ID PREB_HUMAN Reviewed; 417 AA. AC Q9HCU5; Q53SZ8; Q9UH94; DT 24-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 2. DT 27-MAR-2024, entry version 182. DE RecName: Full=Prolactin regulatory element-binding protein; DE AltName: Full=Mammalian guanine nucleotide exchange factor mSec12; GN Name=PREB; Synonyms=SEC12; 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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY. RX PubMed=10920239; DOI=10.1007/s003350010142; RA Taylor Clelland C.L., Levy B., McKie J.M., Duncan A.M.V., Hirschhorn K., RA Bancroft C.; RT "Cloning and characterization of human PREB; a gene that maps to a genomic RT region associated with trisomy 2p syndrome."; RL Mamm. Genome 11:675-681(2000). RN [2] RP NUCLEOTIDE SEQUENCE. RA Edgar A.J., Polak J.M.; RT "The human and mouse homologues of rat prolactin regulatory element binding RT protein."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=12735795; DOI=10.1186/1471-2164-4-18; RA Edgar A.J.; RT "The gene structure and expression of human ABHD1: overlapping RT polyadenylation signal sequence with Sec12."; RL BMC Genomics 4:18-18(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Lung, and Uterus; 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 [8] 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). RN [9] RP INTERACTION WITH MIA2, AND SUBCELLULAR LOCATION. RX PubMed=25202031; DOI=10.1083/jcb.201312062; RA Saito K., Yamashiro K., Shimazu N., Tanabe T., Kontani K., Katada T.; RT "Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is RT required for collagen export."; RL J. Cell Biol. 206:751-762(2014). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP INTERACTION WITH MIA2. RX PubMed=27170179; DOI=10.1091/mbc.e16-03-0180; RA Tanabe T., Maeda M., Saito K., Katada T.; RT "Dual function of cTAGE5 in collagen export from the endoplasmic RT reticulum."; RL Mol. Biol. Cell 27:2008-2013(2016). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=28442536; DOI=10.1083/jcb.201703084; RA Maeda M., Katada T., Saito K.; RT "TANGO1 recruits Sec16 to coordinately organize ER exit sites for efficient RT secretion."; RL J. Cell Biol. 216:1731-1743(2017). CC -!- FUNCTION: Guanine nucleotide exchange factor that specifically CC activates the small GTPase SAR1B. Mediates the recruitment of SAR1B and CC other COPII coat components to endoplasmic reticulum membranes and is CC therefore required for the formation of COPII transport vesicles from CC the ER. {ECO:0000250|UniProtKB:Q9WTV0, ECO:0000250|UniProtKB:Q9WUQ2}. CC -!- FUNCTION: Was first identified based on its probable role in the CC regulation of pituitary gene transcription. Binds to the prolactin gene CC (PRL) promoter and seems to activate transcription. CC {ECO:0000250|UniProtKB:Q9WTV0}. CC -!- SUBUNIT: Interacts with SAR1B (GDP-bound form) (By similarity). CC Interacts with MIA2; recruits PREB to endoplasmic reticulum exit sites CC (PubMed:25202031, PubMed:27170179). Interacts with CIDEB; facilitating CC loading of SCAP-SREBP into COPII vesicles (By similarity). CC {ECO:0000250|UniProtKB:Q9WUQ2, ECO:0000269|PubMed:25202031, CC ECO:0000269|PubMed:27170179}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q9WTV0}; Single-pass membrane protein CC {ECO:0000250|UniProtKB:Q9WTV0}. Nucleus {ECO:0000250|UniProtKB:Q9WTV0}. CC Note=Concentrates at endoplasmic reticulum exit sites (ERES), also CC known as transitional endoplasmic reticulum (tER). CC {ECO:0000269|PubMed:25202031, ECO:0000269|PubMed:28442536}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10920239, CC ECO:0000269|PubMed:12735795}. 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; AF226684; AAG01692.1; -; mRNA. DR EMBL; AF203687; AAF19192.1; -; mRNA. DR EMBL; AF227166; AAF74572.1; -; Genomic_DNA. DR EMBL; AK023064; BAB14385.1; -; mRNA. DR EMBL; AC013403; AAX93170.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00627.1; -; Genomic_DNA. DR EMBL; BC002765; AAH02765.1; -; mRNA. DR EMBL; BC012890; AAH12890.1; -; mRNA. DR EMBL; BC016472; AAH16472.1; -; mRNA. DR EMBL; BC041032; AAH41032.1; -; mRNA. DR CCDS; CCDS1738.1; -. DR RefSeq; NP_001317414.1; NM_001330485.1. DR RefSeq; NP_001317415.1; NM_001330486.1. DR RefSeq; NP_037520.1; NM_013388.5. DR PDB; 5TF2; X-ray; 2.80 A; A=1-389. DR PDBsum; 5TF2; -. DR AlphaFoldDB; Q9HCU5; -. DR SMR; Q9HCU5; -. DR BioGRID; 115419; 204. DR CORUM; Q9HCU5; -. DR IntAct; Q9HCU5; 34. DR MINT; Q9HCU5; -. DR STRING; 9606.ENSP00000260643; -. DR TCDB; 8.A.92.1.10; the g-protein AlphaBetaGama complex (gpc) family. DR iPTMnet; Q9HCU5; -. DR PhosphoSitePlus; Q9HCU5; -. DR SwissPalm; Q9HCU5; -. DR BioMuta; PREB; -. DR DMDM; 55977881; -. DR EPD; Q9HCU5; -. DR jPOST; Q9HCU5; -. DR MassIVE; Q9HCU5; -. DR MaxQB; Q9HCU5; -. DR PaxDb; 9606-ENSP00000260643; -. DR PeptideAtlas; Q9HCU5; -. DR ProteomicsDB; 81801; -. DR Pumba; Q9HCU5; -. DR Antibodypedia; 3012; 141 antibodies from 27 providers. DR DNASU; 10113; -. DR Ensembl; ENST00000260643.7; ENSP00000260643.2; ENSG00000138073.14. DR GeneID; 10113; -. DR KEGG; hsa:10113; -. DR MANE-Select; ENST00000260643.7; ENSP00000260643.2; NM_013388.6; NP_037520.1. DR UCSC; uc002rix.3; human. DR AGR; HGNC:9356; -. DR CTD; 10113; -. DR DisGeNET; 10113; -. DR GeneCards; PREB; -. DR HGNC; HGNC:9356; PREB. DR HPA; ENSG00000138073; Low tissue specificity. DR MIM; 606395; gene. DR neXtProt; NX_Q9HCU5; -. DR OpenTargets; ENSG00000138073; -. DR PharmGKB; PA33727; -. DR VEuPathDB; HostDB:ENSG00000138073; -. DR eggNOG; KOG0771; Eukaryota. DR GeneTree; ENSGT00390000018031; -. DR HOGENOM; CLU_054579_1_0_1; -. DR InParanoid; Q9HCU5; -. DR OMA; YYVQPRI; -. DR OrthoDB; 2727235at2759; -. DR PhylomeDB; Q9HCU5; -. DR TreeFam; TF314383; -. DR PathwayCommons; Q9HCU5; -. DR Reactome; R-HSA-204005; COPII-mediated vesicle transport. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR Reactome; R-HSA-5694530; Cargo concentration in the ER. DR SignaLink; Q9HCU5; -. DR SIGNOR; Q9HCU5; -. DR BioGRID-ORCS; 10113; 758 hits in 1158 CRISPR screens. DR ChiTaRS; PREB; human. DR GeneWiki; PREB; -. DR GenomeRNAi; 10113; -. DR Pharos; Q9HCU5; Tbio. DR PRO; PR:Q9HCU5; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9HCU5; Protein. DR Bgee; ENSG00000138073; Expressed in right lobe of liver and 191 other cell types or tissues. DR ExpressionAtlas; Q9HCU5; baseline and differential. DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central. DR GO; GO:0051020; F:GTPase binding; IEA:Ensembl. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB. DR GO; GO:0048208; P:COPII vesicle coating; ISS:UniProtKB. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; ISS:UniProtKB. DR GO; GO:0032527; P:protein exit from endoplasmic reticulum; IMP:UniProtKB. DR GO; GO:0009306; P:protein secretion; IBA:GO_Central. DR GO; GO:0003400; P:regulation of COPII vesicle coating; IBA:GO_Central. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam. DR InterPro; IPR045260; Sec12-like. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR23284; PROLACTIN REGULATORY ELEMENT BINDING PROTEIN; 1. DR PANTHER; PTHR23284:SF0; PROLACTIN REGULATORY ELEMENT-BINDING PROTEIN; 1. DR Pfam; PF00400; WD40; 2. DR SMART; SM00320; WD40; 4. DR SUPFAM; SSF50998; Quinoprotein alcohol dehydrogenase-like; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q9HCU5; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; DNA-binding; Endoplasmic reticulum; KW ER-Golgi transport; Membrane; Nitration; Nucleus; Protein transport; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Transmembrane; Transmembrane helix; Transport; WD repeat. FT CHAIN 1..417 FT /note="Prolactin regulatory element-binding protein" FT /id="PRO_0000051154" FT TOPO_DOM 1..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 389..409 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 410..417 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REPEAT 4..50 FT /note="WD 1" FT REPEAT 58..97 FT /note="WD 2" FT REPEAT 127..183 FT /note="WD 3" FT REPEAT 187..224 FT /note="WD 4" FT REPEAT 230..287 FT /note="WD 5" FT REPEAT 291..329 FT /note="WD 6" FT REPEAT 334..385 FT /note="WD 7" FT REGION 101..130 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 109..130 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 10 FT /note="3'-nitrotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9WUQ2" FT CONFLICT 19 FT /note="L -> F (in Ref. 1; AAG01692)" FT /evidence="ECO:0000305" FT STRAND 16..22 FT /evidence="ECO:0007829|PDB:5TF2" FT TURN 23..26 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 27..33 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 42..52 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 57..66 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 72..78 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 89..97 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 139..148 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 166..173 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 177..182 FT /evidence="ECO:0007829|PDB:5TF2" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 188..193 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 199..204 FT /evidence="ECO:0007829|PDB:5TF2" FT HELIX 206..208 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 210..214 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 226..231 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 245..254 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 262..272 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:5TF2" FT TURN 287..289 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 292..297 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 303..308 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 312..319 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 324..328 FT /evidence="ECO:0007829|PDB:5TF2" FT TURN 329..332 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 333..338 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 346..351 FT /evidence="ECO:0007829|PDB:5TF2" FT HELIX 358..362 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 368..373 FT /evidence="ECO:0007829|PDB:5TF2" FT STRAND 376..382 FT /evidence="ECO:0007829|PDB:5TF2" SQ SEQUENCE 417 AA; 45468 MW; 7FD490A641202D19 CRC64; MGRRRAPELY RAPFPLYALQ VDPSTGLLIA AGGGGAAKTG IKNGVHFLQL ELINGRLSAS LLHSHDTETR ATMNLALAGD ILAAGQDAHC QLLRFQAHQQ QGNKAEKAGS KEQGPRQRKG AAPAEKKCGA ETQHEGLELR VENLQAVQTD FSSDPLQKVV CFNHDNTLLA TGGTDGYVRV WKVPSLEKVL EFKAHEGEIE DLALGPDGKL VTVGRDLKAS VWQKDQLVTQ LHWQENGPTF SSTPYRYQAC RFGQVPDQPA GLRLFTVQIP HKRLRQPPPC YLTAWDGSNF LPLRTKSCGH EVVSCLDVSE SGTFLGLGTV TGSVAIYIAF SLQCLYYVRE AHGIVVTDVA FLPEKGRGPE LLGSHETALF SVAVDSRCQL HLLPSRRSVP VWLLLLLCVG LIIVTILLLQ SAFPGFL //