CI072_RAT
ID CI072_RAT Reviewed; 481 AA.
AC Q66HC3;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Guanine nucleotide exchange factor C9orf72 homolog {ECO:0000305};
GN Name=C9orf72 {ECO:0000312|RGD:1359108};
GN Synonyms=Dennd9 {ECO:0000250|UniProtKB:Q6DFW0},
GN Dennl72 {ECO:0000250|UniProtKB:Q96LT7};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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).
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 regulator of autophagy initiation by interacting with
CC the ULK1/ATG1 kinase complex and modulating its protein kinase
CC activity. As part of the C9orf72-SMCR8 complex, stimulates RAB8A and
CC RAB11A GTPase activity in vitro (By similarity). Positively regulates
CC initiation of autophagy by regulating the RAB1A-dependent trafficking
CC of the ULK1/ATG1 kinase complex to the phagophore which leads to
CC autophagosome formation. Acts as a regulator of mTORC1 signaling by
CC promoting phosphorylation of mTORC1 substrates. Plays a role in
CC endosomal trafficking. May be involved in regulating the maturation of
CC phagosomes to lysosomes. Promotes the lysosomal localization and
CC lysosome-mediated degradation of CARM1 which leads to inhibition of
CC starvation-induced lipid metabolism (By similarity). Regulates actin
CC dynamics in motor neurons by inhibiting the GTP-binding activity of
CC ARF6, leading to ARF6 inactivation. This reduces the activity of the
CC LIMK1 and LIMK2 kinases which are responsible for phosphorylation and
CC inactivation of CFL1/cofilin, leading to cofilin activation. Positively
CC regulates axon extension and axon growth cone size in spinal motor
CC neurons. Required for SMCR8 protein expression and localization at
CC pre- and post-synaptic compartments in the forebrain, also regulates
CC protein abundance of RAB3A and GRIA1/GLUR1 in post-synaptic
CC compartments in the forebrain and hippocampus (By similarity). Plays a
CC role within the hematopoietic system in restricting inflammation and
CC the development of autoimmunity. {ECO:0000250|UniProtKB:Q6DFW0,
CC ECO:0000250|UniProtKB:Q96LT7}.
CC -!- SUBUNIT: Component of the C9orf72-SMCR8 complex, at least composed of
CC C9orf72, SMCR8 and WDR41 (By similarity). The complex is formed of two
CC protomers, each individually consisting of one molecule each of
CC C9orf72, SMCR8 and WDR41 (By similarity). The protomers homodimerize
CC via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-
CC terminus) (By similarity). Within each protomer SMCR8 (via DENN domain)
CC acts as a bridging protein between WDR41 (via C-terminus and N-
CC terminus) and C9orf72 (via C-terminus) (By similarity). The C9orf72-
CC SMCR8 complex associates with the ULK1/ATG1 kinase complex. Interacts
CC with ULK1/ATG1 kinase complex members ULK1, ATG13 and RB1CC1. Interacts
CC with SMCR8; the interaction is direct (By similarity). Interacts with
CC HNRNPA1, HNRNPA2B1 and UBQLN2. Interacts with small Rab GTPase RAB1A;
CC the interaction mediates recruitment of RAB1A to the ULK1/ATG1 kinase
CC complex. Also interacts with small Rab GTPase RAB7A. Interacts with
CC cofilin (By similarity). Interacts with GTP-binding proteins ARF1 and
CC ARF6. Interacts with the DLG4/PSD-95 (By similarity). Interacts with
CC CARM1 (via PH domain-like fold) (By similarity).
CC {ECO:0000250|UniProtKB:Q6DFW0, ECO:0000250|UniProtKB:Q96LT7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q96LT7}. Endosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Lysosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q96LT7}. Secreted
CC {ECO:0000250|UniProtKB:Q96LT7}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q96LT7}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q96LT7}. Perikaryon
CC {ECO:0000250|UniProtKB:Q6DFW0}. Note=Detected in the cytoplasm of
CC neurons from brain tissue. Detected in the nucleus in fibroblasts.
CC Associates with cytoplasmic stress granules following cellular stress.
CC During corticogenesis, transitions from being predominantly cytoplasmic
CC to a more even nucleocytoplasmic distribution.
CC {ECO:0000250|UniProtKB:Q6DFW0, ECO:0000250|UniProtKB:Q96LT7}.
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DR EMBL; BC081927; AAH81927.1; -; mRNA.
DR RefSeq; NP_001007703.1; NM_001007702.1.
DR AlphaFoldDB; Q66HC3; -.
DR SMR; Q66HC3; -.
DR STRING; 10116.ENSRNOP00000013181; -.
DR PhosphoSitePlus; Q66HC3; -.
DR PaxDb; Q66HC3; -.
DR Ensembl; ENSRNOT00000013181; ENSRNOP00000013181; ENSRNOG00000009478.
DR GeneID; 313155; -.
DR KEGG; rno:313155; -.
DR UCSC; RGD:1359108; rat.
DR CTD; 313155; -.
DR RGD; 1359108; RGD1359108.
DR eggNOG; ENOG502QSST; Eukaryota.
DR InParanoid; Q66HC3; -.
DR OrthoDB; 1434762at2759; -.
DR PhylomeDB; Q66HC3; -.
DR TreeFam; TF313315; -.
DR PRO; PR:Q66HC3; -.
DR Proteomes; UP000002494; Chromosome 5.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; IEA:Ensembl.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0090543; C:Flemming body; IEA:Ensembl.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; ISO:RGD.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0044304; C:main axon; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; ISS:UniProtKB.
DR GO; GO:1904425; P:negative regulation of GTP binding; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0110053; P:regulation of actin filament organization; ISS:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR InterPro; IPR027819; C9orf72.
DR PANTHER; PTHR31855; PTHR31855; 1.
DR Pfam; PF15019; C9orf72-like; 1.
DR PROSITE; PS51835; DENN_C9ORF72; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Cell projection; Cytoplasm; Cytoplasmic vesicle; Endosome;
KW Guanine-nucleotide releasing factor; Lysosome; Nucleus; Reference proteome;
KW Secreted.
FT CHAIN 1..481
FT /note="Guanine nucleotide exchange factor C9orf72 homolog"
FT /id="PRO_0000089713"
FT DOMAIN 23..194
FT /note="uDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 200..343
FT /note="cDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 370..464
FT /note="dDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT REGION 461..481
FT /note="Required for the homodimerization of the C9orf72-
FT SMCR8 complex"
FT /evidence="ECO:0000250|UniProtKB:Q96LT7"
SQ SEQUENCE 481 AA; 54306 MW; 1C7DA1A7F1CBFE46 CRC64;
MSTICPPPSP AVAKTEIALS GESPLLAATF AYWDNILGPR VRHIWAPKTD QVLLSDGEIT
FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE
LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIVLE GTERMEDQGQ SIIPMLTGEV
IPVMELLASM RSHSVPEDLD IADTVLNDDD IGDSCHEGFL LNAISSHLQT CGCSVVVGSS
AEKVNKIVRT LCLFLTPAER KCSRLCEAES SFKYESGLFV QGLLKDATGS FVLPFRQVMY
APYPTTHIDV DVNTVKQMPP CHEHIYNQRR YMRSELTAFW RATSEEDMAQ DTIIYTDESF
TPDLNIFQDV LHRDTLVKAF LDQVFHLKPG LSLRSTFLAQ FLLILHRKAL TLIKYIEDDT
QKGKKPFKSL RNLKIDLDLT AEGDLNIIMA LAEKIKPGLH SFIFGRPFYT SVQERDVLMT
F
