UN45B_HUMAN
ID UN45B_HUMAN Reviewed; 931 AA.
AC Q8IWX7; Q495Q8; Q495Q9;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Protein unc-45 homolog B {ECO:0000305};
DE Short=Unc-45B;
DE AltName: Full=SMUNC45;
GN Name=UNC45B {ECO:0000312|HGNC:HGNC:14304}; Synonyms=CMYA4, UNC45;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=12356907; DOI=10.1242/jcs.00108;
RA Price M.G., Landsverk M.L., Barral J.M., Epstein H.F.;
RT "Two mammalian UNC-45 isoforms are related to distinct cytoskeletal and
RT muscle-specific functions.";
RL J. Cell Sci. 115:4013-4023(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ILE-60.
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH UBE4B.
RX PubMed=17369820; DOI=10.1038/ncb1554;
RA Janiesch P.C., Kim J., Mouysset J., Barikbin R., Lochmueller H.,
RA Cassata G., Krause S., Hoppe T.;
RT "The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to
RT human myopathy.";
RL Nat. Cell Biol. 9:379-390(2007).
RN [4]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-496.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [5]
RP INVOLVEMENT IN CTRCT43, VARIANT CTRCT43 TRP-805, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=24549050; DOI=10.1038/ejhg.2014.21;
RA Hansen L., Comyn S., Mang Y., Lind-Thomsen A., Myhre L., Jean F.,
RA Eiberg H., Tommerup N., Rosenberg T., Pilgrim D.;
RT "The myosin chaperone UNC45B is involved in lens development and autosomal
RT dominant juvenile cataract.";
RL Eur. J. Hum. Genet. 22:1290-1297(2014).
RN [6]
RP VARIANT MFM11 GLN-754.
RX PubMed=31852522; DOI=10.1186/s40478-019-0869-1;
RA Dafsari H.S., Kocaturk N.M., Daimagueler H.S., Brunn A., Doetsch J.,
RA Weis J., Deckert M., Cirak S.;
RT "Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B
RT are a cause for congenital myopathy.";
RL Acta Neuropathol. Commun. 7:211-211(2019).
RN [7]
RP VARIANTS MFM11 PRO-403; ARG-514 AND GLN-754, CHARACTERIZATION OF VARIANTS
RP MFM11 PRO-403; ARG-514 AND GLN-754, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=33217308; DOI=10.1016/j.ajhg.2020.11.002;
RA Donkervoort S., Kutzner C.E., Hu Y., Lornage X., Rendu J., Stojkovic T.,
RA Baets J., Neuhaus S.B., Tanboon J., Maroofian R., Bolduc V., Mroczek M.,
RA Conijn S., Kuntz N.L., Toepf A., Monges S., Lubieniecki F., McCarty R.M.,
RA Chao K.R., Governali S., Boehm J., Boonyapisit K., Malfatti E.,
RA Sangruchi T., Horkayne-Szakaly I., Hedberg-Oldfors C., Efthymiou S.,
RA Noguchi S., Djeddi S., Iida A., di Rosa G., Fiorillo C., Salpietro V.,
RA Darin N., Faure J., Houlden H., Oldfors A., Nishino I., de Ridder W.,
RA Straub V., Pokrzywa W., Laporte J., Foley A.R., Romero N.B., Ottenheijm C.,
RA Hoppe T., Boennemann C.G.;
RT "Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive
RT Myopathy with Eccentric Cores.";
RL Am. J. Hum. Genet. 107:1078-1095(2020).
CC -!- FUNCTION: Acts as a co-chaperone for HSP90 and is required for proper
CC folding of the myosin motor domain. Plays a role in sarcomere formation
CC during muscle cell development. Is necessary for normal early lens
CC development. {ECO:0000250|UniProtKB:Q6DGE9,
CC ECO:0000250|UniProtKB:Q8CGY6}.
CC -!- SUBUNIT: Interacts with HSP90 in an ATP-independent manner (By
CC similarity). Interacts with UBE4B; the interaction may target UNC45B
CC for proteasomal degradation (PubMed:17369820).
CC {ECO:0000250|UniProtKB:Q8CGY6, ECO:0000269|PubMed:17369820}.
CC -!- INTERACTION:
CC Q8IWX7; P08238: HSP90AB1; NbExp=2; IntAct=EBI-9363363, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250|UniProtKB:Q6DGE9}. Cytoplasm, myofibril, sarcomere, A band
CC {ECO:0000269|PubMed:33217308}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q6DGE9}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8CGY6}. Note=Expressed at the Z line and in the
CC perinuclear region of myofibrils. Translocates to the A band in
CC response to stress conditions and fibril damage.
CC {ECO:0000250|UniProtKB:Q6DGE9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IWX7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWX7-2; Sequence=VSP_020586;
CC Name=3;
CC IsoId=Q8IWX7-3; Sequence=VSP_020587;
CC -!- TISSUE SPECIFICITY: Expressed in eye lens tissues. Expressed in muscle
CC (at protein level) (PubMed:33217308). {ECO:0000269|PubMed:24549050,
CC ECO:0000269|PubMed:33217308}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 43-day and 54-day embryonic eye
CC development. {ECO:0000269|PubMed:24549050}.
CC -!- DISEASE: Cataract 43 (CTRCT43) [MIM:616279]: An opacification of the
CC crystalline lens of the eye that frequently results in visual
CC impairment or blindness. Opacities vary in morphology, are often
CC confined to a portion of the lens, and may be static or progressive. In
CC general, the more posteriorly located and dense an opacity, the greater
CC the impact on visual function. {ECO:0000269|PubMed:24549050}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myopathy, myofibrillar, 11 (MFM11) [MIM:619178]: A form of
CC myofibrillar myopathy, a group of chronic neuromuscular disorders
CC characterized at ultrastructural level by disintegration of the
CC sarcomeric Z disk and myofibrils, and replacement of the normal
CC myofibrillar markings by small dense granules, or larger hyaline
CC masses, or amorphous material. MFM11 is an autosomal recessive form
CC characterized by onset of slowly progressive proximal muscle weakness
CC in the first decade of life. More variable features may include
CC decreased respiratory forced vital capacity, variable cardiac features,
CC and calf hypertrophy. Skeletal muscle biopsy shows myopathic changes
CC with variation in fiber size, type 1 fiber predominance, centralized
CC nuclei, eccentrically placed core-like lesions, and distortion of the
CC myofibrillary pattern with Z-line streaming and abnormal myofibrillar
CC aggregates or inclusions. {ECO:0000269|PubMed:31852522,
CC ECO:0000269|PubMed:33217308}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF539794; AAO13384.1; -; mRNA.
DR EMBL; BC101062; AAI01063.1; -; mRNA.
DR EMBL; BC101063; AAI01064.1; -; mRNA.
DR CCDS; CCDS11292.1; -. [Q8IWX7-1]
DR CCDS; CCDS45648.1; -. [Q8IWX7-3]
DR CCDS; CCDS76993.1; -. [Q8IWX7-2]
DR RefSeq; NP_001028748.1; NM_001033576.1. [Q8IWX7-3]
DR RefSeq; NP_001253981.1; NM_001267052.1. [Q8IWX7-3]
DR RefSeq; NP_001295210.1; NM_001308281.1. [Q8IWX7-2]
DR RefSeq; NP_775259.1; NM_173167.3. [Q8IWX7-1]
DR RefSeq; XP_016879723.1; XM_017024234.1. [Q8IWX7-2]
DR AlphaFoldDB; Q8IWX7; -.
DR SMR; Q8IWX7; -.
DR BioGRID; 127021; 20.
DR IntAct; Q8IWX7; 11.
DR STRING; 9606.ENSP00000268876; -.
DR iPTMnet; Q8IWX7; -.
DR PhosphoSitePlus; Q8IWX7; -.
DR BioMuta; UNC45B; -.
DR DMDM; 74762485; -.
DR EPD; Q8IWX7; -.
DR jPOST; Q8IWX7; -.
DR MassIVE; Q8IWX7; -.
DR PaxDb; Q8IWX7; -.
DR PeptideAtlas; Q8IWX7; -.
DR PRIDE; Q8IWX7; -.
DR ProteomicsDB; 70922; -. [Q8IWX7-1]
DR ProteomicsDB; 70923; -. [Q8IWX7-2]
DR ProteomicsDB; 70924; -. [Q8IWX7-3]
DR Antibodypedia; 2894; 164 antibodies from 28 providers.
DR DNASU; 146862; -.
DR Ensembl; ENST00000268876.9; ENSP00000268876.4; ENSG00000141161.12. [Q8IWX7-1]
DR Ensembl; ENST00000394570.7; ENSP00000378071.2; ENSG00000141161.12. [Q8IWX7-3]
DR Ensembl; ENST00000591048.2; ENSP00000468335.1; ENSG00000141161.12. [Q8IWX7-2]
DR GeneID; 146862; -.
DR KEGG; hsa:146862; -.
DR MANE-Select; ENST00000394570.7; ENSP00000378071.2; NM_001267052.2; NP_001253981.1. [Q8IWX7-3]
DR UCSC; uc002hja.3; human. [Q8IWX7-1]
DR CTD; 146862; -.
DR DisGeNET; 146862; -.
DR GeneCards; UNC45B; -.
DR HGNC; HGNC:14304; UNC45B.
DR HPA; ENSG00000141161; Group enriched (heart muscle, skeletal muscle, tongue).
DR MalaCards; UNC45B; -.
DR MIM; 611220; gene.
DR MIM; 616279; phenotype.
DR MIM; 619178; phenotype.
DR neXtProt; NX_Q8IWX7; -.
DR OpenTargets; ENSG00000141161; -.
DR Orphanet; 98991; Early-onset nuclear cataract.
DR Orphanet; 441447; Early-onset posterior subcapsular cataract.
DR PharmGKB; PA26655; -.
DR VEuPathDB; HostDB:ENSG00000141161; -.
DR eggNOG; KOG4151; Eukaryota.
DR GeneTree; ENSGT00940000157654; -.
DR HOGENOM; CLU_007331_0_0_1; -.
DR InParanoid; Q8IWX7; -.
DR OMA; CDPERAN; -.
DR OrthoDB; 1059433at2759; -.
DR PhylomeDB; Q8IWX7; -.
DR TreeFam; TF314096; -.
DR PathwayCommons; Q8IWX7; -.
DR SignaLink; Q8IWX7; -.
DR BioGRID-ORCS; 146862; 11 hits in 1066 CRISPR screens.
DR ChiTaRS; UNC45B; human.
DR GenomeRNAi; 146862; -.
DR Pharos; Q8IWX7; Tbio.
DR PRO; PR:Q8IWX7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IWX7; protein.
DR Bgee; ENSG00000141161; Expressed in left ventricle myocardium and 81 other tissues.
DR Genevisible; Q8IWX7; HS.
DR GO; GO:0031672; C:A band; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0051879; F:Hsp90 protein binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0002088; P:lens development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR Gene3D; 1.25.10.10; -; 2.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR024660; UCS_central_dom.
DR Pfam; PF11701; UNC45-central; 1.
DR SMART; SM00185; ARM; 4.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Chaperone; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant;
KW Myofibrillar myopathy; Myogenesis; Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..931
FT /note="Protein unc-45 homolog B"
FT /id="PRO_0000249892"
FT REPEAT 6..39
FT /note="TPR 1"
FT REPEAT 43..76
FT /note="TPR 2"
FT REPEAT 77..110
FT /note="TPR 3"
FT REPEAT 169..208
FT /note="ARM 1"
FT REPEAT 211..250
FT /note="ARM 2"
FT REPEAT 751..790
FT /note="ARM 3"
FT VAR_SEQ 485..565
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020586"
FT VAR_SEQ 564..565
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020587"
FT VARIANT 60
FT /note="V -> I (in dbSNP:rs16970659)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027506"
FT VARIANT 199
FT /note="A -> V (in dbSNP:rs35749208)"
FT /id="VAR_052630"
FT VARIANT 377
FT /note="K -> R (in dbSNP:rs41389545)"
FT /id="VAR_052631"
FT VARIANT 403
FT /note="S -> P (in MFM11; mislocated away from the A-band to
FT the Z-disk)"
FT /evidence="ECO:0000269|PubMed:33217308"
FT /id="VAR_085393"
FT VARIANT 496
FT /note="D -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035870"
FT VARIANT 514
FT /note="C -> R (in MFM11; unknown pathological significance;
FT mislocated away from the A-band to the Z-disk;
FT dbSNP:rs775340790)"
FT /evidence="ECO:0000269|PubMed:33217308"
FT /id="VAR_085394"
FT VARIANT 754
FT /note="R -> Q (in MFM11; mislocated away from the A-band to
FT the Z-disk)"
FT /evidence="ECO:0000269|PubMed:31852522,
FT ECO:0000269|PubMed:33217308"
FT /id="VAR_085395"
FT VARIANT 805
FT /note="R -> W (in CTRCT43; dbSNP:rs370424081)"
FT /evidence="ECO:0000269|PubMed:24549050"
FT /id="VAR_073375"
FT VARIANT 852
FT /note="I -> N (in dbSNP:rs11654824)"
FT /id="VAR_027507"
SQ SEQUENCE 931 AA; 103733 MW; A4F457349AAEAB76 CRC64;
MAEVEAVQLK EEGNRHFQLQ DYKAATNSYS QALKLTKDKA LLATLYRNRA ACGLKTESYV
QAASDASRAI DINSSDIKAL YRRCQALEHL GKLDQAFKDV QRCATLEPRN QNFQEMLRRL
NTSIQEKLRV QFSTDSRVQK MFEILLDENS EADKREKAAN NLIVLGREEA GAEKIFQNNG
VALLLQLLDT KKPELVLAAV RTLSGMCSGH QARATVILHA VRIDRICSLM AVENEEMSLA
VCNLLQAIID SLSGEDKREH RGKEEALVLD TKKDLKQITS HLLDMLVSKK VSGQGRDQAL
NLLNKNVPRK DLAIHDNSRT IYVVDNGLRK ILKVVGQVPD LPSCLPLTDN TRMLASILIN
KLYDDLRCDP ERDHFRKICE EYITGKFDPQ DMDKNLNAIQ TVSGILQGPF DLGNQLLGLK
GVMEMMVALC GSERETDQLV AVEALIHAST KLSRATFIIT NGVSLLKQIY KTTKNEKIKI
RTLVGLCKLG SAGGTDYGLR QFAEGSTEKL AKQCRKWLCN MSIDTRTRRW AVEGLAYLTL
DADVKDDFVQ DVPALQAMFE LAKAGTSDKT ILYSVATTLV NCTNSYDVKE VIPELVQLAK
FSKQHVPEEH PKDKKDFIDM RVKRLLKAGV ISALACMVKA DSAILTDQTK ELLARVFLAL
CDNPKDRGTI VAQGGGKALI PLALEGTDVG KVKAAHALAK IAAVSNPDIA FPGERVYEVV
RPLVRLLDTQ RDGLQNYEAL LGLTNLSGRS DKLRQKIFKE RALPDIENYM FENHDQLRQA
ATECMCNMVL HKEVQERFLA DGNDRLKLVV LLCGEDDDKV QNAAAGALAM LTAAHKKLCL
KMTQVTTQWL EILQRLCLHD QLSVQHRGLV IAYNLLAADA ELAKKLVESE LLEILTVVGK
QEPDEKKAEV VQTARECLIK CMDYGFIKPV S
