Reviewed, UniProtKB/Swiss-Prot P58335 (ANTR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Anthrax toxin receptor 2
Alternative name(s):
    Capillary morphogenesis gene 2 protein
      Short name=CMG-2

Gene names

Name:	ANTXR2
Synonyms:	CMG2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	489 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 cellular interactions with laminin and the extracellular matrix.
Subunit structure	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.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Note= Expressed at the cell surface. Isoform 2: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Note= Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane. Isoform 3: Secreted.
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.
Involvement in 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. 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.
Sequence similarities	Belongs to the ATR family. Contains 1 VWFA domain.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane
Ligand	Metal-binding
Molecular function	Receptor
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LRP6	O75581	1	EBI-456840,EBI-910915
pagA	P13423	4	EBI-456840,EBI-456868	From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P58335-1)

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.

Notes: Expressed at the cell surface.

Isoform 2 (identifier: P58335-2)

The sequence of this isoform differs from the canonical sequence as follows:
     213-315: Missing.

Notes: Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane.

Isoform 3 (identifier: P58335-3)

The sequence of this isoform differs from the canonical sequence as follows:
     290-322: TLDVSVSFNGGKSVISGSLIVTATECSNGIAAI → WGLTVTQAGVKWHDLTHCTFGLSGSGDPPTSAS
     323-489: Missing.

Notes: No experimental confirmation available.

Isoform 4 (identifier: P58335-4)

The sequence of this isoform differs from the canonical sequence as follows:
     477-489: VCIWECIEKELTA → GRCINFSRVPSQ

Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Potential

Chain

34 – 489

456

Anthrax toxin receptor 2

PRO_0000002694

Regions

Topological domain

34 – 318

285

Extracellular Potential

Transmembrane

319 – 341

23

Potential

Topological domain

342 – 489

148

Cytoplasmic Potential

Domain

44 – 213

170

VWFA

Compositional bias

352 – 360

9

Poly-Pro

Compositional bias

362 – 366

5

Poly-Glu

Sites

Metal binding

52

1

Divalent metal cation

Metal binding

54

1

Divalent metal cation

Metal binding

118

1

Divalent metal cation

Amino acid modifications

Glycosylation

250

1

N-linked (GlcNAc...) Potential

Glycosylation

260

1

N-linked (GlcNAc...) Potential

Disulfide bond

39 ↔ 218

Natural variations

Alternative sequence

213 – 315

103

Missing in isoform 2.

VSP_008343

Alternative sequence

290 – 322

33

TLDVS…GIAAI → WGLTVTQAGVKWHDLTHCTF GLSGSGDPPTSAS in isoform 3.

VSP_008344

Alternative sequence

323 – 489

167

Missing in isoform 3.

VSP_008345

Alternative sequence

477 – 489

13

VCIWE…KELTA → GRCINFSRVPSQ in isoform 4.

VSP_008346

Natural variant

45

1

L → P in ISH.

VAR_022687

Natural variant

105

1

G → D in JHF.

VAR_022688

Natural variant

189

1

I → T in ISH.

VAR_022689

Natural variant

218

1

C → R in ISH.

VAR_022690

Natural variant

293

1

V → VQ in JHF.

VAR_022691

Natural variant

329

1

L → R in JHF.

VAR_022692

Natural variant

357

1

P → A: dbSNP rs12647691.

VAR_022693

Natural variant

381

1

Y → C in JHF.

VAR_022694

Secondary structure

1

.

.

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.

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.

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489

Helix Strand Turn

Details...

Beta strand

43 – 50

8

Helix

53 – 58

6

Helix

59 – 72

14

Beta strand

79 – 96

18

Helix

99 – 110

12

Helix

120 – 134

15

Helix

136 – 138

3

Beta strand

139 – 147

9

Helix

155 – 168

14

Beta strand

172 – 177

6

Helix

183 – 189

7

Beta strand

190 – 192

3

Helix

193 – 195

3

Beta strand

196 – 204

9

Helix

205 – 214

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 4. Checksum: B9F679DB75B6E2B7	FASTA	489	53,692
	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
	Isoform 2 [UniParc]. Checksum: 0F9B2D6688EAB17A		386	42,919
	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 NSSNGIAAII VILVLLLLLG IGLMWWFWPL 250 260 270 280 290 300 CCKVVIKDPP PPPPPAPKEE EEEPLPTKKW PTVDASYYGG RGVGGIKRME VRWGDKGSTE 310 320 330 340 350 360 EGARLEKAKN AVVKIPEETE EPIRPRPPRP KPTHQPPQTK WYTPIKGRLD ALWALLRRQY 370 380 DRVSLMRPQE GDEVCIWECI EKELTA
	Isoform 3 [UniParc]. Checksum: 19D061AAFBE6CFF8		322	34,763
	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 APILNKAGEW GLTVTQAGVK 310 320 WHDLTHCTFG LSGSGDPPTS AS
	Isoform 4 [UniParc]. Checksum: 1FF5E0144CE750F6		488	53,519
	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 PQEGDEGRCI NFSRVPSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Bell S.E., Mavila A., Salazar R., Bayless K.J., Kanagala S., Maxwell S.A., Davis G.E. J. Cell Sci. 114:2755-2773(2001) [PubMed: 11683410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
[2]	"Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor." Scobie H.M., Rainey G.J.A., Bradley K.A., Young J.A.T. Proc. Natl. Acad. Sci. U.S.A. 100:5170-5174(2003) [PubMed: 12700348] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH ANTHRAX TOXIN. Tissue: Placenta.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-489 (ISOFORM 3), VARIANT ALA-357. Tissue: Synovial cell.
[4]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Aortic endothelium.
[5]	The German cDNA consortium Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 137-489 (ISOFORM 4), VARIANT ALA-357. Tissue: Lymph node.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 248-489 (ISOFORM 4). Tissue: Brain.
[7]	"Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process." Abrami L., Liu S., Cosson P., Leppla S.H., van der Goot F.G. J. Cell Biol. 160:321-328(2003) [PubMed: 12551953] [Abstract] Cited for: INTERACTION WITH ANTHRAX TOXIN, CLATHRIN-DEPENDENT INTERNALIZATION.
[8]	"Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway." Abrami L., Lindsay M., Parton R.G., Leppla S.H., van der Goot F.G. J. Cell Biol. 166:645-651(2004) [PubMed: 15337774] [Abstract] Cited for: INTERNALIZATION.
[9]	"Crystal structure of a complex between anthrax toxin and its host cell receptor." Santelli E., Bankston L.A., Leppla S.H., Liddington R.C. Nature 430:905-908(2004) [PubMed: 15243628] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-212 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS.
[10]	"Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor." Lacy D.B., Wigelsworth D.J., Scobie H.M., Young J.A.T., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 101:6367-6372(2004) [PubMed: 15079089] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 38-217.
[11]	"Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation." Lacy D.B., Wigelsworth D.J., Melnyk R.A., Harrison S.C., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 101:13147-13151(2004) [PubMed: 15326297] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 38-218 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS.
[12]	"Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis." 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. Am. J. Hum. Genet. 73:791-800(2003) [PubMed: 14508707] [Abstract] Cited for: VARIANTS ISH PRO-45; THR-189 AND ARG-218, VARIANTS JHF GLN-293 INS AND CYS-381, VARIANT