CLGN_MOUSE
ID CLGN_MOUSE Reviewed; 611 AA.
AC P52194; Q80YU3; Q9D2K5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Calmegin;
DE AltName: Full=A2/6;
DE AltName: Full=Calnexin-T;
DE AltName: Full=MEG 1 antigen;
DE Flags: Precursor;
GN Name=Clgn; Synonyms=Meg1;
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], CALCIUM-BINDING, DEVELOPMENTAL STAGE, AND
RP TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Testis;
RX PubMed=8126001; DOI=10.1016/s0021-9258(17)37349-0;
RA Watanabe D., Yamada K., Nishina Y., Tajima Y., Koshimizu U., Nagata A.,
RA Nishimune Y.;
RT "Molecular cloning of a novel Ca(2+)-binding protein (calmegin)
RT specifically expressed during male meiotic germ cell development.";
RL J. Biol. Chem. 269:7744-7749(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CALCIUM-BINDING, AND TISSUE SPECIFICITY.
RC STRAIN=CD-1; TISSUE=Testis;
RX PubMed=8188695; DOI=10.1016/s0021-9258(17)36765-0;
RA Ohsako S., Hayashi Y., Bunick D.;
RT "Molecular cloning and sequencing of calnexin-t. An abundant male germ
RT cell-specific calcium-binding protein of the endoplasmic reticulum.";
RL J. Biol. Chem. 269:14140-14148(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=9434179; DOI=10.1016/s0378-1119(97)00537-4;
RA Tanaka H., Ikawa M., Tsuchida J., Nozaki M., Suzuki M., Fujiwara T.,
RA Okabe M., Nishimune Y.;
RT "Cloning and characterization of the human Calmegin gene encoding putative
RT testis-specific chaperone.";
RL Gene 204:159-163(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9177349; DOI=10.1038/42484;
RA Ikawa M., Wada I., Kominami K., Watanabe D., Toshimori K., Nishimune Y.,
RA Okabe M.;
RT "The putative chaperone calmegin is required for sperm fertility.";
RL Nature 387:607-611(1997).
RN [7]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=10495883; DOI=10.1679/aohc.62.283;
RA Yoshinaga K., Tanii I., Toshimori K.;
RT "Molecular chaperone calmegin localization to the endoplasmic reticulum of
RT meiotic and post-meiotic germ cells in the mouse testis.";
RL Arch. Histol. Cytol. 62:283-293(1999).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH ADAM1B AND ADAM2, AND
RP TISSUE SPECIFICITY.
RX PubMed=11784061; DOI=10.1006/dbio.2001.0462;
RA Ikawa M., Nakanishi T., Yamada S., Wada I., Kominami K., Tanaka H.,
RA Nozaki M., Nishimune Y., Okabe M.;
RT "Calmegin is required for fertilin alpha/beta heterodimerization and sperm
RT fertility.";
RL Dev. Biol. 240:254-261(2001).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15151931; DOI=10.1095/biolreprod.104.028647;
RA Nakanishi T., Isotani A., Yamaguchi R., Ikawa M., Baba T., Suarez S.S.,
RA Okabe M.;
RT "Selective passage through the uterotubal junction of sperm from a mixed
RT population produced by chimeras of calmegin-knockout and wild-type male
RT mice.";
RL Biol. Reprod. 71:959-965(2004).
RN [10]
RP FUNCTION.
RX PubMed=16870943; DOI=10.1095/biolreprod.106.052977;
RA Yamaguchi R., Yamagata K., Ikawa M., Moss S.B., Okabe M.;
RT "Aberrant distribution of ADAM3 in sperm from both angiotensin-converting
RT enzyme (Ace)- and calmegin (Clgn)-deficient mice.";
RL Biol. Reprod. 75:760-766(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-578; SER-580; SER-582;
RP SER-592 AND SER-595, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, and Testis;
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).
CC -!- FUNCTION: Functions during spermatogenesis as a chaperone for a range
CC of client proteins that are important for sperm adhesion onto the egg
CC zona pellucida and for subsequent penetration of the zona pellucida.
CC Required for normal sperm migration from the uterus into the oviduct.
CC Required for normal male fertility. Binds calcium ions.
CC {ECO:0000269|PubMed:11784061, ECO:0000269|PubMed:15151931,
CC ECO:0000269|PubMed:16870943, ECO:0000269|PubMed:9177349}.
CC -!- SUBUNIT: Interacts with PDILT and PPIB (By similarity). Interacts with
CC ADAM2. Interacts with ADAM1A, ADAM1B and ADAM3; these are protein-
CC coding genes in mouse but may be pseudogenes in other organisms.
CC {ECO:0000250, ECO:0000269|PubMed:11784061}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10495883}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:10495883}.
CC -!- TISSUE SPECIFICITY: Detected in testis (at protein level). Detected in
CC testis. {ECO:0000269|PubMed:11784061, ECO:0000269|PubMed:8126001,
CC ECO:0000269|PubMed:8188695, ECO:0000269|PubMed:9177349,
CC ECO:0000269|PubMed:9434179}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed during male meiotic germ
CC cell development. First detected in early pachytene spermatocytes.
CC Expression is highest in elongating and round spermatids and decreases
CC thereafter. Not detectable in mature spermatids.
CC {ECO:0000269|PubMed:10495883, ECO:0000269|PubMed:8126001}.
CC -!- DISRUPTION PHENOTYPE: Male mice show normal mating behavior and produce
CC morphologically normal sperm, but are nearly sterile. Mutant sperm fail
CC to adhere to the egg zona pellucida and are generally unable to
CC penetrate the egg extracellular matrix. In addition, mutant sperm
CC display defects in migration from the uterus into the oviduct.
CC {ECO:0000269|PubMed:11784061, ECO:0000269|PubMed:15151931,
CC ECO:0000269|PubMed:9177349}.
CC -!- SIMILARITY: Belongs to the calreticulin family. {ECO:0000305}.
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DR EMBL; D14117; BAA03180.1; -; mRNA.
DR EMBL; U08373; AAA20599.1; -; mRNA.
DR EMBL; D86323; BAA22591.1; -; mRNA.
DR EMBL; AK019534; BAB31782.1; ALT_SEQ; mRNA.
DR EMBL; BC050767; AAH50767.1; -; mRNA.
DR CCDS; CCDS22452.1; -.
DR PIR; A53418; A53418.
DR PIR; A54086; A54086.
DR RefSeq; NP_001316556.1; NM_001329627.1.
DR RefSeq; NP_034034.2; NM_009904.4.
DR RefSeq; XP_011246600.1; XM_011248298.2.
DR AlphaFoldDB; P52194; -.
DR SMR; P52194; -.
DR BioGRID; 198750; 1.
DR DIP; DIP-47581N; -.
DR IntAct; P52194; 4.
DR MINT; P52194; -.
DR STRING; 10090.ENSMUSP00000105457; -.
DR iPTMnet; P52194; -.
DR PhosphoSitePlus; P52194; -.
DR MaxQB; P52194; -.
DR PaxDb; P52194; -.
DR PeptideAtlas; P52194; -.
DR PRIDE; P52194; -.
DR ProteomicsDB; 283382; -.
DR Antibodypedia; 16228; 194 antibodies from 29 providers.
DR DNASU; 12745; -.
DR Ensembl; ENSMUST00000002259; ENSMUSP00000002259; ENSMUSG00000002190.
DR Ensembl; ENSMUST00000109831; ENSMUSP00000105457; ENSMUSG00000002190.
DR GeneID; 12745; -.
DR KEGG; mmu:12745; -.
DR UCSC; uc009mkd.1; mouse.
DR CTD; 1047; -.
DR MGI; MGI:107472; Clgn.
DR VEuPathDB; HostDB:ENSMUSG00000002190; -.
DR eggNOG; KOG0675; Eukaryota.
DR GeneTree; ENSGT00950000182915; -.
DR HOGENOM; CLU_018224_2_0_1; -.
DR InParanoid; P52194; -.
DR OMA; RVGCGEW; -.
DR OrthoDB; 775337at2759; -.
DR PhylomeDB; P52194; -.
DR TreeFam; TF300618; -.
DR BioGRID-ORCS; 12745; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Clgn; mouse.
DR PRO; PR:P52194; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P52194; protein.
DR Bgee; ENSMUSG00000002190; Expressed in spermatocyte and 69 other tissues.
DR Genevisible; P52194; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IMP:MGI.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:MGI.
DR GO; GO:0007338; P:single fertilization; IGI:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR Gene3D; 2.10.250.10; -; 1.
DR InterPro; IPR001580; Calret/calnex.
DR InterPro; IPR018124; Calret/calnex_CS.
DR InterPro; IPR009033; Calreticulin/calnexin_P_dom_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR PANTHER; PTHR11073; PTHR11073; 1.
DR Pfam; PF00262; Calreticulin; 1.
DR PRINTS; PR00626; CALRETICULIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF63887; SSF63887; 1.
DR PROSITE; PS00803; CALRETICULIN_1; 1.
DR PROSITE; PS00804; CALRETICULIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Calcium; Chaperone; Developmental protein; Differentiation;
KW Disulfide bond; Endoplasmic reticulum; Meiosis; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Spermatogenesis; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..611
FT /note="Calmegin"
FT /id="PRO_0000004211"
FT TOPO_DOM 20..471
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 472..492
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..611
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 267..280
FT /note="1-1"
FT REPEAT 284..297
FT /note="1-2"
FT REPEAT 303..316
FT /note="1-3"
FT REPEAT 322..335
FT /note="1-4"
FT REPEAT 339..352
FT /note="2-1"
FT REPEAT 356..369
FT /note="2-2"
FT REPEAT 370..383
FT /note="2-3"
FT REPEAT 384..397
FT /note="2-4"
FT REGION 254..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..350
FT /note="Interaction with PPIB"
FT /evidence="ECO:0000250"
FT REGION 517..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..297
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..333
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..604
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P27824"
FT MOD_RES 561
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14967"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27824"
FT DISULFID 151..185
FT /evidence="ECO:0000250"
FT DISULFID 351..355
FT /evidence="ECO:0000250"
FT CONFLICT 76..79
FT /note="LSKA -> YQS (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="E -> Q (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="E -> D (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 133..135
FT /note="ADK -> GAIN (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="K -> Q (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="A -> P (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="R -> K (in Ref. 1; BAA03180, 2; AAA20599 and 3;
FT BAA22591)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="A -> D (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 432
FT /note="E -> D (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="A -> P (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="A -> P (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="E -> D (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="A -> T (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="E -> D (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 549
FT /note="V -> L (in Ref. 2; AAA20599)"
FT /evidence="ECO:0000305"
FT CONFLICT 577..578
FT /note="LS -> AE (in Ref. 4; BAB31782)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 611 AA; 69431 MW; D70A3C418229DA00 CRC64;
MRFQGVGLCL GLLFITVNAD FMDDGVEVED FSENSDESNI KDEPSSGTFK YKTPQPIGEV
YFTETFDSGN LAGWVLSKAK KDDMDSEIAI YDGRWEIEEL KENQVPGDRG LVLKSKAKHH
AIAAVLEKPF IFADKPLIVQ YEVNFQDGID CGGAYIKLLA DTGDLILENF YDKTSYTIMF
GPDKCGEDYK LHLIFRHKHP KTGVFEEKHA KPPDVDLKEF FTDRKTHLYT LVMNPDDTFE
VLIDQKVVNQ GTLLDDVVPP INPPREIDDP SDKKPEEWDD RAKIPDPTAV RPEDWDENEP
AQIEDSSAVK PDGWLDDEPK FIPNPKAEKP EDWSDDMDGE WEAPHIPNPA CQIGCGEWKP
PMIDNPKYKG IWRPPMINNP NYQGLWSPQK IPNPDYFEDD HPFLLTSFSA LGLELWSMTP
DIYFDNFIIC SEKEVADQWA TDGWELKIMV ANANEPGVLR QLVIAAEERP WLWLMYLVMA
GLPVALVASF CWPRKVKKKY EDTGPKKTEL CKLQSKAALE QEAEEEKAPE KPEDVQEEKK
PGEAEVVTVE KEVIGEPEEK SKEDRETLEG QEEVSKLSKS GSEDEMKDAD ESPGSGDAPL
KSLRKRRVRK D
