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   13-FEB-2019, entry version 181.
DE   RecName: Full=Calmegin;
DE   Flags: Precursor;
GN   Name=CLGN;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   putative 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling 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.,
RA   Buerckstuemmer T., 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
CC       range of client proteins that are important for sperm adhesion
CC       onto the egg zona pellucida and for subsequent penetration of the
CC       zona pellucida. Required for normal sperm migration from the
CC       uterus into the oviduct. Required for normal male fertility. Binds
CC       calcium ions (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with PPIB. Interacts with ADAM2 (By
CC       similarity). Interacts with PDILT. {ECO:0000250,
CC       ECO:0000269|PubMed:17507649}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC       type 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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Detected in testis (at protein level).
CC       Detected in 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_001130675.1. [O14967-1]
DR   RefSeq; NP_004353.1; NM_004362.2. [O14967-1]
DR   UniGene; Hs.86368; -.
DR   ProteinModelPortal; O14967; -.
DR   SMR; O14967; -.
DR   BioGrid; 107477; 39.
DR   IntAct; O14967; 12.
DR   STRING; 9606.ENSP00000326699; -.
DR   iPTMnet; O14967; -.
DR   PhosphoSitePlus; O14967; -.
DR   SwissPalm; O14967; -.
DR   BioMuta; CLGN; -.
DR   EPD; O14967; -.
DR   jPOST; O14967; -.
DR   MaxQB; O14967; -.
DR   PaxDb; O14967; -.
DR   PeptideAtlas; O14967; -.
DR   PRIDE; O14967; -.
DR   ProteomicsDB; 48342; -.
DR   DNASU; 1047; -.
DR   Ensembl; ENST00000325617; ENSP00000326699; ENSG00000153132. [O14967-1]
DR   Ensembl; ENST00000414773; ENSP00000392782; ENSG00000153132. [O14967-1]
DR   GeneID; 1047; -.
DR   KEGG; hsa:1047; -.
DR   UCSC; uc003iii.4; human. [O14967-1]
DR   CTD; 1047; -.
DR   DisGeNET; 1047; -.
DR   EuPathDB; HostDB:ENSG00000153132.12; -.
DR   GeneCards; CLGN; -.
DR   HGNC; HGNC:2060; CLGN.
DR   HPA; CAB020709; -.
DR   HPA; HPA048761; -.
DR   HPA; HPA058627; -.
DR   MIM; 601858; gene.
DR   neXtProt; NX_O14967; -.
DR   OpenTargets; ENSG00000153132; -.
DR   PharmGKB; PA26587; -.
DR   eggNOG; KOG0675; Eukaryota.
DR   eggNOG; ENOG410XP7T; LUCA.
DR   GeneTree; ENSGT00940000153639; -.
DR   HOGENOM; HOG000192436; -.
DR   HOVERGEN; HBG005407; -.
DR   InParanoid; O14967; -.
DR   KO; K09551; -.
DR   OMA; KTSYTIM; -.
DR   OrthoDB; 775337at2759; -.
DR   PhylomeDB; O14967; -.
DR   TreeFam; TF300618; -.
DR   ChiTaRS; CLGN; human.
DR   GeneWiki; Calmegin; -.
DR   GenomeRNAi; 1047; -.
DR   PRO; PR:O14967; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   Bgee; ENSG00000153132; Expressed in 148 organ(s), highest expression level in heart right ventricle.
DR   ExpressionAtlas; O14967; baseline and differential.
DR   Genevisible; O14967; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR   GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
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:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR   GO; GO:0007338; P:single fertilization; TAS:ProtInc.
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.
DR   PROSITE; PS00805; CALRETICULIN_REPEAT; 2.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Calcium; Chaperone;
KW   Complete proteome; Disulfide bond; Endoplasmic reticulum; Membrane;
KW   Phosphoprotein; Polymorphism; Reference proteome; Repeat; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   CHAIN        20    610       Calmegin.
FT                                /FTId=PRO_0000004210.
FT   TOPO_DOM     20    471       Lumenal. {ECO:0000255}.
FT   TRANSMEM    472    492       Helical. {ECO:0000255}.
FT   TOPO_DOM    493    610       Cytoplasmic. {ECO:0000255}.
FT   REPEAT      267    280       1-1.
FT   REPEAT      284    297       1-2.
FT   REPEAT      303    316       1-3.
FT   REPEAT      322    335       1-4.
FT   REPEAT      339    352       2-1.
FT   REPEAT      356    369       2-2.
FT   REPEAT      370    383       2-3.
FT   REPEAT      384    397       2-4.
FT   REGION      317    350       Interaction with PPIB. {ECO:0000250}.
FT   MOD_RES     128    128       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P27824}.
FT   MOD_RES     560    560       Phosphoserine.
FT                                {ECO:0000244|PubMed:17081983}.
FT   MOD_RES     576    576       Phosphoserine.
FT                                {ECO:0000244|PubMed:17081983}.
FT   MOD_RES     579    579       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P52194}.
FT   MOD_RES     581    581       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P52194}.
FT   MOD_RES     591    591       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P52194}.
FT   MOD_RES     594    594       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P52194}.
FT   MOD_RES     601    601       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P27824}.
FT   DISULFID    151    185       {ECO:0000250}.
FT   DISULFID    351    355       {ECO:0000250}.
FT   VAR_SEQ      54    211       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055517.
FT   VAR_SEQ     378    424       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055518.
FT   VARIANT     160    160       A -> S (in dbSNP:rs2567241).
FT                                /FTId=VAR_024400.
FT   VARIANT     290    290       V -> I (in dbSNP:rs2175563).
FT                                /FTId=VAR_033776.
FT   VARIANT     352    352       R -> W (in dbSNP:rs12513290).
FT                                /FTId=VAR_048590.
FT   CONFLICT    232    232       V -> A (in Ref. 2; BAG63520).
FT                                {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
//