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 08-MAY-2019, entry version 157. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Hirschhorn K., Bancroft C.; RT "Cloning and characterization of human PREB; a gene that maps to a RT genomic 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 RT binding 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., 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 [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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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., 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 [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 RT project: 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., 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). 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 RT is 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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 RT efficient 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 recruitement of CC SAR1B and other COPII coat components to endoplasmic reticulum CC membranes and is therefore required for the formation of COPII CC transport vesicles from the ER. {ECO:0000250|UniProtKB:Q9WTV0, CC 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 CC gene (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 CC sites (PubMed:25202031, PubMed:27170179). 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 CC {ECO:0000250|UniProtKB:Q9WTV0}. Note=Concentrates at endoplasmic CC reticulum exit sites (ERES), also known as transitional CC endoplasmic reticulum (tER). {ECO:0000269|PubMed:25202031, CC 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 SMR; Q9HCU5; -. DR BioGrid; 115419; 27. DR CORUM; Q9HCU5; -. DR IntAct; Q9HCU5; 22. DR MINT; Q9HCU5; -. DR STRING; 9606.ENSP00000260643; -. DR iPTMnet; Q9HCU5; -. DR PhosphoSitePlus; Q9HCU5; -. DR SwissPalm; Q9HCU5; -. DR BioMuta; PREB; -. DR DMDM; 55977881; -. DR EPD; Q9HCU5; -. DR jPOST; Q9HCU5; -. DR MaxQB; Q9HCU5; -. DR PaxDb; Q9HCU5; -. DR PeptideAtlas; Q9HCU5; -. DR PRIDE; Q9HCU5; -. DR ProteomicsDB; 81801; -. DR DNASU; 10113; -. DR Ensembl; ENST00000260643; ENSP00000260643; ENSG00000138073. DR GeneID; 10113; -. DR KEGG; hsa:10113; -. DR UCSC; uc002rix.3; human. DR CTD; 10113; -. DR DisGeNET; 10113; -. DR GeneCards; PREB; -. DR HGNC; HGNC:9356; PREB. DR HPA; HPA013582; -. DR HPA; HPA014133; -. DR MIM; 606395; gene. DR neXtProt; NX_Q9HCU5; -. DR OpenTargets; ENSG00000138073; -. DR PharmGKB; PA33727; -. DR eggNOG; KOG0771; Eukaryota. DR eggNOG; ENOG410XRQK; LUCA. DR GeneTree; ENSGT00390000018031; -. DR HOGENOM; HOG000045302; -. DR InParanoid; Q9HCU5; -. DR KO; K14003; -. DR OMA; AHSMFVT; -. DR OrthoDB; 828247at2759; -. DR PhylomeDB; Q9HCU5; -. DR TreeFam; TF314383; -. 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 ChiTaRS; PREB; human. DR GeneWiki; PREB; -. DR GenomeRNAi; 10113; -. DR PRO; PR:Q9HCU5; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; ENSG00000138073; Expressed in 217 organ(s), highest expression level in right lobe of liver. DR ExpressionAtlas; Q9HCU5; baseline and differential. DR Genevisible; Q9HCU5; HS. DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; IEA:GOC. DR GO; GO:0030176; C:integral component of 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; IBA:GO_Central. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome. DR GO; GO:0005090; F:Sar 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:0036498; P:IRE1-mediated unfolded protein response; TAS:Reactome. 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 InterPro; IPR011047; Quinoprotein_ADH-like_supfam. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR017986; WD40_repeat_dom. DR Pfam; PF00400; WD40; 1. DR SMART; SM00320; WD40; 4. DR SUPFAM; SSF50998; SSF50998; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Complete proteome; DNA-binding; KW Endoplasmic reticulum; ER-Golgi transport; Membrane; Nitration; KW Nucleus; Protein transport; Reference proteome; Repeat; Transcription; KW Transcription regulation; Transmembrane; Transmembrane helix; KW Transport; WD repeat. FT CHAIN 1 417 Prolactin regulatory element-binding FT protein. FT /FTId=PRO_0000051154. FT TOPO_DOM 1 388 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 389 409 Helical. {ECO:0000255}. FT TOPO_DOM 410 417 Lumenal. {ECO:0000255}. FT REPEAT 4 50 WD 1. FT REPEAT 58 97 WD 2. FT REPEAT 127 183 WD 3. FT REPEAT 187 224 WD 4. FT REPEAT 230 287 WD 5. FT REPEAT 291 329 WD 6. FT REPEAT 334 385 WD 7. FT MOD_RES 10 10 Nitrated tyrosine. FT {ECO:0000250|UniProtKB:Q9WUQ2}. FT CONFLICT 19 19 L -> F (in Ref. 1; AAG01692). FT {ECO:0000305}. FT STRAND 16 22 {ECO:0000244|PDB:5TF2}. FT TURN 23 26 {ECO:0000244|PDB:5TF2}. FT STRAND 27 33 {ECO:0000244|PDB:5TF2}. FT STRAND 38 40 {ECO:0000244|PDB:5TF2}. FT STRAND 42 52 {ECO:0000244|PDB:5TF2}. FT STRAND 57 66 {ECO:0000244|PDB:5TF2}. FT STRAND 72 78 {ECO:0000244|PDB:5TF2}. FT STRAND 81 86 {ECO:0000244|PDB:5TF2}. FT STRAND 89 97 {ECO:0000244|PDB:5TF2}. FT STRAND 139 148 {ECO:0000244|PDB:5TF2}. FT STRAND 152 154 {ECO:0000244|PDB:5TF2}. FT STRAND 157 162 {ECO:0000244|PDB:5TF2}. FT STRAND 166 173 {ECO:0000244|PDB:5TF2}. FT STRAND 177 182 {ECO:0000244|PDB:5TF2}. FT TURN 183 185 {ECO:0000244|PDB:5TF2}. FT STRAND 188 193 {ECO:0000244|PDB:5TF2}. FT STRAND 199 204 {ECO:0000244|PDB:5TF2}. FT HELIX 206 208 {ECO:0000244|PDB:5TF2}. FT STRAND 210 214 {ECO:0000244|PDB:5TF2}. FT STRAND 219 223 {ECO:0000244|PDB:5TF2}. FT STRAND 226 231 {ECO:0000244|PDB:5TF2}. FT STRAND 245 254 {ECO:0000244|PDB:5TF2}. FT STRAND 262 272 {ECO:0000244|PDB:5TF2}. FT STRAND 281 286 {ECO:0000244|PDB:5TF2}. FT TURN 287 289 {ECO:0000244|PDB:5TF2}. FT STRAND 292 297 {ECO:0000244|PDB:5TF2}. FT STRAND 303 308 {ECO:0000244|PDB:5TF2}. FT STRAND 312 319 {ECO:0000244|PDB:5TF2}. FT STRAND 324 328 {ECO:0000244|PDB:5TF2}. FT TURN 329 332 {ECO:0000244|PDB:5TF2}. FT STRAND 333 338 {ECO:0000244|PDB:5TF2}. FT STRAND 341 344 {ECO:0000244|PDB:5TF2}. FT STRAND 346 351 {ECO:0000244|PDB:5TF2}. FT HELIX 358 362 {ECO:0000244|PDB:5TF2}. FT STRAND 368 373 {ECO:0000244|PDB:5TF2}. FT STRAND 376 382 {ECO:0000244|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 //