Reviewed, UniProtKB/Swiss-Prot Q9BZ11 (ADA33_HUMAN)

Names and origin

Protein names

Recommended name:
    ADAM 33
    EC=3.4.24.-
Alternative name(s):
    A disintegrin and metalloproteinase domain 33

Gene names

Name:	ADAM33
ORF Names:	UNQ873/PRO1891

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	813 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)

Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in all tissues, except liver, with high expression in placenta, lung, spleen and veins.
Domain	The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity.
Involvement in disease	Defects in ADAM33 may be a cause of susceptibility to asthma.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	proteolysis Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB
Molecular function	metalloendopeptidase activity Ref.1 Non-traceable author statement. Source: UniProtKB zinc ion binding Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BZ11-1)

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.

Isoform 2 (identifier: Q9BZ11-2)

The sequence of this isoform differs from the canonical sequence as follows:
     636-661: Missing.

Notes: Described in Ref.1.

Isoform 3 (identifier: Q9BZ11-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-478: Missing.
     636-661: Missing.

Notes: No experimental confirmation available. By similarity with mouse isoform.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 29

29

Potential

Propeptide

30 – 203

174

By similarity

Chain

204 – 813

610

ADAM 33

Regions

Topological domain

30 – 701

672

Extracellular Potential

Transmembrane

702 – 722

21

Potential

Topological domain

723 – 813

91

Cytoplasmic Potential

Domain

210 – 409

200

Peptidase M12B

Domain

417 – 503

87

Disintegrin

Domain

649 – 681

33

EGF-like

Motif

131 – 138

8

Cysteine switch By similarity

Compositional bias

503 – 648

146

Cys-rich

Sites

Active site

346

1

By similarity

Metal binding

133

1

Zinc (in inhibited form) By similarity

Metal binding

345

1

Zinc (catalytic)

Metal binding

349

1

Zinc (catalytic)

Metal binding

355

1

Zinc (catalytic)

Amino acid modifications

Modified residue

269

1

Phosphoserine

Glycosylation

109

1

N-linked (GlcNAc...) Potential

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Glycosylation

231

1

N-linked (GlcNAc...)

Glycosylation

276

1

N-linked (GlcNAc...)

Glycosylation

448

1

N-linked (GlcNAc...) Potential

Disulfide bond

320 ↔ 404

Disulfide bond

360 ↔ 388

Disulfide bond

361 ↔ 371

Disulfide bond

475 ↔ 495

By similarity

Disulfide bond

653 ↔ 663

By similarity

Disulfide bond

657 ↔ 669

By similarity

Disulfide bond

671 ↔ 680

By similarity

Natural variations

Alternative sequence

1 – 478

478

Missing in isoform 3.

Alternative sequence

636 – 661

26

Missing in isoform 2 and isoform 3.

Natural variant

109

1

N → S: dbSNP rs41467948.

Natural variant

178

1

T → A: dbSNP rs3918392.

Natural variant

272

1

T → M

Natural variant

316

1

V → I

Natural variant

336

1

P → S: dbSNP rs41483049.

Natural variant

365

1

A → S

Natural variant

441

1

D → E

Natural variant

515

1

W → R

Natural variant

612

1

L → H

Natural variant

710

1

V → I

Natural variant

739

1

C → G

Natural variant

742

1

D → Y

Natural variant

764

1

M → T: dbSNP rs2280091.

Natural variant

774

1

P → S: dbSNP rs2280090.

Experimental info

Sequence conflict

802

1

Missing in AAM80482 and AAM80483. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

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.

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.

.

.

.

.

.

.

.

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813

Helix Strand Turn

Details...

Beta strand

210 – 218

9

Helix

220 – 225

6

Turn

226 – 228

3

Helix

230 – 249

20

Turn

250 – 252

3

Beta strand

253 – 262

10

Beta strand

264 – 266

3

Helix

275 – 292

18

Beta strand

296 – 304

9

Turn

322 – 324

3

Beta strand

326 – 330

5

Beta strand

333 – 335

3

Helix

336 – 350

15

Helix

366 – 368

3

Helix

387 – 398

12

Turn

399 – 402

4

Helix

403 – 405

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 27, 2002. Version 2. Checksum: 90713A99668D5569	FASTA	813	87,739
	10 20 30 40 50 60 MGWRPRRARG TPLLLLLLLL LLWPVPGAGV LQGHIPGQPV TPHWVLDGQP WRTVSLEEPV 70 80 90 100 110 120 SKPDMGLVAL EAEGQELLLE LEKNHRLLAP GYIETHYGPD GQPVVLAPNH TDHCHYQGRV 130 140 150 160 170 180 RGFPDSWVVL CTCSGMSGLI TLSRNASYYL RPWPPRGSKD FSTHEIFRME QLLTWKGTCG 190 200 210 220 230 240 HRDPGNKAGM TSLPGGPQSR GRREARRTRK YLELYIVADH TLFLTRHRNL NHTKQRLLEV 250 260 270 280 290 300 ANYVDQLLRT LDIQVALTGL EVWTERDRSR VTQDANATLW AFLQWRRGLW AQRPHDSAQL 310 320 330 340 350 360 LTGRAFQGAT VGLAPVEGMC RAESSGGVST DHSELPIGAA ATMAHEIGHS LGLSHDPDGC 370 380 390 400 410 420 CVEAAAESGG CVMAAATGHP FPRVFSACSR RQLRAFFRKG GGACLSNAPD PGLPVPPALC 430 440 450 460 470 480 GNGFVEAGEE CDCGPGQECR DLCCFAHNCS LRPGAQCAHG DCCVRCLLKP AGALCRQAMG 490 500 510 520 530 540 DCDLPEFCTG TSSHCPPDVY LLDGSPCARG SGYCWDGACP TLEQQCQQLW GPGSHPAPEA 550 560 570 580 590 600 CFQVVNSAGD AHGNCGQDSE GHFLPCAGRD ALCGKLQCQG GKPSLLAPHM VPVDSTVHLD 610 620 630 640 650 660 GQEVTCRGAL ALPSAQLDLL GLGLVEPGTQ CGPRMVCQSR RCRKNAFQEL QRCLTACHSH 670 680 690 700 710 720 GVCNSNHNCH CAPGWAPPFC DKPGFGGSMD SGPVQAENHD TFLLAMLLSV LLPLLPGAGL 730 740 750 760 770 780 AWCCYRLPGA HLQRCSWGCR RDPACSGPKD GPHRDHPLGG VHPMELGPTA TGQPWPLDPE 790 800 810 NSHEPSSHPE KPLPAVSPDP QADQVQMPRS CLW
	Isoform 2 [UniParc]. Checksum: CBAF1B08B263A890		787	84,724
	10 20 30 40 50 60 MGWRPRRARG TPLLLLLLLL LLWPVPGAGV LQGHIPGQPV TPHWVLDGQP WRTVSLEEPV 70 80 90 100 110 120 SKPDMGLVAL EAEGQELLLE LEKNHRLLAP GYIETHYGPD GQPVVLAPNH TDHCHYQGRV 130 140 150 160 170 180 RGFPDSWVVL CTCSGMSGLI TLSRNASYYL RPWPPRGSKD FSTHEIFRME QLLTWKGTCG 190 200 210 220 230 240 HRDPGNKAGM TSLPGGPQSR GRREARRTRK YLELYIVADH TLFLTRHRNL NHTKQRLLEV 250 260 270 280 290 300 ANYVDQLLRT LDIQVALTGL EVWTERDRSR VTQDANATLW AFLQWRRGLW AQRPHDSAQL 310 320 330 340 350 360 LTGRAFQGAT VGLAPVEGMC RAESSGGVST DHSELPIGAA ATMAHEIGHS LGLSHDPDGC 370 380 390 400 410 420 CVEAAAESGG CVMAAATGHP FPRVFSACSR RQLRAFFRKG GGACLSNAPD PGLPVPPALC 430 440 450 460 470 480 GNGFVEAGEE CDCGPGQECR DLCCFAHNCS LRPGAQCAHG DCCVRCLLKP AGALCRQAMG 490 500 510 520 530 540 DCDLPEFCTG TSSHCPPDVY LLDGSPCARG SGYCWDGACP TLEQQCQQLW GPGSHPAPEA 550 560 570 580 590 600 CFQVVNSAGD AHGNCGQDSE GHFLPCAGRD ALCGKLQCQG GKPSLLAPHM VPVDSTVHLD 610 620 630 640 650 660 GQEVTCRGAL ALPSAQLDLL GLGLVEPGTQ CGPRMVCNSN HNCHCAPGWA PPFCDKPGFG 670 680 690 700 710 720 GSMDSGPVQA ENHDTFLLAM LLSVLLPLLP GAGLAWCCYR LPGAHLQRCS WGCRRDPACS 730 740 750 760 770 780 GPKDGPHRDH PLGGVHPMEL GPTATGQPWP LDPENSHEPS SHPEKPLPAV SPDPQADQVQ MPRSCLW
	Isoform 3 [UniParc]. Checksum: A60AC04E056CF264		309	32,554
	10 20 30 40 50 60 MGDCDLPEFC TGTSSHCPPD VYLLDGSPCA RGSGYCWDGA CPTLEQQCQQ LWGPGSHPAP 70 80 90 100 110 120 EACFQVVNSA GDAHGNCGQD SEGHFLPCAG RDALCGKLQC QGGKPSLLAP HMVPVDSTVH 130 140 150 160 170 180 LDGQEVTCRG ALALPSAQLD LLGLGLVEPG TQCGPRMVCN SNHNCHCAPG WAPPFCDKPG 190 200 210 220 230 240 FGGSMDSGPV QAENHDTFLL AMLLSVLLPL LPGAGLAWCC YRLPGAHLQR CSWGCRRDPA 250 260 270 280 290 300 CSGPKDGPHR DHPLGGVHPM ELGPTATGQP WPLDPENSHE PSSHPEKPLP AVSPDPQADQ VQMPRSCLW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity." Yoshinaka T., Nishii K., Yamada K., Sawada H., Nishiwaki E., Smith K., Yoshino K., Ishiguro H., Higashiyama S. Gene 282:227-236(2002) [PubMed: 11814695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Testis.
[2]	"Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness." Van Eerdewegh P., Little R.D., Dupuis J., Del Mastro R.G., Falls K., Simon J., Torrey D., Pandit S., McKenny J., Braunschweiger K., Walsh A., Liu Z., Hayward B., Folz C., Manning S.P., Bawa A., Saracino L., Thackston M. , Benchekroun Y., Capparell N., Wang M., Adair R., Feng Y., Dubois J., FitzGerald M.G., Huang H., Gibson R., Allen K.M., Pedan A., Danzig M.R., Umland S.P., Egan R.W., Cuss F.M., Rorke S., Clough J.B., Holloway J.W., Holgate S.T., Keith T.P. Nature 418:426-430(2002) [PubMed: 12110844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN ASTHMA. Tissue: Uterus.
[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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Stanaway I.B., Nguyen C.P., Gildersleeve H., Johnson E.J., Swanson J.E., McFarland I., Park C., Nickerson D.A. Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-109; ALA-178; MET-272; ILE-316; SER-336; SER-365; GLU-441; ARG-515; HIS-612; ILE-710; GLY-739; TYR-742; THR-764 AND SER-774.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,