ID   CLGN_HUMAN              Reviewed;         610 AA.
AC   O14967; B3KS90; B4DXV8; D3DNY8;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   28-JAN-2026, entry version 218.
DE   RecName: Full=Calmegin;
DE   Flags: Precursor;
GN   Name=CLGN;
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), AND TISSUE SPECIFICITY.
RC   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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Testis;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560 AND SER-576, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [6]
RP   INTERACTION WITH PDILT.
RX   PubMed=17507649; DOI=10.1091/mbc.e07-02-0147;
RA   van Lith M., Karala A.R., Bown D., Gatehouse J.A., Ruddock L.W.,
RA   Saunders P.T.K., Benham A.M.;
RT   "A developmentally regulated chaperone complex for the endoplasmic
RT   reticulum of male haploid germ cells.";
RL   Mol. Biol. Cell 18:2795-2804(2007).
RN   [7]
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).
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with PPIB. Interacts with ADAM2 (By similarity).
CC       Interacts with PDILT. {ECO:0000250, ECO:0000269|PubMed:17507649}.
CC   -!- INTERACTION:
CC       O14967; Q96GX1: TCTN2; NbExp=6; IntAct=EBI-3907005, EBI-11349465;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC       I membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O14967-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O14967-2; Sequence=VSP_055517, VSP_055518;
CC   -!- TISSUE SPECIFICITY: Detected in testis (at protein level). Detected in
CC       testis. {ECO:0000269|PubMed:9434179}.
CC   -!- SIMILARITY: Belongs to the calreticulin family. {ECO:0000305}.
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DR   EMBL; D86322; BAA22590.1; -; mRNA.
DR   EMBL; AK093096; BAG52652.1; -; mRNA.
DR   EMBL; AK302149; BAG63520.1; -; mRNA.
DR   EMBL; CH471056; EAX05099.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX05100.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX05101.1; -; Genomic_DNA.
DR   EMBL; BC028357; AAH28357.1; -; mRNA.
DR   CCDS; CCDS3751.1; -. [O14967-1]
DR   RefSeq; NP_001124147.1; NM_001130675.2. [O14967-1]
DR   RefSeq; NP_004353.1; NM_004362.3. [O14967-1]
DR   AlphaFoldDB; O14967; -.
DR   SMR; O14967; -.
DR   BioGRID; 107477; 352.
DR   FunCoup; O14967; 590.
DR   IntAct; O14967; 468.
DR   MINT; O14967; -.
DR   STRING; 9606.ENSP00000392782; -.
DR   ChEMBL; CHEMBL4295653; -.
DR   GlyGen; O14967; 1 site, 2 O-linked glycans (1 site).
DR   iPTMnet; O14967; -.
DR   PhosphoSitePlus; O14967; -.
DR   SwissPalm; O14967; -.
DR   BioMuta; CLGN; -.
DR   jPOST; O14967; -.
DR   MassIVE; O14967; -.
DR   PaxDb; 9606-ENSP00000326699; -.
DR   PeptideAtlas; O14967; -.
DR   ProteomicsDB; 48342; -. [O14967-1]
DR   Pumba; O14967; -.
DR   Antibodypedia; 16228; 211 antibodies from 32 providers.
DR   DNASU; 1047; -.
DR   Ensembl; ENST00000325617.10; ENSP00000326699.5; ENSG00000153132.14. [O14967-1]
DR   Ensembl; ENST00000414773.5; ENSP00000392782.1; ENSG00000153132.14. [O14967-1]
DR   GeneID; 1047; -.
DR   KEGG; hsa:1047; -.
DR   MANE-Select; ENST00000325617.10; ENSP00000326699.5; NM_004362.3; NP_004353.1.
DR   UCSC; uc003iii.4; human. [O14967-1]
DR   AGR; HGNC:2060; -.
DR   ClinPGx; PA26587; -.
DR   CTD; 1047; -.
DR   DisGeNET; 1047; -.
DR   GeneCards; CLGN; -.
DR   HGNC; HGNC:2060; CLGN.
DR   HPA; ENSG00000153132; Tissue enhanced (heart muscle, testis).
DR   MIM; 601858; gene.
DR   OpenTargets; ENSG00000153132; -.
DR   VEuPathDB; HostDB:ENSG00000153132; -.
DR   eggNOG; KOG0675; Eukaryota.
DR   GeneTree; ENSGT00950000182915; -.
DR   HOGENOM; CLU_018224_2_0_1; -.
DR   InParanoid; O14967; -.
DR   OMA; KHAKPPN; -.
DR   OrthoDB; 1938156at2759; -.
DR   PAN-GO; O14967; 4 GO annotations based on evolutionary models.
DR   PhylomeDB; O14967; -.
DR   PathwayCommons; O14967; -.
DR   SignaLink; O14967; -.
DR   Agora; ENSG00000153132; -.
DR   BioGRID-ORCS; 1047; 14 hits in 1151 CRISPR screens.
DR   ChiTaRS; CLGN; human.
DR   GeneWiki; Calmegin; -.
DR   GenomeRNAi; 1047; -.
DR   Pharos; O14967; Tbio.
DR   PRO; PR:O14967; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; O14967; protein.
DR   Bgee; ENSG00000153132; Expressed in heart right ventricle and 138 other cell types or tissues.
DR   ExpressionAtlas; O14967; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR   GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR   GO; GO:0044183; F:protein folding chaperone; IEA:Ensembl.
DR   GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR   GO; GO:0007339; P:binding of sperm to zona pellucida; IEA:Ensembl.
DR   GO; GO:0036503; P:ERAD pathway; IBA:GO_Central.
DR   GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR   GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR   GO; GO:0007338; P:single fertilization; TAS:ProtInc.
DR   FunFam; 2.10.250.10:FF:000001; Calnexin homolog; 1.
DR   FunFam; 2.60.120.200:FF:000430; Si:ch211-274f20.2; 1.
DR   Gene3D; 2.60.120.200; -; 1.
DR   Gene3D; 2.10.250.10; Calreticulin/calnexin, P domain; 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:SF7; CALMEGIN; 1.
DR   PANTHER; PTHR11073; CALRETICULIN AND CALNEXIN; 1.
DR   Pfam; PF00262; Calreticulin; 1.
DR   PRINTS; PR00626; CALRETICULIN.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR   SUPFAM; SSF63887; P-domain of calnexin/calreticulin; 1.
DR   PROSITE; PS00803; CALRETICULIN_1; 1.
DR   PROSITE; PS00804; CALRETICULIN_2; 1.
DR   PROSITE; PS00805; CALRETICULIN_REPEAT; 2.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Calcium; Chaperone; Disulfide bond;
KW   Endoplasmic reticulum; Membrane; Phosphoprotein; Proteomics identification;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..610
FT                   /note="Calmegin"
FT                   /id="PRO_0000004210"
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..610
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          258..338
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          521..610
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        263..284
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        317..332
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        521..548
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        549..571
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        601..610
FT                   /note="Basic 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         560
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17081983"
FT   MOD_RES         576
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17081983"
FT   MOD_RES         579
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52194"
FT   MOD_RES         581
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52194"
FT   MOD_RES         591
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52194"
FT   MOD_RES         594
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P52194"
FT   MOD_RES         601
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   VAR_SEQ         54..211
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055517"
FT   VAR_SEQ         378..424
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055518"
FT   VARIANT         160
FT                   /note="A -> S (in dbSNP:rs2567241)"
FT                   /id="VAR_024400"
FT   VARIANT         290
FT                   /note="V -> I (in dbSNP:rs2175563)"
FT                   /id="VAR_033776"
FT   VARIANT         352
FT                   /note="R -> W (in dbSNP:rs12513290)"
FT                   /id="VAR_048590"
FT   CONFLICT        232
FT                   /note="V -> A (in Ref. 2; BAG63520)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   610 AA;  70039 MW;  F024FC4010D42D7E CRC64;
     MHFQAFWLCL GLLFISINAE FMDDDVETED FEENSEEIDV NESELSSEIK YKTPQPIGEV
     YFAETFDSGR LAGWVLSKAK KDDMDEEISI YDGRWEIEEL KENQVPGDRG LVLKSRAKHH
     AISAVLAKPF IFADKPLIVQ YEVNFQDGID CGGAYIKLLA DTDDLILENF YDKTSYIIMF
     GPDKCGEDYK LHFIFRHKHP KTGVFEEKHA KPPDVDLKKF FTDRKTHLYT LVMNPDDTFE
     VLVDQTVVNK GSLLEDVVPP IKPPKEIEDP NDKKPEEWDE RAKIPDPSAV KPEDWDESEP
     AQIEDSSVVK PAGWLDDEPK FIPDPNAEKP DDWNEDTDGE WEAPQILNPA CRIGCGEWKP
     PMIDNPKYKG VWRPPLVDNP NYQGIWSPRK IPNPDYFEDD HPFLLTSFSA LGLELWSMTS
     DIYFDNFIIC SEKEVADHWA ADGWRWKIMI ANANKPGVLK QLMAAAEGHP WLWLIYLVTA
     GVPIALITSF CWPRKVKKKH KDTEYKKTDI CIPQTKGVLE QEEKEEKAAL EKPMDLEEEK
     KQNDGEMLEK EEESEPEEKS EEEIEIIEGQ EESNQSNKSG SEDEMKEADE STGSGDGPIK
     SVRKRRVRKD
//