AMNLS_MOUSE
ID AMNLS_MOUSE Reviewed; 458 AA.
AC Q99JB7; Q5I0U1; Q99MP9;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Protein amnionless;
DE Contains:
DE RecName: Full=Soluble protein amnionless;
DE Flags: Precursor;
GN Name=Amn;
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 [GENOMIC DNA / MRNA], DISRUPTION PHENOTYPE, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=129/SvJ, and RIII;
RX PubMed=11279523; DOI=10.1038/86912;
RA Kalantry S., Manning S., Haub O., Tomihara-Newberger C., Lee H.-G.,
RA Fangman J., Disteche C.M., Manova K., Lacy E.;
RT "The amnionless gene, essential for mouse gastrulation, encodes a visceral-
RT endoderm-specific protein with an extracellular cysteine-rich domain.";
RL Nat. Genet. 27:412-416(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 DISRUPTION PHENOTYPE.
RX PubMed=9851841; DOI=10.1006/dbio.1998.9034;
RA Tomihara-Newberger C., Haub O., Lee H.-G., Soares V., Manova K., Lacy E.;
RT "The amn gene product is required in extraembryonic tissues for the
RT generation of middle primitive streak derivatives.";
RL Dev. Biol. 204:34-54(1998).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH CUBN, TISSUE SPECIFICITY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=15342463; DOI=10.1242/dev.01341;
RA Strope S., Rivi R., Metzger T., Manova K., Lacy E.;
RT "Mouse amnionless, which is required for primitive streak assembly,
RT mediates cell-surface localization and endocytic function of cubilin on
RT visceral endoderm and kidney proximal tubules.";
RL Development 131:4787-4795(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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).
CC -!- FUNCTION: Membrane-bound component of the endocytic receptor formed by
CC AMN and CUBN. Required for normal CUBN glycosylation and trafficking to
CC the cell surface (PubMed:15342463). The complex formed by AMN and CUBN
CC is required for efficient absorption of vitamin B12 (By similarity).
CC Required for normal CUBN-mediated protein transport in the kidney
CC (PubMed:15342463). {ECO:0000250|UniProtKB:Q9BXJ7,
CC ECO:0000269|PubMed:15342463}.
CC -!- SUBUNIT: Interacts (via extracellular region) with CUBN/cubilin
CC (PubMed:15342463). This gives rise to a huge complex containing one AMN
CC chain and three CUBN chains (By similarity).
CC {ECO:0000250|UniProtKB:Q9BXJ7, ECO:0000269|PubMed:15342463}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15342463}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q9BXJ7}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9BXJ7}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q9BXJ7}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q9BXJ7}. Membrane, coated pit
CC {ECO:0000250|UniProtKB:Q9BXJ7}.
CC -!- TISSUE SPECIFICITY: Expressed in polarized epithelial cells which are
CC specialized in resorption or transport, specifically kidney proximal
CC tubules and intestinal epithelium. {ECO:0000269|PubMed:15342463}.
CC -!- DEVELOPMENTAL STAGE: Detected in primitive endoderm at 4.5 dpc, and on
CC the apical surface of the visceral endoderm from 5.5 dpc to 8.5 dpc.
CC Expressed in mesonephric tubules at 11.5-12.5 dpc and in the
CC metanephric kidney beginning at 14.5 dpc. Expressed in the intestine
CC from 16.5 dpc. {ECO:0000269|PubMed:11279523}.
CC -!- DOMAIN: The complex formed by AMN and CUBN is composed of a 400
CC Angstrom long stem and a globular crown region. The stem region is
CC probably formed by AMN and the CUBN N-terminal region, including the
CC EGF-like domains. The crown is probably formed by the CUBN CUB domains.
CC {ECO:0000250|UniProtKB:F1SAM7}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9BXJ7}.
CC -!- PTM: A soluble form arises by proteolytic removal of the membrane
CC anchor. {ECO:0000250|UniProtKB:Q9BXJ7}.
CC -!- DISRUPTION PHENOTYPE: Full embryonic lethality at about 10.5 dpc with
CC failure of primitive middle streak assembly and absence of trunk
CC mesoderm formation. {ECO:0000269|PubMed:11279523,
CC ECO:0000269|PubMed:15342463, ECO:0000269|PubMed:9851841}.
CC -!- MISCELLANEOUS: The role of Amn in embryonic development seems to be
CC species specific. In mice, null mutations lead to embryonic lethality.
CC Human mutations give rise to much milder symptoms. {ECO:0000305}.
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DR EMBL; AF320615; AAK37476.1; -; Genomic_DNA.
DR EMBL; AF320616; AAK37477.1; -; Genomic_DNA.
DR EMBL; AF320619; AAK37478.1; -; mRNA.
DR EMBL; BC087954; AAH87954.1; -; mRNA.
DR CCDS; CCDS36564.1; -.
DR RefSeq; NP_291081.2; NM_033603.3.
DR AlphaFoldDB; Q99JB7; -.
DR SMR; Q99JB7; -.
DR ComplexPortal; CPX-5847; Cubam cobalamin uptake receptor complex.
DR STRING; 10090.ENSMUSP00000021707; -.
DR GlyGen; Q99JB7; 2 sites.
DR iPTMnet; Q99JB7; -.
DR PhosphoSitePlus; Q99JB7; -.
DR jPOST; Q99JB7; -.
DR MaxQB; Q99JB7; -.
DR PaxDb; Q99JB7; -.
DR PeptideAtlas; Q99JB7; -.
DR PRIDE; Q99JB7; -.
DR ProteomicsDB; 296403; -.
DR Antibodypedia; 13; 55 antibodies from 22 providers.
DR DNASU; 93835; -.
DR Ensembl; ENSMUST00000021707; ENSMUSP00000021707; ENSMUSG00000021278.
DR GeneID; 93835; -.
DR KEGG; mmu:93835; -.
DR UCSC; uc007pcp.1; mouse.
DR CTD; 81693; -.
DR MGI; MGI:1934943; Amn.
DR VEuPathDB; HostDB:ENSMUSG00000021278; -.
DR eggNOG; ENOG502QUUQ; Eukaryota.
DR GeneTree; ENSGT00390000007463; -.
DR HOGENOM; CLU_050471_0_0_1; -.
DR InParanoid; Q99JB7; -.
DR OMA; PWICADL; -.
DR OrthoDB; 827066at2759; -.
DR PhylomeDB; Q99JB7; -.
DR TreeFam; TF323790; -.
DR BioGRID-ORCS; 93835; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Amn; mouse.
DR PRO; PR:Q99JB7; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q99JB7; protein.
DR Bgee; ENSMUSG00000021278; Expressed in intestinal villus and 74 other tissues.
DR Genevisible; Q99JB7; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0031528; C:microvillus membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0038024; F:cargo receptor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0009235; P:cobalamin metabolic process; ISO:MGI.
DR GO; GO:0015889; P:cobalamin transport; ISO:MGI.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISO:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:MGI.
DR GO; GO:0097017; P:renal protein absorption; IMP:MGI.
DR InterPro; IPR026112; AMN.
DR PANTHER; PTHR14995; PTHR14995; 1.
DR Pfam; PF14828; Amnionless; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coated pit; Developmental protein; Disulfide bond; Endosome;
KW Glycoprotein; Membrane; Protein transport; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT CHAIN 20..458
FT /note="Protein amnionless"
FT /id="PRO_0000020703"
FT CHAIN 20..?
FT /note="Soluble protein amnionless"
FT /id="PRO_0000447652"
FT TOPO_DOM 20..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 203..254
FT /note="VWFC"
FT REGION 67..87
FT /note="Interaction with CUBN"
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT CARBOHYD 27
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..96
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT DISULFID 137..213
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT DISULFID 205..211
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT DISULFID 223..249
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT DISULFID 234..250
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
FT DISULFID 239..253
FT /evidence="ECO:0000250|UniProtKB:Q9BXJ7"
SQ SEQUENCE 458 AA; 48696 MW; 00789EE67C35443F CRC64;
MGALGRVLLW LQLCAMTRAA YKLWVPNTSF DTASNWNQNR TPCAGDAVQF PADKMVSVLV
RDSHAISDML LPLDGELVLA SGAALSAAGG DSDPACNPGA PLLFRNPDRF SWLDPHLWSS
GTQAPGLFSV DAERVPCSYD DVLFPRDGSF RVALGPGPNP VHVRSVSAVG QTFSRDEDLT
AFLASREGRL RFHGSGALRV GSQACTDASG CVCGNAEMLP WICASLLQPL GGRCPQAACQ
DPLLPQGQCC DLCGAIVSLT HDPTFDLERY RARLLDLFLK QPQYQGLQVA VSKVLRDAHT
EIQVVLVETE HATGAAGQLG HALLQDAVAQ GSVLGIVSAT LRQSGKPMTA DSELNQSSSG
AGLAGGVAAL VLLALLGTVL LLLHRSGRLR WRRHEDAEPV SAGLPLGFRN PIFDAIVFKQ
QPSVELPDSA QKVDILDIDT KFGCFVNPLF AGEAEAEA
