SMR8A_DANRE
ID SMR8A_DANRE Reviewed; 853 AA.
AC E7FA21;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Guanine nucleotide exchange protein smcr8a;
DE AltName: Full=Smith-Magenis syndrome chromosomal region candidate gene 8 protein homolog A;
GN Name=smcr8a {ECO:0000312|ZFIN:ZDB-GENE-071212-4};
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 GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
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; BX649440; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_687034.3; XM_681942.8.
DR AlphaFoldDB; E7FA21; -.
DR SMR; E7FA21; -.
DR STRING; 7955.ENSDARP00000069232; -.
DR PaxDb; E7FA21; -.
DR PRIDE; E7FA21; -.
DR Ensembl; ENSDART00000074746; ENSDARP00000069232; ENSDARG00000052818.
DR GeneID; 558696; -.
DR CTD; 558696; -.
DR ZFIN; ZDB-GENE-071212-4; smcr8a.
DR eggNOG; ENOG502QSW2; Eukaryota.
DR GeneTree; ENSGT00390000010052; -.
DR HOGENOM; CLU_013891_0_0_1; -.
DR InParanoid; E7FA21; -.
DR OMA; KPVKHWV; -.
DR OrthoDB; 692565at2759; -.
DR PhylomeDB; E7FA21; -.
DR TreeFam; TF330880; -.
DR PRO; PR:E7FA21; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000052818; Expressed in blastula and 20 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0006914; P:autophagy; IEA:UniProtKB-KW.
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 3: Inferred from homology;
KW Autophagy; Cytoplasm; Guanine-nucleotide releasing factor; Nucleus;
KW Reference proteome.
FT CHAIN 1..853
FT /note="Guanine nucleotide exchange protein smcr8a"
FT /id="PRO_0000439892"
FT DOMAIN 47..219
FT /note="uDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT DOMAIN 316..753
FT /note="cDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT DOMAIN 762..826
FT /note="dDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178"
FT REGION 272..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 853 AA; 95427 MW; 8D1C0A1B99202FB4 CRC64;
MIGSPDVVAF TKEDDFGDSF SDPLSLPDEF SVPLFTHAAN ANPWTKTSYA KFSKDFILIS
EFSEQVGPQP LLTIPSDPKV CGTFDLNYFS LRIMSVDYQA SFVGHPPGSN YPKLNFVEDS
KVVLGDSKEG AFAYVHHLTL YDLEARGFVR PFCMAYISAD ERKIMQQFQE LSSEFSKASE
CLKSGNRKAF ANELEKKLKD LEYTRSVLHK ETELQKMNNG CYSTQAIEKA NELANVEKSI
YEHKDLLRQI TSYPSRRKRD VDFVQCEAEK PPVMDETLKD TNPSDSAENT VETESRKSSY
TPQLIKAKSA KCFDKRLKTL EELCDTSFFL QTLEQLNAVE KSFRGDLCFI YTSQIDRALV
SKQRVTSFLF EAEHDWEDGG ASKNFSIPSN NPTIPILNFS GEPLSLDSYT TCIDVDHLKP
GVESGEGPPE SSTSDITQET SEAADTETKG SFSSDKSIEA LGSVSPSSLQ TNFFDGLERR
SKISIPSYSD NASSSIAVPH RRSDGNLVQM DAACCIGQDG FIFEDPLPEL AQECCGDTVV
NQEPLSLLHG DPALQMDYIL EESPNMGLTF SELNTSVLSE EVAKINIEDV FDRTSFMSIS
TSSDRAVSPF TYGSALTVKQ KKKAGHSALR FIRQYPFAQQ AISCLLSGRT LVILGVDEGT
VRKLVNALFI FVPNLGKYGE TVQPWLSTPF QLTDLQRWKL IGLQRAVSPA GSSILHSLNR
YSRYISILDC DNKTLRCPPY KGTLISHLAD HRTQIKRGST YFLHIQGMLT QLTAKAFLYT
FCHHIHLPMD INDQGSVTSR RTNFLLQLGY TVEESKIIQY LSELIKQHYI HGSAKVGNPS
FSFNYTTSYL YKI
