CREL2_MOUSE
ID CREL2_MOUSE Reviewed; 350 AA.
AC Q9CYA0;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Protein disulfide isomerase Creld2 {ECO:0000305};
DE EC=5.3.4.1 {ECO:0000305|PubMed:23956175};
DE AltName: Full=Cysteine-rich with EGF-like domain protein 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=Creld2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Lung;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, 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).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN COMPLEX WITH MANF; MATN3
RP AND PDIA4, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP CYS-32 AND CYS-264.
RX PubMed=23956175; DOI=10.1093/hmg/ddt383;
RA Hartley C.L., Edwards S., Mullan L., Bell P.A., Fresquet M.,
RA Boot-Handford R.P., Briggs M.D.;
RT "Armet/Manf and Creld2 are components of a specialized ER stress response
RT provoked by inappropriate formation of disulphide bonds: implications for
RT genetic skeletal diseases.";
RL Hum. Mol. Genet. 22:5262-5275(2013).
CC -!- FUNCTION: Protein disulfide isomerase (Probable). Might play a role in
CC the unfolded protein response (Probable). May regulate transport of
CC alpha4-beta2 neuronal acetylcholine receptor (By similarity).
CC {ECO:0000250|UniProtKB:Q6UXH1, ECO:0000305|PubMed:23956175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Catalyzes the rearrangement of -S-S- bonds in proteins.;
CC EC=5.3.4.1; Evidence={ECO:0000305|PubMed:23956175};
CC -!- SUBUNIT: Interacts with CHRNA4 (By similarity). Component of a complex
CC containing at least CRELD2, MANF, MATN3 and PDIA4 (PubMed:23956175).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q6UXH1,
CC ECO:0000269|PubMed:23956175}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q6UXH1}.
CC -!- TISSUE SPECIFICITY: Expressed in chondrocytes (at protein level).
CC {ECO:0000269|PubMed:23956175}.
CC -!- DEVELOPMENTAL STAGE: Expressed from birth.
CC {ECO:0000269|PubMed:23956175}.
CC -!- MISCELLANEOUS: Secreted under some pathological conditions such as
CC skeletal diseases. {ECO:0000269|PubMed:23956175}.
CC -!- SIMILARITY: Belongs to the CRELD family. {ECO:0000305}.
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DR EMBL; AK017880; BAB30986.1; -; mRNA.
DR EMBL; AK165884; BAE38436.1; -; mRNA.
DR EMBL; BC047370; AAH47370.1; -; mRNA.
DR CCDS; CCDS27733.1; -.
DR RefSeq; NP_083996.1; NM_029720.2.
DR AlphaFoldDB; Q9CYA0; -.
DR BioGRID; 218289; 5.
DR IntAct; Q9CYA0; 16.
DR MINT; Q9CYA0; -.
DR STRING; 10090.ENSMUSP00000024042; -.
DR GlyConnect; 2248; 2 N-Linked glycans (1 site).
DR GlyGen; Q9CYA0; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9CYA0; -.
DR PhosphoSitePlus; Q9CYA0; -.
DR EPD; Q9CYA0; -.
DR jPOST; Q9CYA0; -.
DR MaxQB; Q9CYA0; -.
DR PaxDb; Q9CYA0; -.
DR PeptideAtlas; Q9CYA0; -.
DR PRIDE; Q9CYA0; -.
DR ProteomicsDB; 285307; -.
DR Antibodypedia; 200; 211 antibodies from 25 providers.
DR DNASU; 76737; -.
DR Ensembl; ENSMUST00000024042; ENSMUSP00000024042; ENSMUSG00000023272.
DR GeneID; 76737; -.
DR KEGG; mmu:76737; -.
DR UCSC; uc007xep.1; mouse.
DR CTD; 79174; -.
DR MGI; MGI:1923987; Creld2.
DR VEuPathDB; HostDB:ENSMUSG00000023272; -.
DR eggNOG; KOG4260; Eukaryota.
DR GeneTree; ENSGT00940000160071; -.
DR HOGENOM; CLU_038974_1_0_1; -.
DR InParanoid; Q9CYA0; -.
DR OMA; DQEACVD; -.
DR OrthoDB; 883628at2759; -.
DR PhylomeDB; Q9CYA0; -.
DR TreeFam; TF316507; -.
DR BioGRID-ORCS; 76737; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Creld2; mouse.
DR PRO; PR:Q9CYA0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9CYA0; protein.
DR Bgee; ENSMUSG00000023272; Expressed in prostate gland ventral lobe and 267 other tissues.
DR Genevisible; Q9CYA0; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IEA:UniProtKB-EC.
DR CDD; cd00064; FU; 2.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR002049; LE_dom.
DR Pfam; PF07645; EGF_CA; 2.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00261; FU; 2.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 2.
PE 1: Evidence at protein level;
KW Calcium; Disulfide bond; EGF-like domain; Endoplasmic reticulum;
KW Glycoprotein; Isomerase; Redox-active center; Reference proteome; Repeat;
KW Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..350
FT /note="Protein disulfide isomerase Creld2"
FT /id="PRO_0000256246"
FT DOMAIN 134..176
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 191..238
FT /note="FU 1"
FT REPEAT 251..298
FT /note="FU 2"
FT DOMAIN 288..329
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT MOTIF 29..32
FT /note="CXXC"
FT /evidence="ECO:0000305|PubMed:23956175"
FT MOTIF 261..264
FT /note="CXXC"
FT /evidence="ECO:0000305|PubMed:23956175"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..32
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:23956175"
FT DISULFID 138..152
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 146..164
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 166..175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 261..264
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:23956175"
FT DISULFID 292..306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 299..315
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 317..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT MUTAGEN 32
FT /note="C->A: Substrate-trapping mutant."
FT /evidence="ECO:0000269|PubMed:23956175"
FT MUTAGEN 264
FT /note="C->A: Does not act as a substrate-trapping mutant."
FT /evidence="ECO:0000269|PubMed:23956175"
SQ SEQUENCE 350 AA; 38220 MW; 781D7389B1944231 CRC64;
MHLLLAAAFG LLLLLPPPGA VASRKPTMCQ RCRTLVDKFN QGMANTARKN FGGGNTAWEE
KTLSKYEFSE IRLLEIMEGL CDSSDFECNQ LLEQQEEQLE AWWQTLKKEH PNLFEWFCVH
TLKACCLPGT YGPDCQECQG GSERPCSGNG YCSGDGSRQG DGSCQCHTGY KGPLCIDCTD
GFFSLQRNET HSICSACDES CKTCSGPSNK DCIQCEVGWA RVEDACVDVD ECAAETSPCS
DGQYCENVNG SYTCEDCDST CVGCTGKGPA NCKECIAGYT KESGQCTDID ECSLEEKACK
RKNENCYNVP GSFVCVCPEG FEETEDACVQ TAEGKVTEEN PTQPPSREDL
