PKHM1_HUMAN
ID PKHM1_HUMAN Reviewed; 1056 AA.
AC Q9Y4G2; Q6P2R5; Q8TEL9; Q9NPP5; Q9NYA0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Pleckstrin homology domain-containing family M member 1 {ECO:0000305};
DE Short=PH domain-containing family M member 1;
DE AltName: Full=162 kDa adapter protein;
DE Short=AP162;
GN Name=PLEKHM1 {ECO:0000312|HGNC:HGNC:29017}; Synonyms=KIAA0356;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 82-1056, TISSUE SPECIFICITY, FUNCTION, AND
RP INTERACTION WITH SIALYL-LEX POSITIVE MUCIN.
RC TISSUE=Colon carcinoma;
RX PubMed=12820725; DOI=10.1023/a:1022256610674;
RA Hartel-Schenk S., Gratchev A., Hanski M.-L., Ogorek D., Trendelenburg G.,
RA Hummel M., Hoepfner M., Scheruebl H., Zeitz M., Hanski C.;
RT "Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an
RT apoptotic signal transduction pathway.";
RL Glycoconj. J. 18:915-923(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 425-1056.
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 528-832.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, INTERACTION WITH RAB7, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-1021; CYS-1024; HIS-1029 AND CYS-1032.
RX PubMed=20943950; DOI=10.1091/mbc.e10-06-0495;
RA Tabata K., Matsunaga K., Sakane A., Sasaki T., Noda T., Yoshimori T.;
RT "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway
RT via a novel Rab7-binding domain.";
RL Mol. Biol. Cell 21:4162-4172(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH RAB7A; VPS41 AND
RP S.TYPHIMURIUM SIFA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 720-LYS--LEU-722; GLU-729 AND ARG-769.
RX PubMed=25500191; DOI=10.1016/j.chom.2014.11.011;
RA McEwan D.G., Richter B., Claudi B., Wigge C., Wild P., Farhan H.,
RA McGourty K., Coxon F.P., Franz-Wachtel M., Perdu B., Akutsu M.,
RA Habermann A., Kirchof A., Helfrich M.H., Odgren P.R., Van Hul W.,
RA Frangakis A.S., Rajalingam K., Macek B., Holden D.W., Bumann D., Dikic I.;
RT "PLEKHM1 regulates Salmonella-containing vacuole biogenesis and
RT infection.";
RL Cell Host Microbe 17:58-71(2015).
RN [10]
RP FUNCTION, INTERACTION WITH VPS41; VPS11; VPS39; GABARAP; GABARAPL;
RP GABARAPL2; MAP1LC3A; MAP1LC3B AND MAP1LC3C, SUBUNIT, SUBCELLULAR LOCATION,
RP AND DOMAIN.
RX PubMed=25498145; DOI=10.1016/j.molcel.2014.11.006;
RA McEwan D.G., Popovic D., Gubas A., Terawaki S., Suzuki H., Stadel D.,
RA Coxon F.P., Miranda de Stegmann D., Bhogaraju S., Maddi K., Kirchof A.,
RA Gatti E., Helfrich M.H., Wakatsuki S., Behrends C., Pierre P., Dikic I.;
RT "PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and
RT LC3/GABARAP proteins.";
RL Mol. Cell 57:39-54(2015).
RN [11]
RP FUNCTION, INTERACTION WITH ARL8A; ARL8B; RAB7A; VPS41; VPS11; VPS18 AND
RP VPS33A, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-60; HIS-63 AND
RP 119-ARG--ARG-123.
RX PubMed=28325809; DOI=10.1083/jcb.201607085;
RA Marwaha R., Arya S.B., Jagga D., Kaur H., Tuli A., Sharma M.;
RT "The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to
RT lysosomes.";
RL J. Cell Biol. 216:1051-1070(2017).
RN [12]
RP INVOLVEMENT IN OPTB6.
RX PubMed=17404618; DOI=10.1172/jci30328;
RA van Wesenbeeck L., Odgren P.R., Coxon F.P., Frattini A., Moens P.,
RA Perdu B., MacKay C.A., Van Hul E., Timmermanns J.-P., Vanhoenacker F.,
RA Jacobs R., Peruzzi B., Teti A., Helfrich M.H., Rogers M.J., Villa A.,
RA Van Hul W.;
RT "Involvement of PLEKHM1 in osteoclastic vesicular transport and
RT osteopetrosis in incisors absent rats and humans.";
RL J. Clin. Invest. 117:919-930(2007).
RN [13]
RP INVOLVEMENT IN OPTA3, AND VARIANT OPTA3 CYS-714.
RX PubMed=17997709; DOI=10.1359/jbmr.071107;
RA Del Fattore A., Fornari R., Van Wesenbeeck L., de Freitas F.,
RA Timmermans J.P., Peruzzi B., Cappariello A., Rucci N., Spera G.,
RA Helfrich M.H., Van Hul W., Migliaccio S., Teti A.;
RT "A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin
RT homolog domain containing family M (with run domain) member 1 (PLEKHM1),
RT impairs vesicular acidification and increases TRACP secretion in
RT osteoclasts.";
RL J. Bone Miner. Res. 23:380-391(2008).
RN [14]
RP INVOLVEMENT IN OPTA3.
RX PubMed=27291868; DOI=10.1002/jbmr.2885;
RA Bo T., Yan F., Guo J., Lin X., Zhang H., Guan Q., Wang H., Fang L., Gao L.,
RA Zhao J., Xu C.;
RT "Characterization of a Relatively Malignant Form of Osteopetrosis Caused by
RT a Novel Mutation in the PLEKHM1 Gene.";
RL J. Bone Miner. Res. 31:1979-1987(2016).
CC -!- FUNCTION: Acts as a multivalent adapter protein that regulates Rab7-
CC dependent and HOPS complex-dependent fusion events in the endolysosomal
CC system and couples autophagic and the endocytic trafficking pathways.
CC Acts as a dual effector of RAB7A and ARL8B that simultaneously binds
CC these GTPases, bringing about clustering and fusion of late endosomes
CC and lysosomes (PubMed:25498145, PubMed:28325809). Required for late
CC stages of endolysosomal maturation, facilitating both endocytosis-
CC mediated degradation of growth factor receptors and autophagosome
CC clearance. Interaction with Arl8b is a crucial factor in the terminal
CC maturation of autophagosomes and to mediate autophagosome-lysosome
CC fusion (PubMed:25498145). Positively regulates lysosome peripheral
CC distribution and ruffled border formation in osteoclasts (By
CC similarity). May be involved in negative regulation of endocytic
CC transport from early endosome to late endosome/lysosome implicating its
CC association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-
CC mediated transduction of apoptotic signals (PubMed:12820725). Involved
CC in bone resorption (By similarity). {ECO:0000250|UniProtKB:Q5PQS0,
CC ECO:0000250|UniProtKB:Q7TSI1, ECO:0000269|PubMed:12820725,
CC ECO:0000269|PubMed:20943950, ECO:0000269|PubMed:25498145,
CC ECO:0000269|PubMed:28325809}.
CC -!- FUNCTION: (Microbial infection) In case of infection contributes to
CC Salmonella typhimurium pathogenesis by supporting the integrity of the
CC Salmonella-containing vacuole (SCV) probably in concert with the HOPS
CC complex and Rab7. {ECO:0000269|PubMed:25500191}.
CC -!- SUBUNIT: Interacts (via N- and C-terminus) with RAB7A (GTP-bound form)
CC (PubMed:20943950, PubMed:25500191, PubMed:28325809). Simultaneously
CC interacts with RAB7A and ARL8B; bringing about clustering and fusion of
CC late endosomes and lysosomes (PubMed:28325809). Interacts (via RUN
CC domain) with ARL8B (GTP-bound form); the interaction is required for
CC PLEKHM1 localization to lysosomes and for ARL8B function in delivery
CC and degradation of endocytic and autophagic cargo in lysosomes
CC (PubMed:28325809). PLEKHM1 and PLEKHM2 compete for interaction with
CC ARL8B (PubMed:28325809). Interacts with ARL8A; the interaction is
CC weaker than with ARL8B (PubMed:28325809). Interacts with VPS41, VPS11,
CC VPS18, VPS33A and VPS39; indicative for an association with the HOPS
CC complex; the interactions with, at least, VPS41, VPS11, VPS18 and
CC VPS33A require ARL8B (PubMed:25500191, PubMed:25498145,
CC PubMed:28325809). Interacts with GABARAP, GABARAPL, GABARAPL2,
CC MAP1LC3A, MAP1LC3B and MAP1LC3C (PubMed:25498145). Interacts with
CC PAFAH1B (By similarity). Interacts (via N- and C-terminus) with NDEL1
CC (By similarity). Interacts (via C-terminus) with MAP3K7 (By
CC similarity). Interacts (via N- and C-terminus) with FAM98A (By
CC similarity). Interacts (via C-terminus) with DEF8; this interaction is
CC weak but increased in a RAB7A-dependent manner (By similarity). In
CC colon carcinoma and breast carcinoma cells, it interacts with sialyl-
CC lex-positive protein (PubMed:12820725). {ECO:0000250|UniProtKB:Q7TSI1,
CC ECO:0000269|PubMed:12820725, ECO:0000269|PubMed:20943950,
CC ECO:0000269|PubMed:25498145, ECO:0000269|PubMed:28325809}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Salmonella typhimurium
CC sifA. {ECO:0000269|PubMed:25500191}.
CC -!- SUBCELLULAR LOCATION: Autolysosome membrane
CC {ECO:0000269|PubMed:25498145}. Endosome membrane
CC {ECO:0000269|PubMed:20943950}. Late endosome membrane
CC {ECO:0000269|PubMed:28325809}. Lysosome membrane
CC {ECO:0000269|PubMed:25498145, ECO:0000269|PubMed:25500191,
CC ECO:0000269|PubMed:28325809}. Note=In case of infection colocalizes
CC with Salmonella typhimurium sifA in proximity of Salmonella-containing
CC vacuole (SCV) (PubMed:25500191). {ECO:0000269|PubMed:25498145,
CC ECO:0000269|PubMed:25500191}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta, liver, prostate, thymus,
CC spleen, ovary, colon, colon carcinoma and peripheral blood lymphocytes
CC (PBL). Weakly expressed in brain, lung, kidney, and testis. No
CC expression in heart, skeletal muscle, pancreas and small intestine.
CC Predominantly expressed in the breast carcinoma cell line MCF-7.
CC {ECO:0000269|PubMed:12820725, ECO:0000269|PubMed:9205841}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and LC3A/B/C.
CC {ECO:0000269|PubMed:25498145}.
CC -!- DISEASE: Osteopetrosis, autosomal recessive 6 (OPTB6) [MIM:611497]: A
CC rare genetic disease characterized by abnormally dense bone, due to
CC defective resorption of immature bone. Osteopetrosis occurs in two
CC forms: a severe autosomal recessive form occurring in utero, infancy,
CC or childhood, and a benign autosomal dominant form occurring in
CC adolescence or adulthood. Recessive osteopetrosis commonly manifests in
CC early infancy with macrocephaly, feeding difficulties, evolving
CC blindness and deafness, bone marrow failure, severe anemia, and
CC hepatosplenomegaly. Deafness and blindness are generally thought to
CC represent effects of pressure on nerves. {ECO:0000269|PubMed:17404618}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Osteopetrosis, autosomal dominant 3 (OPTA3) [MIM:618107]: A
CC form of osteopetrosis, a rare genetic disease characterized by
CC abnormally dense bone, due to defective resorption of immature bone.
CC Osteopetrosis occurs in two forms: a severe autosomal recessive form
CC occurring in utero, infancy, or childhood, and an autosomal dominant
CC form occurring in adolescence or adulthood. OPTA3 is characterized by
CC typical features of osteopetrosis such as fractures after minor trauma,
CC early tooth loss, anemia, hepatosplenomegaly, and a generalized
CC increase in bone mineral density. Some patients exhibit localized
CC osteosclerosis and generalized osteopenia.
CC {ECO:0000269|PubMed:17997709, ECO:0000269|PubMed:27291868}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Sialyl-lex is a carcinoma associated antigen.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20813.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB91652.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB002354; BAA20813.2; ALT_INIT; mRNA.
DR EMBL; BC064361; AAH64361.1; -; mRNA.
DR EMBL; AJ002220; CAB91652.1; ALT_INIT; mRNA.
DR EMBL; AK074103; BAB84929.1; -; mRNA.
DR EMBL; AL389948; CAB97526.1; -; mRNA.
DR CCDS; CCDS32671.1; -.
DR RefSeq; NP_055613.1; NM_014798.2.
DR RefSeq; XP_006722264.1; XM_006722201.3.
DR RefSeq; XP_011523825.1; XM_011525523.2.
DR RefSeq; XP_011523826.1; XM_011525524.1.
DR RefSeq; XP_016880940.1; XM_017025451.1.
DR RefSeq; XP_016880942.1; XM_017025453.1.
DR PDB; 5DPR; X-ray; 2.50 A; A/B/C/D=627-638.
DR PDB; 5DPS; X-ray; 2.00 A; A/B/C=627-638.
DR PDB; 5DPT; X-ray; 2.90 A; A/B=627-638.
DR PDB; 5DPW; X-ray; 2.19 A; B/D/F/H/J/L/N/P=629-642.
DR PDBsum; 5DPR; -.
DR PDBsum; 5DPS; -.
DR PDBsum; 5DPT; -.
DR PDBsum; 5DPW; -.
DR AlphaFoldDB; Q9Y4G2; -.
DR SMR; Q9Y4G2; -.
DR BioGRID; 115178; 28.
DR IntAct; Q9Y4G2; 11.
DR MINT; Q9Y4G2; -.
DR STRING; 9606.ENSP00000389913; -.
DR GlyGen; Q9Y4G2; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9Y4G2; -.
DR PhosphoSitePlus; Q9Y4G2; -.
DR BioMuta; PLEKHM1; -.
DR DMDM; 160419247; -.
DR EPD; Q9Y4G2; -.
DR jPOST; Q9Y4G2; -.
DR MassIVE; Q9Y4G2; -.
DR MaxQB; Q9Y4G2; -.
DR PaxDb; Q9Y4G2; -.
DR PeptideAtlas; Q9Y4G2; -.
DR PRIDE; Q9Y4G2; -.
DR ProteomicsDB; 86202; -.
DR Antibodypedia; 30012; 146 antibodies from 27 providers.
DR DNASU; 9842; -.
DR Ensembl; ENST00000430334.8; ENSP00000389913.3; ENSG00000225190.11.
DR Ensembl; ENST00000613787.3; ENSP00000479066.1; ENSG00000277111.3.
DR Ensembl; ENST00000617688.2; ENSP00000483820.1; ENSG00000276358.2.
DR GeneID; 9842; -.
DR KEGG; hsa:9842; -.
DR MANE-Select; ENST00000430334.8; ENSP00000389913.3; NM_014798.3; NP_055613.1.
DR UCSC; uc002ija.4; human.
DR CTD; 9842; -.
DR DisGeNET; 9842; -.
DR GeneCards; PLEKHM1; -.
DR HGNC; HGNC:29017; PLEKHM1.
DR HPA; ENSG00000225190; Tissue enhanced (esophagus).
DR MalaCards; PLEKHM1; -.
DR MIM; 611466; gene.
DR MIM; 611497; phenotype.
DR MIM; 618107; phenotype.
DR neXtProt; NX_Q9Y4G2; -.
DR OpenTargets; ENSG00000225190; -.
DR Orphanet; 210110; Intermediate osteopetrosis.
DR PharmGKB; PA134906881; -.
DR VEuPathDB; HostDB:ENSG00000225190; -.
DR eggNOG; KOG1829; Eukaryota.
DR GeneTree; ENSGT00940000155111; -.
DR HOGENOM; CLU_011318_0_0_1; -.
DR InParanoid; Q9Y4G2; -.
DR OMA; HVLNCDL; -.
DR OrthoDB; 177737at2759; -.
DR PhylomeDB; Q9Y4G2; -.
DR TreeFam; TF317067; -.
DR PathwayCommons; Q9Y4G2; -.
DR SignaLink; Q9Y4G2; -.
DR BioGRID-ORCS; 9842; 41 hits in 1074 CRISPR screens.
DR ChiTaRS; PLEKHM1; human.
DR GeneWiki; PLEKHM1; -.
DR GenomeRNAi; 9842; -.
DR Pharos; Q9Y4G2; Tbio.
DR PRO; PR:Q9Y4G2; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y4G2; protein.
DR Bgee; ENSG00000225190; Expressed in lower esophagus mucosa and 93 other tissues.
DR ExpressionAtlas; Q9Y4G2; baseline and differential.
DR Genevisible; Q9Y4G2; HS.
DR GO; GO:0044754; C:autolysosome; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IDA:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR CDD; cd00029; C1; 1.
DR CDD; cd13321; PH_PLEKHM1; 1.
DR Gene3D; 1.20.58.900; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR042827; PLEKHM1_PH.
DR InterPro; IPR004012; Run_dom.
DR InterPro; IPR037213; Run_dom_sf.
DR InterPro; IPR025258; Zf-RING_9.
DR Pfam; PF02759; RUN; 1.
DR Pfam; PF13901; zf-RING_9; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM01175; DUF4206; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00593; RUN; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Cytoplasmic vesicle; Disease variant; Endosome;
KW Lysosome; Membrane; Metal-binding; Osteopetrosis; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; Transport; Zinc;
KW Zinc-finger.
FT CHAIN 1..1056
FT /note="Pleckstrin homology domain-containing family M
FT member 1"
FT /id="PRO_0000309335"
FT DOMAIN 41..183
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT DOMAIN 534..625
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 683..777
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 986..1040
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 215..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 451..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 654..1056
FT /note="Interaction with RAB7A"
FT /evidence="ECO:0000269|PubMed:25500191"
FT MOTIF 632..638
FT /note="LIR"
FT /evidence="ECO:0000305"
FT COMPBIAS 218..238
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSI1"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSI1"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSI1"
FT VARIANT 377
FT /note="R -> H (in dbSNP:rs1859059)"
FT /id="VAR_036932"
FT VARIANT 714
FT /note="R -> C (in OPTA3; unknown pathological significance;
FT dbSNP:rs559224144)"
FT /evidence="ECO:0000269|PubMed:17997709"
FT /id="VAR_081102"
FT MUTAGEN 60
FT /note="H->A: Strongly reduces interaction with ARL8B. No
FT effect on interaction with RAB7A. No effect on late
FT endosome and lysosome clustering. Loss of interaction with
FT ARL8B as well as late endosome and lysosome clustering;
FT when associated with 119-A--A-123."
FT /evidence="ECO:0000269|PubMed:28325809"
FT MUTAGEN 63
FT /note="H->A: No effect on interaction with ARL8B. No effect
FT on interaction with RAB7A."
FT /evidence="ECO:0000269|PubMed:28325809"
FT MUTAGEN 119..123
FT /note="RAWLR->AAWLA: Reduces interaction with ARL8B. No
FT effect on interaction with RAB7A. Loss of interaction with
FT ARL8B as well as late endosome and lysosome clustering;
FT when associated with A-60."
FT /evidence="ECO:0000269|PubMed:28325809"
FT MUTAGEN 720..722
FT /note="Missing: Disrupts interaction with RAB7A."
FT /evidence="ECO:0000269|PubMed:25500191"
FT MUTAGEN 729
FT /note="E->A: Disrupts interaction with RAB7A."
FT /evidence="ECO:0000269|PubMed:25500191"
FT MUTAGEN 769
FT /note="R->A: Disrupts interaction with RAB7A."
FT /evidence="ECO:0000269|PubMed:25500191"
FT MUTAGEN 1021
FT /note="C->G: Disrupts interaction with Rab7 and no
FT localization to endososmal membranes; when associated with
FT G-1024, L-1029 and G-1032."
FT /evidence="ECO:0000269|PubMed:20943950"
FT MUTAGEN 1024
FT /note="C->G: Disrupts interaction with Rab7 and no
FT localization to endososmal membranes; when associated with
FT G-1021, L-1029 and G-1032."
FT /evidence="ECO:0000269|PubMed:20943950"
FT MUTAGEN 1029
FT /note="H->L: Disrupts interaction with Rab7 and no
FT localization to endososmal membranes; when associated with
FT G-1021, G-1024 and G-1032."
FT /evidence="ECO:0000269|PubMed:20943950"
FT MUTAGEN 1032
FT /note="C->G: Disrupts interaction with Rab7and no
FT localization to endososmal membranes; when associated with
FT G-1021, G-1024 and L-1029."
FT /evidence="ECO:0000269|PubMed:20943950"
FT CONFLICT 429..436
FT /note="VVSSPTSP -> GLRPVSAR (in Ref. 4; BAB84929)"
FT /evidence="ECO:0000305"
FT CONFLICT 817
FT /note="A -> G (in Ref. 4; BAB84929)"
FT /evidence="ECO:0000305"
FT STRAND 635..637
FT /evidence="ECO:0007829|PDB:5DPW"
SQ SEQUENCE 1056 AA; 117443 MW; 24004093CFA89079 CRC64;
MLSVVENGLD PQAAIPVIKK KLVGSVKALQ KQYVSLDTVV TSEDGDANTM CSALEAVFIH
GLHAKHIRAE AGGKRKKSAH QKPLPQPVFW PLLKAVTHKH IISELEHLTF VNTDVGRCRA
WLRLALNDGL MECYLKLLLQ EQARLHEYYQ PTALLRDAEE GEFLLSFLQG LTSLSFELSY
KSAILNEWTL TPLALSGLCP LSELDPLSTS GAELQRKESL DSISHSSGSE DIEVHHSGHK
IRRNQKLTAS SLSLDTASSS QLSCSLNSDS CLLQENGSKS PDHCEEPMSC DSDLGTANAE
DSDRSLQEVL LEFSKAQVNS VPTNGLSQET EIPTPQASLS LHGLNTSTYL HCEAPAEPLP
AQAASGTQDG VHVQEPRPQA PSPLDLQQPV ESTSGQQPSS TVSETAREVG QGNGLQKAQA
HDGAGLKLVV SSPTSPKNKS WISEDDFYRP SREQPLESAS DHPIASYRGT PGSRPGLHRH
FSQEPRKNCS LGALDQACVP SPGRRQAQAA PSQGHKSFRV VHRRQMGLSN PFRGLMKLGT
VERRGAMGIW KELFCELSPL EFRLYLSNEE HTCVENCSLL RCESVGPAHS DGRFELVFSG
KKLALRASSQ DEAEDWLDRV REALQKVRPQ QEDEWVNVQY PDQPEEPPEA PQGCLSPSDL
LSEPAALQGT QFDWSSAQVP EPDAIKESLL YLYMDRTWMP YIFSLSLEAL KCFRIRNNEK
MLSDSHGVET IRDILPDTSL GGPSFFKIIT AKAVLKLQAG NAEEAALWRD LVRKVLASYL
ETAEEAVTLG GSLDENCQEV LKFATRENGF LLQYLVAIPM EKGLDSQGCF CAGCSRQIGF
SFVRPKLCAF SGLYYCDICH QDDASVIPAR IIHNWDLTKR PICRQALKFL TQIRAQPLIN
LQMVNASLYE HVERMHLIGR RREQLKLLGD YLGLCRSGAL KELSKRLNHR NYLLESPHRF
SVADLQQIAD GVYEGFLKAL IEFASQHVYH CDLCTQRGFI CQICQHHDII FPFEFDTTVR
CAECKTVFHQ SCQAVVKKGC PRCARRRKYQ EQNIFA
