ID AL2CL_HUMAN Reviewed; 953 AA. AC Q60I27; Q32MA1; Q6AI56; Q6ZNC5; Q6ZNC7; Q6ZTL4; Q86YD2; Q8N9U1; AC Q8NAL7; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 18-SEP-2019, entry version 120. DE RecName: Full=ALS2 C-terminal-like protein; GN Name=ALS2CL; 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] (ISOFORM 1), FUNCTION, INTERACTION WITH RP RAB5A, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Liver; 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 RT half of ALS2, binds to Rab5 and modulates endosome dynamics."; RL FEBS Lett. 575:64-70(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 4 AND 6). RC TISSUE=Placenta, Tongue, Trachea, and Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 293-953 (ISOFORM 1). RC TISSUE=Prostate; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-392 (ISOFORM 1), AND RP VARIANT GLN-45. RC TISSUE=Cervix; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] 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 [8] RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH ALS2, AND SUBCELLULAR RP 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). RN [9] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-280 AND PHE-576. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) for CC Rab5 GTPase. Regulates the ALS2-mediated endosome dynamics. CC {ECO:0000269|PubMed:15388334, ECO:0000269|PubMed:16473597, CC ECO:0000269|PubMed:17239822}. CC -!- SUBUNIT: Homodimer. Forms a heteromeric complex with ALS2 (By CC similarity). Interacts with ALS2 and RAB5A. {ECO:0000250, CC ECO:0000269|PubMed:15388334, 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 CC in the cytoplasm, particularly to the leading edges of the cells. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q60I27-1; Sequence=Displayed; CC Name=2; CC IsoId=Q60I27-2; Sequence=VSP_030170; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q60I27-3; Sequence=VSP_030169; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=Q60I27-4; Sequence=VSP_030168, VSP_030171; CC Note=No experimental confirmation available.; CC Name=5; CC IsoId=Q60I27-5; Sequence=VSP_030168; CC Name=6; CC IsoId=Q60I27-6; Sequence=VSP_043859; CC -!- TISSUE SPECIFICITY: Expressed in heart and kidney. CC {ECO:0000269|PubMed:15388334}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD18450.1; Type=Frameshift; Positions=878; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB107015; BAD51817.1; -; mRNA. DR EMBL; AK092455; BAC03895.1; -; mRNA. DR EMBL; AK093844; BAC04237.1; -; mRNA. DR EMBL; AK131273; BAD18450.1; ALT_FRAME; mRNA. DR EMBL; AK131270; BAD18448.1; -; mRNA. DR EMBL; AK126505; BAC86572.1; -; mRNA. DR EMBL; AC104304; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC134504; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471055; EAW64777.1; -; Genomic_DNA. DR EMBL; BC042906; AAH42906.1; -; mRNA. DR EMBL; BC061883; AAH61883.1; -; mRNA. DR EMBL; BC075825; AAH75825.1; -; mRNA. DR EMBL; BC109233; AAI09234.1; -; mRNA. DR EMBL; CR627258; CAH10367.1; -; mRNA. DR CCDS; CCDS2743.1; -. [Q60I27-1] DR RefSeq; NP_001177636.1; NM_001190707.1. [Q60I27-1] DR RefSeq; NP_667340.2; NM_147129.4. [Q60I27-1] DR RefSeq; XP_005265082.1; XM_005265025.1. [Q60I27-3] DR SMR; Q60I27; -. DR BioGrid; 129223; 1. DR IntAct; Q60I27; 6. DR STRING; 9606.ENSP00000313670; -. DR iPTMnet; Q60I27; -. DR PhosphoSitePlus; Q60I27; -. DR BioMuta; ALS2CL; -. DR DMDM; 74708351; -. DR EPD; Q60I27; -. DR jPOST; Q60I27; -. DR MassIVE; Q60I27; -. DR MaxQB; Q60I27; -. DR PaxDb; Q60I27; -. DR PeptideAtlas; Q60I27; -. DR PRIDE; Q60I27; -. DR ProteomicsDB; 65869; -. [Q60I27-1] DR ProteomicsDB; 65870; -. [Q60I27-2] DR ProteomicsDB; 65871; -. [Q60I27-3] DR ProteomicsDB; 65872; -. [Q60I27-4] DR ProteomicsDB; 65873; -. [Q60I27-5] DR ProteomicsDB; 65874; -. [Q60I27-6] DR DNASU; 259173; -. DR Ensembl; ENST00000318962; ENSP00000313670; ENSG00000178038. [Q60I27-1] DR Ensembl; ENST00000415953; ENSP00000413223; ENSG00000178038. [Q60I27-1] DR GeneID; 259173; -. DR KEGG; hsa:259173; -. DR UCSC; uc003cpx.3; human. [Q60I27-1] DR CTD; 259173; -. DR DisGeNET; 259173; -. DR GeneCards; ALS2CL; -. DR HGNC; HGNC:20605; ALS2CL. DR HPA; CAB046465; -. DR HPA; HPA048301; -. DR MIM; 612402; gene. DR neXtProt; NX_Q60I27; -. DR OpenTargets; ENSG00000178038; -. DR PharmGKB; PA134949717; -. DR eggNOG; KOG0231; Eukaryota. DR eggNOG; COG4642; LUCA. DR GeneTree; ENSGT00940000161305; -. DR HOGENOM; HOG000148768; -. DR InParanoid; Q60I27; -. DR OMA; GICEYST; -. DR OrthoDB; 37470at2759; -. DR PhylomeDB; Q60I27; -. DR TreeFam; TF331793; -. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR GenomeRNAi; 259173; -. DR Pharos; Q60I27; -. DR PRO; PR:Q60I27; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; ENSG00000178038; Expressed in 216 organ(s), highest expression level in left lobe of thyroid gland. DR ExpressionAtlas; Q60I27; baseline and differential. DR Genevisible; Q60I27; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0007032; P:endosome organization; IGI:MGI. DR Gene3D; 1.20.1050.80; -; 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; 7. 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; Complete proteome; Cytoplasm; GTPase activation; KW Polymorphism; Reference proteome; Repeat. FT CHAIN 1 953 ALS2 C-terminal-like protein. FT /FTId=PRO_0000313849. FT REPEAT 358 380 MORN 1. FT REPEAT 381 403 MORN 2. FT REPEAT 409 431 MORN 3. FT REPEAT 432 452 MORN 4. FT REPEAT 459 479 MORN 5. FT REPEAT 483 505 MORN 6. FT REPEAT 506 528 MORN 7. FT REPEAT 529 552 MORN 8. FT DOMAIN 796 942 VPS9. {ECO:0000255|PROSITE- FT ProRule:PRU00550}. FT VAR_SEQ 1 763 Missing (in isoform 4 and isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_030168. FT VAR_SEQ 1 653 Missing (in isoform 6). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043859. FT VAR_SEQ 1 485 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_030169. FT VAR_SEQ 1 199 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_030170. FT VAR_SEQ 896 953 IQHLGAEIHLIRDMMDPNHTGGLYDFLLTALESCYEHIQKE FT DMRLHRLPGHWHSRELW -> WGSQGPEKGGSQPGCWGARG FT RVRTTPQVSSHPGQRSFPSCLSATGLFSLSPSLSWWGGVLQ FT NSAPGSRDPPDP (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_030171. FT VARIANT 29 29 Q -> R (in dbSNP:rs59661801). FT /FTId=VAR_061554. FT VARIANT 45 45 E -> Q (in dbSNP:rs7642448). FT {ECO:0000269|PubMed:17974005}. FT /FTId=VAR_037791. FT VARIANT 280 280 Q -> E (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_037792. FT VARIANT 576 576 L -> F (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_037793. FT CONFLICT 172 172 L -> P (in Ref. 2; BAD18448). FT {ECO:0000305}. FT CONFLICT 430 430 E -> G (in Ref. 2; BAD18448). FT {ECO:0000305}. FT CONFLICT 711 711 E -> G (in Ref. 2; BAD18450). FT {ECO:0000305}. FT CONFLICT 893 893 R -> H (in Ref. 2; BAD18448). FT {ECO:0000305}. SQ SEQUENCE 953 AA; 107748 MW; 1BBC38A16E6A1168 CRC64; MCNPEEAALL RLEEVFSATL AHVNSLVLQP LLPAAPDPSD PWGRECLRLL QQLHKSSQQL WEVTEESLHS LQERLRYPDS TGLESLLLLR GADRVLQAHI EYIESYTSCM VVQAFQKAAK RRSEYWRGQR KALRQLLSGV SSEGSVGASL GQALHQPLAH HVQQYVLLLL SLGDTIGEHH PTRELVVNAV TLFGNLQSFM KQELDQAVAT QALWHTLRGR LRDVLCTPAH RLLQDSQDVP VTVAPLRAER VLLFDDALVL LQGHNVHTFD LKLVWVDPGQ DGCTFHLLTP EEEFSFCAKD SQGQAVWQWK VTWAVHQALH GKKDFPVLGA GLEPSQPPDC RCAEYTFQAE GRLCQATYEG EWCRGRPHGK GTLKWPDGRN HVGNFCQGLE HGFGIRLLPQ ASEDKFDCYK CHWREGSMCG YGICEYSTDE VYKGYFQEGL RHGFGVLESG PQAPQPFRYT GHWERGQRSG YGIEEDGDRG ERYIGMWQAG QRHGPGVMVT QAGVCYQGTF QADKTVGPGI LLSEDDSLYE GTFTRDLTLM GKGKVTFPNG FTLEGSFGSG AGRGLHTQGV LDTAALPPDP SSTCKRQLGV GAFPVESRWQ GVYSPFRDFV CAGCPRDLQE ALLGFDVQSS RELRRSQDYL SCERTHPEDS VGSMEDILEE LLQHREPKAL QLYLRKALSN SLHPLGKLLR TLMLTFQATY AGVGANKHLQ ELAQEEVKQH AQELWAAYRG LLRVALERKG QALEEDEDTE TRDLQVHGLV LPLMLPSFYS ELFTLYLLLH EREDSFYSQG IANLSLFPDT QLLEFLDVQK HLWPLKDLTL TSNQRYSLVR DKCFLSATEC LQKIMTTVDP REKLEVLERT YGEIEGTVSR VLGREYKLPM DDLLPLLIYV VSRARIQHLG AEIHLIRDMM DPNHTGGLYD FLLTALESCY EHIQKEDMRL HRLPGHWHSR ELW //