MZB1_HUMAN
ID MZB1_HUMAN Reviewed; 189 AA.
AC Q8WU39; D2IYS0; Q7Z6N2; Q96RL5; Q9P0T3;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Marginal zone B- and B1-cell-specific protein;
DE AltName: Full=Mesenteric estrogen-dependent adipose 7;
DE Short=MEDA-7;
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=MEDA7, PACAP; ORFNames=HSPC190;
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 2), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INDUCTION, AND INTERACTION WITH CASP2 AND CASP9.
RX PubMed=11350957; DOI=10.1074/jbc.m100684200;
RA Bonfoco E., Li E., Kolbinger F., Cooper N.R.;
RT "Characterization of a novel proapoptotic caspase-2- and caspase-9-binding
RT protein.";
RL J. Biol. Chem. 276:29242-29250(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF CYS-50; CYS-53; CYS-95; CYS-143; CYS-171
RP AND CYS-178.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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] (ISOFORM 5).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=B-cell, 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=12792799;
RA Katoh M., Katoh M.;
RT "MGC29506 gene, frequently down-regulated in intestinal-type gastric
RT cancer, encodes secreted-type protein with conserved cysteine residues.";
RL Int. J. Oncol. 23:235-241(2003).
RN [9]
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., Buerckstuemmer T.,
RA 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 [10]
RP SUBCELLULAR LOCATION, INDUCTION, 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 (By similarity). Isoform 2 may be
CC involved in regulation of apoptosis. Helps to diversify peripheral B-
CC cell functions by regulating Ca(2+) stores, antibody secretion and
CC integrin activation. {ECO:0000250, ECO:0000269|PubMed:11350957,
CC ECO:0000269|PubMed:21688198}.
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 (By similarity). Isoform 2 interacts with
CC CASP2 and CASP9. Interacts with HSP90B1 and PDIA3 in a calcium-
CC dependent manner (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q8WU39; Q99816: TSG101; NbExp=3; IntAct=EBI-7212043, EBI-346882;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:19805157}. Secreted {ECO:0000269|PubMed:21688198}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:11350957}. Note=Diffuse granular localization in
CC the cytoplasm surrounding the nucleus (PubMed:11350957).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8WU39-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WU39-2; Sequence=VSP_031281;
CC Name=3;
CC IsoId=Q8WU39-3; Sequence=VSP_031280, VSP_038332;
CC Name=4;
CC IsoId=Q8WU39-4; Sequence=VSP_038333, VSP_038334;
CC Name=5;
CC IsoId=Q8WU39-5; Sequence=VSP_039073, VSP_039074;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in adult
CC brain, small intestine and lymphoid tissues such as thymus and spleen.
CC Expression is frequently lower in intestinal-type gastric cancer. In
CC obese patients, more abundant in omental than in subcutaneous fat.
CC {ECO:0000269|PubMed:11350957, ECO:0000269|PubMed:12792799,
CC ECO:0000269|PubMed:19805157}.
CC -!- INDUCTION: Down-regulated in primary B-cells early after ligand-
CC stimulated activation. Up-regulated in bacterial lipopolysaccharides
CC (LPS)-stimulated peritoneal macrophages. {ECO:0000269|PubMed:11350957,
CC ECO:0000269|PubMed:21688198}.
CC -!- PTM: Forms an interchain disulfide bond with IgM monomers.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major.
CC -!- SIMILARITY: Belongs to the MZB1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF36110.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AF338109; AAK84085.1; -; mRNA.
DR EMBL; AF151024; AAF36110.1; ALT_SEQ; mRNA.
DR EMBL; BP366737; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; GQ477350; ACY74343.1; -; mRNA.
DR EMBL; AK292706; BAF85395.1; -; mRNA.
DR EMBL; AL698690; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC135457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009931; AAH09931.2; -; mRNA.
DR EMBL; BC021275; AAH21275.1; -; mRNA.
DR CCDS; CCDS47273.1; -. [Q8WU39-1]
DR RefSeq; NP_057543.2; NM_016459.3. [Q8WU39-1]
DR PDB; 7AAH; X-ray; 1.40 A; A/B=23-185.
DR PDBsum; 7AAH; -.
DR AlphaFoldDB; Q8WU39; -.
DR SMR; Q8WU39; -.
DR BioGRID; 119399; 11.
DR IntAct; Q8WU39; 3.
DR MINT; Q8WU39; -.
DR STRING; 9606.ENSP00000303920; -.
DR GlyGen; Q8WU39; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WU39; -.
DR PhosphoSitePlus; Q8WU39; -.
DR BioMuta; MZB1; -.
DR DMDM; 74730663; -.
DR jPOST; Q8WU39; -.
DR MassIVE; Q8WU39; -.
DR MaxQB; Q8WU39; -.
DR PaxDb; Q8WU39; -.
DR PeptideAtlas; Q8WU39; -.
DR PRIDE; Q8WU39; -.
DR ProteomicsDB; 74625; -. [Q8WU39-1]
DR ProteomicsDB; 74626; -. [Q8WU39-2]
DR ProteomicsDB; 74627; -. [Q8WU39-3]
DR ProteomicsDB; 74628; -. [Q8WU39-4]
DR Antibodypedia; 26772; 101 antibodies from 24 providers.
DR DNASU; 51237; -.
DR Ensembl; ENST00000302125.9; ENSP00000303920.8; ENSG00000170476.16. [Q8WU39-1]
DR Ensembl; ENST00000417694.6; ENSP00000415420.2; ENSG00000170476.16. [Q8WU39-4]
DR Ensembl; ENST00000503481.5; ENSP00000423205.1; ENSG00000170476.16. [Q8WU39-2]
DR GeneID; 51237; -.
DR KEGG; hsa:51237; -.
DR MANE-Select; ENST00000302125.9; ENSP00000303920.8; NM_016459.4; NP_057543.2.
DR UCSC; uc003lei.4; human. [Q8WU39-1]
DR CTD; 51237; -.
DR DisGeNET; 51237; -.
DR GeneCards; MZB1; -.
DR HGNC; HGNC:30125; MZB1.
DR HPA; ENSG00000170476; Tissue enhanced (intestine, lymphoid tissue).
DR MIM; 609447; gene.
DR neXtProt; NX_Q8WU39; -.
DR OpenTargets; ENSG00000170476; -.
DR VEuPathDB; HostDB:ENSG00000170476; -.
DR eggNOG; ENOG502S4B7; Eukaryota.
DR GeneTree; ENSGT00390000002716; -.
DR HOGENOM; CLU_2014477_0_0_1; -.
DR InParanoid; Q8WU39; -.
DR OMA; MWQHLAK; -.
DR OrthoDB; 1464647at2759; -.
DR PhylomeDB; Q8WU39; -.
DR PathwayCommons; Q8WU39; -.
DR SignaLink; Q8WU39; -.
DR BioGRID-ORCS; 51237; 12 hits in 1061 CRISPR screens.
DR ChiTaRS; MZB1; human.
DR GenomeRNAi; 51237; -.
DR Pharos; Q8WU39; Tbio.
DR PRO; PR:Q8WU39; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8WU39; protein.
DR Bgee; ENSG00000170476; Expressed in thymus and 135 other tissues.
DR ExpressionAtlas; Q8WU39; baseline and differential.
DR Genevisible; Q8WU39; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0033622; P:integrin activation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR InterPro; IPR021852; DUF3456.
DR Pfam; PF11938; DUF3456; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm; Disulfide bond;
KW Endoplasmic reticulum; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..189
FT /note="Marginal zone B- and B1-cell-specific protein"
FT /id="PRO_0000318740"
FT MOTIF 186..189
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT DISULFID 50..178
FT /evidence="ECO:0000250"
FT DISULFID 53..171
FT /evidence="ECO:0000250"
FT DISULFID 95..143
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..92
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031280"
FT VAR_SEQ 60..189
FT /note="MWQNLAKAETKLHTSNSGGRRELSELVYTDVLDRSCSRNWQDYGVREVDQVK
FT RLTGPGLSEGPEPSISVMVTGGPWPTRLSRTCLHYLGEFGEDQIYEAHQQGRGALEALL
FT CGGPQGACSEKVSATREEL -> SLLVPDVAKSGKGRDQTSYLKLWGAAGAERVGLHGC
FT PGPELLPELAGLRSSRSGPSETSHRPRT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11350957"
FT /id="VSP_031281"
FT VAR_SEQ 60..75
FT /note="MWQNLAKAETKLHTSN -> RLCSYPPHLPLTEQQS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11042152"
FT /id="VSP_038333"
FT VAR_SEQ 60..62
FT /note="MWQ -> AHP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_039073"
FT VAR_SEQ 63..189
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_039074"
FT VAR_SEQ 76..189
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11042152"
FT /id="VSP_038334"
FT VAR_SEQ 93..101
FT /note="RSCSRNWQD -> MPAELWLTS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038332"
FT MUTAGEN 50
FT /note="C->S: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT MUTAGEN 53
FT /note="C->S: No significant activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT MUTAGEN 95
FT /note="C->S: No significant activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT MUTAGEN 143
FT /note="C->S: No significant activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT MUTAGEN 171
FT /note="C->S: No significant activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT MUTAGEN 178
FT /note="C->S: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:19805157"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:7AAH"
FT HELIX 49..70
FT /evidence="ECO:0007829|PDB:7AAH"
FT HELIX 84..94
FT /evidence="ECO:0007829|PDB:7AAH"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:7AAH"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:7AAH"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:7AAH"
FT HELIX 135..150
FT /evidence="ECO:0007829|PDB:7AAH"
FT HELIX 152..161
FT /evidence="ECO:0007829|PDB:7AAH"
FT HELIX 163..171
FT /evidence="ECO:0007829|PDB:7AAH"
SQ SEQUENCE 189 AA; 20694 MW; C71AED212D3393D3 CRC64;
MRLSLPLLLL LLGAWAIPGG LGDRAPLTAT APQLDDEEMY SAHMPAHLRC DACRAVAYQM
WQNLAKAETK LHTSNSGGRR ELSELVYTDV LDRSCSRNWQ DYGVREVDQV KRLTGPGLSE
GPEPSISVMV TGGPWPTRLS RTCLHYLGEF GEDQIYEAHQ QGRGALEALL CGGPQGACSE
KVSATREEL
