CREG1_HUMAN
ID CREG1_HUMAN Reviewed; 220 AA.
AC O75629; B2RDD4; Q8N9A3;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Protein CREG1;
DE AltName: Full=Cellular repressor of E1A-stimulated genes 1;
DE Flags: Precursor;
GN Name=CREG1; Synonyms=CREG; ORFNames=UNQ727/PRO1409;
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], AND FUNCTION.
RX PubMed=9710587; DOI=10.1128/mcb.18.9.5032;
RA Veal E., Eisenstein M., Tseng Z.H., Gill G.;
RT "A cellular repressor of E1A-stimulated genes that inhibits activation by
RT E2F.";
RL Mol. Cell. Biol. 18:5032-5041(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Placenta;
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 [7]
RP PROTEIN SEQUENCE OF 32-46.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=10815803; DOI=10.1038/sj.onc.1203529;
RA Veal E., Groisman R., Eisenstein M., Gill G.;
RT "The secreted glycoprotein CREG enhances differentiation of NTERA-2 human
RT embryonal carcinoma cells.";
RL Oncogene 19:2120-2128(2000).
RN [9]
RP INTERACTION WITH IGF2R, AND FUNCTION.
RX PubMed=12934103; DOI=10.1038/sj.onc.1206670;
RA Di Bacco A., Gill G.;
RT "The secreted glycoprotein CREG inhibits cell growth dependent on the
RT mannose-6-phosphate/insulin-like growth factor II receptor.";
RL Oncogene 22:5436-5445(2003).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-160; ASN-193 AND ASN-216.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 49-220, AND SUBUNIT.
RX PubMed=16344469; DOI=10.1073/pnas.0505071102;
RA Sacher M., Di Bacco A., Lunin V.V., Ye Z., Wagner J., Gill G., Cygler M.;
RT "The crystal structure of CREG, a secreted glycoprotein involved in
RT cellular growth and differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:18326-18331(2005).
CC -!- FUNCTION: May contribute to the transcriptional control of cell growth
CC and differentiation. Antagonizes transcriptional activation and
CC cellular transformation by the adenovirus E1A protein. The
CC transcriptional control activity of cell growth requires interaction
CC with IGF2R. {ECO:0000269|PubMed:12934103, ECO:0000269|PubMed:9710587}.
CC -!- SUBUNIT: Homodimer. Interacts with IGF2R; the interaction is dependent
CC on glycosylation. {ECO:0000269|PubMed:12934103,
CC ECO:0000269|PubMed:16344469}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10815803}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10815803,
CC ECO:0000269|PubMed:19159218}.
CC -!- SIMILARITY: Belongs to the CREG family. {ECO:0000305}.
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DR EMBL; AF084523; AAC34861.1; -; mRNA.
DR EMBL; AY359071; AAQ89430.1; -; mRNA.
DR EMBL; AK095456; BAC04550.1; -; mRNA.
DR EMBL; AK315497; BAG37881.1; -; mRNA.
DR EMBL; AL031733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90795.1; -; Genomic_DNA.
DR EMBL; BC006786; AAH06786.1; -; mRNA.
DR EMBL; BC008628; AAH08628.1; -; mRNA.
DR CCDS; CCDS1262.1; -.
DR RefSeq; NP_003842.1; NM_003851.2.
DR PDB; 1XHN; X-ray; 1.95 A; A/B/C/D=49-220.
DR PDBsum; 1XHN; -.
DR AlphaFoldDB; O75629; -.
DR SMR; O75629; -.
DR BioGRID; 114332; 35.
DR IntAct; O75629; 9.
DR MINT; O75629; -.
DR STRING; 9606.ENSP00000359540; -.
DR GlyConnect; 1653; 13 N-Linked glycans (3 sites).
DR GlyGen; O75629; 5 sites, 12 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; O75629; -.
DR PhosphoSitePlus; O75629; -.
DR BioMuta; CREG1; -.
DR CPTAC; CPTAC-1487; -.
DR EPD; O75629; -.
DR jPOST; O75629; -.
DR MassIVE; O75629; -.
DR MaxQB; O75629; -.
DR PaxDb; O75629; -.
DR PeptideAtlas; O75629; -.
DR PRIDE; O75629; -.
DR ProteomicsDB; 50128; -.
DR Antibodypedia; 20531; 331 antibodies from 34 providers.
DR DNASU; 8804; -.
DR Ensembl; ENST00000370509.5; ENSP00000359540.4; ENSG00000143162.9.
DR GeneID; 8804; -.
DR KEGG; hsa:8804; -.
DR MANE-Select; ENST00000370509.5; ENSP00000359540.4; NM_003851.3; NP_003842.1.
DR UCSC; uc001gel.4; human.
DR CTD; 8804; -.
DR DisGeNET; 8804; -.
DR GeneCards; CREG1; -.
DR HGNC; HGNC:2351; CREG1.
DR HPA; ENSG00000143162; Low tissue specificity.
DR MIM; 618055; gene.
DR neXtProt; NX_O75629; -.
DR OpenTargets; ENSG00000143162; -.
DR PharmGKB; PA26869; -.
DR VEuPathDB; HostDB:ENSG00000143162; -.
DR eggNOG; KOG3374; Eukaryota.
DR GeneTree; ENSGT00390000005914; -.
DR HOGENOM; CLU_083635_3_1_1; -.
DR InParanoid; O75629; -.
DR OMA; CAHIIFV; -.
DR OrthoDB; 1252017at2759; -.
DR PhylomeDB; O75629; -.
DR TreeFam; TF324680; -.
DR PathwayCommons; O75629; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; O75629; -.
DR BioGRID-ORCS; 8804; 12 hits in 1088 CRISPR screens.
DR ChiTaRS; CREG1; human.
DR EvolutionaryTrace; O75629; -.
DR GeneWiki; CREG1; -.
DR GenomeRNAi; 8804; -.
DR Pharos; O75629; Tbio.
DR PRO; PR:O75629; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75629; protein.
DR Bgee; ENSG00000143162; Expressed in upper leg skin and 208 other tissues.
DR ExpressionAtlas; O75629; baseline and differential.
DR Genevisible; O75629; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR Gene3D; 2.30.110.10; -; 1.
DR InterPro; IPR014631; CREG.
DR InterPro; IPR012349; Split_barrel_FMN-bd.
DR PIRSF; PIRSF036911; CREG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Glycoprotein; Growth regulation;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 32..220
FT /note="Protein CREG1"
FT /id="PRO_0000006203"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CONFLICT 52..59
FT /note="Missing (in Ref. 4; BAC04550)"
FT /evidence="ECO:0000305"
FT HELIX 55..65
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 112..119
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 149..158
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 164..174
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 176..180
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 188..200
FT /evidence="ECO:0007829|PDB:1XHN"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:1XHN"
FT HELIX 211..216
FT /evidence="ECO:0007829|PDB:1XHN"
SQ SEQUENCE 220 AA; 24075 MW; 0DB95A1E4149CD7C CRC64;
MAGLSRGSAR ALLAALLAST LLALLVSPAR GRGGRDHGDW DEASRLPPLP PREDAARVAR
FVTHVSDWGA LATISTLEAV RGRPFADVLS LSDGPPGAGS GVPYFYLSPL QLSVSNLQEN
PYATLTMTLA QTNFCKKHGF DPQSPLCVHI MLSGTVTKVN ETEMDIAKHS LFIRHPEMKT
WPSSHNWFFA KLNITNIWVL DYFGGPKIVT PEEYYNVTVQ
