AMNLS_CANLF
ID AMNLS_CANLF Reviewed; 458 AA.
AC Q6UKI2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 63.
DE RecName: Full=Protein amnionless;
DE Contains:
DE RecName: Full=Soluble protein amnionless;
DE Flags: Precursor;
GN Name=AMN;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14576052; DOI=10.1182/blood-2003-08-2852;
RA Fyfe J.C., Madsen M., Hoejrup P., Christensen E.I., Tanner S.M.,
RA de la Chapelle A., He Q., Moestrup S.K.;
RT "The functional cobalamin (vitamin B12)-intrinsic factor receptor is a
RT novel complex of cubilin and amnionless.";
RL Blood 103:1573-1579(2004).
RN [2]
RP POSSIBLE INVOLVEMENT IN CANINE MGA1.
RX PubMed=14722725; DOI=10.1007/s00335-003-2280-1;
RA He Q., Fyfe J.C., Schaeffer A.A., Kilkenney A., Werner P., Kirkness E.F.,
RA Henthorn P.S.;
RT "Canine Imerslund-Grasbeck syndrome maps to a region orthologous to
RT HSA14q.";
RL Mamm. Genome 14:758-764(2003).
RN [3]
RP INVOLVEMENT IN CANINE MGA1, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=15845892; DOI=10.1182/blood-2005-03-1197;
RA He Q., Madsen M., Kilkenney A., Gregory B., Christensen E.I., Vorum H.,
RA Hoejrup P., Schaeffer A.A., Kirkness E.F., Tanner S.M., de la Chapelle A.,
RA Giger U., Moestrup S.K., Fyfe J.C.;
RT "Amnionless function is required for cubilin brush-border expression and
RT intrinsic factor-cobalamin (vitamin B12) absorption in vivo.";
RL Blood 106:1447-1453(2005).
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. The complex formed by AMN and CUBN is required for
CC efficient absorption of vitamin B12. Required for normal CUBN-mediated
CC protein transport in the kidney. {ECO:0000269|PubMed:15845892}.
CC -!- SUBUNIT: Interacts (via extracellular region) with CUBN/cubilin
CC (PubMed:15845892). 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:15845892}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9BXJ7}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q9BXJ7}. Cell membrane
CC {ECO:0000305|PubMed:15845892}; 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 -!- SUBCELLULAR LOCATION: [Soluble protein amnionless]: Secreted
CC {ECO:0000269|PubMed:15845892}.
CC -!- TISSUE SPECIFICITY: Detected in kidney (at protein level). Detected in
CC kidney and ileum. {ECO:0000269|PubMed:15845892}.
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:0000269|PubMed:15845892}.
CC -!- PTM: A soluble form arises by proteolytic removal of the membrane
CC anchor. {ECO:0000269|PubMed:15845892}.
CC -!- DISEASE: Note=Defects in AMN are a cause of a canine form of
CC megaloblastic anemia 1 (MGA1). {ECO:0000269|PubMed:15845892,
CC ECO:0000305|PubMed:14722725}.
CC -!- MISCELLANEOUS: The role of Amn in embryonic development seems to be
CC species specific. In mice, null mutations lead to embryonic lethality.
CC Canine mutations give rise to much milder symptoms. {ECO:0000305}.
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DR EMBL; AY368152; AAR13399.1; -; mRNA.
DR RefSeq; NP_001002960.1; NM_001002960.1.
DR AlphaFoldDB; Q6UKI2; -.
DR SMR; Q6UKI2; -.
DR GeneID; 403434; -.
DR KEGG; cfa:403434; -.
DR CTD; 81693; -.
DR InParanoid; Q6UKI2; -.
DR OrthoDB; 827066at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IMP:CACAO.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008104; P:protein localization; IBA:GO_Central.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
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; Disulfide bond; Endosome; Glycoprotein;
KW Membrane; Protein transport; Reference proteome; Secreted; 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_0000020701"
FT CHAIN 20..?
FT /note="Soluble protein amnionless"
FT /evidence="ECO:0000305"
FT /id="PRO_0000447650"
FT TOPO_DOM 20..366
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 367..387
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 388..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 REGION 422..446
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 35
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; 47618 MW; 4927E33B466B8D5A CRC64;
MGALGRALLW LQLCALARAA YKLWVPTTDF EAAANWSQNR TPCAGAVVQF PADKAVSVVV
RASHGFSDML LPRDGEFVLA SGAGFGAADA GRDPDCGAGA PALFLDPDRF SWHDPRLWRS
GDAARGLFSV DAERVPCRHD DVVFPPDASF RVGLGPGARP ARVRSVQVLG QTFTRDEDLA
AFLASRAGRL RFHGPGALRV GPGACADPSG CVCGDAEVQP WICAALLQPL GGRCPPAACP
DALRPEGQCC DLCGAIVSLT HGPTFDIERY RARLLRAFLP QYPGLQAAVS KVRRRPGPHT
EVQVVLAETG PQPGGAGRLA RALLADVAEH GEALGVLSAT ARESGAPVGD GSAAGPLGSG
SRAGLAGGVA AGLLLLLLAL AAGLLLLRRA PRLRWTKRER LVATPVEAPL GFSNPVFDVA
GSVGPVPRTP QPPPAQQAGS SSTSRSYFVN PLFAEAEA
