ID PEF1_HUMAN Reviewed; 284 AA.
AC Q9UBV8;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 10-MAY-2017, entry version 150.
DE RecName: Full=Peflin {ECO:0000303|PubMed:10486255};
DE AltName: Full=PEF protein with a long N-terminal hydrophobic domain {ECO:0000303|PubMed:10486255};
DE AltName: Full=Penta-EF hand domain-containing protein 1 {ECO:0000312|HGNC:HGNC:30009};
GN Name=PEF1 {ECO:0000312|HGNC:HGNC:30009}; Synonyms=ABP32;
GN ORFNames=UNQ1845/PRO3573 {ECO:0000303|PubMed:12975309};
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 [MRNA].
RX PubMed=10486255; DOI=10.1006/bbrc.1999.1189;
RA Kitaura Y., Watanabe M., Satoh H., Kawai T., Hitomi K., Maki M.;
RT "Peflin, a novel member of the five-EF-hand-protein family, is similar
RT to the apoptosis-linked gene 2 (ALG-2) protein but possesses
RT nonapeptide repeats in the N-terminal hydrophobic region.";
RL Biochem. Biophys. Res. Commun. 263:68-75(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Shibata M., Noguchi J.;
RT "A putative calcium binding protein that has five EF-hand motifs.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(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 MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate, and Skin;
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PDCD6.
RX PubMed=11278427; DOI=10.1074/jbc.M008649200;
RA Kitaura Y., Matsumoto S., Satoh H., Hitomi K., Maki M.;
RT "Peflin and ALG-2, members of the penta-EF-hand protein family, form a
RT heterodimer that dissociates in a Ca2+-dependent manner.";
RL J. Biol. Chem. 276:14053-14058(2001).
RN [8]
RP INTERACTION WITH PDCD6.
RX PubMed=11883899; DOI=10.1006/abbi.2001.2736;
RA Kitaura Y., Satoh H., Takahashi H., Shibata H., Maki M.;
RT "Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized
RT by dimerization through their fifth EF-hand regions.";
RL Arch. Biochem. Biophys. 399:12-18(2002).
RN [9]
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PDCD6, UBIQUITINATION
RP AT LYS-137, AND MUTAGENESIS OF LYS-137; LYS-165 AND LYS-167.
RX PubMed=27716508; DOI=10.1016/j.cell.2016.09.026;
RA McGourty C.A., Akopian D., Walsh C., Gorur A., Werner A., Schekman R.,
RA Bautista D., Rape M.;
RT "Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co-
RT adaptor.";
RL Cell 167:525-538(2016).
CC -!- FUNCTION: Calcium-binding protein that acts as an adapter that
CC bridges unrelated proteins or stabilizes weak protein-protein
CC complexes in response to calcium. Together with PDCD6, acts as
CC calcium-dependent adapter for the BCR(KLHL12) complex, a complex
CC involved in endoplasmic reticulum (ER)-Golgi transport by
CC regulating the size of COPII coats (PubMed:27716508). In response
CC to cytosolic calcium increase, the heterodimer formed with PDCD6
CC interacts with, and bridges together the BCR(KLHL12) complex and
CC SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31
CC and subsequent collagen export, which is required for neural crest
CC specification (PubMed:27716508). Its role in the heterodimer
CC formed with PDCD6 is however unclear: some evidences show that
CC PEF1 and PDCD6 work together and promote association between PDCD6
CC and SEC31 in presence of calcium (PubMed:27716508). Other reports
CC show that PEF1 dissociates from PDCD6 in presence of calcium, and
CC may act as a negative regulator of PDCD6 (PubMed:11278427). Also
CC acts as a negative regulator of ER-Golgi transport; possibly by
CC inhibiting interaction between PDCD6 and SEC31 (By similarity).
CC {ECO:0000250|UniProtKB:Q641Z8, ECO:0000269|PubMed:11278427,
CC ECO:0000269|PubMed:27716508}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes (via the EF-hand 5) with
CC PDCD6 (PubMed:11278427, PubMed:11883899, PubMed:27716508).
CC Dissociates from PDCD6 in presence of calcium (PubMed:11278427).
CC {ECO:0000269|PubMed:11278427, ECO:0000269|PubMed:11883899,
CC ECO:0000269|PubMed:27716508}.
CC -!- INTERACTION:
CC Q13137:CALCOCO2; NbExp=4; IntAct=EBI-724639, EBI-739580;
CC D3DR37:CEP55; NbExp=3; IntAct=EBI-724639, EBI-10173536;
CC Q15038:DAZAP2; NbExp=5; IntAct=EBI-724639, EBI-724310;
CC Q01844:EWSR1; NbExp=3; IntAct=EBI-724639, EBI-739737;
CC Q6PJQ5:FOXR2; NbExp=5; IntAct=EBI-724639, EBI-8468543;
CC O14964:HGS; NbExp=3; IntAct=EBI-724639, EBI-740220;
CC Q53G59:KLHL12; NbExp=7; IntAct=EBI-724639, EBI-740929;
CC O75340:PDCD6; NbExp=11; IntAct=EBI-724639, EBI-352915;
CC Q5JUK2:SOHLH1; NbExp=4; IntAct=EBI-724639, EBI-12288855;
CC Q92734:TFG; NbExp=5; IntAct=EBI-724639, EBI-357061;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11278427}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q641Z8}. Membrane
CC {ECO:0000269|PubMed:11278427}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11278427}. Cytoplasmic vesicle, COPII-coated
CC vesicle membrane {ECO:0000269|PubMed:27716508}; Peripheral
CC membrane protein {ECO:0000305}. Note=Membrane-associated in the
CC presence of Ca(2+) (PubMed:11278427). Localizes to endoplasmic
CC reticulum exit site (ERES) (By similarity).
CC {ECO:0000250|UniProtKB:Q641Z8, ECO:0000269|PubMed:11278427}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex.
CC {ECO:0000269|PubMed:27716508}.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB026628; BAA85163.1; -; mRNA.
DR EMBL; AB018357; BAA84922.1; -; mRNA.
DR EMBL; AY359011; AAQ89370.1; -; mRNA.
DR EMBL; AK001420; BAA91680.1; -; mRNA.
DR EMBL; CR542139; CAG46936.1; -; mRNA.
DR EMBL; BC002773; AAH02773.1; -; mRNA.
DR EMBL; BC012561; AAH12561.1; -; mRNA.
DR CCDS; CCDS345.1; -.
DR RefSeq; NP_036524.1; NM_012392.3.
DR UniGene; Hs.470417; -.
DR ProteinModelPortal; Q9UBV8; -.
DR SMR; Q9UBV8; -.
DR BioGrid; 139275; 28.
DR IntAct; Q9UBV8; 49.
DR MINT; MINT-5003645; -.
DR STRING; 9606.ENSP00000362807; -.
DR iPTMnet; Q9UBV8; -.
DR PhosphoSitePlus; Q9UBV8; -.
DR BioMuta; PEF1; -.
DR DMDM; 74761895; -.
DR REPRODUCTION-2DPAGE; IPI00018235; -.
DR EPD; Q9UBV8; -.
DR MaxQB; Q9UBV8; -.
DR PaxDb; Q9UBV8; -.
DR PeptideAtlas; Q9UBV8; -.
DR PRIDE; Q9UBV8; -.
DR DNASU; 553115; -.
DR Ensembl; ENST00000373703; ENSP00000362807; ENSG00000162517.
DR GeneID; 553115; -.
DR KEGG; hsa:553115; -.
DR UCSC; uc001bth.3; human.
DR CTD; 553115; -.
DR GeneCards; PEF1; -.
DR HGNC; HGNC:30009; PEF1.
DR HPA; HPA061608; -.
DR MIM; 610033; gene.
DR neXtProt; NX_Q9UBV8; -.
DR OpenTargets; ENSG00000162517; -.
DR PharmGKB; PA142671184; -.
DR eggNOG; KOG0037; Eukaryota.
DR eggNOG; ENOG410YKQK; LUCA.
DR GeneTree; ENSGT00620000087734; -.
DR HOGENOM; HOG000231983; -.
DR HOVERGEN; HBG004492; -.
DR InParanoid; Q9UBV8; -.
DR OMA; PSMQLDR; -.
DR OrthoDB; EOG091G0ISY; -.
DR PhylomeDB; Q9UBV8; -.
DR TreeFam; TF314682; -.
DR GeneWiki; PEF1; -.
DR GenomeRNAi; 553115; -.
DR PRO; PR:Q9UBV8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR Bgee; ENSG00000162517; -.
DR CleanEx; HS_PEF1; -.
DR Genevisible; Q9UBV8; HS.
DR GO; GO:0030127; C:COPII vesicle coat; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:GOC.
DR GO; GO:0060090; F:binding, bridging; IMP:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0048208; P:COPII vesicle coating; IMP:UniProtKB.
DR GO; GO:0006888; P:ER to Golgi vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:0014032; P:neural crest cell development; IMP:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0051592; P:response to calcium ion; IPI:UniProtKB.
DR CDD; cd00051; EFh; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW Calcium; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Isopeptide bond; Membrane; Metal-binding;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 284 Peflin.
FT /FTId=PRO_0000247045.
FT REPEAT 21 29 1. {ECO:0000305}.
FT REPEAT 31 39 2. {ECO:0000305}.
FT REPEAT 41 49 3. {ECO:0000305}.
FT REPEAT 50 58 4. {ECO:0000305}.
FT REPEAT 59 67 5. {ECO:0000305}.
FT REPEAT 76 84 6. {ECO:0000305}.
FT REPEAT 85 92 7. {ECO:0000305}.
FT REPEAT 93 100 8. {ECO:0000305}.
FT REPEAT 101 109 9. {ECO:0000305}.
FT DOMAIN 114 149 EF-hand 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT DOMAIN 155 183 EF-hand 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT DOMAIN 181 216 EF-hand 3. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT DOMAIN 217 253 EF-hand 4. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT DOMAIN 254 283 EF-hand 5. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT CA_BIND 127 138 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT CA_BIND 194 205 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00448}.
FT REGION 21 109 9 X 9 AA approximate tandem repeat of
FT [AP]-P-G-G-P-Y-G-G-P-P. {ECO:0000305}.
FT REGION 204 284 Required for interaction with PDCD6.
FT {ECO:0000269|PubMed:11883899}.
FT CROSSLNK 137 137 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT {ECO:0000305|PubMed:27716508}.
FT MUTAGEN 137 137 K->R: Decreased ubiquitination by the
FT BCR(KLHL12) E3 ubiquitin ligase complex.
FT {ECO:0000269|PubMed:27716508}.
FT MUTAGEN 165 165 K->R: Does not affect ubiquitination by
FT the BCR(KLHL12) E3 ubiquitin ligase
FT complex. {ECO:0000269|PubMed:27716508}.
FT MUTAGEN 167 167 K->R: Does not affect ubiquitination by
FT the BCR(KLHL12) E3 ubiquitin ligase
FT complex. {ECO:0000269|PubMed:27716508}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 118 146 ismart:EFh [T]
FT MYHIT 186 212 ipfam:EF-hand_6 [T]
FT MYHIT 194 206 ipat:EF_HAND_1 [T]
FT MYHIT 127 139 ipat:EF_HAND_1 [T]
FT MYHIT 181 216 iprf:EF_HAND_2 [T]
FT MYHIT 185 213 ismart:EFh [T]
FT MYHIT 155 183 ismart:EFh [T]
FT MYHIT 120 179 ipfam:EF-hand_7 [T]
FT MYHIT 114 149 iprf:EF_HAND_2 [T]
SQ SEQUENCE 284 AA; 30381 MW; 2E9AA5750CB7A68A CRC64;
MASYPYRQGC PGAAGQAPGA PPGSYYPGPP NSGGQYGSGL PPGGGYGGPA PGGPYGPPAG
GGPYGHPNPG MFPSGTPGGP YGGAAPGGPY GQPPPSSYGA QQPGLYGQGG APPNVDPEAY
SWFQSVDSDH SGYISMKELK QALVNCNWSS FNDETCLMMI NMFDKTKSGR IDVYGFSALW
KFIQQWKNLF QQYDRDRSGS ISYTELQQAL SQMGYNLSPQ FTQLLVSRYC PRSANPAMQL
DRFIQVCTQL QVLTEAFREK DTAVQGNIRL SFEDFVTMTA SRML
//
|
