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 24-JAN-2024, entry version 169. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 38. DR IntAct; O75629; 9. DR MINT; O75629; -. DR STRING; 9606.ENSP00000359540; -. DR GlyConnect; 1653; 13 N-Linked glycans (3 sites). DR GlyCosmos; O75629; 4 sites, 13 glycans. 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; 9606-ENSP00000359540; -. DR PeptideAtlas; O75629; -. DR ProteomicsDB; 50128; -. DR Pumba; O75629; -. DR Antibodypedia; 20531; 361 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 AGR; HGNC:2351; -. 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; AQTPYCR; -. DR OrthoDB; 56593at2759; -. 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 1168 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 210 other cell types or tissues. DR ExpressionAtlas; O75629; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005768; C:endosome; IEA:Ensembl. 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:0006914; P:autophagy; IEA:Ensembl. DR GO; GO:0006897; P:endocytosis; IEA:Ensembl. DR GO; GO:0007042; P:lysosomal lumen acidification; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:ProtInc. DR InterPro; IPR014631; CREG. DR InterPro; IPR012349; Split_barrel_FMN-bd. DR PANTHER; PTHR13343; CREG1 PROTEIN; 1. DR PANTHER; PTHR13343:SF21; PROTEIN CREG1; 1. DR Pfam; PF13883; Pyrid_oxidase_2; 1. DR PIRSF; PIRSF036911; CREG; 1. DR SUPFAM; SSF50475; FMN-binding split barrel; 1. DR Genevisible; O75629; HS. 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 //