Full text data of DNAJB2
DNAJB2
(HSJ1, HSPF3)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
DnaJ homolog subfamily B member 2 (DnaJ protein homolog 1; Heat shock 40 kDa protein 3; Heat shock protein J1; HSJ-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
DnaJ homolog subfamily B member 2 (DnaJ protein homolog 1; Heat shock 40 kDa protein 3; Heat shock protein J1; HSJ-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P25686
ID DNJB2_HUMAN Reviewed; 324 AA.
AC P25686; A8K9P6; Q8IUK1; Q8IUK2; Q96F52;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-SEP-2007, sequence version 3.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=DnaJ homolog subfamily B member 2;
DE AltName: Full=DnaJ protein homolog 1;
DE AltName: Full=Heat shock 40 kDa protein 3;
DE AltName: Full=Heat shock protein J1;
DE Short=HSJ-1;
GN Name=DNAJB2; Synonyms=HSJ1, HSPF3;
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 [GENOMIC DNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=1599432;
RA Cheetham M.E., Brion J.-P., Anderton B.H.;
RT "Human homologues of the bacterial heat-shock protein DnaJ are
RT preferentially expressed in neurons.";
RL Biochem. J. 284:469-476(1992).
RN [2]
RP SEQUENCE REVISION TO 214.
RA Cheetham M.E.;
RL Submitted (JUL-1998) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Colon, and Lymph;
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 SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [7]
RP INVOLVEMENT IN DSMA5.
RX PubMed=22522442; DOI=10.1002/ana.22684;
RA Blumen S.C., Astord S., Robin V., Vignaud L., Toumi N., Cieslik A.,
RA Achiron A., Carasso R.L., Gurevich M., Braverman I., Blumen N.,
RA Munich A., Barkats M., Viollet L.;
RT "A rare recessive distal hereditary motor neuropathy with HSJ1
RT chaperone mutation.";
RL Ann. Neurol. 71:509-519(2012).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=3;
CC IsoId=P25686-3; Sequence=Displayed;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay.
CC Ref.1 (AAA09035) sequence differs from that shown due to a
CC frameshift in position 288;
CC Name=2; Synonyms=HSJ1A;
CC IsoId=P25686-2; Sequence=VSP_001286, VSP_001287;
CC -!- TISSUE SPECIFICITY: Brain (neuronal layers). Weakly, in skeletal
CC muscle and spleen.
CC -!- DISEASE: Distal spinal muscular atrophy, autosomal recessive, 5
CC (DSMA5) [MIM:614881]: An autosomal recessive neurologic disorder
CC characterized by young adult onset of slowly progressive distal
CC muscle weakness and atrophy resulting in gait impairment and loss
CC of reflexes due to impaired function of motor nerves. Sensation
CC and cognition are not impaired. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 J domain.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
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; S37375; AAA09034.1; -; mRNA.
DR EMBL; S37374; AAA09035.1; ALT_FRAME; mRNA.
DR EMBL; X63368; CAA44968.2; -; Genomic_DNA.
DR EMBL; X63368; CAA44969.2; -; Genomic_DNA.
DR EMBL; BT007088; AAP35751.1; -; mRNA.
DR EMBL; AK292761; BAF85450.1; -; mRNA.
DR EMBL; BC011609; AAH11609.1; -; mRNA.
DR EMBL; BC047056; AAH47056.1; -; mRNA.
DR PIR; S23508; S23508.
DR RefSeq; NP_001034639.1; NM_001039550.1.
DR RefSeq; NP_006727.2; NM_006736.5.
DR UniGene; Hs.77768; -.
DR PDB; 2LGW; NMR; -; A=1-91.
DR PDBsum; 2LGW; -.
DR ProteinModelPortal; P25686; -.
DR SMR; P25686; 1-69.
DR DIP; DIP-29051N; -.
DR IntAct; P25686; 5.
DR MINT; MINT-1192251; -.
DR STRING; 9606.ENSP00000338019; -.
DR PhosphoSite; P25686; -.
DR DMDM; 158518384; -.
DR PaxDb; P25686; -.
DR PRIDE; P25686; -.
DR DNASU; 3300; -.
DR Ensembl; ENST00000336576; ENSP00000338019; ENSG00000135924.
DR Ensembl; ENST00000392086; ENSP00000375936; ENSG00000135924.
DR GeneID; 3300; -.
DR KEGG; hsa:3300; -.
DR UCSC; uc002vkx.1; human.
DR CTD; 3300; -.
DR GeneCards; GC02P220143; -.
DR HGNC; HGNC:5228; DNAJB2.
DR HPA; HPA036268; -.
DR MIM; 604139; gene.
DR MIM; 614881; phenotype.
DR neXtProt; NX_P25686; -.
DR Orphanet; 314485; Young adult-onset distal hereditary motor neuropathy.
DR PharmGKB; PA27415; -.
DR eggNOG; COG0484; -.
DR HOGENOM; HOG000111538; -.
DR HOVERGEN; HBG066998; -.
DR InParanoid; P25686; -.
DR KO; K09508; -.
DR OMA; RGPRHSG; -.
DR OrthoDB; EOG7KSX9F; -.
DR ChiTaRS; DNAJB2; human.
DR GeneWiki; DNAJB2; -.
DR GenomeRNAi; 3300; -.
DR NextBio; 13093; -.
DR PRO; PR:P25686; -.
DR ArrayExpress; P25686; -.
DR Bgee; P25686; -.
DR CleanEx; HS_DNAJB2; -.
DR Genevestigator; P25686; -.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0070628; F:proteasome binding; IDA:BHF-UCL.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IGI:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IGI:UniProtKB.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:BHF-UCL.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; IDA:BHF-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR Gene3D; 1.10.287.110; -; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR018253; DnaJ_domain_CS.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR Pfam; PF00226; DnaJ; 1.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM00726; UIM; 2.
DR SUPFAM; SSF46565; SSF46565; 1.
DR PROSITE; PS00636; DNAJ_1; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone;
KW Complete proteome; Neurodegeneration; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 324 DnaJ homolog subfamily B member 2.
FT /FTId=PRO_0000071018.
FT DOMAIN 1 71 J.
FT REPEAT 210 226 UIM 1.
FT REPEAT 250 269 UIM 2.
FT MOD_RES 2 2 N-acetylalanine (By similarity).
FT VAR_SEQ 275 277 GGR -> DVF (in isoform 2).
FT /FTId=VSP_001286.
FT VAR_SEQ 278 324 Missing (in isoform 2).
FT /FTId=VSP_001287.
FT VARIANT 270 270 G -> R (in dbSNP:rs34127289).
FT /FTId=VAR_048910.
FT CONFLICT 214 214 L -> R (in Ref. 1; AAA09034/AAA09035).
FT HELIX 4 7
FT STRAND 8 10
FT HELIX 16 29
FT TURN 32 34
FT HELIX 40 57
FT HELIX 59 70
SQ SEQUENCE 324 AA; 35580 MW; 0154ED3E29F34B4A CRC64;
MASYYEILDV PRSASADDIK KAYRRKALQW HPDKNPDNKE FAEKKFKEVA EAYEVLSDKH
KREIYDRYGR EGLTGTGTGP SRAEAGSGGP GFTFTFRSPE EVFREFFGSG DPFAELFDDL
GPFSELQNRG SRHSGPFFTF SSSFPGHSDF SSSSFSFSPG AGAFRSVSTS TTFVQGRRIT
TRRIMENGQE RVEVEEDGQL KSVTINGVPD DLALGLELSR REQQPSVTSR SGGTQVQQTP
ASCPLDSDLS EDEDLQLAMA YSLSEMEAAG KKPAGGREAQ HRRQGRPKAQ HQDPGLGGTQ
EGARGEATKR SPSPEEKASR CLIL
//
ID DNJB2_HUMAN Reviewed; 324 AA.
AC P25686; A8K9P6; Q8IUK1; Q8IUK2; Q96F52;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-SEP-2007, sequence version 3.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=DnaJ homolog subfamily B member 2;
DE AltName: Full=DnaJ protein homolog 1;
DE AltName: Full=Heat shock 40 kDa protein 3;
DE AltName: Full=Heat shock protein J1;
DE Short=HSJ-1;
GN Name=DNAJB2; Synonyms=HSJ1, HSPF3;
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 [GENOMIC DNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=1599432;
RA Cheetham M.E., Brion J.-P., Anderton B.H.;
RT "Human homologues of the bacterial heat-shock protein DnaJ are
RT preferentially expressed in neurons.";
RL Biochem. J. 284:469-476(1992).
RN [2]
RP SEQUENCE REVISION TO 214.
RA Cheetham M.E.;
RL Submitted (JUL-1998) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Colon, and Lymph;
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 SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [7]
RP INVOLVEMENT IN DSMA5.
RX PubMed=22522442; DOI=10.1002/ana.22684;
RA Blumen S.C., Astord S., Robin V., Vignaud L., Toumi N., Cieslik A.,
RA Achiron A., Carasso R.L., Gurevich M., Braverman I., Blumen N.,
RA Munich A., Barkats M., Viollet L.;
RT "A rare recessive distal hereditary motor neuropathy with HSJ1
RT chaperone mutation.";
RL Ann. Neurol. 71:509-519(2012).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Experimental confirmation may be lacking for some
CC isoforms;
CC Name=3;
CC IsoId=P25686-3; Sequence=Displayed;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay.
CC Ref.1 (AAA09035) sequence differs from that shown due to a
CC frameshift in position 288;
CC Name=2; Synonyms=HSJ1A;
CC IsoId=P25686-2; Sequence=VSP_001286, VSP_001287;
CC -!- TISSUE SPECIFICITY: Brain (neuronal layers). Weakly, in skeletal
CC muscle and spleen.
CC -!- DISEASE: Distal spinal muscular atrophy, autosomal recessive, 5
CC (DSMA5) [MIM:614881]: An autosomal recessive neurologic disorder
CC characterized by young adult onset of slowly progressive distal
CC muscle weakness and atrophy resulting in gait impairment and loss
CC of reflexes due to impaired function of motor nerves. Sensation
CC and cognition are not impaired. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 J domain.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
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; S37375; AAA09034.1; -; mRNA.
DR EMBL; S37374; AAA09035.1; ALT_FRAME; mRNA.
DR EMBL; X63368; CAA44968.2; -; Genomic_DNA.
DR EMBL; X63368; CAA44969.2; -; Genomic_DNA.
DR EMBL; BT007088; AAP35751.1; -; mRNA.
DR EMBL; AK292761; BAF85450.1; -; mRNA.
DR EMBL; BC011609; AAH11609.1; -; mRNA.
DR EMBL; BC047056; AAH47056.1; -; mRNA.
DR PIR; S23508; S23508.
DR RefSeq; NP_001034639.1; NM_001039550.1.
DR RefSeq; NP_006727.2; NM_006736.5.
DR UniGene; Hs.77768; -.
DR PDB; 2LGW; NMR; -; A=1-91.
DR PDBsum; 2LGW; -.
DR ProteinModelPortal; P25686; -.
DR SMR; P25686; 1-69.
DR DIP; DIP-29051N; -.
DR IntAct; P25686; 5.
DR MINT; MINT-1192251; -.
DR STRING; 9606.ENSP00000338019; -.
DR PhosphoSite; P25686; -.
DR DMDM; 158518384; -.
DR PaxDb; P25686; -.
DR PRIDE; P25686; -.
DR DNASU; 3300; -.
DR Ensembl; ENST00000336576; ENSP00000338019; ENSG00000135924.
DR Ensembl; ENST00000392086; ENSP00000375936; ENSG00000135924.
DR GeneID; 3300; -.
DR KEGG; hsa:3300; -.
DR UCSC; uc002vkx.1; human.
DR CTD; 3300; -.
DR GeneCards; GC02P220143; -.
DR HGNC; HGNC:5228; DNAJB2.
DR HPA; HPA036268; -.
DR MIM; 604139; gene.
DR MIM; 614881; phenotype.
DR neXtProt; NX_P25686; -.
DR Orphanet; 314485; Young adult-onset distal hereditary motor neuropathy.
DR PharmGKB; PA27415; -.
DR eggNOG; COG0484; -.
DR HOGENOM; HOG000111538; -.
DR HOVERGEN; HBG066998; -.
DR InParanoid; P25686; -.
DR KO; K09508; -.
DR OMA; RGPRHSG; -.
DR OrthoDB; EOG7KSX9F; -.
DR ChiTaRS; DNAJB2; human.
DR GeneWiki; DNAJB2; -.
DR GenomeRNAi; 3300; -.
DR NextBio; 13093; -.
DR PRO; PR:P25686; -.
DR ArrayExpress; P25686; -.
DR Bgee; P25686; -.
DR CleanEx; HS_DNAJB2; -.
DR Genevestigator; P25686; -.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0070628; F:proteasome binding; IDA:BHF-UCL.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IGI:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IGI:UniProtKB.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:BHF-UCL.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; IDA:BHF-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR Gene3D; 1.10.287.110; -; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR018253; DnaJ_domain_CS.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR Pfam; PF00226; DnaJ; 1.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM00726; UIM; 2.
DR SUPFAM; SSF46565; SSF46565; 1.
DR PROSITE; PS00636; DNAJ_1; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone;
KW Complete proteome; Neurodegeneration; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 324 DnaJ homolog subfamily B member 2.
FT /FTId=PRO_0000071018.
FT DOMAIN 1 71 J.
FT REPEAT 210 226 UIM 1.
FT REPEAT 250 269 UIM 2.
FT MOD_RES 2 2 N-acetylalanine (By similarity).
FT VAR_SEQ 275 277 GGR -> DVF (in isoform 2).
FT /FTId=VSP_001286.
FT VAR_SEQ 278 324 Missing (in isoform 2).
FT /FTId=VSP_001287.
FT VARIANT 270 270 G -> R (in dbSNP:rs34127289).
FT /FTId=VAR_048910.
FT CONFLICT 214 214 L -> R (in Ref. 1; AAA09034/AAA09035).
FT HELIX 4 7
FT STRAND 8 10
FT HELIX 16 29
FT TURN 32 34
FT HELIX 40 57
FT HELIX 59 70
SQ SEQUENCE 324 AA; 35580 MW; 0154ED3E29F34B4A CRC64;
MASYYEILDV PRSASADDIK KAYRRKALQW HPDKNPDNKE FAEKKFKEVA EAYEVLSDKH
KREIYDRYGR EGLTGTGTGP SRAEAGSGGP GFTFTFRSPE EVFREFFGSG DPFAELFDDL
GPFSELQNRG SRHSGPFFTF SSSFPGHSDF SSSSFSFSPG AGAFRSVSTS TTFVQGRRIT
TRRIMENGQE RVEVEEDGQL KSVTINGVPD DLALGLELSR REQQPSVTSR SGGTQVQQTP
ASCPLDSDLS EDEDLQLAMA YSLSEMEAAG KKPAGGREAQ HRRQGRPKAQ HQDPGLGGTQ
EGARGEATKR SPSPEEKASR CLIL
//
MIM
604139
*RECORD*
*FIELD* NO
604139
*FIELD* TI
*604139 DNAJ/HSP40 HOMOLOG, SUBFAMILY B, MEMBER 2; DNAJB2
;;HEAT-SHOCK PROTEIN, DNAJ-LIKE 1; HSJ1;;
read moreHEAT-SHOCK 40-KD PROTEIN 3; HSPF3
*FIELD* TX
DESCRIPTION
The DNAJB2 gene encodes a molecular cochaperone member of the heat shock
protein family. These proteins play important cellular roles in correct
protein folding, in the response to protein misfolding, and in the
degradation of misfolded proteins (summary by Blumen et al., 2012).
CLONING
The E. coli heat-shock protein DnaJ has been implicated in protein
folding and protein complex dissociation. By screening a human frontal
cortex cDNA expression library with antibody against paired helical
filament proteins (see 157140), Cheetham et al. (1992) identified a
novel gene, HSJ1, which shows sequence similarity to DnaJ. They isolated
cDNAs corresponding to 2 alternatively spliced HSJ1 transcripts that
differ by the presence or absence of a 1.1-kb insert. The cDNA lacking
the insert encodes a deduced protein of 277 amino acids, whereas the
cDNA containing the insert has an alternative C-terminal sequence that
is 74 amino acids longer. The similarity between the HSJ1 and DnaJ
proteins is restricted to the N-terminal region. In addition, the
N-terminal and central regions of the HSJ1 proteins share sequence
similarity with those regions of SIS1, a yeast homolog of DnaJ. Western
blot analysis of human brain homogenates using antibodies against HSJ1
detected proteins with apparent molecular masses of approximately 42 and
36 kD. Northern blot analysis detected 3.0- and 2.0-kb HSJ1 transcripts
in human brain; no HSJ1 expression was found in the other tissues
examined. RNase protection analysis showed that HSJ1 is expressed almost
exclusively in the brain, with the highest levels in the frontal cortex
and hippocampus. In situ hybridization of human brain sections detected
HSJ1 mRNA mainly in the neuronal layers.
DNAJB2 isoform b is more abundant in brain than isoform a (Borrell-Pages
et al., 2006).
GENE STRUCTURE
The DNAJB2 gene contains 10 exons and encodes 2 main transcripts,
isoform a, encoded by exons 2-10, and isoform b, encoded by exons 2-9
(summary by Blumen et al., 2012).
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HSJ1
gene to chromosome 2 (TMAP Cda0vf12).
GENE FUNCTION
Borrell-Pages et al. (2006) found that Hsj1 proteins protected rat
striatal neurons from polyQ-huntingtin (613004)-induced cell death.
Hsj1a reduced intranuclear inclusions by acting as a typical chaperone
that unfolds misfolded proteins, whereas Hsj1b had a neuroprotective
effect by inhibiting cell death without any major effects in
polyQ-huntingtin aggregation. Hsj1b mediated its beneficial effects by
promoting release of BDNF (113505) from the Golgi apparatus in neuronal
cells. Postmortem brain tissue from patients with Huntington disease
(HD; 143100) showed significantly decreased levels of HSJ1b compared to
controls. Treatment with cystamine, a transglutaminase inhibitor,
increased Hsj1b levels and increased levels of BDNF in mouse neuronal
cells and in a mouse model of Huntington disease and showed a
neuroprotective effect. Treatment of rodent and primate models of HD
with cystamine and cysteamine resulted in a transient increase in
peripheral blood levels of BDNF in these animals.
Blumen et al. (2012) demonstrated that cotransfection of either DNAJB2
isoform reduced aggregation of mutant SOD1 (147450) in motor neuron-like
cells. The antiaggregating effect was even more pronounced when both
isoforms were transfected into these cells. These findings indicated
that DNAJB2 has a neuroprotective effect in motor neurons.
MOLECULAR GENETICS
In 3 sibs, born of Moroccan Jewish Israeli parents, with autosomal
recessive distal spinal muscular atrophy-5 (DSMA5; 614881), Blumen et
al. (2012) identified a homozygous splice site mutation in the DNAJB2
gene (604139.0001). The mutation was identified by homozygosity mapping
followed by candidate gene sequencing. Patient fibroblasts showed
decreased levels of DNAJB2 isoform b compared to controls, and nuclear
and cytoplasmic expression of DNAJB2 was decreased compared to controls.
Transfection of the DNAJB2 truncating mutant into motor neuron-like
cells did not reduce aggregation of mutant SOD1, whereas transfection of
wildtype DNAJB2 suppressed aggregation. The findings indicated that loss
of function of DNAJB2 play a determining role in this disorder. The
disorder was characterized by young adult onset of slowly progressive
distal muscle weakness and atrophy resulting in gait impairment and loss
of reflexes. Sensation and cognition were not impaired. Direct
sequencing of coding exons of the DNAJB2 gene in 40 additional patients
with distal spinal muscular atrophy did not identify any mutations.
*FIELD* AV
.0001
SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL RECESSIVE, 5
DNAJB2, IVS5DS, G-A, +1
In 3 sibs, born of Moroccan Jewish Israeli parents, with autosomal
recessive distal spinal muscular atrophy-5 (DSMA5; 614881), Blumen et
al. (2012) identified a homozygous G-to-A transition in the donor splice
site of exon 5 of the DNAJB2 gene (352+1G-A), resulting in the addition
of 2 aberrant transcripts containing partial or complete retention of
exon 5 and resulting in premature termination. However, the wildtype
DNAJB2 transcript was also detected in patient fibroblasts. The
unaffected mother was heterozygous for the mutation, which was not found
in 400 European or 120 Moroccan Jewish control chromosomes. The mutation
was identified by homozygosity mapping followed by candidate gene
sequencing. Patient fibroblasts showed decreased levels of DNAJB2
isoform b compared to controls and absent expression of isoform a.
Immunofluorescent studies showed decreased nuclear and cytoplasmic
expression of DNAJB2 in patient fibroblasts compared to controls.
Transfection of the DNAJB2 truncating mutant into motor neuron-like
cells did not reduce aggregation of mutant SOD1 (147450), whereas
transfection of wildtype DNAJB2 suppressed aggregation. The findings
indicated that loss of function of DNAJB2 play a determining role in
this disorder.
*FIELD* RF
1. Blumen, S. C.; Astord, S.; Robin, V.; Vignaud, L.; Toumi, N.; Cieslik,
A.; Achiron, A.; Carasso, R. L.; Gurevich, M.; Braverman, I.; Blumen,
N.; Munich, A.; Barkats, M.; Viollet, L.: A rare recessive distal
hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71:
509-519, 2012.
2. Borrell-Pages, M.; Canals, J. M.; Cordelieres, F. P.; Parker, J.
A.; Pineda, J. R.; Grange, G.; Bryson, E. A.; Guillermier, M.; Hirsch,
E.; Hantraye, P.; Cheetham, M. E.; Neri, C.; Alberch, J.; Brouillet,
E.; Saudou, F.; Humbert, S.: Cystamine and cysteamine increase brain
levels of BDNF in Huntington disease via HSJ1b and transglutaminase. J.
Clin. Invest. 116: 1410-1424, 2006.
3. Cheetham, M. E.; Brion, J.-P.; Anderton, B. H.: Human homologues
of the bacterial heat-shock protein DnaJ are preferentially expressed
in neurons. Biochem. J. 284: 469-476, 1992.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/17/2012
George E. Tiller - updated: 2/5/2001
Ada Hamosh - updated: 3/14/2000
*FIELD* CD
Patti M. Sherman: 8/23/1999
*FIELD* ED
carol: 09/26/2013
terry: 10/19/2012
carol: 10/18/2012
ckniffin: 10/17/2012
carol: 8/17/2007
carol: 3/13/2001
carol: 3/12/2001
cwells: 2/5/2001
cwells: 1/31/2001
mgross: 5/9/2000
alopez: 3/14/2000
mgross: 8/30/1999
psherman: 8/24/1999
*RECORD*
*FIELD* NO
604139
*FIELD* TI
*604139 DNAJ/HSP40 HOMOLOG, SUBFAMILY B, MEMBER 2; DNAJB2
;;HEAT-SHOCK PROTEIN, DNAJ-LIKE 1; HSJ1;;
read moreHEAT-SHOCK 40-KD PROTEIN 3; HSPF3
*FIELD* TX
DESCRIPTION
The DNAJB2 gene encodes a molecular cochaperone member of the heat shock
protein family. These proteins play important cellular roles in correct
protein folding, in the response to protein misfolding, and in the
degradation of misfolded proteins (summary by Blumen et al., 2012).
CLONING
The E. coli heat-shock protein DnaJ has been implicated in protein
folding and protein complex dissociation. By screening a human frontal
cortex cDNA expression library with antibody against paired helical
filament proteins (see 157140), Cheetham et al. (1992) identified a
novel gene, HSJ1, which shows sequence similarity to DnaJ. They isolated
cDNAs corresponding to 2 alternatively spliced HSJ1 transcripts that
differ by the presence or absence of a 1.1-kb insert. The cDNA lacking
the insert encodes a deduced protein of 277 amino acids, whereas the
cDNA containing the insert has an alternative C-terminal sequence that
is 74 amino acids longer. The similarity between the HSJ1 and DnaJ
proteins is restricted to the N-terminal region. In addition, the
N-terminal and central regions of the HSJ1 proteins share sequence
similarity with those regions of SIS1, a yeast homolog of DnaJ. Western
blot analysis of human brain homogenates using antibodies against HSJ1
detected proteins with apparent molecular masses of approximately 42 and
36 kD. Northern blot analysis detected 3.0- and 2.0-kb HSJ1 transcripts
in human brain; no HSJ1 expression was found in the other tissues
examined. RNase protection analysis showed that HSJ1 is expressed almost
exclusively in the brain, with the highest levels in the frontal cortex
and hippocampus. In situ hybridization of human brain sections detected
HSJ1 mRNA mainly in the neuronal layers.
DNAJB2 isoform b is more abundant in brain than isoform a (Borrell-Pages
et al., 2006).
GENE STRUCTURE
The DNAJB2 gene contains 10 exons and encodes 2 main transcripts,
isoform a, encoded by exons 2-10, and isoform b, encoded by exons 2-9
(summary by Blumen et al., 2012).
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the HSJ1
gene to chromosome 2 (TMAP Cda0vf12).
GENE FUNCTION
Borrell-Pages et al. (2006) found that Hsj1 proteins protected rat
striatal neurons from polyQ-huntingtin (613004)-induced cell death.
Hsj1a reduced intranuclear inclusions by acting as a typical chaperone
that unfolds misfolded proteins, whereas Hsj1b had a neuroprotective
effect by inhibiting cell death without any major effects in
polyQ-huntingtin aggregation. Hsj1b mediated its beneficial effects by
promoting release of BDNF (113505) from the Golgi apparatus in neuronal
cells. Postmortem brain tissue from patients with Huntington disease
(HD; 143100) showed significantly decreased levels of HSJ1b compared to
controls. Treatment with cystamine, a transglutaminase inhibitor,
increased Hsj1b levels and increased levels of BDNF in mouse neuronal
cells and in a mouse model of Huntington disease and showed a
neuroprotective effect. Treatment of rodent and primate models of HD
with cystamine and cysteamine resulted in a transient increase in
peripheral blood levels of BDNF in these animals.
Blumen et al. (2012) demonstrated that cotransfection of either DNAJB2
isoform reduced aggregation of mutant SOD1 (147450) in motor neuron-like
cells. The antiaggregating effect was even more pronounced when both
isoforms were transfected into these cells. These findings indicated
that DNAJB2 has a neuroprotective effect in motor neurons.
MOLECULAR GENETICS
In 3 sibs, born of Moroccan Jewish Israeli parents, with autosomal
recessive distal spinal muscular atrophy-5 (DSMA5; 614881), Blumen et
al. (2012) identified a homozygous splice site mutation in the DNAJB2
gene (604139.0001). The mutation was identified by homozygosity mapping
followed by candidate gene sequencing. Patient fibroblasts showed
decreased levels of DNAJB2 isoform b compared to controls, and nuclear
and cytoplasmic expression of DNAJB2 was decreased compared to controls.
Transfection of the DNAJB2 truncating mutant into motor neuron-like
cells did not reduce aggregation of mutant SOD1, whereas transfection of
wildtype DNAJB2 suppressed aggregation. The findings indicated that loss
of function of DNAJB2 play a determining role in this disorder. The
disorder was characterized by young adult onset of slowly progressive
distal muscle weakness and atrophy resulting in gait impairment and loss
of reflexes. Sensation and cognition were not impaired. Direct
sequencing of coding exons of the DNAJB2 gene in 40 additional patients
with distal spinal muscular atrophy did not identify any mutations.
*FIELD* AV
.0001
SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL RECESSIVE, 5
DNAJB2, IVS5DS, G-A, +1
In 3 sibs, born of Moroccan Jewish Israeli parents, with autosomal
recessive distal spinal muscular atrophy-5 (DSMA5; 614881), Blumen et
al. (2012) identified a homozygous G-to-A transition in the donor splice
site of exon 5 of the DNAJB2 gene (352+1G-A), resulting in the addition
of 2 aberrant transcripts containing partial or complete retention of
exon 5 and resulting in premature termination. However, the wildtype
DNAJB2 transcript was also detected in patient fibroblasts. The
unaffected mother was heterozygous for the mutation, which was not found
in 400 European or 120 Moroccan Jewish control chromosomes. The mutation
was identified by homozygosity mapping followed by candidate gene
sequencing. Patient fibroblasts showed decreased levels of DNAJB2
isoform b compared to controls and absent expression of isoform a.
Immunofluorescent studies showed decreased nuclear and cytoplasmic
expression of DNAJB2 in patient fibroblasts compared to controls.
Transfection of the DNAJB2 truncating mutant into motor neuron-like
cells did not reduce aggregation of mutant SOD1 (147450), whereas
transfection of wildtype DNAJB2 suppressed aggregation. The findings
indicated that loss of function of DNAJB2 play a determining role in
this disorder.
*FIELD* RF
1. Blumen, S. C.; Astord, S.; Robin, V.; Vignaud, L.; Toumi, N.; Cieslik,
A.; Achiron, A.; Carasso, R. L.; Gurevich, M.; Braverman, I.; Blumen,
N.; Munich, A.; Barkats, M.; Viollet, L.: A rare recessive distal
hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71:
509-519, 2012.
2. Borrell-Pages, M.; Canals, J. M.; Cordelieres, F. P.; Parker, J.
A.; Pineda, J. R.; Grange, G.; Bryson, E. A.; Guillermier, M.; Hirsch,
E.; Hantraye, P.; Cheetham, M. E.; Neri, C.; Alberch, J.; Brouillet,
E.; Saudou, F.; Humbert, S.: Cystamine and cysteamine increase brain
levels of BDNF in Huntington disease via HSJ1b and transglutaminase. J.
Clin. Invest. 116: 1410-1424, 2006.
3. Cheetham, M. E.; Brion, J.-P.; Anderton, B. H.: Human homologues
of the bacterial heat-shock protein DnaJ are preferentially expressed
in neurons. Biochem. J. 284: 469-476, 1992.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/17/2012
George E. Tiller - updated: 2/5/2001
Ada Hamosh - updated: 3/14/2000
*FIELD* CD
Patti M. Sherman: 8/23/1999
*FIELD* ED
carol: 09/26/2013
terry: 10/19/2012
carol: 10/18/2012
ckniffin: 10/17/2012
carol: 8/17/2007
carol: 3/13/2001
carol: 3/12/2001
cwells: 2/5/2001
cwells: 1/31/2001
mgross: 5/9/2000
alopez: 3/14/2000
mgross: 8/30/1999
psherman: 8/24/1999
MIM
614881
*RECORD*
*FIELD* NO
614881
*FIELD* TI
#614881 SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL RECESSIVE, 5; DSMA5
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read moredistal spinal muscular atrophy-5 (DSMA5) can be caused by homozygous
mutation in the DNAJB2 gene (604139) on chromosome 2q35.
DESCRIPTION
DSMA5 is an autosomal recessive neurologic disorder characterized by
young adult onset of slowly progressive distal muscle weakness and
atrophy resulting in gait impairment and loss of reflexes due to
impaired function of motor nerves. Sensation and cognition are not
impaired (summary by Blumen et al., 2012).
For a general phenotypic description and a discussion of genetic
heterogeneity of distal SMA, see HMN1 (182960).
CLINICAL FEATURES
Blumen et al. (2012) reported 3 adult sibs, born of Moroccan Jewish
Israeli parents, with distal muscle weakness. The parents' consanguinity
was probable, but not certain. The proband presented at age 18 years
with difficulty walking due to distal lower limb weakness and foot drop.
Her older sibs had onset of a similar disorder at ages 23 and 20 years.
All sibs had slowly progressive weakness, hypotonia, and muscle atrophy
of the lower limbs, more pronounced distally. Knee and ankle jerks were
absent; 1 patient had pes cavus. The 2 older sibs used a wheelchair and
the proband used a walker. The upper limbs were relatively spared,
although both triceps and biceps reflexes were absent in all patients.
One patient had mild dysphonic speech, but none had cognitive, sensory,
cerebellar, or autonomic symptoms. Nerve conduction studies showed
decreased motor amplitudes in the peroneal and tibial regions.
Electromyography showed severe denervation of distal, and later,
proximal muscles of the lower limbs with mild denervation of some
intrinsic hand muscles.
INHERITANCE
The transmission pattern in the family with DSMA5 reported by Blumen et
al. (2012) was consistent with autosomal recessive inheritance.
MAPPING
By homozygosity mapping of a Moroccan Jewish Israeli family with
autosomal recessive distal spinal muscular atrophy, Blumen et al. (2012)
found linkage to a 7.6-Mb region on chromosome 2q34-q36.1 between D2S128
and D2S339 (maximum lod score of 3.091 at D2S2248).
MOLECULAR GENETICS
In 3 sibs with DSMA5, Blumen et al. (2012) identified a homozygous
splice site mutation in the DNAJB2 gene (604139.0001). The mutation was
found by homozygosity mapping followed by candidate gene analysis.
Mutations in the DNAJB2 gene were not found in 40 additional patients
with distal spinal muscular atrophy.
*FIELD* RF
1. Blumen, S. C.; Astord, S.; Robin, V.; Vignaud, L.; Toumi, N.; Cieslik,
A.; Achiron, A.; Carasso, R. L.; Gurevich, M.; Braverman, I.; Blumen,
N.; Munich, A.; Barkats, M.; Viollet, L.: A rare recessive distal
hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71:
509-519, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
SKELETAL:
[Feet];
Pes cavus (1 patient)
MUSCLE, SOFT TISSUE:
Distal muscle atrophy, lower limbs more severely affected than upper
limbs;
Distal muscle weakness, lower limbs more severely affected than upper
limbs;
Proximal muscle weakness, lower limbs, mild
NEUROLOGIC:
[Central nervous system];
Impaired gait;
Foot drop;
[Peripheral nervous system];
Areflexia of the upper and lower limbs;
Decreased amplitudes of motor nerves in the lower limbs seen on nerve
conduction studies
VOICE:
Dysphonia, mild (1 patient)
MISCELLANEOUS:
Onset in young adulthood (range 18 to 23 years);
Slowly progressive;
One family has been reported (last curated October 2012);
Two of 3 patients became wheelchair-bound
MOLECULAR BASIS:
Caused by mutation in the DNAJ/HSP40 homolog, subfamily B, member
2 gene (DNAJB2, 604139.0001)
*FIELD* CD
Cassandra L. Kniffin: 10/17/2012
*FIELD* ED
joanna: 11/21/2012
ckniffin: 10/17/2012
*FIELD* CD
Cassandra L. Kniffin: 10/17/2012
*FIELD* ED
carol: 10/18/2012
ckniffin: 10/17/2012
*RECORD*
*FIELD* NO
614881
*FIELD* TI
#614881 SPINAL MUSCULAR ATROPHY, DISTAL, AUTOSOMAL RECESSIVE, 5; DSMA5
*FIELD* TX
A number sign (#) is used with this entry because autosomal recessive
read moredistal spinal muscular atrophy-5 (DSMA5) can be caused by homozygous
mutation in the DNAJB2 gene (604139) on chromosome 2q35.
DESCRIPTION
DSMA5 is an autosomal recessive neurologic disorder characterized by
young adult onset of slowly progressive distal muscle weakness and
atrophy resulting in gait impairment and loss of reflexes due to
impaired function of motor nerves. Sensation and cognition are not
impaired (summary by Blumen et al., 2012).
For a general phenotypic description and a discussion of genetic
heterogeneity of distal SMA, see HMN1 (182960).
CLINICAL FEATURES
Blumen et al. (2012) reported 3 adult sibs, born of Moroccan Jewish
Israeli parents, with distal muscle weakness. The parents' consanguinity
was probable, but not certain. The proband presented at age 18 years
with difficulty walking due to distal lower limb weakness and foot drop.
Her older sibs had onset of a similar disorder at ages 23 and 20 years.
All sibs had slowly progressive weakness, hypotonia, and muscle atrophy
of the lower limbs, more pronounced distally. Knee and ankle jerks were
absent; 1 patient had pes cavus. The 2 older sibs used a wheelchair and
the proband used a walker. The upper limbs were relatively spared,
although both triceps and biceps reflexes were absent in all patients.
One patient had mild dysphonic speech, but none had cognitive, sensory,
cerebellar, or autonomic symptoms. Nerve conduction studies showed
decreased motor amplitudes in the peroneal and tibial regions.
Electromyography showed severe denervation of distal, and later,
proximal muscles of the lower limbs with mild denervation of some
intrinsic hand muscles.
INHERITANCE
The transmission pattern in the family with DSMA5 reported by Blumen et
al. (2012) was consistent with autosomal recessive inheritance.
MAPPING
By homozygosity mapping of a Moroccan Jewish Israeli family with
autosomal recessive distal spinal muscular atrophy, Blumen et al. (2012)
found linkage to a 7.6-Mb region on chromosome 2q34-q36.1 between D2S128
and D2S339 (maximum lod score of 3.091 at D2S2248).
MOLECULAR GENETICS
In 3 sibs with DSMA5, Blumen et al. (2012) identified a homozygous
splice site mutation in the DNAJB2 gene (604139.0001). The mutation was
found by homozygosity mapping followed by candidate gene analysis.
Mutations in the DNAJB2 gene were not found in 40 additional patients
with distal spinal muscular atrophy.
*FIELD* RF
1. Blumen, S. C.; Astord, S.; Robin, V.; Vignaud, L.; Toumi, N.; Cieslik,
A.; Achiron, A.; Carasso, R. L.; Gurevich, M.; Braverman, I.; Blumen,
N.; Munich, A.; Barkats, M.; Viollet, L.: A rare recessive distal
hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71:
509-519, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
SKELETAL:
[Feet];
Pes cavus (1 patient)
MUSCLE, SOFT TISSUE:
Distal muscle atrophy, lower limbs more severely affected than upper
limbs;
Distal muscle weakness, lower limbs more severely affected than upper
limbs;
Proximal muscle weakness, lower limbs, mild
NEUROLOGIC:
[Central nervous system];
Impaired gait;
Foot drop;
[Peripheral nervous system];
Areflexia of the upper and lower limbs;
Decreased amplitudes of motor nerves in the lower limbs seen on nerve
conduction studies
VOICE:
Dysphonia, mild (1 patient)
MISCELLANEOUS:
Onset in young adulthood (range 18 to 23 years);
Slowly progressive;
One family has been reported (last curated October 2012);
Two of 3 patients became wheelchair-bound
MOLECULAR BASIS:
Caused by mutation in the DNAJ/HSP40 homolog, subfamily B, member
2 gene (DNAJB2, 604139.0001)
*FIELD* CD
Cassandra L. Kniffin: 10/17/2012
*FIELD* ED
joanna: 11/21/2012
ckniffin: 10/17/2012
*FIELD* CD
Cassandra L. Kniffin: 10/17/2012
*FIELD* ED
carol: 10/18/2012
ckniffin: 10/17/2012