MZB1_MOUSE
ID MZB1_MOUSE Reviewed; 188 AA.
AC Q9D8I1; D2IYS1; Q6P3D3; Q8BU13; Q8K2M5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Marginal zone B- and B1-cell-specific protein;
DE AltName: Full=Plasma cell-induced resident endoplasmic reticulum protein;
DE Short=Plasma cell-induced resident ER protein;
DE Short=pERp1;
DE AltName: Full=Proapoptotic caspase adapter protein;
DE Flags: Precursor;
GN Name=Mzb1; Synonyms=Pacap;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN ER CHAPERONE
RP COMPLEX, DEVELOPMENTAL STAGE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19805157; DOI=10.1073/pnas.0811591106;
RA Shimizu Y., Meunier L., Hendershot L.M.;
RT "pERp1 is significantly up-regulated during plasma cell differentiation and
RT contributes to the oxidative folding of immunoglobulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17013-17018(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Small intestine, and Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISULFIDE BONDS, MUTAGENESIS OF CYS-49; CYS-52; CYS-94; CYS-142; CYS-170
RP AND CYS-177, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19805154; DOI=10.1073/pnas.0903036106;
RA van Anken E., Pena F., Hafkemeijer N., Christis C., Romijn E.P.,
RA Grauschopf U., Oorschot V.M., Pertel T., Engels S., Ora A., Lastun V.,
RA Glockshuber R., Klumperman J., Heck A.J., Luban J., Braakman I.;
RT "Efficient IgM assembly and secretion require the plasma cell induced
RT endoplasmic reticulum protein pERp1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:17019-17024(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY, FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND INTERACTION WITH HSP90B1 AND PDIA3.
RX PubMed=21093319; DOI=10.1016/j.immuni.2010.11.013;
RA Flach H., Rosenbaum M., Duchniewicz M., Kim S., Zhang S.L., Cahalan M.D.,
RA Mittler G., Grosschedl R.;
RT "Mzb1 protein regulates calcium homeostasis, antibody secretion, and
RT integrin activation in innate-like B cells.";
RL Immunity 33:723-735(2010).
RN [7]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=21688198; DOI=10.1007/s00125-011-2212-7;
RA Zhang H., Chen X., Sairam M.R.;
RT "Novel hormone-regulated genes in visceral adipose tissue: cloning and
RT identification of proinflammatory cytokine-like mouse and human MEDA-7:
RT implications for obesity, insulin resistance and the metabolic syndrome.";
RL Diabetologia 54:2368-2380(2011).
CC -!- FUNCTION: Associates with immunoglobulin M (IgM) heavy and light chains
CC and promotes IgM assembly and secretion. May exert its effect by acting
CC as a molecular chaperone or as an oxidoreductase as it displays a low
CC level of oxidoreductase activity. Helps to diversify peripheral B-cell
CC functions by regulating Ca(2+) stores, antibody secretion and integrin
CC activation.
CC -!- FUNCTION: Acts as a hormone-regulated adipokine/pro-inflammatory
CC cytokine that is implicated in causing chronic inflammation, affecting
CC cellular expansion and blunting insulin response in adipocytes. May
CC have a role in the onset of insulin resistance.
CC -!- SUBUNIT: Part of the ER chaperone complex, a multi-protein complex in
CC the endoplasmic reticulum containing a large number of molecular
CC chaperones which associates with unassembled incompletely folded
CC immunoglobulin heavy chains. Interacts with HSP90B1 and PDIA3 in a
CC calcium-dependent manner. {ECO:0000269|PubMed:19805157,
CC ECO:0000269|PubMed:21093319}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:19805154}. Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:21093319}. Secreted {ECO:0000269|PubMed:21688198}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the spleen and lymph
CC nodes. Abundantly expressed in marginal zone B and B1 cells. High
CC expression in mesenteric adipose tissue (MAT). Expressed also in
CC pancreas, perigonadal adipose tissue (PAT), uterus, subcutaneous
CC adipose tissue, heart, muscle, ovary and liver. Very low expression is
CC detected in brown adipose tissue. In PAT, significantly higher
CC expression in stromal-vascular cell than in adipocytes. Expressed in
CC macrophage RAW 264.7 cell line. Down-regulated in For-knockout female
CC MAT at 5 months (obese state) followed by steep up-regulation at 9
CC months (prediabetic condition) when mutants progress towards the
CC metabolic syndrome. {ECO:0000269|PubMed:19805154,
CC ECO:0000269|PubMed:21093319, ECO:0000269|PubMed:21688198}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during plasma cell differentiation.
CC {ECO:0000269|PubMed:19805154, ECO:0000269|PubMed:19805157}.
CC -!- PTM: Forms an interchain disulfide bond with IgM monomers.
CC -!- SIMILARITY: Belongs to the MZB1 family. {ECO:0000305}.
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DR EMBL; GQ477351; ACY74344.1; -; mRNA.
DR EMBL; AK008016; BAB25410.1; -; mRNA.
DR EMBL; AK088094; BAC40141.1; -; mRNA.
DR EMBL; BC030674; AAH30674.1; -; mRNA.
DR EMBL; BC064044; AAH64044.1; -; mRNA.
DR CCDS; CCDS29145.1; -.
DR RefSeq; NP_081498.2; NM_027222.3.
DR AlphaFoldDB; Q9D8I1; -.
DR SMR; Q9D8I1; -.
DR DIP; DIP-48984N; -.
DR IntAct; Q9D8I1; 1.
DR STRING; 10090.ENSMUSP00000025211; -.
DR ChEMBL; CHEMBL3259485; -.
DR PhosphoSitePlus; Q9D8I1; -.
DR MaxQB; Q9D8I1; -.
DR PaxDb; Q9D8I1; -.
DR PeptideAtlas; Q9D8I1; -.
DR PRIDE; Q9D8I1; -.
DR ProteomicsDB; 252633; -.
DR Antibodypedia; 26772; 101 antibodies from 24 providers.
DR DNASU; 69816; -.
DR Ensembl; ENSMUST00000025211; ENSMUSP00000025211; ENSMUSG00000024353.
DR GeneID; 69816; -.
DR KEGG; mmu:69816; -.
DR UCSC; uc008emm.2; mouse.
DR CTD; 51237; -.
DR MGI; MGI:1917066; Mzb1.
DR VEuPathDB; HostDB:ENSMUSG00000024353; -.
DR eggNOG; ENOG502S4B7; Eukaryota.
DR GeneTree; ENSGT00390000002716; -.
DR HOGENOM; CLU_113467_1_0_1; -.
DR InParanoid; Q9D8I1; -.
DR OMA; MWQHLAK; -.
DR OrthoDB; 1464647at2759; -.
DR PhylomeDB; Q9D8I1; -.
DR TreeFam; TF329450; -.
DR BioGRID-ORCS; 69816; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Mzb1; mouse.
DR PRO; PR:Q9D8I1; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9D8I1; protein.
DR Bgee; ENSMUSG00000024353; Expressed in spleen and 55 other tissues.
DR ExpressionAtlas; Q9D8I1; baseline and differential.
DR Genevisible; Q9D8I1; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0033622; P:integrin activation; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR InterPro; IPR021852; DUF3456.
DR Pfam; PF11938; DUF3456; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Endoplasmic reticulum; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..188
FT /note="Marginal zone B- and B1-cell-specific protein"
FT /id="PRO_0000318741"
FT MOTIF 185..188
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT DISULFID 49..177
FT /evidence="ECO:0000269|PubMed:19805154"
FT DISULFID 52..170
FT /evidence="ECO:0000269|PubMed:19805154"
FT DISULFID 94..142
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 49
FT /note="C->A: Reduced electrophoretic mobility; when
FT associated with A-52."
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 52
FT /note="C->A: Reduced electrophoretic mobility; when
FT associated with A-49."
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 94
FT /note="C->A: Small loss of electrophoretic mobility."
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 142
FT /note="C->A: Small loss of electrophoretic mobility."
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 170
FT /note="C->A: Reduced electrophoretic mobility; when
FT associated with A-177."
FT /evidence="ECO:0000269|PubMed:19805154"
FT MUTAGEN 177
FT /note="C->A: Reduced electrophoretic mobility; when
FT associated with A-170."
FT /evidence="ECO:0000269|PubMed:19805154"
FT CONFLICT 6
FT /note="P -> T (in Ref. 2; BAC40141)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="F -> L (in Ref. 1; ACY74344 and 2; BAB25410)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="P -> H (in Ref. 1; ACY74344 and 2; BAB25410)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="N -> S (in Ref. 2; BAB25410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 188 AA; 20580 MW; 101640BE6E9B0A93 CRC64;
MRLPLPLLLL FGCRAILGSA GDRVSLSASA PTLDDEEKYS AHMPAHLRCD ACRAVAFQMG
QRLAKAEAKS HTPDASGLQE LSESTYTDVL DQTCSQNWQS YGVHEVNQMK RLTGPGLSKG
PEPRISVMIS GGPWPNRLSK TCFHYLGEFG EDQIYEAYRQ GQANLEALLC GGTHGPCSQE
ILAQREEL
