SMR8B_DANRE
ID SMR8B_DANRE Reviewed; 985 AA.
AC Q6PUR7;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Guanine nucleotide exchange protein smcr8b;
DE AltName: Full=Smith-Magenis syndrome chromosomal region candidate gene 8 protein homolog B;
GN Name=smcr8b; Synonyms=smcr8;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney marrow;
RX PubMed=15520368; DOI=10.1073/pnas.0407241101;
RA Song H.-D., Sun X.-J., Deng M., Zhang G.-W., Zhou Y., Wu X.-Y., Sheng Y.,
RA Chen Y., Ruan Z., Jiang C.-L., Fan H.-Y., Zon L.I., Kanki J.P., Liu T.X.,
RA Look A.T., Chen Z.;
RT "Hematopoietic gene expression profile in zebrafish kidney marrow.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16240-16245(2004).
CC -!- FUNCTION: Component of the C9orf72-SMCR8 complex, a complex that has
CC guanine nucleotide exchange factor (GEF) activity and regulates
CC autophagy. In the complex, C9orf72 and SMCR8 probably constitute the
CC catalytic subunits that promote the exchange of GDP to GTP, converting
CC inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form,
CC thereby promoting autophagosome maturation. The C9orf72-SMCR8 complex
CC also acts as a negative regulator of autophagy initiation by
CC interacting with the ATG1/ULK1 kinase complex and inhibiting its
CC protein kinase activity. {ECO:0000250|UniProtKB:Q8TEV9}.
CC -!- SUBUNIT: Component of the C9orf72-SMCR8 complex. The C9orf72-SMCR8
CC complex associates with the ATG1/ULK1 kinase complex.
CC {ECO:0000250|UniProtKB:Q8TEV9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8TEV9}. Nucleus
CC {ECO:0000250|UniProtKB:Q8TEV9}. Note=Localizes mainly in the cytoplasm.
CC {ECO:0000250|UniProtKB:Q8TEV9}.
CC -!- SIMILARITY: Belongs to the SMCR8 family. {ECO:0000305}.
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DR EMBL; AY576998; AAS92636.1; -; mRNA.
DR RefSeq; NP_999967.1; NM_214802.1.
DR AlphaFoldDB; Q6PUR7; -.
DR STRING; 7955.ENSDARP00000005452; -.
DR PaxDb; Q6PUR7; -.
DR GeneID; 407723; -.
DR KEGG; dre:407723; -.
DR CTD; 407723; -.
DR ZFIN; ZDB-GENE-061122-1; smcr8b.
DR eggNOG; ENOG502QSW2; Eukaryota.
DR InParanoid; Q6PUR7; -.
DR OrthoDB; 692565at2759; -.
DR PhylomeDB; Q6PUR7; -.
DR PRO; PR:Q6PUR7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0016242; P:negative regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:1901098; P:positive regulation of autophagosome maturation; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; ISS:UniProtKB.
DR InterPro; IPR037521; FLCN/SMCR8_DENN.
DR InterPro; IPR037520; Folliculin/SMCR8_longin.
DR Pfam; PF11704; Folliculin; 1.
DR PROSITE; PS51834; DENN_FLCN_SMCR8; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Cytoplasm; Guanine-nucleotide releasing factor; Nucleus;
KW Reference proteome.
FT CHAIN 1..985
FT /note="Guanine nucleotide exchange protein smcr8b"
FT /id="PRO_0000287471"
FT DOMAIN 47..225
FT /note="uDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT DOMAIN 390..895
FT /note="cDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT DOMAIN 904..962
FT /note="dDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT REGION 242..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 639..659
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..293
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 985 AA; 110604 MW; 9537F477D64795AD CRC64;
MIGSPDLVAF TKETDFSEIT TDSSVLPEDL SVPMYPYTGD ATPWSKISSA KLKKDFILIS
EFSEQVGPQP LLTVPLETKA CGTFDLNYFS LRIMSVDYQT SLAGSPGYGS FKLNFVEDSK
VVLADSREGV FAYVHHLTLY DLEARGFVRP LCLAYVSSDE NKIIQQFQRI STEFNKVSEC
LKTGNRKNFA NELEVKLRDL EYTRVVLQKE LNTVSVKCSS EREPILNGVH SFERNADEVK
LNEKSSHTDE ISPQEKDGCG NSRKVEVKLE NENRSHFEHE QYGKQRKDKP DKTSCPMPLA
NKNDELASVE KLIQDYKSLL KQVTCYPTRK LRDSEYSPYE PDDLPQSFDL DLDSQFAGPM
LECSVFTYTN TPSQTLQQIN STSSSRFDKR LKTLEELCDD YFYQQALQQL YSIERTFRGD
ACYLYTQQLC RNLLRNLKST NFLFEDPCDL DDDVGLQIGQ STIQQPSFLP APSFLSGPVS
LESYASCVEM VPIKLELGGS SQSQVQHSTL NTPSKDNRPQ VADKSPAEVE MKGEIISAPD
CQGNVESVSN LMKTSISSGD SIEVLGTERS FRSQGANTLV ETAMHRPPPL SSATALEGLK
QGRVPTRRTC SEDSIEVLCI TESISPDELR ASYPCAIDEE SPEQETDEKN SSQYQEDNNE
KSIYVQGKIS ADHENACLKK LHPSVTVTPP DCPLTLEETS FQDSCQATES ATMLLLDEPS
RMVPDDLSDC FSYRSTTAST TSECTFPACL PKDKREGGTR RRRGRVGRAA LQFMRQFPFA
VHAVFSLLSG RTLVVLGSEE AAVRRLVTAL SVYLPHLTKY KDSIQPWTST PLQLTDLLNW
KLIGFDRMCS FNPSSLPHCL DHYSRYLSIL DVDQKTLHCP TYSGSLINLL VEPKSHFKRG
NTYFTFAQSV QSKLVTKAFL LTFSHGHPSP SRPQGSSGTE CFLSELHTDD KKILRYLSEL
IKLHFMEVTP NVLLFSYTTT SIFKL
