HSF2B_MOUSE
ID HSF2B_MOUSE Reviewed; 338 AA.
AC Q9D4G2;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Heat shock factor 2-binding protein {ECO:0000312|MGI:MGI:1921627};
GN Name=Hsf2bp {ECO:0000312|MGI:MGI:1921627};
GN Synonyms=Meilb2 {ECO:0000303|PubMed:30760716, ECO:0000303|PubMed:32345962,
GN ECO:0000303|PubMed:32463460};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|EMBL:BAB30300.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB30300.1};
RC TISSUE=Testis {ECO:0000312|EMBL:BAB30300.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000312|EMBL:EDL40335.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH BNC1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=23707421; DOI=10.1016/j.febslet.2013.04.049;
RA Wu Y., Liao S., Wang X., Wang S., Wang M., Han C.;
RT "HSF2BP represses BNC1 transcriptional activity by sequestering BNC1 to the
RT cytoplasm.";
RL FEBS Lett. 587:2099-2104(2013).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH BRCA2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=31242413; DOI=10.1016/j.celrep.2019.05.096;
RA Brandsma I., Sato K., van Rossum-Fikkert S.E., van Vliet N., Sleddens E.,
RA Reuter M., Odijk H., van den Tempel N., Dekkers D.H.W., Bezstarosti K.,
RA Demmers J.A.A., Maas A., Lebbink J., Wyman C., Essers J., van Gent D.C.,
RA Baarends W.M., Knipscheer P., Kanaar R., Zelensky A.N.;
RT "HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for
RT Mouse Spermatogenesis.";
RL Cell Rep. 27:3790.e7-3798.e7(2019).
RN [6]
RP FUNCTION, INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30760716; DOI=10.1038/s41467-019-08676-2;
RA Zhang J., Fujiwara Y., Yamamoto S., Shibuya H.;
RT "A meiosis-specific BRCA2 binding protein recruits recombinases to DNA
RT double-strand breaks to ensure homologous recombination.";
RL Nat. Commun. 10:722-722(2019).
RN [7]
RP INTERACTION WITH BRME1.
RX PubMed=32460033; DOI=10.1016/j.celrep.2020.107686;
RA Takemoto K., Tani N., Takada-Horisawa Y., Fujimura S., Tanno N., Yamane M.,
RA Okamura K., Sugimoto M., Araki K., Ishiguro K.I.;
RT "Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of
RT RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination.";
RL Cell Rep. 31:107686-107686(2020).
RN [8]
RP FUNCTION, MUTAGENESIS OF SER-167, DISRUPTION PHENOTYPE, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH BRCA2 AND BRME1.
RX PubMed=32845237; DOI=10.7554/elife.56996;
RA Felipe-Medina N., Caburet S., Sanchez-Saez F., Condezo Y.B., de Rooij D.G.,
RA Gomez-H L., Garcia-Valiente R., Todeschini A.L., Duque P.,
RA Sanchez-Martin M.A., Shalev S.A., Llano E., Veitia R.A., Pendas A.M.;
RT "A missense in HSF2BP causing primary ovarian insufficiency affects meiotic
RT recombination by its novel interactor C19ORF57/BRME1.";
RL Elife 9:0-0(2020).
RN [9]
RP FUNCTION, INTERACTION WITH BRME1; BRCA2; SPATA22; MEIOB AND RAD51, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-204.
RX PubMed=32345962; DOI=10.1038/s41467-020-15954-x;
RA Zhang J., Gurusaran M., Fujiwara Y., Zhang K., Echbarthi M., Vorontsov E.,
RA Guo R., Pendlebury D.F., Alam I., Livera G., Emmanuelle M., Wang P.J.,
RA Nandakumar J., Davies O.R., Shibuya H.;
RT "The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs
RT the mitotic BRCA2-RAD51 function in cancer cells.";
RL Nat. Commun. 11:2055-2055(2020).
RN [10]
RP FUNCTION, INTERACTION WITH BRME1, AND SUBCELLULAR LOCATION.
RX PubMed=32463460; DOI=10.1093/nar/gkaa406;
RA Shang Y., Huang T., Liu H., Liu Y., Liang H., Yu X., Li M., Zhai B.,
RA Yang X., Wei Y., Wang G., Chen Z., Wang S., Zhang L.;
RT "MEIOK21: a new component of meiotic recombination bridges required for
RT spermatogenesis.";
RL Nucleic Acids Res. 48:6624-6639(2020).
CC -!- FUNCTION: Meiotic recombination factor component of recombination
CC bridges involved in meiotic double-strand break repair. Modulates the
CC localization of recombinases DMC1:RAD51 to meiotic double-strand break
CC (DSB) sites through the interaction with BRCA2 and its recruitment
CC during meiotic recombination. Indispensable for the DSB repair,
CC homologous synapsis, and crossover formation that are needed for
CC progression past metaphase I, is essential for spermatogenesis and male
CC fertility (PubMed:31242413, PubMed:32345962, PubMed:32463460,
CC PubMed:30760716). Required for proper recombinase recruitment in female
CC meiosis (PubMed:30760716, PubMed:32845237). Inhibits BNC1
CC transcriptional activity during spermatogenesis, probably by
CC sequestering it in the cytoplasm (PubMed:23707421). May be involved in
CC modulating HSF2 activation in testis (By similarity).
CC {ECO:0000250|UniProtKB:O75031, ECO:0000269|PubMed:23707421,
CC ECO:0000269|PubMed:30760716, ECO:0000269|PubMed:31242413,
CC ECO:0000269|PubMed:32345962, ECO:0000269|PubMed:32463460,
CC ECO:0000269|PubMed:32845237}.
CC -!- SUBUNIT: Interacts (via C-terminus) with BNC1 (PubMed:23707421).
CC Associates with HSF2. The interaction seems to occur between the
CC trimerization domain of HSF2 and the N-terminal hydrophilic region of
CC HSF2BP (By similarity). Interacts (via N-terminus) with BRME1
CC (PubMed:32463460, PubMed:32460033, PubMed:32345962). Interacts with
CC BRCA2 and BRME1; the interactions are direct and allow the formation of
CC a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:32463460,
CC PubMed:31242413, PubMed:30760716, PubMed:32845237). The complex
CC BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51
CC (PubMed:32345962, PubMed:30760716). {ECO:0000250|UniProtKB:O75031,
CC ECO:0000269|PubMed:23707421, ECO:0000269|PubMed:30760716,
CC ECO:0000269|PubMed:31242413, ECO:0000269|PubMed:32345962,
CC ECO:0000269|PubMed:32460033, ECO:0000269|PubMed:32463460,
CC ECO:0000269|PubMed:32845237}.
CC -!- INTERACTION:
CC Q9D4G2; O35914: Bnc1; NbExp=4; IntAct=EBI-8527688, EBI-8527667;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23707421,
CC ECO:0000269|PubMed:32845237}. Chromosome {ECO:0000269|PubMed:30760716,
CC ECO:0000269|PubMed:31242413, ECO:0000269|PubMed:32345962,
CC ECO:0000269|PubMed:32463460, ECO:0000269|PubMed:32845237}.
CC Note=Localizes on double-strand breaks (DSBs) in mitotic and meiotic
CC chromosomes. {ECO:0000269|PubMed:30760716, ECO:0000269|PubMed:31242413,
CC ECO:0000269|PubMed:32345962, ECO:0000269|PubMed:32463460,
CC ECO:0000269|PubMed:32845237}.
CC -!- TISSUE SPECIFICITY: Expressed in testis and, to a lesser extent, in
CC lung and muscle. {ECO:0000269|PubMed:23707421,
CC ECO:0000269|PubMed:32345962, ECO:0000269|PubMed:32460033}.
CC -!- DEVELOPMENTAL STAGE: Detected at low levels from birth to 3 days post
CC partum, thereafter the expression level increases from 5 days post
CC partum to adult. In spermatocytes, shows punctate localization along
CC chromosome axes specifically in early meiotic prophase I cells. Foci
CC start to appear from the leptotene stage, reach their greatest number
CC in the zygotene stage, persist until the early pachytene stage, and
CC finally disappear in the late pachytene stage (PubMed:30760716).
CC {ECO:0000269|PubMed:23707421, ECO:0000269|PubMed:30760716}.
CC -!- PTM: Sumoylated by UBE2I in response to MEKK1-mediated stimuli.
CC {ECO:0000250|UniProtKB:O75031}.
CC -!- DISRUPTION PHENOTYPE: Male mutants are infertile (PubMed:31242413,
CC PubMed:30760716). They have smaller-than-normal testes with no sperm
CC (PubMed:31242413, PubMed:30760716). Female mutants exhibit a fertility
CC with 40% reduction in litter size compared to wild-type females. They
CC show reduced follicle formation (PubMed:30760716, PubMed:32845237).
CC Mutant oocytes show a delay in prophase I progression with the majority
CC of cells at zygotene stage in 17.5 days post-coitum (dpc) females
CC (PubMed:32845237). {ECO:0000269|PubMed:30760716,
CC ECO:0000269|PubMed:31242413, ECO:0000269|PubMed:32845237}.
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DR EMBL; AK016553; BAB30300.1; -; mRNA.
DR EMBL; AC138228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT033797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466640; EDL40335.1; -; Genomic_DNA.
DR CCDS; CCDS50056.1; -.
DR RefSeq; NP_083178.1; NM_028902.1.
DR RefSeq; XP_006525094.1; XM_006525031.1.
DR RefSeq; XP_006525095.1; XM_006525032.3.
DR RefSeq; XP_006525096.1; XM_006525033.3.
DR AlphaFoldDB; Q9D4G2; -.
DR SMR; Q9D4G2; -.
DR IntAct; Q9D4G2; 2.
DR MINT; Q9D4G2; -.
DR STRING; 10090.ENSMUSP00000002145; -.
DR PhosphoSitePlus; Q9D4G2; -.
DR PaxDb; Q9D4G2; -.
DR PeptideAtlas; Q9D4G2; -.
DR PRIDE; Q9D4G2; -.
DR ProteomicsDB; 273319; -.
DR Antibodypedia; 9965; 103 antibodies from 22 providers.
DR Ensembl; ENSMUST00000002145; ENSMUSP00000002145; ENSMUSG00000002076.
DR Ensembl; ENSMUST00000238192; ENSMUSP00000157466; ENSMUSG00000002076.
DR GeneID; 74377; -.
DR KEGG; mmu:74377; -.
DR UCSC; uc008bvs.2; mouse.
DR CTD; 11077; -.
DR MGI; MGI:1921627; Hsf2bp.
DR VEuPathDB; HostDB:ENSMUSG00000002076; -.
DR eggNOG; ENOG502QSZY; Eukaryota.
DR GeneTree; ENSGT00390000008490; -.
DR HOGENOM; CLU_068321_1_0_1; -.
DR InParanoid; Q9D4G2; -.
DR OMA; TKFKVLM; -.
DR OrthoDB; 1093123at2759; -.
DR PhylomeDB; Q9D4G2; -.
DR TreeFam; TF331782; -.
DR BioGRID-ORCS; 74377; 4 hits in 78 CRISPR screens.
DR ChiTaRS; Hsf2bp; mouse.
DR PRO; PR:Q9D4G2; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9D4G2; protein.
DR Bgee; ENSMUSG00000002076; Expressed in animal zygote and 87 other tissues.
DR ExpressionAtlas; Q9D4G2; baseline and differential.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IDA:UniProtKB.
DR GO; GO:0007144; P:female meiosis I; IMP:UniProtKB.
DR GO; GO:0007141; P:male meiosis I; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039584; HSF2BP.
DR PANTHER; PTHR15434; PTHR15434; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Chromosome; Coiled coil; Cytoplasm; Reference proteome; Ubl conjugation.
FT CHAIN 1..338
FT /note="Heat shock factor 2-binding protein"
FT /id="PRO_0000437125"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 18..55
FT /note="Interaction with BRME1"
FT /evidence="ECO:0000269|PubMed:32345962"
FT REGION 87..338
FT /note="Interaction with BRCA2"
FT /evidence="ECO:0000269|PubMed:32345962"
FT COILED 12..126
FT /evidence="ECO:0000255"
FT MUTAGEN 167
FT /note="S->L: Mutant females show reduced fertility with
FT smaller litter sizes. Produces DNA repair defects during
FT meiotic prophase I. Reduces loading of BRME1 and HSF2BP at
FT the recombination nodules. Males show a slight non-
FT significant reduction in fertility. No effect on
FT interaction with BRCA2 and BRME1. No effect on subcellular
FT location. Reduces BRME1 expression."
FT /evidence="ECO:0000269|PubMed:32845237"
FT MUTAGEN 204
FT /note="R->T: Abolishes interaction with BRCA2 and location
FT to double-strand breaks in chromosomes."
FT /evidence="ECO:0000269|PubMed:32345962"
SQ SEQUENCE 338 AA; 37963 MW; FE18FF78A3A62D49 CRC64;
MAATVGDGSG TEEACRNMES KEEFVKVRKK DLERLTTEVM QIRDFLPRIL NGELLESFQK
LKMVEKNLER KEQELEQLIM DREHFKARLE TAQADSGREK KEKLALRQQL NEAKQQLLQQ
AEYCTQMGAV TCTLLWGVSS SEEVVKTILG GDKALKFFNI TGQTMESFVK SLDGDVKEVD
SDENQFVFAL AGIVTNVAAI ACGREFLVNS SRVLLDTMLQ LLGDLKPGQC TKLKVLMLMS
LYNVSINSKG LKYITESPGF IPLLWWLLSD PDAEVCLHTL RLIQSVVLEP DVFSKVASEL
QSSLPLQRIL AMSKSRNSHL QSAAQELLED LRALDCNV
