LMBD1_MOUSE
ID LMBD1_MOUSE Reviewed; 537 AA.
AC Q8K0B2; Q3U696; Q8CCL7; Q8R3D6; Q8VH50; Q9CW67;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Lysosomal cobalamin transport escort protein LMBD1 {ECO:0000250|UniProtKB:Q9NUN5};
DE Short=LMBD1;
DE AltName: Full=LMBR1 domain-containing protein 1;
DE AltName: Full=Protein N90b;
GN Name=Lmbrd1 {ECO:0000312|MGI:MGI:1915671};
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 3).
RC STRAIN=A/J;
RA Yao R., Wang Y., You M.;
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow, Olfactory bulb, Spleen, and Visual cortex;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=FVB/N-3; TISSUE=Eye, and Mammary tumor;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-235, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525 AND SER-528, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH INSR; ADAPTER PROTEIN
RP COMPLEX 2 AND CLATHRIN HEAVY CHAIN, MUTAGENESIS OF TYR-229 AND TRP-291, AND
RP MOTIF.
RX PubMed=24078630; DOI=10.1074/jbc.m113.479527;
RA Tseng L.T., Lin C.L., Tzen K.Y., Chang S.C., Chang M.F.;
RT "LMBD1 protein serves as a specific adaptor for insulin receptor
RT internalization.";
RL J. Biol. Chem. 288:32424-32432(2013).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=27061115; DOI=10.1111/jcmm.12844;
RA Buers I., Pennekamp P., Nitschke Y., Lowe C., Skryabin B.V., Rutsch F.;
RT "Lmbrd1 expression is essential for the initiation of gastrulation.";
RL J. Cell. Mol. Med. 20:1523-1533(2016).
CC -!- FUNCTION: Lysosomal membrane chaperone required to export cobalamin
CC (vitamin B12) from the lysosome to the cytosol, allowing its conversion
CC to cofactors. Targets ABCD4 transporter from the endoplasmic reticulum
CC to the lysosome. Then forms a complex with lysosomal ABCD4 and
CC cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane
CC (By similarity). Acts as an adapter protein which plays an important
CC role in mediating and regulating the internalization of the insulin
CC receptor (INSR) (PubMed:24078630). Involved in clathrin-mediated
CC endocytosis of INSR via its interaction with adapter protein complex 2
CC (PubMed:24078630). Essential for the initiation of gastrulation and
CC early formation of mesoderm structures during embryogenesis
CC (PubMed:27061115). {ECO:0000250|UniProtKB:Q9NUN5,
CC ECO:0000269|PubMed:24078630, ECO:0000269|PubMed:27061115}.
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 (PubMed:24078630). {ECO:0000250|UniProtKB:Q9NUN5,
CC ECO:0000269|PubMed:24078630}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9NUN5}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9NUN5}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:24078630}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000269|PubMed:24078630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8K0B2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K0B2-2; Sequence=VSP_021632, VSP_021633;
CC Name=3;
CC IsoId=Q8K0B2-3; Sequence=VSP_021631;
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed with strong signals in the
CC primitive streak and in extraembryonic tissues at 7.5 dpc
CC (PubMed:27061115). During further development, expression is strongest
CC in the neuronal fold at 8.5 dpc (PubMed:27061115).
CC {ECO:0000269|PubMed:27061115}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9NUN5}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality (PubMed:27061115).
CC Embryos show an impaired initiation of gastrulation (PubMed:27061115).
CC {ECO:0000269|PubMed:27061115}.
CC -!- SIMILARITY: Belongs to the LIMR family. LMBRD1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AY061989; AAL38052.1; -; mRNA.
DR EMBL; AK003084; BAB22556.1; -; mRNA.
DR EMBL; AK032560; BAC27926.1; -; mRNA.
DR EMBL; AK152170; BAE31002.1; -; mRNA.
DR EMBL; AK153237; BAE31829.1; -; mRNA.
DR EMBL; AK158982; BAE34756.1; -; mRNA.
DR EMBL; AK167080; BAE39240.1; -; mRNA.
DR EMBL; BC025579; AAH25579.1; -; mRNA.
DR EMBL; BC027774; AAH27774.1; -; mRNA.
DR EMBL; BC031902; AAH31902.1; -; mRNA.
DR EMBL; BC039053; AAH39053.1; -; mRNA.
DR CCDS; CCDS35528.1; -. [Q8K0B2-1]
DR CCDS; CCDS78556.1; -. [Q8K0B2-3]
DR RefSeq; NP_001297412.1; NM_001310483.1. [Q8K0B2-3]
DR RefSeq; NP_080995.2; NM_026719.2. [Q8K0B2-1]
DR AlphaFoldDB; Q8K0B2; -.
DR SMR; Q8K0B2; -.
DR STRING; 10090.ENSMUSP00000140783; -.
DR GlyGen; Q8K0B2; 7 sites.
DR iPTMnet; Q8K0B2; -.
DR PhosphoSitePlus; Q8K0B2; -.
DR SwissPalm; Q8K0B2; -.
DR EPD; Q8K0B2; -.
DR jPOST; Q8K0B2; -.
DR MaxQB; Q8K0B2; -.
DR PaxDb; Q8K0B2; -.
DR PeptideAtlas; Q8K0B2; -.
DR PRIDE; Q8K0B2; -.
DR ProteomicsDB; 292339; -. [Q8K0B2-1]
DR ProteomicsDB; 292340; -. [Q8K0B2-2]
DR ProteomicsDB; 292341; -. [Q8K0B2-3]
DR Antibodypedia; 17627; 91 antibodies from 24 providers.
DR DNASU; 68421; -.
DR Ensembl; ENSMUST00000095062; ENSMUSP00000092672; ENSMUSG00000073725. [Q8K0B2-3]
DR Ensembl; ENSMUST00000191471; ENSMUSP00000140783; ENSMUSG00000073725. [Q8K0B2-1]
DR GeneID; 68421; -.
DR KEGG; mmu:68421; -.
DR UCSC; uc007amt.1; mouse. [Q8K0B2-1]
DR CTD; 55788; -.
DR MGI; MGI:1915671; Lmbrd1.
DR VEuPathDB; HostDB:ENSMUSG00000073725; -.
DR eggNOG; ENOG502QQ2T; Eukaryota.
DR GeneTree; ENSGT00390000002581; -.
DR HOGENOM; CLU_028341_1_0_1; -.
DR InParanoid; Q8K0B2; -.
DR OMA; IITTFTW; -.
DR OrthoDB; 744771at2759; -.
DR PhylomeDB; Q8K0B2; -.
DR TreeFam; TF329170; -.
DR Reactome; R-MMU-9758881; Uptake of dietary cobalamins into enterocytes.
DR Reactome; R-MMU-9758890; Transport of RCbl within the body.
DR BioGRID-ORCS; 68421; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Lmbrd1; mouse.
DR PRO; PR:Q8K0B2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8K0B2; protein.
DR Bgee; ENSMUSG00000073725; Expressed in saccule of membranous labyrinth and 242 other tissues.
DR ExpressionAtlas; Q8K0B2; baseline and differential.
DR Genevisible; Q8K0B2; MM.
DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; IDA:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA: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:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IMP:UniProtKB.
DR GO; GO:0032050; F:clathrin heavy chain binding; IDA:UniProtKB.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0005158; F:insulin receptor binding; IDA:MGI.
DR GO; GO:0140318; F:protein transporter activity; ISO:MGI.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:0007369; P:gastrulation; IMP:UniProtKB.
DR GO; GO:0038016; P:insulin receptor internalization; IMP:UniProtKB.
DR GO; GO:0061462; P:protein localization to lysosome; ISS:UniProtKB.
DR GO; GO:0072665; P:protein localization to vacuole; IBA:GO_Central.
DR InterPro; IPR006876; LMBR1-like_membr_prot.
DR Pfam; PF04791; LMBR1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cobalamin; Cobalt;
KW Cytoplasmic vesicle; Developmental protein; Endocytosis;
KW Endoplasmic reticulum; Gastrulation; Glycoprotein; Lysosome; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..537
FT /note="Lysosomal cobalamin transport escort protein LMBD1"
FT /id="PRO_0000260517"
FT TOPO_DOM 1..7
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..97
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..185
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..361
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 406..426
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 427..483
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..537
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 229..232
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:0000269|PubMed:24078630"
FT MOTIF 291..294
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:0000269|PubMed:24078630"
FT MOD_RES 235
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 454
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..70
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.1"
FT /id="VSP_021631"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_021632"
FT VAR_SEQ 19..20
FT /note="LL -> MQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_021633"
FT MUTAGEN 229
FT /note="Y->A: Significantly reduced interaction with adapter
FT protein complex 2 and disruption of its function in
FT clathrin-mediated endocytosis of INSR."
FT /evidence="ECO:0000269|PubMed:24078630"
FT MUTAGEN 291
FT /note="W->A: Significantly reduced interaction with adapter
FT protein complex 2 and disruption of its function in
FT clathrin-mediated endocytosis of INSR."
FT /evidence="ECO:0000269|PubMed:24078630"
FT CONFLICT 62
FT /note="P -> L (in Ref. 2; BAC27926)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="K -> Q (in Ref. 1; AAL38052)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="S -> P (in Ref. 1; AAL38052)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="G -> D (in Ref. 2; BAE31002/BAE31829)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="W -> R (in Ref. 2; BAB22556)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 61062 MW; 7AAFF431479752F0 CRC64;
MAAAAAELVI GWCIFGLLLL AILAFCWVYV RKYQSQRESE VVSTVTAIFS LAVALITSAL
LPVDIFLVSY MKNQNGTFKD WADANVTVQI ENTVLYGYYT LYSVILFCVF FWIPFVYFYY
EEKDEDDASK CTQIKTALKY TLGFVVICAL LLLVGAFVPL HLPNNNNSTE WEKVKLLFED
LGTGQGLAAL SFSISSLTLI GMLAAITYTA YGMSALPLNL IKGTRSTAYE RLENTEDIEE
VEQHIQTIRS KSKDGRPLPA RDRRALKQCE ERLRTLRKRE RHLEFIENSW WTKFCGALRP
LKIIWGIFFI LVALLFVISL FLSNLDKALH SAGIDSGFII FGTNLSNPLN MLLPLLQTVF
PLDYILITII IMYFIFTSMA GIRNIGIWFF WIRLYKIRRG RTRPQALLFL CMILLLIVLH
TSYMIYSLAP QYVMYGSQNY LIESNITSDA HKGNSTLAVP KRCDADAPKD QCTVTRTYIF
LHKFWFFSAA YYFGNWAFLV VFLIGLIVSC CKGKKSVIEG VDEDSDLSDD EPSAYSA
