ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!
Search for

UniProtKB/Swiss-Prot entry P58335


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

Note: most headings are clickable, even if they don't appear as links. They link to the user manual or other documents.
Entry information
Entry name ANTR2_HUMAN
Primary accession number P58335
Secondary accession numbers Q59E98 Q5JPE9 Q86UI1 Q8N4J8 Q8NB13 Q96NC7
Integrated into Swiss-Prot on November 2, 2001
Sequence was last modified on February 20, 2007 (Sequence version 4)
Annotations were last modified on    September 2, 2008 (Entry version 76)
Name and origin of the protein
Protein name Anthrax toxin receptor 2 [Precursor]
Synonyms Capillary morphogenesis gene 2 protein
CMG-2
Gene name
Name: ANTXR2
Synonyms: CMG2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
PubMed=11683410 [NCBI, ExPASy, EBI, Israel, Japan]
Bell S.E., Mavila A., Salazar R., Bayless K.J., Kanagala S., Maxwell S.A., Davis G.E.;
"Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling.";
J. Cell Sci. 114:2755-2773(2001).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH ANTHRAX TOXIN.
TISSUE=Placenta;
DOI=10.1073/pnas.0431098100; PubMed=12700348 [NCBI, ExPASy, EBI, Israel, Japan]
Scobie H.M., Rainey G.J.A., Bradley K.A., Young J.A.T.;
"Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor.";
Proc. Natl. Acad. Sci. U.S.A. 100:5170-5174(2003).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-489 (ISOFORM 3), AND VARIANT ALA-357.
TISSUE=Synovial cell;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
TISSUE=Aortic endothelium;
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R.;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 137-489 (ISOFORM 4), AND VARIANT ALA-357.
TISSUE=Lymph node;
The German cDNA consortium;
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 248-489 (ISOFORM 4).
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
INTERACTION WITH ANTHRAX TOXIN, AND CLATHRIN-DEPENDENT INTERNALIZATION.
DOI=10.1083/jcb.200211018; PubMed=12551953 [NCBI, ExPASy, EBI, Israel, Japan]
Abrami L., Liu S., Cosson P., Leppla S.H., van der Goot F.G.;
"Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process.";
J. Cell Biol. 160:321-328(2003).
[8]
INTERNALIZATION.
DOI=10.1083/jcb.200312072; PubMed=15337774 [NCBI, ExPASy, EBI, Israel, Japan]
Abrami L., Lindsay M., Parton R.G., Leppla S.H., van der Goot F.G.;
"Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway.";
J. Cell Biol. 166:645-651(2004).
[9]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-212 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS.
DOI=10.1038/nature02763; PubMed=15243628 [NCBI, ExPASy, EBI, Israel, Japan]
Santelli E., Bankston L.A., Leppla S.H., Liddington R.C.;
"Crystal structure of a complex between anthrax toxin and its host cell receptor.";
Nature 430:905-908(2004).
[10]
X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 38-217.
DOI=10.1073/pnas.0401506101; PubMed=15079089 [NCBI, ExPASy, EBI, Israel, Japan]
Lacy D.B., Wigelsworth D.J., Scobie H.M., Young J.A.T., Collier R.J.;
"Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor.";
Proc. Natl. Acad. Sci. U.S.A. 101:6367-6372(2004).
[11]
X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 38-218 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS.
DOI=10.1073/pnas.0405405101; PubMed=15326297 [NCBI, ExPASy, EBI, Israel, Japan]
Lacy D.B., Wigelsworth D.J., Melnyk R.A., Harrison S.C., Collier R.J.;
"Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation.";
Proc. Natl. Acad. Sci. U.S.A. 101:13147-13151(2004).
[12]
VARIANTS ISH PRO-45; THR-189 AND ARG-218, VARIANTS JHF GLN-293 INS AND CYS-381, VARIANT ALA-357, AND TISSUE SPECIFICITY.
DOI=10.1086/378418; PubMed=14508707 [NCBI, ExPASy, EBI, Israel, Japan]
Hanks S., Adams S., Douglas J., Arbour L., Atherton D.J., Balci S., Bode H., Campbell M.E., Feingold M., Keser G., Kleijer W., Mancini G., McGrath J.A., Muntoni F., Nanda A., Teare M.D., Warman M., Pope F.M., Superti-Furga A., Futreal P.A., Rahman N.;
"Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis.";
Am. J. Hum. Genet. 73:791-800(2003).
[13]
VARIANT ISH THR-189, VARIANTS JHF ASP-105 AND ARG-329, AND FUNCTION.
DOI=10.1086/378781; PubMed=12973667 [NCBI, ExPASy, EBI, Israel, Japan]
Dowling O., Difeo A., Ramirez M.C., Tukel T., Narla G., Bonafe L., Kayserili H., Yuksel-Apak M., Paller A.S., Norton K., Teebi A.S., Grum-Tokars V., Martin G.S., Davis G.E., Glucksman M.J., Martignetti J.A.;
"Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis.";
Am. J. Hum. Genet. 73:957-966(2003).
[14]
INVOLVEMENT IN INFANTILE SYSTEMIC HYALINOSIS.
DOI=10.1111/j.1365-2230.2004.01698.x; PubMed=15725249 [NCBI, ExPASy, EBI, Israel, Japan]
Lee J.Y.-Y., Tsai Y.-M., Chao S.-C., Tu Y.-F.;
"Capillary morphogenesis gene-2 mutation in infantile systemic hyalinosis: ultrastructural study and mutation analysis in a Taiwanese infant.";
Clin. Exp. Dermatol. 30:176-179(2005).
Comments
  • FUNCTION: Necessary for cellular interactions with laminin and the extracellular matrix.
  • SUBUNIT: Binds laminin, and possibly also collagen type IV. Binds to the protective antigen (PA) of Bacillus anthracis in a divalent cation-dependent manner, with the following preference: calcium > manganese > magnesium > zinc. Binding of PA leads to heptamerization of the receptor-PA complex.
  • INTERACTION:
    O75581:LRP6; NbExp=1; IntAct=EBI-456840, EBI-910915;
    P13423:pagA (xeno); NbExp=4; IntAct=EBI-456840, EBI-456868;
  • SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=Expressed at the cell surface.
  • SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Note=Expressed predominantly expressed within the endoplasmic reticulum and not at the plasma membrane.
  • SUBCELLULAR LOCATION: Isoform 3: Secreted.
  • ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP58335-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP58335-2
    Features which should be applied to build the isoform sequence: VSP_008343.
    Name3
    Isoform IDP58335-3
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_008344, VSP_008345.
    Name4
    Isoform IDP58335-4
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_008346.
  • TISSUE SPECIFICITY: Expressed in prostate, thymus, ovary, testis, pancreas, colon, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, skeletal muscle, small intestine and spleen.
  • DOMAIN: Binding to PA seems to be effected through the VWA domain.
  • DISEASE: Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures.
  • DISEASE: Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility.
  • MISCELLANEOUS: Upon binding of the protective antigen (PA) of Bacillus anthracis the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway.
  • SIMILARITY: Belongs to the ATR family.
  • SIMILARITY: Contains 1 VWFA domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AY040326; AAK77222.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY233452; AAP04016.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK055636; BAB70976.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK091721; BAC03731.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB209913; BAD93150.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL832851; CAI46157.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC034001; AAH34001.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
UniGene Hs.162963
3D structure databases
PDB
1SHT; X-ray; 1.81 A; X=38-217.[ExPASy / RCSB / EBI]
1SHU; X-ray; 1.50 A; X=38-218.[ExPASy / RCSB / EBI]
1T6B; X-ray; 2.50 A; Y=40-212.[ExPASy / RCSB / EBI]
1TZN; X-ray; 4.30 A; a/b/c/d/e/f/g/h/i/j/k/l/m/o=38-218.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1SHT; -.
1SHU; -.
1T6B; -.
1TZN; -.
ModBase P58335.
Protein-protein interaction databases
IntAct P58335; -.
Organism-specific databases
H-InvDB HIX0004329; -.
HGNC HGNC:21732; ANTXR2.
GenAtlas ANTXR2.
MIM 228600; phenotype. [NCBI / EBI]
236490; phenotype. [NCBI / EBI]
608041; gene. [NCBI / EBI]
Orphanet 2176; Hyalinosis, infantile systemic.
2028; Juvenile hyaline fibromatosis.
PharmGKB PA128394752; -.
GeneCards P58335.
Gene expression databases
ArrayExpress P58335; -.
CleanEx HS_ANTXR2; -.
GermOnline ENSG00000163297; Homo sapiens.
Ontologies
GO
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
QuickGo view.
Family and domain databases
InterPro IPR017360; Anthrax_toxin_rcpt_2.
IPR008399; Anthrax_toxin_rcpt_C.
IPR008400; Anthrax_toxin_rcpt_extracel.
IPR002035; VWF_A.
Graphical view of domain structure.
Pfam PF05586; Ant_C; 1.
PF05587; Anth_Ig; 1.
PF00092; VWA; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF038023; Anthrax_toxin_receptor_2; 1.
PRINTS PR00453; VWFADOMAIN.
SMART SM00327; VWA; 1.
SMART graphical view of domain structure.
PROSITE PS50234; VWFA; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P58335.
Genome annotation databases
Ensembl ENSG00000163297; Homo sapiens. [Contig view]
Phylogenomic databases
HOVERGEN P58335; -.
Other
SOURCE ANTXR2; Homo sapiens.
ProtoNet P58335.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Cell membrane; Disease mutation; Endoplasmic reticulum; Glycoprotein; Membrane; Metal-binding; Polymorphism; Receptor; Secreted; Signal; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    33  33     Potential. 
CHAIN   34   489  456     Anthrax toxin receptor 2. PRO_0000002694
TOPO_DOM   34   318  285     Extracellular (Potential). 
TRANSMEM   319   341  23     Potential. 
TOPO_DOM   342   489  148     Cytoplasmic (Potential). 
DOMAIN   44   213  170     VWFA. 
COMPBIAS   352   360  9     Poly-Pro. 
COMPBIAS   362   366  5     Poly-Glu. 
METAL   52    52        Divalent metal cation. 
METAL   54    54        Divalent metal cation. 
METAL   118   118        Divalent metal cation. 
CARBOHYD   250   250        N-linked (GlcNAc...) (Potential). 
CARBOHYD   260   260        N-linked (GlcNAc...) (Potential). 
DISULFID   39   218         
VAR_SEQ   213   315        Missing (in isoform 2). VSP_008343
VAR_SEQ   290   322        TLDVSVSFNGGKSVISGSLIVTATECSNGIAAI -> WGLTVTQAGVKWHDLTHCTFGLSGSGDPPTSAS (in isoform 3). VSP_008344
VAR_SEQ   323   489        Missing (in isoform 3). VSP_008345
VAR_SEQ   477   489        VCIWECIEKELTA -> GRCINFSRVPSQ (in isoform 4). VSP_008346
VARIANT   45    45  1     L -> P (in ISH). VAR_022687 
VARIANT   105   105  1     G -> D (in JHF). VAR_022688 
VARIANT   189   189  1     I -> T (in ISH). VAR_022689 
VARIANT   218   218  1     C -> R (in ISH). VAR_022690 
VARIANT   293   293  1     V -> VQ (in JHF). VAR_022691
VARIANT   329   329  1     L -> R (in JHF). VAR_022692 
VARIANT   357   357  1     P -> A (in dbSNP:rs12647691 [NCBI]). VAR_022693 
VARIANT   381   381  1     Y -> C (in JHF). VAR_022694 
STRAND   43    50  8      
HELIX   53    58  6      
HELIX   59    72  14      
STRAND   79    96  18      
HELIX   99   110  12      
HELIX   120   134  15      
HELIX   136   138  3      
STRAND   139   147  9      
HELIX   155   168  14      
STRAND   172   177  6      
HELIX   183   189  7      
STRAND   190   192  3      
HELIX   193   195  3      
STRAND   196   204  9      
HELIX   205   214  10      
Sequence information
Length: 489 AA [This is the length of the unprocessed precursor] Molecular weight: 53692 Da [This is the MW of the unprocessed precursor] CRC64: B9F679DB75B6E2B7 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MVAERSPARS PGSWLFPGLW LLVLSGPGGL LRAQEQPSCR RAFDLYFVLD KSGSVANNWI 

        70         80         90        100        110        120 
EIYNFVQQLA ERFVSPEMRL SFIVFSSQAT IILPLTGDRG KISKGLEDLK RVSPVGETYI 

       130        140        150        160        170        180 
HEGLKLANEQ IQKAGGLKTS SIIIALTDGK LDGLVPSYAE KEAKISRSLG ASVYCVGVLD 

       190        200        210        220        230        240 
FEQAQLERIA DSKEQVFPVK GGFQALKGII NSILAQSCTE ILELQPSSVC VGEEFQIVLS 

       250        260        270        280        290        300 
GRGFMLGSRN GSVLCTYTVN ETYTTSVKPV SVQLNSMLCP APILNKAGET LDVSVSFNGG 

       310        320        330        340        350        360 
KSVISGSLIV TATECSNGIA AIIVILVLLL LLGIGLMWWF WPLCCKVVIK DPPPPPPPAP 

       370        380        390        400        410        420 
KEEEEEPLPT KKWPTVDASY YGGRGVGGIK RMEVRWGDKG STEEGARLEK AKNAVVKIPE 

       430        440        450        460        470        480 
ETEEPIRPRP PRPKPTHQPP QTKWYTPIKG RLDALWALLR RQYDRVSLMR PQEGDEVCIW 


ECIEKELTA 

P58335 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

BLAST logo BLAST submission on ExPASy/SIB
or at NCBI (USA)
Tools Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
PROSITE logo ScanProsite, MotifScan SWISS-MODEL Submit a homology modeling request to SWISS-MODEL
NPSA logo NPSA Sequence analysis tools

ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
 Hosted by ch flag SIB Switzerland Mirror sites: Australia  Brazil  Canada  China  Korea
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!