Q9BXJ7 (AMNLS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein amnionless

Gene names

Name:	AMN
ORF Names:	UNQ513/PRO1028

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Necessary for efficient absorption of vitamin B12. May direct the production of trunk mesoderm during development by modulating a bone morphogenetic protein (BMP) signaling pathway in the underlying visceral endoderm By similarity.
Subunit structure	Interacts with CUBN/cubilin. Ref.5
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Tissue specificity	Long isoforms are highly expressed in small intestine, colon and kidney (renal proximal tubule epithelial cells). Shorter isoforms are detected at lower levels in testis, thymus and peripheral blood leukocytes. Ref.4 Ref.5
Involvement in disease	Recessive hereditary megaloblastic anemia 1 (RH-MGA1) [MIM:261100]: Due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.6
Miscellaneous	The mutations described in Ref.4 all affect the N-terminus of the protein; shorter isoforms produced from alternative transcription start sites might still fulfill a role in embryogenesis. This might explain the discrepancy with the embryonic lethality of null mutants in mice.
Sequence similarities	Contains 1 VWFC domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative promoter usage
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	excretion Inferred from electronic annotation. Source: Compara lipid metabolic process Traceable author statement. Source: Reactome lipoprotein metabolic process Traceable author statement. Source: Reactome multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein localization Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 1 isoform produced by alternative promoter usage. [Select]

Note: At least 5 isoforms, 1, 2, 3, 4 and 5, are produced.

Isoform 1 (identifier: Q9BXJ7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 453	434	Protein amnionless		PRO_0000020702
Regions
	Topological domain	20 – 357	338	Extracellular Potential
	Transmembrane	358 – 378	21	Helical; Potential
	Topological domain	379 – 453	75	Cytoplasmic Potential
	Domain	202 – 254	53	VWFC
Amino acid modifications
	Glycosylation	35	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	41	1	T → I in RH-MGA1. Ref.4 Corresponds to variant rs28939377 [ dbSNP | Ensembl ].		VAR_015733
Experimental info
	Sequence conflict	241	1	S → F in AAK28532. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 40AA14EF186A6009	FASTA	453	47,754
	10 20 30 40 50 60 MGVLGRVLLW LQLCALTQAV SKLWVPNTDF DVAANWSQNR TPCAGGAVEF PADKMVSVLV 70 80 90 100 110 120 QEGHAVSDML LPLDGELVLA SGAGFGVSDV GSHLDCGAGE PAVFRDSDRF SWHDPHLWRS 130 140 150 160 170 180 GDEAPGLFFV DAERVPCRHD DVFFPPSASF RVGLGPGASP VRVRSISALG RTFTRDEDLA 190 200 210 220 230 240 VFLASRAGRL RFHGPGALSV GPEDCADPSG CVCGNAEAQP WICAALLQPL GGRCPQAACH 250 260 270 280 290 300 SALRPQGQCC DLCGAVVLLT HGPAFDLERY RARILDTFLG LPQYHGLQVA VSKVPRSSRL 310 320 330 340 350 360 READTEIQVV LVENGPETGG AGRLARALLA DVAENGEALG VLEATMRESG AHVWGSSAAG 370 380 390 400 410 420 LAGGVAAAVL LALLVLLVAP PLLRRAGRLR WRRHEAAAPA GAPLGFRNPV FDVTASEELP 430 440 450 LPRRLSLVPK AAADSTSHSY FVNPLFAGAE AEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain." Kalantry S., Manning S., Haub O., Tomihara-Newberger C., Lee H.-G., Fangman J., Disteche C.M., Manova K., Lacy E. Nat. Genet. 27:412-416(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-230.
[4]	"Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia." Tanner S.M., Aminoff M., Wright F.A., Liyanarachchi S., Kuronen M., Saarinen A., Massika O., Mandel H., Broch H., de la Chapelle A. Nat. Genet. 33:426-429(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 300-323 AND 393-453, TISSUE SPECIFICITY, VARIANT RH-MGA1 ILE-41.
[5]	"The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless." Fyfe J.C., Madsen M., Hoejrup P., Christensen E.I., Tanner S.M., de la Chapelle A., He Q., Moestrup S.K. Blood 103:1573-1579(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CUBN, TISSUE SPECIFICITY.
[6]	"Imerslund-Grasbeck syndrome: new mutation in amnionless." Densupsoontorn N., Sanpakit K., Vijarnsorn C., Pattaragarn A., Kangwanpornsiri C., Jatutipsompol C., Tirapongporn H., Jirapinyo P., Shah N.P., Sturm A.C., Tanner S.M. Pediatr. Int. 54:E19-E21(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RH-MGA1.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF328788 mRNA. Translation: AAK28532.1. AL117209 Genomic DNA. No translation available. AY358468 mRNA. Translation: AAQ89949.1.
IPI	IPI00008857.
RefSeq	NP_112205.2. NM_030943.3.
UniGene	Hs.534494.
3D structure databases
ProteinModelPortal	Q9BXJ7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000299155.
PTM databases
PhosphoSite	Q9BXJ7.
Polymorphism databases
DMDM	296434395.
Proteomic databases
PaxDb	Q9BXJ7.
PRIDE	Q9BXJ7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299155; ENSP00000299155; ENSG00000166126.
GeneID	81693.
KEGG	hsa:81693.
UCSC	uc001ymg.4. human.
Organism-specific databases
CTD	81693.
GeneCards	GC14P103388.
H-InvDB	HIX0011994.
HGNC	HGNC:14604. AMN.
HPA	HPA000817.
MIM	261100. phenotype. 605799. gene.
neXtProt	NX_Q9BXJ7.
Orphanet	35858. Grasbeck-Imerslund disease.
PharmGKB	PA134962814.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG82604.
HOGENOM	HOG000033922.
HOVERGEN	HBG037321.
InParanoid	Q9BXJ7.
OMA	DTEIQVV.
OrthoDB	EOG405S1J.
PhylomeDB	Q9BXJ7.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9BXJ7.
Bgee	Q9BXJ7.
CleanEx	HS_AMN.
Genevestigator	Q9BXJ7.
GermOnline	ENSG00000166126. Homo sapiens.
Family and domain databases
InterPro	IPR026112. AMN. [Graphical view]
PANTHER	PTHR14995. PTHR14995. 1 hit.
PROSITE	PS01208. VWFC_1. False negative. PS50184. VWFC_2. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00115. Cyanocobalamin. DB00200. Hydroxocobalamin.
GenomeRNAi	81693.
NextBio	72043.
SOURCE	Search...

Entry information

Entry name

AMNLS_HUMAN

Accession

Primary (citable) accession number: Q9BXJ7
Secondary accession number(s): Q6UX83

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2003
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.