PKHM1_RAT
ID PKHM1_RAT Reviewed; 1059 AA.
AC Q5PQS0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Pleckstrin homology domain-containing family M member 1 {ECO:0000305};
DE Short=PH domain-containing family M member 1;
GN Name=Plekhm1 {ECO:0000312|RGD:1308010};
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=Lung;
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 [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Required for late stages of endolysosomal maturation,
CC facilitating both endocytosis-mediated degradation of growth factor
CC receptors and autophagosome clearance. Interaction with Arl8b is a
CC crucial factor in the terminal maturation of autophagosomes and to
CC mediate autophagosome-lysosome fusion (By similarity). Positively
CC regulates lysosome peripheral distribution and ruffled border formation
CC in osteoclasts (PubMed:17404618). May be involved in negative
CC regulation of endocytic transport from early endosome to late
CC endosome/lysosome implicating its association with Rab7. May have a
CC role in sialyl-lex-mediated transduction of apoptotic signals (By
CC similarity). Involved in bone resorption (By similarity).
CC {ECO:0000250|UniProtKB:Q7TSI1, ECO:0000250|UniProtKB:Q9Y4G2,
CC ECO:0000269|PubMed:17404618}.
CC -!- SUBUNIT: Interacts (via N- and C-terminus) with RAB7A (GTP-bound form).
CC Simultaneously interacts with RAB7A and ARL8B; bringing about
CC clustering and fusion of late endosomes and lysosomes. Interacts (via
CC RUN domain) with ARL8B (GTP-bound form); the interaction is required
CC for PLEKHM1 localization to lysosomes and for ARL8B function in
CC delivery and degradation of endocytic and autophagic cargo in
CC lysosomes. PLEKHM1 and PLEKHM2 compete for interaction with ARL8B.
CC Interacts with ARL8A; the interaction is weaker than with ARL8B.
CC Interacts with VPS41, VPS11, VPS18, VPS33A and VPS39; indicative for an
CC association with the HOPS complex; the interactions with, at least,
CC VPS41, VPS11, VPS18 and VPS33A require ARL8B (By similarity). Interacts
CC with GABARAP, GABARAPL, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C (By
CC similarity). Interacts with PAFAH1B (By similarity). Interacts (via
CC N- and C-terminus) with NDEL1 (By similarity). Interacts (via C-
CC terminus) with MAP3K7 (By similarity). Interacts (via N- and C-
CC terminus) with FAM98A (By similarity). Interacts (via C-terminus) with
CC DEF8; this interaction is weak but increased in a RAB7A-dependent
CC manner (By similarity). May interact with sialyl-lex-positive protein
CC (By similarity). {ECO:0000250|UniProtKB:Q7TSI1,
CC ECO:0000250|UniProtKB:Q9Y4G2}.
CC -!- SUBCELLULAR LOCATION: Autolysosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4G2}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4G2}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4G2}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4G2}. Note=In case of infection colocalizes
CC with Salmonella typhimurium sifA in proximity of Salmonella-containing
CC vacuole (SCV). {ECO:0000250|UniProtKB:Q9Y4G2}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, skeletal muscle, lung, liver,
CC spleen, brain, heart, kidney and bone. Weakly expressed in monocytes
CC (at protein level). {ECO:0000269|PubMed:17404618}.
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:0000250|UniProtKB:Q9Y4G2}.
CC -!- MISCELLANEOUS: Sialyl-lex is a carcinoma associated antigen.
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; BC087058; AAH87058.1; -; mRNA.
DR RefSeq; NP_001009677.1; NM_001009677.1.
DR AlphaFoldDB; Q5PQS0; -.
DR SMR; Q5PQS0; -.
DR STRING; 10116.ENSRNOP00000034752; -.
DR iPTMnet; Q5PQS0; -.
DR PhosphoSitePlus; Q5PQS0; -.
DR PaxDb; Q5PQS0; -.
DR PRIDE; Q5PQS0; -.
DR Ensembl; ENSRNOT00000037147; ENSRNOP00000034752; ENSRNOG00000028521.
DR GeneID; 303584; -.
DR KEGG; rno:303584; -.
DR UCSC; RGD:1308010; rat.
DR CTD; 9842; -.
DR RGD; 1308010; Plekhm1.
DR eggNOG; KOG1829; Eukaryota.
DR GeneTree; ENSGT00940000155111; -.
DR HOGENOM; CLU_011318_0_0_1; -.
DR InParanoid; Q5PQS0; -.
DR OMA; HVLNCDL; -.
DR OrthoDB; 177737at2759; -.
DR PhylomeDB; Q5PQS0; -.
DR TreeFam; TF317067; -.
DR PRO; PR:Q5PQS0; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000028521; Expressed in duodenum and 18 other tissues.
DR Genevisible; Q5PQS0; RN.
DR GO; GO:0044754; C:autolysosome; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS: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; 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; 2.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cytoplasmic vesicle; Endosome; Lysosome; Membrane;
KW Metal-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; Transport; Zinc; Zinc-finger.
FT CHAIN 1..1059
FT /note="Pleckstrin homology domain-containing family M
FT member 1"
FT /id="PRO_0000309337"
FT DOMAIN 40..182
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT DOMAIN 536..627
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 686..780
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 989..1043
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 218..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..1059
FT /note="Interaction with RAB7A"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G2"
FT MOTIF 634..640
FT /note="LIR"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G2"
FT COMPBIAS 294..334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSI1"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G2"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSI1"
SQ SEQUENCE 1059 AA; 117508 MW; 3D41F53BF6382CAF CRC64;
MLSVENGLDP RAAIQVIKKK LVGSVKALQK QHVSLDTVVT SEDGDANTMC SALEAVFIHG
LHAKYIRAEA GGKRKKHTHQ KPLPQPVFWP LLKAVTHKHI ISDLEHLVFI NTDVGRCRAW
LRLALNDGLM ECYLKLLLQE PARLCEYYQP TALLRDAEEA EFLLSFLQGL TSLSFELSYK
SAILNEWTLT PLSLSGLCPL SELDPLTVSG AELQRKESLD SISHSSGSED IEVQHSGHKI
RRDRKLTASS LSLDTASSSQ LSCSLNSDSC LLQENGPKSP DHSEEPMSYD SDLGTANADD
SDRSLQEVLS EFSKAQVNSA PSSGPSQESD TPMFQTPLSL HSLANSTHLL FEGSEEPFPA
HTSSGTSSGH KHQPQESPDM QPLGTAQAGP AGSTSDQQPS SPVAGAADQG SEPWKALEYG
RVGPKLVVSS PTSPKGKSWI SEDDFCRPPK EHALKNTSDL CISPLQGTPE LRTALHGPFS
QGPRKSCSLG ALDKACVSSL DYRNAQTAPS PAVTQDHKNF CVVHRRQMGL SNPFRGLMKL
GTVARRGAMG IWKEFFCELS PLELRLYLSD EERTCVESCS LLRCEAVGPA HSDGRFELVF
SGKKLALRAS SQDEAEDWLD RVREALQKVR PQQEEEWVNI QYPDQAEDSP EAPPDNLPPY
SALLPEHAGA QGIQPNWTSA QVPEPDAIKE SLLYLYADRT WIPYIFSLSL ESLKCFRVRN
NEKMLSDSHG VETIRDILPD TSLGGPAFFK IITAKAVLKL QAKNTEEAAH WRDLVRKVLA
SYLESVQEAV TLAGSLDENC QEVLKFATRE NGFLLQYLVA IPTEKGLDSQ GCFCAGCSRQ
IGFSFVRPKL CAFSGLYYCD FCHQDDASVI PARIIHNWDL TKRPVCRQAL KFLAQIRAQP
LINLQLVNAS LYEHVERMHL IGRSREQLKL LGDYLGLCRS GALKELSKRL SHRNYLLESP
HKFSVADLQQ IAEGVYEGFL KALIEFASQH VYHCDLCTQR GFICQICHHQ DIIFPFEFDT
TVRCAECRTV FHQSCQAVVR KGCPRCARRR KYQEQNTVS
