; A/B=1-89.
DR PDB; 1QCK; NMR; -; A/B=1-89.
DR PDB; 2BZF; X-ray; 2.87 A; A=1-89.
DR PDB; 2EZX; NMR; -; A/B=1-89.
DR PDB; 2EZY; NMR; -; A/B=1-89.
DR PDB; 2EZZ; NMR; -; A/B=1-89.
DR PDB; 2ODG; NMR; -; A/B=1-89.
DR PDBsum; 1CI4; -.
DR PDBsum; 1QCK; -.
DR PDBsum; 2BZF; -.
DR PDBsum; 2EZX; -.
DR PDBsum; 2EZY; -.
DR PDBsum; 2EZZ; -.
DR PDBsum; 2ODG; -.
DR ProteinModelPortal; O75531; -.
DR SMR; O75531; 1-89.
DR DIP; DIP-50395N; -.
DR IntAct; O75531; 2.
DR MINT; MINT-5002289; -.
DR STRING; 9606.ENSP00000310275; -.
DR PhosphoSite; O75531; -.
DR PaxDb; O75531; -.
DR PeptideAtlas; O75531; -.
DR PRIDE; O75531; -.
DR Ensembl; ENST00000312175; ENSP00000310275; ENSG00000175334.
DR Ensembl; ENST00000445560; ENSP00000416128; ENSG00000175334.
DR Ensembl; ENST00000527348; ENSP00000432867; ENSG00000175334.
DR Ensembl; ENST00000533166; ENSP00000433760; ENSG00000175334.
DR GeneID; 8815; -.
DR KEGG; hsa:8815; -.
DR UCSC; uc001ogo.3; human.
DR CTD; 8815; -.
DR GeneCards; GC11P065769; -.
DR HGNC; HGNC:17397; BANF1.
DR HPA; CAB032896; -.
DR MIM; 603811; gene.
DR MIM; 614008; phenotype.
DR neXtProt; NX_O75531; -.
DR Orphanet; 280576; Nestor-Guillermo progeria syndrome.
DR PharmGKB; PA134903639; -.
DR eggNOG; NOG251829; -.
DR HOVERGEN; HBG029345; -.
DR InParanoid; O75531; -.
DR OMA; DWCEEFL; -.
DR OrthoDB; EOG7HHWVW; -.
DR PhylomeDB; O75531; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR EvolutionaryTrace; O75531; -.
DR GeneWiki; Barrier_to_autointegration_factor_1; -.
DR GenomeRNAi; 8815; -.
DR NextBio; 33066; -.
DR PRO; PR:O75531; -.
DR ArrayExpress; O75531; -.
DR Bgee; O75531; -.
DR CleanEx; HS_BANF1; -.
DR Genevestigator; O75531; -.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0015074; P:DNA integration; IEA:Ensembl.
DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
DR GO; GO:0007077; P:mitotic nuclear envelope disassembly; TAS:Reactome.
DR GO; GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR Gene3D; 1.10.150.40; -; 1.
DR InterPro; IPR004122; BAF_prot.
DR PANTHER; PTHR12912; PTHR12912; 1.
DR Pfam; PF02961; BAF; 1.
DR ProDom; PD019964; PD019964; 1.
DR SMART; SM01023; BAF; 1.
DR SUPFAM; SSF47798; SSF47798; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Complete proteome; Cytoplasm;
KW Disease mutation; DNA-binding; Host-virus interaction; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 89 Barrier-to-autointegration factor.
FT /FTId=PRO_0000221026.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 89 Barrier-to-autointegration factor, N-
FT terminally processed.
FT /FTId=PRO_0000423190.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Barrier-to-
FT autointegration factor, N-terminally
FT processed.
FT MOD_RES 2 2 Phosphothreonine; by VRK1 and VRK2.
FT MOD_RES 3 3 Phosphothreonine; by VRK1 and VRK2.
FT MOD_RES 4 4 Phosphoserine; by VRK1 and VRK2.
FT VARIANT 12 12 A -> T (in NGPS; shows a dramatic
FT reduction in BANF1 protein levels
FT indicating that the mutation impairs
FT protein stability).
FT /FTId=VAR_065954.
FT MUTAGEN 4 4 S->A: Complete loss of phosphorylation.
FT MUTAGEN 4 4 S->E: Complete loss of phosphorylation
FT and mislocalization of EMD in nucleus.
FT MUTAGEN 6 6 K->A: Complete loss of LEMD3/MAN1 and
FT histone H1/H3 binding.
FT MUTAGEN 6 6 K->E: Complete loss of dsDNA and
FT LEMD3/MAN1 binding.
FT MUTAGEN 8 8 R->A: Enhances histone H1/H3 binding.
FT MUTAGEN 8 8 R->E: Complete loss of LEMD3/MAN1
FT binding.
FT MUTAGEN 9 9 D->A: Reduces binding to dsDNA,
FT LEMD3/MAN1 and histone H1/H3.
FT MUTAGEN 14 14 P->A: No effect on LEMD3/MAN1 and
FT enhances histone H1/H3 binding.
FT MUTAGEN 18 18 K->A: No effect on histone H1/H3 binding.
FT MUTAGEN 25 25 G->E: Complete loss of dsDNA, EMD,
FT histone H1/H3 and LEMD3/MAN1 binding.
FT MUTAGEN 25 25 G->Q: Complete loss of EMD binding and
FT reduces dsDNA binding.
FT MUTAGEN 26 26 I->A: Reduces histone H1/H3 and
FT LEMD3/MAN1 binding. Fails to promote HIV-
FT 1 genome integration.
FT MUTAGEN 26 26 I->K: Fails to promote HIV-1 genome
FT integration.
FT MUTAGEN 27 27 G->E: Fails to bind dsDNA.
FT MUTAGEN 27 27 G->Q: Reduces binding to dsDNA.
FT MUTAGEN 29 29 V->A: No effect on histone H1/H3 binding.
FT MUTAGEN 32 32 K->E: No effect on histone H1/H3 binding.
FT MUTAGEN 33 33 K->E: No effect on histone H1/H3 binding.
FT MUTAGEN 37 37 R->A: No effect on histone H1/H3 binding.
FT MUTAGEN 37 37 R->E: Reduces LEMD3/MAN1 binding.
FT MUTAGEN 41 41 K->A: No effect on histone H1/H3 and
FT LEMD3/MAN1 binding.
FT MUTAGEN 41 41 K->E: Reduces histone H1/H3 binding.
FT MUTAGEN 46 46 L->E: Complete loss of dsDNA, histone
FT H1/H3 and LEMD3/MAN1 binding.
FT MUTAGEN 47 47 G->E: Complete loss of EMD, histone H1/h3
FT and LEMD3/MAN1 binding.
FT MUTAGEN 50 50 L->A: Reduces LEMD3/MAN1 binding. No
FT effect on Histone H1/H3 binding.
FT MUTAGEN 50 50 L->K: Fails to promote HIV-1 genome
FT integration.
FT MUTAGEN 51 51 V->E: Complete loss of EMD, and histone
FT H1/H3 binding. Reduces dsDNA and
FT LEMD3/MAN1 binding.
FT MUTAGEN 53 53 K->A: No effect on LEMD3/MAN1 binding.
FT Enhances histone H1/H3 binding.
FT MUTAGEN 53 53 K->E: Complete loss of EMD binding.
FT Reduces LEMD3/MAN1 binding. Enhances
FT histone H1/H3 binding.
FT MUTAGEN 54 54 K->A: Reduces LEMD3/MAN1 binding. No
FT effect on histone H1/H3 binding.
FT MUTAGEN 54 54 K->E: Reduces binding to dsDNA.
FT MUTAGEN 60 60 R->E: No effect on histone H1/H3 binding.
FT MUTAGEN 62 62 W->A: Complete loss of LEMD3/MAN1
FT binding. Enhances histone H1/H3 binding.
FT MUTAGEN 64 64 K->E: Enhances histone H1/H3 binding.
FT MUTAGEN 75 75 R->E: Reduces binding to dsDNA. No effect
FT on histone H1/H3 binding.
FT MUTAGEN 80 80 C->A: No effect on histone H1/H3 and
FT LEMD3/MAN1 binding.
FT MUTAGEN 82 82 R->E: No effect on histone H1/H3 binding.
FT HELIX 5 11
FT HELIX 20 22
FT HELIX 28 36
FT HELIX 42 51
FT TURN 52 54
FT HELIX 56 67
FT HELIX 71 88
SQ SEQUENCE 89 AA; 10059 MW; 9A2180A2D284F5D0 CRC64;
MTTSQKHRDF VAEPMGEKPV GSLAGIGEVL GKKLEERGFD KAYVVLGQFL VLKKDEDLFR
EWLKDTCGAN AKQSRDCFGC LREWCDAFL
//
ID BAF_HUMAN Reviewed; 89 AA.
AC O75531; O60558; Q6FGG7;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Barrier-to-autointegration factor;
DE AltName: Full=Breakpoint cluster region protein 1;
DE Contains:
DE RecName: Full=Barrier-to-autointegration factor, N-terminally processed;
GN Name=BANF1; Synonyms=BAF, BCRG1;
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].
RX PubMed=9465049; DOI=10.1073/pnas.95.4.1528;
RA Lee M.S., Craigie R.;
RT "A previously unidentified host protein protects retroviral DNA from
RT autointegration.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1528-1533(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Uterus;
RX PubMed=9740667; DOI=10.1006/geno.1998.5406;
RA Lynch R.A., Piper M., Bankier A., Bhugra B., Surti U., Liu J.,
RA Buckler A., Dear P.H., Menon A.G.;
RT "Genomic and functional map of the chromosome 14 t(12;14) breakpoint
RT cluster region in uterine leiomyoma.";
RL Genomics 52:17-26(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang J., Liu T., Ye M., Zhang Q., Fu G., Zhou J., Wu J., Shen Y.,
RA Yu M., Chen S., Mao M., Chen Z.;
RT "Human BAF homolog gene.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP FUNCTION IN HIV-1 INTEGRATION, AND MUTAGENESIS OF LYS-6; PRO-14;
RP LYS-18; ILE-26; LYS-41; LEU-50; LYS-53; LYS-54; TRP-62 AND CYS-80.
RX PubMed=11005805; DOI=10.1074/jbc.M002626200;
RA Harris D., Engelman A.;
RT "Both the structure and DNA binding function of the barrier-to-
RT autointegration factor contribute to reconstitution of HIV type 1
RT integration in vitro.";
RL J. Biol. Chem. 275:39671-39677(2000).
RN [7]
RP MULTIMERIZATION.
RX PubMed=10908652; DOI=10.1073/pnas.150240197;
RA Zheng R., Ghirlando R., Lee M.S., Mizuuchi K., Krause M., Craigie R.;
RT "Barrier-to-autointegration factor (BAF) bridges DNA in a discrete,
RT higher-order nucleoprotein complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8997-9002(2000).
RN [8]
RP INTERACTION WITH EMD.
RX PubMed=11792822;
RA Haraguchi T., Koujin T., Segura-Totten M., Lee K.K., Matsuoka Y.,
RA Yoneda Y., Wilson K.L., Hiraoka Y.;
RT "BAF is required for emerin assembly into the reforming nuclear
RT envelope.";
RL J. Cell Sci. 114:4575-4585(2001).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF LYS-6; ASP-9; GLY-25; GLY-27; LEU-46;
RP GLY-47; VAL-51; LYS-53; LYS-54 AND ARG-75.
RX PubMed=12163470; DOI=10.1083/jcb.200202019;
RA Segura-Totten M., Kowalski A.K., Craigie R., Wilson K.L.;
RT "Barrier-to-autointegration factor: major roles in chromatin
RT decondensation and nuclear assembly.";
RL J. Cell Biol. 158:475-485(2002).
RN [10]
RP INTERACTION WITH HIV-1 PRE-INTEGRATION COMPLEX.
RX PubMed=12663813; DOI=10.1128/JVI.77.8.5030-5036.2003;
RA Lin C.W., Engelman A.;
RT "The barrier-to-autointegration factor is a component of functional
RT human immunodeficiency virus type 1 preintegration complexes.";
RL J. Virol. 77:5030-5036(2003).
RN [11]
RP INTERACTION WITH HIV-1 MATRIX PROTEIN.
RX PubMed=14645565; DOI=10.1128/JVI.77.24.13084-13092.2003;
RA Mansharamani M., Graham D.R., Monie D., Lee K.K., Hildreth J.E.,
RA Siliciano R.F., Wilson K.L.;
RT "Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is
RT a host component of human immunodeficiency virus type 1 virions.";
RL J. Virol. 77:13084-13092(2003).
RN [12]
RP INTERACTION WITH LEMD3/MAN1, AND MUTAGENESIS OF LYS-6; ARG-8; ASP-9;
RP PRO-14; GLY-25; ILE-26; ARG-37; LYS-41; LEU-46; GLY-47; LEU-50;
RP VAL-51; LYS-53; LYS-54; TRP-62 AND CYS-80.
RX PubMed=15681850; DOI=10.1074/jbc.M413020200;
RA Mansharamani M., Wilson K.L.;
RT "Direct binding of nuclear membrane protein MAN1 to emerin in vitro
RT and two modes of binding to barrier-to-autointegration factor.";
RL J. Biol. Chem. 280:13863-13870(2005).
RN [13]
RP INTERACTION WITH HISTONE H1/H3, AND MUTAGENESIS OF LYS-6; ARG-8;
RP ASP-9; PRO-14; LYS-18; GLY-25; ILE-26; VAL-29; LYS-32; LYS-33; ARG-37;
RP LYS-41; LEU-46; GLY-47; LEU-50; VAL-51; LYS-53; LYS-54; ARG-60;
RP TRP-62; LYS-64; ARG-75; CYS-80 AND ARG-82.
RX PubMed=16203725; DOI=10.1074/jbc.M509917200;
RA de Oca R.M., Lee K.K., Wilson K.L.;
RT "Binding of barrier to autointegration factor (BAF) to histone H3 and
RT selected linker histones including H1.1.";
RL J. Biol. Chem. 280:42252-42262(2005).
RN [14]
RP PHOSPHORYLATION AT SER-4, AND MUTAGENESIS OF SER-4.
RX PubMed=16371512; DOI=10.1091/mbc.E05-04-0356;
RA Bengtsson L., Wilson K.L.;
RT "Barrier-to-autointegration factor phosphorylation on Ser-4 regulates
RT emerin binding to lamin A in vitro and emerin localization in vivo.";
RL Mol. Biol. Cell 17:1154-1163(2006).
RN [15]
RP INTERACTION WITH BAFL.
RX PubMed=16337940; DOI=10.1016/j.yexcr.2005.11.013;
RA Tifft K.E., Segura-Totten M., Lee K.K., Wilson K.L.;
RT "Barrier-to-autointegration factor-like (BAF-L): a proposed regulator
RT of BAF.";
RL Exp. Cell Res. 312:478-487(2006).
RN [16]
RP PHOSPHORYLATION AT THR-2; THR-3 AND SER-4, AND SUBCELLULAR LOCATION.
RX PubMed=16495336; DOI=10.1091/mbc.E05-12-1179;
RA Nichols R.J., Wiebe M.S., Traktman P.;
RT "The vaccinia-related kinases phosphorylate the N' terminus of BAF,
RT regulating its interaction with DNA and its retention in the
RT nucleus.";
RL Mol. Biol. Cell 17:2451-2464(2006).
RN [17]
RP FUNCTION.
RX PubMed=16680152; DOI=10.1038/nature04682;
RA Jacque J.-M., Stevenson M.;
RT "The inner-nuclear-envelope protein emerin regulates HIV-1
RT infectivity.";
RL Nature 441:641-645(2006).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP PHOSPHORYLATION, DEPHOSPHORYLATION, AND INTERACTION WITH ANKLE2.
RX PubMed=22770216; DOI=10.1016/j.cell.2012.04.043;
RA Asencio C., Davidson I.F., Santarella-Mellwig R., Ly-Hartig T.B.,
RA Mall M., Wallenfang M.R., Mattaj I.W., Gorjanacz M.;
RT "Coordination of kinase and phosphatase activities by Lem4 enables
RT nuclear envelope reassembly during mitosis.";
RL Cell 150:122-135(2012).
RN [23]
RP REVIEW.
RX PubMed=15130582; DOI=10.1016/j.tcb.2004.03.004;
RA Segura-Totten M., Wilson K.L.;
RT "BAF: roles in chromatin, nuclear structure and retrovirus
RT integration.";
RL Trends Cell Biol. 14:261-266(2004).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=9783751; DOI=10.1038/2345;
RA Cai M., Huang Y., Zheng R., Wei S.Q., Ghirlando R., Lee M.S.,
RA Craigie R., Gronenborn A.M., Clore G.M.;
RT "Solution structure of the cellular factor BAF responsible for
RT protecting retroviral DNA from autointegration.";
RL Nat. Struct. Biol. 5:903-909(1998).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF HOMODIMER.
RX PubMed=10924106; DOI=10.1021/bi000572w;
RA Umland T.C., Wei S.-Q., Craigie R., Davies D.R.;
RT "Structural basis of DNA bridging by barrier-to-autointegration
RT factor.";
RL Biochemistry 39:9130-9138(2000).
RN [26]
RP VARIANT NGPS THR-12.
RX PubMed=21549337; DOI=10.1016/j.ajhg.2011.04.010;
RA Puente X.S., Quesada V., Osorio F.G., Cabanillas R., Cadinanos J.,
RA Fraile J.M., Ordonez G.R., Puente D.A., Gutierrez-Fernandez A.,
RA Fanjul-Fernandez M., Levy N., Freije J.M., Lopez-Otin C.;
RT "Exome sequencing and functional analysis identifies BANF1 mutation as
RT the cause of a hereditary progeroid syndrome.";
RL Am. J. Hum. Genet. 88:650-656(2011).
CC -!- FUNCTION: Plays fundamental roles in nuclear assembly, chromatin
CC organization, gene expression and gonad development. May potently
CC compress chromatin structure and be involved in membrane
CC recruitment and chromatin decondensation during nuclear assembly.
CC Contains 2 non-specific dsDNA-binding sites which may promote DNA
CC cross-bridging. Exploited by retroviruses for inhibiting self-
CC destructing autointegration of retroviral DNA, thereby promoting
CC integration of viral DNA into the host chromosome. EMD and BAF are
CC cooperative cofactors of HIV-1 infection. Association of EMD with
CC the viral DNA requires the presence of BAF and viral integrase.
CC The association of viral DNA with chromatin requires the presence
CC of BAF and EMD.
CC -!- SUBUNIT: Homodimer. Heterodimerizes with BAFL. Interacts with
CC ANKLE2/LEM4, leading to decreased phosphorylation by VRK1 and
CC promoting dephosphorylation by protein phosphatase 2A (PP2A).
CC Binds non-specifically to double-stranded DNA, and is found as a
CC hexamer or dodecamer upon DNA binding. Binds to LEM domain-
CC containing nuclear proteins such as LEMD3/MAN1, TMPO/LAP2 and EMD
CC (emerin). Interacts with CRX and LMNA (lamin-A). Binds linker
CC histone H1.1 and core histones H3 with in vitro affinities of 500-
CC 900 and 100-200 nM. Interacts with HIV-1 pre-integration complex
CC in cytoplasm by binding to viral matrix protein and Gag
CC polyprotein.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Chromosome.
CC Note=Significantly enriched at the nuclear inner membrane,
CC diffusely throughout the nucleus during interphase and
CC concentrated at the chromosomes during the M-phase. May be
CC included in HIV-1 virions via its interaction with viral GAG
CC polyprotein. The phosphorylated form (by VRK1) shows a cytoplasmic
CC localization.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in colon, brain,
CC heart, kidney, liver, lung, ovary, pancreas, placenta, prostate,
CC skeletal muscle, small intestine, spleen and testis. Not detected
CC in thymus and peripheral blood leukocytes.
CC -!- DOMAIN: Has a helix-hairpin-helix (HhH) structural motif conserved
CC among proteins that bind non-specifically to DNA.
CC -!- DOMAIN: LEM domain proteins bind centrally on the BAF dimer,
CC whereas DNA binds to the left and right sides.
CC -!- PTM: Ser-4 is the major site of phosphorylation as compared to
CC Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4
CC disrupts its ability to bind DNA and reduces its ability to bind
CC LEM domain-containing proteins. Non phosphorylated BAF seems to
CC enhance binding between EMD and LMNA. Dephosphorylated by protein
CC phosphatase 2A (PP2A) following interaction with ANKLE2/LEM4
CC during mitotic exit, leading to mitotic nuclear envelope
CC reassembly.
CC -!- DISEASE: Nestor-Guillermo progeria syndrome (NGPS) [MIM:614008]:
CC An atypical progeroid syndrome characterized by normal development
CC in the first years of life, later followed by the emergence of
CC generalized lipoatrophy, severe osteoporosis, and marked
CC osteolysis. The atrophic facial subcutaneous fat pad and the
CC marked osteolysis of the maxilla and mandible result in a typical
CC pseudosenile facial appearance with micrognathia, prominent
CC subcutaneous venous patterning, a convex nasal ridge, and
CC proptosis. Cognitive development is completely normal. Patients do
CC not have cardiovascular dysfunction, atherosclerosis, or metabolic
CC anomalies. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the BAF family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC08964.1; Type=Frameshift; Positions=87;
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DR EMBL; AF070447; AAC23575.1; -; mRNA.
DR EMBL; AF044773; AAC08964.1; ALT_FRAME; mRNA.
DR EMBL; AF068235; AAD15901.1; -; mRNA.
DR EMBL; CR542140; CAG46937.1; -; mRNA.
DR EMBL; BC005942; AAH05942.1; -; mRNA.
DR EMBL; BC107702; AAI07703.1; -; mRNA.
DR RefSeq; NP_001137457.1; NM_001143985.1.
DR RefSeq; NP_003851.1; NM_003860.3.
DR UniGene; Hs.433759; -.
DR PDB; 1CI4; X-ray; 1.90 A; A/B=1-89.
DR PDB; 1QCK; NMR; -; A/B=1-89.
DR PDB; 2BZF; X-ray; 2.87 A; A=1-89.
DR PDB; 2EZX; NMR; -; A/B=1-89.
DR PDB; 2EZY; NMR; -; A/B=1-89.
DR PDB; 2EZZ; NMR; -; A/B=1-89.
DR PDB; 2ODG; NMR; -; A/B=1-89.
DR PDBsum; 1CI4; -.
DR PDBsum; 1QCK; -.
DR PDBsum; 2BZF; -.
DR PDBsum; 2EZX; -.
DR PDBsum; 2EZY; -.
DR PDBsum; 2EZZ; -.
DR PDBsum; 2ODG; -.
DR ProteinModelPortal; O75531; -.
DR SMR; O75531; 1-89.
DR DIP; DIP-50395N; -.
DR IntAct; O75531; 2.
DR MINT; MINT-5002289; -.
DR STRING; 9606.ENSP00000310275; -.
DR PhosphoSite; O75531; -.
DR PaxDb; O75531; -.
DR PeptideAtlas; O75531; -.
DR PRIDE; O75531; -.
DR Ensembl; ENST00000312175; ENSP00000310275; ENSG00000175334.
DR Ensembl; ENST00000445560; ENSP00000416128; ENSG00000175334.
DR Ensembl; ENST00000527348; ENSP00000432867; ENSG00000175334.
DR Ensembl; ENST00000533166; ENSP00000433760; ENSG00000175334.
DR GeneID; 8815; -.
DR KEGG; hsa:8815; -.
DR UCSC; uc001ogo.3; human.
DR CTD; 8815; -.
DR GeneCards; GC11P065769; -.
DR HGNC; HGNC:17397; BANF1.
DR HPA; CAB032896; -.
DR MIM; 603811; gene.
DR MIM; 614008; phenotype.
DR neXtProt; NX_O75531; -.
DR Orphanet; 280576; Nestor-Guillermo progeria syndrome.
DR PharmGKB; PA134903639; -.
DR eggNOG; NOG251829; -.
DR HOVERGEN; HBG029345; -.
DR InParanoid; O75531; -.
DR OMA; DWCEEFL; -.
DR OrthoDB; EOG7HHWVW; -.
DR PhylomeDB; O75531; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR EvolutionaryTrace; O75531; -.
DR GeneWiki; Barrier_to_autointegration_factor_1; -.
DR GenomeRNAi; 8815; -.
DR NextBio; 33066; -.
DR PRO; PR:O75531; -.
DR ArrayExpress; O75531; -.
DR Bgee; O75531; -.
DR CleanEx; HS_BANF1; -.
DR Genevestigator; O75531; -.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0015074; P:DNA integration; IEA:Ensembl.
DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
DR GO; GO:0007077; P:mitotic nuclear envelope disassembly; TAS:Reactome.
DR GO; GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR Gene3D; 1.10.150.40; -; 1.
DR InterPro; IPR004122; BAF_prot.
DR PANTHER; PTHR12912; PTHR12912; 1.
DR Pfam; PF02961; BAF; 1.
DR ProDom; PD019964; PD019964; 1.
DR SMART; SM01023; BAF; 1.
DR SUPFAM; SSF47798; SSF47798; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Complete proteome; Cytoplasm;
KW Disease mutation; DNA-binding; Host-virus interaction; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1 89 Barrier-to-autointegration factor.
FT /FTId=PRO_0000221026.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 89 Barrier-to-autointegration factor, N-
FT terminally processed.
FT /FTId=PRO_0000423190.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Barrier-to-
FT autointegration factor, N-terminally
FT processed.
FT MOD_RES 2 2 Phosphothreonine; by VRK1 and VRK2.
FT MOD_RES 3 3 Phosphothreonine; by VRK1 and VRK2.
FT MOD_RES 4 4 Phosphoserine; by VRK1 and VRK2.
FT VARIANT 12 12 A -> T (in NGPS; shows a dramatic
FT reduction in BANF1 protein levels
FT indicating that the mutation impairs
FT protein stability).
FT /FTId=VAR_065954.
FT MUTAGEN 4 4 S->A: Complete loss of phosphorylation.
FT MUTAGEN 4 4 S->E: Complete loss of phosphorylation
FT and mislocalization of EMD in nucleus.
FT MUTAGEN 6 6 K->A: Complete loss of LEMD3/MAN1 and
FT histone H1/H3 binding.
FT MUTAGEN 6 6 K->E: Complete loss of dsDNA and
FT LEMD3/MAN1 binding.
FT MUTAGEN 8 8 R->A: Enhances histone H1/H3 binding.
FT MUTAGEN 8 8 R->E: Complete loss of LEMD3/MAN1
FT binding.
FT MUTAGEN 9 9 D->A: Reduces binding to dsDNA,
FT LEMD3/MAN1 and histone H1/H3.
FT MUTAGEN 14 14 P->A: No effect on LEMD3/MAN1 and
FT enhances histone H1/H3 binding.
FT MUTAGEN 18 18 K->A: No effect on histone H1/H3 binding.
FT MUTAGEN 25 25 G->E: Complete loss of dsDNA, EMD,
FT histone H1/H3 and LEMD3/MAN1 binding.
FT MUTAGEN 25 25 G->Q: Complete loss of EMD binding and
FT reduces dsDNA binding.
FT MUTAGEN 26 26 I->A: Reduces histone H1/H3 and
FT LEMD3/MAN1 binding. Fails to promote HIV-
FT 1 genome integration.
FT MUTAGEN 26 26 I->K: Fails to promote HIV-1 genome
FT integration.
FT MUTAGEN 27 27 G->E: Fails to bind dsDNA.
FT MUTAGEN 27 27 G->Q: Reduces binding to dsDNA.
FT MUTAGEN 29 29 V->A: No effect on histone H1/H3 binding.
FT MUTAGEN 32 32 K->E: No effect on histone H1/H3 binding.
FT MUTAGEN 33 33 K->E: No effect on histone H1/H3 binding.
FT MUTAGEN 37 37 R->A: No effect on histone H1/H3 binding.
FT MUTAGEN 37 37 R->E: Reduces LEMD3/MAN1 binding.
FT MUTAGEN 41 41 K->A: No effect on histone H1/H3 and
FT LEMD3/MAN1 binding.
FT MUTAGEN 41 41 K->E: Reduces histone H1/H3 binding.
FT MUTAGEN 46 46 L->E: Complete loss of dsDNA, histone
FT H1/H3 and LEMD3/MAN1 binding.
FT MUTAGEN 47 47 G->E: Complete loss of EMD, histone H1/h3
FT and LEMD3/MAN1 binding.
FT MUTAGEN 50 50 L->A: Reduces LEMD3/MAN1 binding. No
FT effect on Histone H1/H3 binding.
FT MUTAGEN 50 50 L->K: Fails to promote HIV-1 genome
FT integration.
FT MUTAGEN 51 51 V->E: Complete loss of EMD, and histone
FT H1/H3 binding. Reduces dsDNA and
FT LEMD3/MAN1 binding.
FT MUTAGEN 53 53 K->A: No effect on LEMD3/MAN1 binding.
FT Enhances histone H1/H3 binding.
FT MUTAGEN 53 53 K->E: Complete loss of EMD binding.
FT Reduces LEMD3/MAN1 binding. Enhances
FT histone H1/H3 binding.
FT MUTAGEN 54 54 K->A: Reduces LEMD3/MAN1 binding. No
FT effect on histone H1/H3 binding.
FT MUTAGEN 54 54 K->E: Reduces binding to dsDNA.
FT MUTAGEN 60 60 R->E: No effect on histone H1/H3 binding.
FT MUTAGEN 62 62 W->A: Complete loss of LEMD3/MAN1
FT binding. Enhances histone H1/H3 binding.
FT MUTAGEN 64 64 K->E: Enhances histone H1/H3 binding.
FT MUTAGEN 75 75 R->E: Reduces binding to dsDNA. No effect
FT on histone H1/H3 binding.
FT MUTAGEN 80 80 C->A: No effect on histone H1/H3 and
FT LEMD3/MAN1 binding.
FT MUTAGEN 82 82 R->E: No effect on histone H1/H3 binding.
FT HELIX 5 11
FT HELIX 20 22
FT HELIX 28 36
FT HELIX 42 51
FT TURN 52 54
FT HELIX 56 67
FT HELIX 71 88
SQ SEQUENCE 89 AA; 10059 MW; 9A2180A2D284F5D0 CRC64;
MTTSQKHRDF VAEPMGEKPV GSLAGIGEVL GKKLEERGFD KAYVVLGQFL VLKKDEDLFR
EWLKDTCGAN AKQSRDCFGC LREWCDAFL
//
MIM
603811
*RECORD*
*FIELD* NO
603811
*FIELD* TI
*603811 BARRIER-TO-AUTOINTEGRATION FACTOR 1; BANF1
;;BARRIER-TO-AUTOINTEGRATION FACTOR; BAF
read more*FIELD* TX
CLONING
Lee and Craigie (1998) purified a host cell protein, which they termed
BAF, that protects viral DNA from autointegration (integration into
itself, rather than into the host genome). By sequence analysis and RACE
using mRNA from NIH 3T3 fibroblasts, the authors obtained a full-length
cDNA encoding BAF. The deduced 89-amino acid BAF protein has a
calculated molecular mass of 10.1 kD and likely exists as a dimer.
Expression of the BAF gene resulted in a protein that was active in an
autointegration barrier assay.
BIOCHEMICAL FEATURES
- Crystal Structure
Umland et al. (2000) determined the crystal structure of homodimeric BAF
to 1.9-angstrom resolution. They identified a helix-hairpin-helix motif
that mediates nonspecific DNA binding. Binding occurs through
interactions between amide groups of the peptide chain and phosphate
groups of the DNA backbone.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the BANF1
gene to chromosome 11 (TMAP WI-8432). Lynch et al. (1998) mapped a BANF1
pseudogene, which they called BCRP1, to chromosome 14q24.1-q24.2 (see
BCRP2; 603812).
GENE FUNCTION
Zheng et al. (2000) demonstrated that BAF can bridge double-stranded DNA
into a highly ordered nucleoprotein complex. Whereas BAF alone was a
dimer in solution, upon binding DNA, BAF formed a dodecamer with DNA
bound at multiple discrete sites in the complex. The interactions
between BAF and DNA were entirely nonspecific with respect to DNA
sequence. By RNA interference, Zheng et al. (2000) demonstrated a role
of BAF in mitosis in C. elegans. Embryo development in worms injected
with double-stranded BAF RNA arrested at an early stage, and chromosomes
showed a defect in chromatin segregation during mitosis.
Lee et al. (2001) determined that BAF binds the N-terminal LEM domain of
emerin (300384).
Haraguchi et al. (2001) visualized colocalization between emerin and BAF
at the 'core' region of chromosomes during telophase in HeLa cells. An
emerin mutant defective in BAF binding in vitro failed to localize at
the core in vivo and subsequently failed to localize at the reformed
nuclear envelope. In HeLa cells expressing a BAF mutant that did not
show core localization, endogenous emerin failed to localize at the core
region during telophase and did not assemble into the nuclear envelope
during the subsequent interphase. This BAF mutant also dominantly
dislocalized LAP2-beta (188380) and lamin A (150330) from the nuclear
envelope. Haraguchi et al. (2001) concluded that BAF is required for the
assembly of emerin and A-type lamins at the reforming nuclear envelope
during telophase and may mediate their stability in the subsequent
interphase.
Jacque and Stevenson (2006) examined susceptibility of primary
macrophages to human immunodeficiency virus (HIV)-1 infection following
short interfering RNA (siRNA)-mediated silencing of nuclear lamins and
several lamin-associated proteins. They found that silencing of emerin
and BAF prevented infection with HIV-1, but not murine leukemia virus,
by preventing integration of the virus into host DNA. Chromatin
immunoprecipitation analysis identified emerin and BAF as cooperative
cofactors of HIV-1, and mutation analysis showed that viral cDNA did not
associate with BAF defective in emerin binding or with emerin lacking
the LEM domain. Jacque and Stevenson (2006) concluded that HIV-1 cDNA,
upon entering the nucleus, must interact with emerin to contact
chromatin, and they suggested that molecules that prevent this
interaction might promote abortive HIV-1 infection of a cell.
MOLECULAR GENETICS
In 2 unrelated Spanish patients with childhood-onset progeria associated
with severe osteolysis (614008), Puente et al. (2011) identified
homozygosity for a missense mutation in the BANF1 gene (A12T;
603811.0001). The presence of a common homozygous haplotype in the 2
patients, who were from geographically distant regions, suggested that
A12T represented a founder mutation.
*FIELD* AV
.0001
NESTOR-GUILLERMO PROGERIA SYNDROME
BANF1, ALA12THR
In 2 unrelated Spanish patients with childhood-onset progeria associated
with severe osteolysis (614008), Puente et al. (2011) identified
homozygosity for a 34G-A transition in the BANF1 gene, resulting in an
ala12-to-thr (A12T) substitution at a highly conserved residue. The
mutation, which was present in heterozygosity in the unaffected parents
from both families, was not found in more than 400 Spanish chromosomes.
The 2 patients, who were from geographically distant regions of Spain,
shared a common homozygous haplotype, which suggested the occurrence of
a founder mutation. Fibroblasts from both patients showed a dramatic
reduction in BAF protein levels, indicating that the A12T mutation
impairs protein stability. In addition, the progeroid fibroblasts
displayed profound abnormalities in the nuclear lamina, including blebs
and abnormal distribution of emerin (300384), an interaction partner of
BAF.
*FIELD* RF
1. Haraguchi, T.; Koujin, T.; Segura-Totten, M.; Lee, K. K.; Matsuoka,
Y.; Yoneda, Y.; Wilson, K. L.; Hiraoka, Y.: BAF is required for emerin
assembly into the reforming nuclear envelope. J. Cell Sci. 114:
4575-4585, 2001.
2. Jacque, J.-M.; Stevenson, M.: The inner-nuclear-envelope protein
emerin regulates HIV-1 infectivity. Nature 441: 641-645, 2006.
3. Lee, K. K.; Haraguchi, T.; Lee, R. S.; Koujin, T.; Hiraoka, Y.;
Wilson, K. L.: Distinct functional domains in emerin bind lamin A
and DNA-bridging protein BAF. J. Cell Sci. 114: 4567-4573, 2001.
4. Lee, M. S.; Craigie, R.: A previously unidentified host protein
protects retroviral DNA from autointegration. Proc. Nat. Acad. Sci. 95:
1528-1533, 1998.
5. Lynch, R. A.; Piper, M.; Bankier, A.; Bhugra, B.; Surti, U.; Liu,
J.; Buckler, A.; Dear, P. H.; Menon, A. G.: Genomic and functional
map of the chromosome 14 t(12;14) breakpoint cluster region in uterine
leiomyoma. Genomics 52: 17-26, 1998.
6. Puente, X. S.; Quesada, V.; Osorio, F. G.; Cabanillas, R.; Cadinanos,
J.; Fraile, J. M.; Ordonez, G. R.; Puente, D. A.; Gutierrez-Fernandez,
A.; Fanjul-Fernandez, M.; Levy, N.; Freije, J. M. P.; Lopez-Otin,
C.: Exome sequencing and functional analysis identifies BANF1 mutation
as the cause of a hereditary progeroid syndrome. Am. J. Hum. Genet. 88:
650-656, 2011.
7. Umland, T. C.; Wei, S.-Q.; Craigie, R.; Davies, D. R.: Structural
basis of DNA bridging by barrier-to-autointegration factor. Biochemistry 39:
9130-9138, 2000.
8. Zheng, R.; Ghirlando, R.; Lee, M. S.; Mizuuchi, K.; Krause, M.;
Craigie, R.: Barrier-to-autointegration factor (BAF) bridges DNA
in a discrete, higher-order nucleoprotein complex. Proc. Nat. Acad.
Sci. 97: 8997-9002, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 5/25/2011
Paul J. Converse - updated: 6/19/2006
Patricia A. Hartz - updated: 5/19/2003
*FIELD* CD
Jennifer P. Macke: 5/17/1999
*FIELD* ED
joanna: 01/25/2012
carol: 5/25/2011
terry: 5/25/2011
mgross: 6/19/2006
mgross: 5/23/2003
mgross: 5/19/2003
carol: 2/21/2003
alopez: 7/20/1999
alopez: 5/18/1999
alopez: 5/17/1999
*RECORD*
*FIELD* NO
603811
*FIELD* TI
*603811 BARRIER-TO-AUTOINTEGRATION FACTOR 1; BANF1
;;BARRIER-TO-AUTOINTEGRATION FACTOR; BAF
read more*FIELD* TX
CLONING
Lee and Craigie (1998) purified a host cell protein, which they termed
BAF, that protects viral DNA from autointegration (integration into
itself, rather than into the host genome). By sequence analysis and RACE
using mRNA from NIH 3T3 fibroblasts, the authors obtained a full-length
cDNA encoding BAF. The deduced 89-amino acid BAF protein has a
calculated molecular mass of 10.1 kD and likely exists as a dimer.
Expression of the BAF gene resulted in a protein that was active in an
autointegration barrier assay.
BIOCHEMICAL FEATURES
- Crystal Structure
Umland et al. (2000) determined the crystal structure of homodimeric BAF
to 1.9-angstrom resolution. They identified a helix-hairpin-helix motif
that mediates nonspecific DNA binding. Binding occurs through
interactions between amide groups of the peptide chain and phosphate
groups of the DNA backbone.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the BANF1
gene to chromosome 11 (TMAP WI-8432). Lynch et al. (1998) mapped a BANF1
pseudogene, which they called BCRP1, to chromosome 14q24.1-q24.2 (see
BCRP2; 603812).
GENE FUNCTION
Zheng et al. (2000) demonstrated that BAF can bridge double-stranded DNA
into a highly ordered nucleoprotein complex. Whereas BAF alone was a
dimer in solution, upon binding DNA, BAF formed a dodecamer with DNA
bound at multiple discrete sites in the complex. The interactions
between BAF and DNA were entirely nonspecific with respect to DNA
sequence. By RNA interference, Zheng et al. (2000) demonstrated a role
of BAF in mitosis in C. elegans. Embryo development in worms injected
with double-stranded BAF RNA arrested at an early stage, and chromosomes
showed a defect in chromatin segregation during mitosis.
Lee et al. (2001) determined that BAF binds the N-terminal LEM domain of
emerin (300384).
Haraguchi et al. (2001) visualized colocalization between emerin and BAF
at the 'core' region of chromosomes during telophase in HeLa cells. An
emerin mutant defective in BAF binding in vitro failed to localize at
the core in vivo and subsequently failed to localize at the reformed
nuclear envelope. In HeLa cells expressing a BAF mutant that did not
show core localization, endogenous emerin failed to localize at the core
region during telophase and did not assemble into the nuclear envelope
during the subsequent interphase. This BAF mutant also dominantly
dislocalized LAP2-beta (188380) and lamin A (150330) from the nuclear
envelope. Haraguchi et al. (2001) concluded that BAF is required for the
assembly of emerin and A-type lamins at the reforming nuclear envelope
during telophase and may mediate their stability in the subsequent
interphase.
Jacque and Stevenson (2006) examined susceptibility of primary
macrophages to human immunodeficiency virus (HIV)-1 infection following
short interfering RNA (siRNA)-mediated silencing of nuclear lamins and
several lamin-associated proteins. They found that silencing of emerin
and BAF prevented infection with HIV-1, but not murine leukemia virus,
by preventing integration of the virus into host DNA. Chromatin
immunoprecipitation analysis identified emerin and BAF as cooperative
cofactors of HIV-1, and mutation analysis showed that viral cDNA did not
associate with BAF defective in emerin binding or with emerin lacking
the LEM domain. Jacque and Stevenson (2006) concluded that HIV-1 cDNA,
upon entering the nucleus, must interact with emerin to contact
chromatin, and they suggested that molecules that prevent this
interaction might promote abortive HIV-1 infection of a cell.
MOLECULAR GENETICS
In 2 unrelated Spanish patients with childhood-onset progeria associated
with severe osteolysis (614008), Puente et al. (2011) identified
homozygosity for a missense mutation in the BANF1 gene (A12T;
603811.0001). The presence of a common homozygous haplotype in the 2
patients, who were from geographically distant regions, suggested that
A12T represented a founder mutation.
*FIELD* AV
.0001
NESTOR-GUILLERMO PROGERIA SYNDROME
BANF1, ALA12THR
In 2 unrelated Spanish patients with childhood-onset progeria associated
with severe osteolysis (614008), Puente et al. (2011) identified
homozygosity for a 34G-A transition in the BANF1 gene, resulting in an
ala12-to-thr (A12T) substitution at a highly conserved residue. The
mutation, which was present in heterozygosity in the unaffected parents
from both families, was not found in more than 400 Spanish chromosomes.
The 2 patients, who were from geographically distant regions of Spain,
shared a common homozygous haplotype, which suggested the occurrence of
a founder mutation. Fibroblasts from both patients showed a dramatic
reduction in BAF protein levels, indicating that the A12T mutation
impairs protein stability. In addition, the progeroid fibroblasts
displayed profound abnormalities in the nuclear lamina, including blebs
and abnormal distribution of emerin (300384), an interaction partner of
BAF.
*FIELD* RF
1. Haraguchi, T.; Koujin, T.; Segura-Totten, M.; Lee, K. K.; Matsuoka,
Y.; Yoneda, Y.; Wilson, K. L.; Hiraoka, Y.: BAF is required for emerin
assembly into the reforming nuclear envelope. J. Cell Sci. 114:
4575-4585, 2001.
2. Jacque, J.-M.; Stevenson, M.: The inner-nuclear-envelope protein
emerin regulates HIV-1 infectivity. Nature 441: 641-645, 2006.
3. Lee, K. K.; Haraguchi, T.; Lee, R. S.; Koujin, T.; Hiraoka, Y.;
Wilson, K. L.: Distinct functional domains in emerin bind lamin A
and DNA-bridging protein BAF. J. Cell Sci. 114: 4567-4573, 2001.
4. Lee, M. S.; Craigie, R.: A previously unidentified host protein
protects retroviral DNA from autointegration. Proc. Nat. Acad. Sci. 95:
1528-1533, 1998.
5. Lynch, R. A.; Piper, M.; Bankier, A.; Bhugra, B.; Surti, U.; Liu,
J.; Buckler, A.; Dear, P. H.; Menon, A. G.: Genomic and functional
map of the chromosome 14 t(12;14) breakpoint cluster region in uterine
leiomyoma. Genomics 52: 17-26, 1998.
6. Puente, X. S.; Quesada, V.; Osorio, F. G.; Cabanillas, R.; Cadinanos,
J.; Fraile, J. M.; Ordonez, G. R.; Puente, D. A.; Gutierrez-Fernandez,
A.; Fanjul-Fernandez, M.; Levy, N.; Freije, J. M. P.; Lopez-Otin,
C.: Exome sequencing and functional analysis identifies BANF1 mutation
as the cause of a hereditary progeroid syndrome. Am. J. Hum. Genet. 88:
650-656, 2011.
7. Umland, T. C.; Wei, S.-Q.; Craigie, R.; Davies, D. R.: Structural
basis of DNA bridging by barrier-to-autointegration factor. Biochemistry 39:
9130-9138, 2000.
8. Zheng, R.; Ghirlando, R.; Lee, M. S.; Mizuuchi, K.; Krause, M.;
Craigie, R.: Barrier-to-autointegration factor (BAF) bridges DNA
in a discrete, higher-order nucleoprotein complex. Proc. Nat. Acad.
Sci. 97: 8997-9002, 2000.
*FIELD* CN
Marla J. F. O'Neill - updated: 5/25/2011
Paul J. Converse - updated: 6/19/2006
Patricia A. Hartz - updated: 5/19/2003
*FIELD* CD
Jennifer P. Macke: 5/17/1999
*FIELD* ED
joanna: 01/25/2012
carol: 5/25/2011
terry: 5/25/2011
mgross: 6/19/2006
mgross: 5/23/2003
mgross: 5/19/2003
carol: 2/21/2003
alopez: 7/20/1999
alopez: 5/18/1999
alopez: 5/17/1999
MIM
614008
*RECORD*
*FIELD* NO
614008
*FIELD* TI
#614008 NESTOR-GUILLERMO PROGERIA SYNDROME; NGPS
;;PROGERIA SYNDROME, CHILDHOOD-ONSET, WITH OSTEOLYSIS; PSCOO
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
Nestor-Guillermo progeria syndrome is caused by homozygous mutation in
the BANF1 gene (603811) on chromosome 11q13.
CLINICAL FEATURES
Puente et al. (2011) studied a consanguineous Spanish family in which
the 31-year-old male proband exhibited an atypical form of progeria.
Born to third-cousin healthy parents, the proband showed normal
development until 2 years of age, when he experienced failure to thrive
and his skin became dry and atrophic with small light-brown spots over
the thorax, scalp, and limbs. He also developed generalized lipoatrophy,
severe osteoporosis, and marked osteolysis. The atrophic facial
subcutaneous fat pad and the marked osteolysis of the maxilla and
mandible resulted in a typical pseudosenile facial appearance with
micrognathia, prominent subcutaneous venous patterning, convex nasal
ridge, and proptosis. Cognitive development was completely normal.
Features that differed from other forms of progeria included his age,
height of 145 cm (underestimated due to severe scoliosis), presence of
eyebrows and eyelashes, persistence of scalp hair to 12 years of age,
very severe osteolysis involving the mandible, clavicles, ribs, distal
phalanges, and radius, and the absence of coronary dysfunction,
atherosclerosis, or metabolic anomalies. A 24-year-old unrelated Spanish
man with an almost identical phenotype was also studied. Despite
thorough cardiovascular examination, neither patient showed signs of
ischemia or atherosclerosis, and neither had insulin resistance,
diabetes mellitus, or hypertriglyceridemia.
Cabanillas et al. (2011) described in detail the 2 patients from
unrelated Spanish families who were originally studied by Puente et al.
(2011), noting that the phenotype was designated 'Nestor-Guillermo'
progeria syndrome using the names of these 2 patients. In addition to
other progeric features, the 32-year-old index patient had severe
progressive scoliosis from 18 years of age and developed secondary
pulmonary hypertension by 27 years of age. On examination he had dyspnea
upon minor exertion, with a severe restrictive spirometry pattern.
Echocardiography showed moderate tricuspid insufficiency, severe mitral
regurgitation, and pulmonary hypertension. Electrocardiogram showed
sinus tachycardia, with dilation of both atria and right bundle branch
block, without signs of ischemia. Doppler ultrasound of the carotid
arteries showed no arteriosclerosis, and computed angiography of the
coronary arteries showed no coronary calcification or stenosis; his
blood pressure was normal. Examination of the second patient revealed a
progeria phenotype almost identical to the index case; however, this
patient had only mild scoliosis without impact on cardiovascular
function. Cardiovascular examination showed no signs of ischemia or
atherosclerosis, and blood pressure was normal; electrocardiogram
revealed sinus tachycardia and right bundle branch block. Laboratory
values in both patients were normal except for low 25-OH-vitamin D and
very low leptin; in addition, the index patient had a low fasting
glucose. Cabanillas et al. (2011) defined NGPS as a chronic progeria
because of the patients' slow clinical course and relatively long
survival, despite early onset of disease.
MAPPING
In a consanguineous Spanish family in which the proband had an atypical
progeroid syndrome and was negative for mutations in the LMNA (150330)
and ZMPSTE24 (606480) genes, Puente et al. (2011) performed exon
enrichment followed by massively parallel sequencing on DNA samples from
the proband and both parents under an assumption of an autosomal
recessive mode of inheritance. They identified 4 variants that were
heterozygous in the parents and homozygous in the proband, 3 of which
were located in a long contiguous stretch of homozygosity on chromosome
11q13.
MOLECULAR GENETICS
In a consanguineous Spanish family in which the proband had an atypical
progeroid syndrome, Puente et al. (2011) analyzed 4 candidate genes and
identified homozygosity for a missense mutation in the BANF1 gene (A12T;
603811.0001) on chromosome 11 that was also found to be present in
homozygosity in an unrelated Spanish patient with a nearly identical
phenotype. The unaffected parents in both families were heterozygous for
the mutation. The presence of a common homozygous haplotype in the 2
patients, who were from geographically distant regions of Spain,
suggested that A12T represented a founder mutation.
*FIELD* RF
1. Cabanillas, R.; Cadinanos, J.; Villameytide, J. A. F.; Perez, M.;
Longo, J.; Richard, J. M.; Alvarez, R.; Duran, N. S.; Illan, R.; Gonzalez,
D. J.; Lopez-Otin, C.: Nestor-Guillermo progeria syndrome: a novel
premature aging condition with early onset and chronic development
caused by BANF1 mutations. Am. J. Med. Genet. 155A: 2617-2625, 2011.
2. Puente, X. S.; Quesada, V.; Osorio, F. G.; Cabanillas, R.; Cadinanos,
J.; Fraile, J. M.; Ordonez, G. R.; Puente, D. A.; Gutierrez-Fernandez,
A.; Fanjul-Fernandez, M.; Levy, N.; Freije, J. M. P.; Lopez-Otin,
C.: Exome sequencing and functional analysis identifies BANF1 mutation
as the cause of a hereditary progeroid syndrome. Am. J. Hum. Genet. 88:
650-656, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Other];
Failure to thrive
HEAD AND NECK:
[Face];
Micrognathia;
Mandibular osteolysis;
Midface hypoplasia;
[Eyes];
Proptosis;
Sparse eyebrows;
Sparse eyelashes;
[Nose];
Convex nasal ridge;
[Mouth];
Restricted opening of mouth;
[Teeth];
Dental crowding
CARDIOVASCULAR:
[Heart];
Sinus tachycardia;
Right bundle branch block [Vascular];
Prominent subcutaneous venous patterning;
Pulmonary hypertension (secondary to scoliosis, in some patients)
RESPIRATORY:
[Lung];
Dyspnea on exertion (secondary to scoliosis, in some patients)
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Osteolysis of clavicles;
Osteolysis of ribs
SKELETAL:
Stiff joints;
Joint contractures;
Osteoporosis, severe;
Osteolysis, severe (of mandible, clavicles, ribs, distal phalanges,
and radii);
[Skull];
Delayed closure of anterior fontanel;
Widely open cranial sutures;
[Spine];
Scoliosis;
[Limbs];
Mobility restriction of elbows and knees;
Osteolysis of radii;
[Hands];
Mobility restriction of hands and fingers;
Osteolysis of distal phalanges
SKIN, NAILS, HAIR:
[Skin];
Patchy hyperpigmentation;
[Hair];
Sparse eyebrows;
Sparse eyelashes;
Scalp hair sparse to absent, beginning in second decade of life
MUSCLE, SOFT TISSUE:
Lipoatrophy, generalized
LABORATORY ABNORMALITIES:
Very low leptin level;
Low 25-OH-vitamin D level;
Low fasting glucose (in some patients)
MISCELLANEOUS:
In contrast to other forms of progeria, these patients do not have
atherosclerosis, cardiac ischemia, or metabolic abnormalities;
Two patients from Spain have been reported (as of January 2012)
MOLECULAR BASIS:
Caused by mutation in the barrier-to-autointegration factor-1 gene
(BANF1, 603811.0001)
*FIELD* CN
Marla J. F. O'Neill - updated: 1/26/2012
*FIELD* CD
Marla J. F. O'Neill: 5/25/2011
*FIELD* ED
joanna: 01/27/2012
joanna: 1/26/2012
joanna: 5/25/2011
*FIELD* CN
Marla J. F. O'Neill - updated: 1/26/2012
*FIELD* CD
Marla J. F. O'Neill: 5/25/2011
*FIELD* ED
carol: 01/27/2012
terry: 1/26/2012
carol: 6/7/2011
carol: 6/1/2011
joanna: 5/25/2011
carol: 5/25/2011
*RECORD*
*FIELD* NO
614008
*FIELD* TI
#614008 NESTOR-GUILLERMO PROGERIA SYNDROME; NGPS
;;PROGERIA SYNDROME, CHILDHOOD-ONSET, WITH OSTEOLYSIS; PSCOO
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
Nestor-Guillermo progeria syndrome is caused by homozygous mutation in
the BANF1 gene (603811) on chromosome 11q13.
CLINICAL FEATURES
Puente et al. (2011) studied a consanguineous Spanish family in which
the 31-year-old male proband exhibited an atypical form of progeria.
Born to third-cousin healthy parents, the proband showed normal
development until 2 years of age, when he experienced failure to thrive
and his skin became dry and atrophic with small light-brown spots over
the thorax, scalp, and limbs. He also developed generalized lipoatrophy,
severe osteoporosis, and marked osteolysis. The atrophic facial
subcutaneous fat pad and the marked osteolysis of the maxilla and
mandible resulted in a typical pseudosenile facial appearance with
micrognathia, prominent subcutaneous venous patterning, convex nasal
ridge, and proptosis. Cognitive development was completely normal.
Features that differed from other forms of progeria included his age,
height of 145 cm (underestimated due to severe scoliosis), presence of
eyebrows and eyelashes, persistence of scalp hair to 12 years of age,
very severe osteolysis involving the mandible, clavicles, ribs, distal
phalanges, and radius, and the absence of coronary dysfunction,
atherosclerosis, or metabolic anomalies. A 24-year-old unrelated Spanish
man with an almost identical phenotype was also studied. Despite
thorough cardiovascular examination, neither patient showed signs of
ischemia or atherosclerosis, and neither had insulin resistance,
diabetes mellitus, or hypertriglyceridemia.
Cabanillas et al. (2011) described in detail the 2 patients from
unrelated Spanish families who were originally studied by Puente et al.
(2011), noting that the phenotype was designated 'Nestor-Guillermo'
progeria syndrome using the names of these 2 patients. In addition to
other progeric features, the 32-year-old index patient had severe
progressive scoliosis from 18 years of age and developed secondary
pulmonary hypertension by 27 years of age. On examination he had dyspnea
upon minor exertion, with a severe restrictive spirometry pattern.
Echocardiography showed moderate tricuspid insufficiency, severe mitral
regurgitation, and pulmonary hypertension. Electrocardiogram showed
sinus tachycardia, with dilation of both atria and right bundle branch
block, without signs of ischemia. Doppler ultrasound of the carotid
arteries showed no arteriosclerosis, and computed angiography of the
coronary arteries showed no coronary calcification or stenosis; his
blood pressure was normal. Examination of the second patient revealed a
progeria phenotype almost identical to the index case; however, this
patient had only mild scoliosis without impact on cardiovascular
function. Cardiovascular examination showed no signs of ischemia or
atherosclerosis, and blood pressure was normal; electrocardiogram
revealed sinus tachycardia and right bundle branch block. Laboratory
values in both patients were normal except for low 25-OH-vitamin D and
very low leptin; in addition, the index patient had a low fasting
glucose. Cabanillas et al. (2011) defined NGPS as a chronic progeria
because of the patients' slow clinical course and relatively long
survival, despite early onset of disease.
MAPPING
In a consanguineous Spanish family in which the proband had an atypical
progeroid syndrome and was negative for mutations in the LMNA (150330)
and ZMPSTE24 (606480) genes, Puente et al. (2011) performed exon
enrichment followed by massively parallel sequencing on DNA samples from
the proband and both parents under an assumption of an autosomal
recessive mode of inheritance. They identified 4 variants that were
heterozygous in the parents and homozygous in the proband, 3 of which
were located in a long contiguous stretch of homozygosity on chromosome
11q13.
MOLECULAR GENETICS
In a consanguineous Spanish family in which the proband had an atypical
progeroid syndrome, Puente et al. (2011) analyzed 4 candidate genes and
identified homozygosity for a missense mutation in the BANF1 gene (A12T;
603811.0001) on chromosome 11 that was also found to be present in
homozygosity in an unrelated Spanish patient with a nearly identical
phenotype. The unaffected parents in both families were heterozygous for
the mutation. The presence of a common homozygous haplotype in the 2
patients, who were from geographically distant regions of Spain,
suggested that A12T represented a founder mutation.
*FIELD* RF
1. Cabanillas, R.; Cadinanos, J.; Villameytide, J. A. F.; Perez, M.;
Longo, J.; Richard, J. M.; Alvarez, R.; Duran, N. S.; Illan, R.; Gonzalez,
D. J.; Lopez-Otin, C.: Nestor-Guillermo progeria syndrome: a novel
premature aging condition with early onset and chronic development
caused by BANF1 mutations. Am. J. Med. Genet. 155A: 2617-2625, 2011.
2. Puente, X. S.; Quesada, V.; Osorio, F. G.; Cabanillas, R.; Cadinanos,
J.; Fraile, J. M.; Ordonez, G. R.; Puente, D. A.; Gutierrez-Fernandez,
A.; Fanjul-Fernandez, M.; Levy, N.; Freije, J. M. P.; Lopez-Otin,
C.: Exome sequencing and functional analysis identifies BANF1 mutation
as the cause of a hereditary progeroid syndrome. Am. J. Hum. Genet. 88:
650-656, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Other];
Failure to thrive
HEAD AND NECK:
[Face];
Micrognathia;
Mandibular osteolysis;
Midface hypoplasia;
[Eyes];
Proptosis;
Sparse eyebrows;
Sparse eyelashes;
[Nose];
Convex nasal ridge;
[Mouth];
Restricted opening of mouth;
[Teeth];
Dental crowding
CARDIOVASCULAR:
[Heart];
Sinus tachycardia;
Right bundle branch block [Vascular];
Prominent subcutaneous venous patterning;
Pulmonary hypertension (secondary to scoliosis, in some patients)
RESPIRATORY:
[Lung];
Dyspnea on exertion (secondary to scoliosis, in some patients)
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Osteolysis of clavicles;
Osteolysis of ribs
SKELETAL:
Stiff joints;
Joint contractures;
Osteoporosis, severe;
Osteolysis, severe (of mandible, clavicles, ribs, distal phalanges,
and radii);
[Skull];
Delayed closure of anterior fontanel;
Widely open cranial sutures;
[Spine];
Scoliosis;
[Limbs];
Mobility restriction of elbows and knees;
Osteolysis of radii;
[Hands];
Mobility restriction of hands and fingers;
Osteolysis of distal phalanges
SKIN, NAILS, HAIR:
[Skin];
Patchy hyperpigmentation;
[Hair];
Sparse eyebrows;
Sparse eyelashes;
Scalp hair sparse to absent, beginning in second decade of life
MUSCLE, SOFT TISSUE:
Lipoatrophy, generalized
LABORATORY ABNORMALITIES:
Very low leptin level;
Low 25-OH-vitamin D level;
Low fasting glucose (in some patients)
MISCELLANEOUS:
In contrast to other forms of progeria, these patients do not have
atherosclerosis, cardiac ischemia, or metabolic abnormalities;
Two patients from Spain have been reported (as of January 2012)
MOLECULAR BASIS:
Caused by mutation in the barrier-to-autointegration factor-1 gene
(BANF1, 603811.0001)
*FIELD* CN
Marla J. F. O'Neill - updated: 1/26/2012
*FIELD* CD
Marla J. F. O'Neill: 5/25/2011
*FIELD* ED
joanna: 01/27/2012
joanna: 1/26/2012
joanna: 5/25/2011
*FIELD* CN
Marla J. F. O'Neill - updated: 1/26/2012
*FIELD* CD
Marla J. F. O'Neill: 5/25/2011
*FIELD* ED
carol: 01/27/2012
terry: 1/26/2012
carol: 6/7/2011
carol: 6/1/2011
joanna: 5/25/2011
carol: 5/25/2011