AL2CL_MOUSE
ID AL2CL_MOUSE Reviewed; 952 AA.
AC Q60I26; Q6KAQ8; Q8C0K7; Q8K468; Q8R222;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=ALS2 C-terminal-like protein;
GN Name=Als2cl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RX PubMed=12140191; DOI=10.1093/hmg/11.16.1887;
RA Mitchem K.L., Hibbard E., Beyer L.A., Bosom K., Dootz G.A., Dolan D.F.,
RA Johnson K.R., Raphael Y., Kohrman D.C.;
RT "Mutation of the novel gene Tmie results in sensory cell defects in the
RT inner ear of spinner, a mouse model of human hearing loss DFNB6.";
RL Hum. Mol. Genet. 11:1887-1898(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RAB5A, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=15388334; DOI=10.1016/j.febslet.2004.07.092;
RA Hadano S., Otomo A., Suzuki-Utsunomiya K., Kunita R., Yanagisawa Y.,
RA Showguchi-Miyata J., Mizumura H., Ikeda J.-E.;
RT "ALS2CL, the novel protein highly homologous to the carboxy-terminal half
RT of ALS2, binds to Rab5 and modulates endosome dynamics.";
RL FEBS Lett. 575:64-70(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT by screening of terminal sequences of cDNA clones randomly sampled from
RT size-fractionated libraries.";
RL DNA Res. 11:127-135(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon;
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).
RN [6]
RP FUNCTION.
RX PubMed=16473597; DOI=10.1016/s0076-6879(05)03026-0;
RA Hadano S., Ikeda J.-E.;
RT "Purification and functional analyses of ALS2 and its homologue.";
RL Methods Enzymol. 403:310-321(2005).
RN [7]
RP HOMODIMERIZATION, INTERACTION WITH ALS2, AND SUBCELLULAR LOCATION.
RX PubMed=17239822; DOI=10.1016/j.bbrc.2006.12.229;
RA Suzuki-Utsunomiya K., Hadano S., Otomo A., Kunita R., Mizumura H.,
RA Osuga H., Ikeda J.-E.;
RT "ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome
RT dynamics.";
RL Biochem. Biophys. Res. Commun. 354:491-497(2007).
CC -!- FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) for Rab5
CC GTPase. Regulates the ALS2-mediated endosome dynamics (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:16473597}.
CC -!- SUBUNIT: Homodimer. Forms a heteromeric complex with ALS2. Interacts
CC with ALS2 and RAB5A. {ECO:0000269|PubMed:15388334,
CC ECO:0000269|PubMed:17239822}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15388334,
CC ECO:0000269|PubMed:17239822}. Note=Distributed onto the vesicular
CC compartments in the cytoplasm with strong punctated staining.
CC Colocalizes with RAB5A onto the vesicular/membranous compartments in
CC the cytoplasm, particularly to the leading edges of the cells (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q60I26-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60I26-2; Sequence=VSP_030173;
CC Name=3;
CC IsoId=Q60I26-3; Sequence=VSP_030172;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, liver and kidney.
CC {ECO:0000269|PubMed:15388334}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD21399.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD21399.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AF481142; AAM89221.1; -; mRNA.
DR EMBL; AB107016; BAD51818.1; -; mRNA.
DR EMBL; AK131149; BAD21399.1; ALT_SEQ; Transcribed_RNA.
DR EMBL; AK030815; BAC27145.1; -; mRNA.
DR EMBL; AK053076; BAC35257.1; -; mRNA.
DR EMBL; AK155451; BAE33270.1; -; mRNA.
DR EMBL; BC022645; AAH22645.1; -; mRNA.
DR EMBL; BC117928; AAI17929.1; -; mRNA.
DR EMBL; BC117929; AAI17930.1; -; mRNA.
DR CCDS; CCDS23579.1; -. [Q60I26-1]
DR RefSeq; NP_001139531.1; NM_001146059.1.
DR RefSeq; NP_001139532.1; NM_001146060.1.
DR RefSeq; NP_666340.3; NM_146228.4.
DR RefSeq; XP_006512166.1; XM_006512103.2.
DR RefSeq; XP_017168843.1; XM_017313354.1.
DR RefSeq; XP_017168844.1; XM_017313355.1.
DR RefSeq; XP_017168845.1; XM_017313356.1.
DR RefSeq; XP_017168846.1; XM_017313357.1.
DR RefSeq; XP_017168847.1; XM_017313358.1.
DR AlphaFoldDB; Q60I26; -.
DR SMR; Q60I26; -.
DR STRING; 10090.ENSMUSP00000115718; -.
DR iPTMnet; Q60I26; -.
DR PhosphoSitePlus; Q60I26; -.
DR MaxQB; Q60I26; -.
DR PaxDb; Q60I26; -.
DR PeptideAtlas; Q60I26; -.
DR PRIDE; Q60I26; -.
DR ProteomicsDB; 296162; -. [Q60I26-1]
DR ProteomicsDB; 296163; -. [Q60I26-2]
DR ProteomicsDB; 296164; -. [Q60I26-3]
DR DNASU; 235633; -.
DR GeneID; 235633; -.
DR KEGG; mmu:235633; -.
DR UCSC; uc009rvc.2; mouse. [Q60I26-1]
DR CTD; 259173; -.
DR MGI; MGI:2447532; Als2cl.
DR eggNOG; KOG0231; Eukaryota.
DR InParanoid; Q60I26; -.
DR OrthoDB; 37470at2759; -.
DR PhylomeDB; Q60I26; -.
DR TreeFam; TF331793; -.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR BioGRID-ORCS; 235633; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Als2cl; mouse.
DR PRO; PR:Q60I26; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60I26; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; IPI:MGI.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0007032; P:endosome organization; ISO:MGI.
DR GO; GO:0008104; P:protein localization; IDA:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IBA:GO_Central.
DR Gene3D; 1.20.1050.80; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR003409; MORN.
DR InterPro; IPR003123; VPS9.
DR InterPro; IPR037191; VPS9_dom_sf.
DR Pfam; PF02493; MORN; 6.
DR Pfam; PF02204; VPS9; 1.
DR SMART; SM00698; MORN; 7.
DR SUPFAM; SSF109993; SSF109993; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS51205; VPS9; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; GTPase activation; Reference proteome;
KW Repeat.
FT CHAIN 1..952
FT /note="ALS2 C-terminal-like protein"
FT /id="PRO_0000313850"
FT REPEAT 358..380
FT /note="MORN 1"
FT REPEAT 381..403
FT /note="MORN 2"
FT REPEAT 409..431
FT /note="MORN 3"
FT REPEAT 432..454
FT /note="MORN 4"
FT REPEAT 459..481
FT /note="MORN 5"
FT REPEAT 483..505
FT /note="MORN 6"
FT REPEAT 506..528
FT /note="MORN 7"
FT REPEAT 529..552
FT /note="MORN 8"
FT DOMAIN 795..941
FT /note="VPS9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550"
FT VAR_SEQ 1..692
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030172"
FT VAR_SEQ 645..747
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15449545"
FT /id="VSP_030173"
FT CONFLICT 141
FT /note="S -> N (in Ref. 1; AAM89221 and 4; BAC35257)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="C -> R (in Ref. 1; AAM89221 and 4; BAC35257)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="H -> R (in Ref. 1; AAM89221 and 4; BAC35257/
FT BAC27145)"
FT /evidence="ECO:0000305"
FT CONFLICT 939
FT /note="P -> L (in Ref. 1; AAM89221 and 4; BAC35257/
FT BAC27145)"
FT /evidence="ECO:0000305"
FT CONFLICT 950
FT /note="D -> E (in Ref. 1; AAM89221, 4; BAC35257/BAC27145
FT and 5; AAH22645)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 952 AA; 108146 MW; 8D730F53AA313A08 CRC64;
MSSSEEADLL RLEEVFSTTL ARTISLILQP LLLADPEPSD PCGKECLRLL QQLHESAQRL
WYVTEQSLLS LRQRLYHPPS KGLEAVLLLS NADHVLQAHM EYIKSYTDCV VAQAFQKVSK
KRSEFWRSQR KALRQLLSSG SSEGSVGTTM CQALRQPLSQ HVQKYLLLLL SLRDTLDESH
PAQELVMHAI TLFGNLQSFM GQALDQAVAT QALWHSLSSR LRDVLCSPAH RLLQDSQDIP
VVVTPLRAER VLLFDDSLVL LQGHNTHTFD LKLVWVKPGQ DKCVLHILTP EEEISFCTRD
PQGQVVWQWK VTQAVCQALC GKKDFPVLGS GRETSVPPEC RCVAYTFCRE GRLCQATYDG
EWCRAKPHGK GTLKWPDGRN HVGTFYQGLE HGFGICLVPQ ASEDKFDCYK CHWREGRMCE
YGICEYGTDE VYKGYFQAGL RHGFGILESA PQAPQPFRYT GHWERGQRSG YGIEEDRDRG
ERYIGMWQAD QRHGPGVVVT QAGVCYQGTF QGDKMAGPGI LLCEDDSLYE GTFTRDLTLL
GKGKVTFPNG FTLDGSFSSG TDKGLYTQGV LDTAALPPDP SSTRKRQLGL GTFPVESRWQ
GVYSPFRDFL RLGCPGEQQE ALLGFHTQSS RELRKSQECL CCERSHPEDC VGSMEDTLKE
LLQHRKPKAL QQYLRKALSN SRHPLGQLLR TLMLTFQATY SGIGANKHLQ EMAQEEVKQH
ARELWAAYRG LLKVALQHQG QTLEEENMET RDLQVHGLLL PLILPSFYSE LFTLYLLLHE
REDGLYSRGI TNLSLFPDTK LLEFLDVQKH LWPLKDLKLT SNQRYSLVRD KCFLTATECL
QKIITTVHPR EKLEVLEKTY GEIEATVSRV LGCKYKLPMD DLLPLLIYVV SRARIQHLGA
EIHLIRDMMD PVHTGGLHDF LLTALESCYE HIQKEDMRPH HLPGHWDARD LW
