LMBD1_MACFA
ID LMBD1_MACFA Reviewed; 540 AA.
AC Q4R5E3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Lysosomal cobalamin transport escort protein LMBD1 {ECO:0000250|UniProtKB:Q9NUN5};
DE Short=LMBD1;
DE AltName: Full=LMBR1 domain-containing protein 1;
GN Name=LMBRD1; ORFNames=QnpA-16111;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Parietal cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Lysosomal membrane chaperone required to export cobalamin
CC (vitamin B12) from lysosome to the cytosol, allowing its conversion to
CC cofactors. Targets ABCD4 transporter from the endoplasmic reticulum to
CC the lysosomal membrane. Then forms a complex with lysosomal transporter
CC ABCD4 and cytoplasmic MMACHC to transport cobalamin across the
CC lysosomal membrane (By similarity). Acts as an adapter protein which
CC plays an important role in mediating and regulating the internalization
CC of the insulin receptor (INSR) (By similarity). Involved in clathrin-
CC mediated endocytosis of INSR via its interaction with adapter protein
CC complex 2 (By similarity). Essential for the initiation of gastrulation
CC and early formation of mesoderm structures during embryogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q8K0B2,
CC ECO:0000250|UniProtKB:Q9NUN5}.
CC -!- SUBUNIT: Interacts with ABCD4; this interaction induces the
CC translocation of ABCD4 from the endoplasmic reticulum to the lysosome.
CC Interacts with ABCD4 and MMACHC; this interaction ensures the transport
CC of cobalamin from the lysosome to the cytoplasm (By similarity).
CC Interacts with INSR, adapter protein complex 2 and clathrin heavy chain
CC (By similarity). {ECO:0000250|UniProtKB:Q8K0B2,
CC ECO:0000250|UniProtKB:Q9NUN5}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:Q9NUN5};
CC Multi-pass membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8K0B2}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, clathrin-coated vesicle
CC {ECO:0000250|UniProtKB:Q8K0B2}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9NUN5}.
CC -!- SIMILARITY: Belongs to the LIMR family. LMBRD1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AB169601; BAE01682.1; -; mRNA.
DR RefSeq; NP_001270189.1; NM_001283260.1.
DR AlphaFoldDB; Q4R5E3; -.
DR SMR; Q4R5E3; -.
DR STRING; 9541.XP_005552670.1; -.
DR GeneID; 101865499; -.
DR CTD; 55788; -.
DR VEuPathDB; HostDB:ENSMFAG00000028262; -.
DR eggNOG; ENOG502QQ2T; Eukaryota.
DR OMA; IITTFTW; -.
DR OrthoDB; 744771at2759; -.
DR Proteomes; UP000233100; Chromosome 4.
DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; ISS:UniProtKB.
DR GO; GO:0032050; F:clathrin heavy chain binding; ISS:UniProtKB.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB.
DR GO; GO:0007369; P:gastrulation; ISS:UniProtKB.
DR GO; GO:0038016; P:insulin receptor internalization; ISS:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; ISS:UniProtKB.
DR InterPro; IPR006876; LMBR1-like_membr_prot.
DR Pfam; PF04791; LMBR1; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cobalamin; Cobalt; Cytoplasmic vesicle;
KW Developmental protein; Endocytosis; Gastrulation; Glycoprotein; Lysosome;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..540
FT /note="Lysosomal cobalamin transport escort protein LMBD1"
FT /id="PRO_0000260516"
FT TOPO_DOM 1..10
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..71
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..100
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..121
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 122..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..364
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..408
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 430..486
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..507
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..540
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 232..235
FT /note="YERL motif; mediates interaction with adapter
FT protein complex 2 and is essential for its function in
FT clathrin-mediated endocytosis of INSR"
FT /evidence="ECO:0000250|UniProtKB:Q8K0B2"
FT MOTIF 294..297
FT /note="WTKF motif; mediates interaction with adapter
FT protein complex 2 and is essential for its function in
FT clathrin-mediated endocytosis of INSR"
FT /evidence="ECO:0000250|UniProtKB:Q8K0B2"
FT MOD_RES 238
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8K0B2"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN5"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NUN5"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 457
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 540 AA; 61501 MW; B223EF85B8DAA584 CRC64;
MATPGAASAE LVIGWCIFGL LLLAILAFCW IYVRKYQSRR ESEVVSTITA IFSLAIALIT
SALLPVDIFL VSYMKNQNGT FKDWANANVS RQIEDTVLYG YYTLYSVILF CVFFWIPFVY
FYYEEKDDDD TSKCTQIKTA LKYTLGFVVI CALLLLVGAF VPLNVPNNKN STEWEKVKFL
FEELGSSHGL AALSFSISSL TLIGMLAAIT YTAYGMSALP LNLIKGTRSA AYERLENTED
IEEVEQHIQT IKSKSKDGRP LPARDKRALK QFEERLRTLK KRERHLEFIE NSWWTKFCGA
LRPLKIIWGI FFILVALLFV ISLFLSNLDK ALHSAGIDSG FIIFGANLSN PLNMLLPLLQ
TVFPLDYILI TIIIMYFIFT SMAGIRNIGI WFFWIRLYKI RRGRTRPQAL LFLCMILLLI
VLHTSYMIYS LAPQYVMYGS QNYLIETNIT SDNHKGNSTL SVPKRCDADA PEDQCTVTRT
YLFLHKFWFF SAAYYFGNWA FLGVFLIGLI VSCCKGKKSV IEGVDEDSDI SDDEPSVYSV
