Q10741 (ADA10_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disintegrin and metalloproteinase domain-containing protein 10
Short name=ADAM 10
EC=3.4.24.81

Alternative name(s):
Kuzbanian protein homolog
Mammalian disintegrin-metalloprotease
Myelin-associated metalloproteinase
CD_antigen=CD156c

Gene names

Name:	ADAM10
Synonyms:	MADM

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	748 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	Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Controls also the proteolytic processing of Notch. May regulate the EFNA5-EPHA3 signaling By similarity. Ref.2
Catalytic activity	Endopeptidase of broad specificity.
Cofactor	Binds 1 zinc ion By similarity.
Subunit structure	Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with EPHA2 By similarity.
Subcellular location	Golgi apparatus membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Note: The protealytically actived form is localized mainly in the plasma membrane whereas the proenzyme is found intracellularly in the Golgi.
Tissue specificity	Expressed at low level in kidney, spleen, lung, adrenal, heart and peripheral nerve.
Induction	By interleukin-1 alpha in nasal cartilage.
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.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Cell membrane Golgi apparatus Membrane
Domain	SH3-binding Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Notch signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB in utero embryonic development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell Golgi-associated vesicle Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Propeptide

20 – 213

194

By similarity

PRO_0000029064

Chain

214 – 748

535

Disintegrin and metalloproteinase domain-containing protein 10

PRO_0000029065

Regions

Topological domain

20 – 672

653

Extracellular Potential

Transmembrane

673 – 696

24

Helical; Potential

Topological domain

697 – 748

52

Cytoplasmic Potential

Domain

220 – 456

237

Peptidase M12B

Domain

457 – 551

95

Disintegrin

Motif

171 – 178

8

Cysteine switch By similarity

Motif

708 – 715

8

SH3-binding Potential

Motif

722 – 728

7

SH3-binding Potential

Compositional bias

555 – 595

41

Cys-rich

Sites

Active site

384

1

Metal binding

173

1

Zinc; in inhibited form By similarity

Metal binding

383

1

Zinc; catalytic By similarity

Metal binding

387

1

Zinc; catalytic By similarity

Metal binding

393

1

Zinc; catalytic By similarity

Amino acid modifications

Glycosylation

267

1

N-linked (GlcNAc...) Potential

Glycosylation

278

1

N-linked (GlcNAc...) Potential

Glycosylation

439

1

N-linked (GlcNAc...) Potential

Glycosylation

551

1

N-linked (GlcNAc...) Potential

Disulfide bond

222 ↔ 313

By similarity

Disulfide bond

344 ↔ 451

By similarity

Disulfide bond

399 ↔ 435

By similarity

Disulfide bond

503 ↔ 511

Disulfide bond

524 ↔ 543

By similarity

Disulfide bond

530 ↔ 562

Disulfide bond

555 ↔ 567

Disulfide bond

572 ↔ 598

Disulfide bond

580 ↔ 607

Disulfide bond

582 ↔ 597

Experimental info

Mutagenesis

384

1

E → A: Decreased stimulated and constitutive secretion of APP. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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748

Helix Strand Turn

Details...

Helix

505 – 507

3

Beta strand

523 – 525

3

Beta strand

529 – 531

3

Turn

556 – 559

4

Beta strand

560 – 569

10

Helix

571 – 575

5

Beta strand

578 – 580

3

Helix

592 – 594

3

Beta strand

597 – 599

3

Helix

604 – 606

3

Helix

616 – 619

4

Turn

633 – 636

4

Beta strand

637 – 639

3

Sequences

	Sequence		Length	Mass (Da)
	Q10741 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 202E29830611F9E1	FASTA	748	84,188
	10 20 30 40 50 60 MVLLRVLILL LSWVAGLGGQ YGNPLNKYIR HYEGLSYDVD SLHQKHQRAK RAVSHEDQFL 70 80 90 100 110 120 RLDFHAHGRH FNLRMKRDTS LFSEEFRVET SNAVLDYDTS HIYTGHIYGE EGSFSHGSVI 130 140 150 160 170 180 DGRFEGFIQT HGGTFYVEPA ERYIKDRTLP FHSVIYHEDD IKYPHKYGPQ GGCADHSVFE 190 200 210 220 230 240 RMRKYQMTGV EEVTQTPQEK HAINGPELLR KKRTTVAEKN TCQLYIQTDH LFFKYYGTRE 250 260 270 280 290 300 AVIAQISSHV KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF 310 320 330 340 350 360 LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY SDGKKKSLNT 370 380 390 400 410 420 GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT PGESKNLGQK ENGNYIMYAR 430 440 450 460 470 480 ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN CFVESGQPIC GNGMVEQGEE CDCGYSDQCK 490 500 510 520 530 540 DECCYDANQP EGKKCKLKPG KQCSPSQGPC CTAHCAFKSK TEKCRDDSDC AKEGICNGIT 550 560 570 580 590 600 ALCPASDPKP NFTDCNRHTQ VCINGQCAGS ICEKHGLEEC TCASSDGKDD KELCHVCCMK 610 620 630 640 650 660 KMEPSTCAST GSVQWNKYFL GRTITLQPGS PCNDFRGYCD VFMRCRLVDA DGPLARLKKA 670 680 690 700 710 720 IFSPELYENI AEWIVAYWWA VLLMGIALIM LMAGFIKICS VHTPSSNPKL PPPKPLPGTL 730 740 KRRRPPQPIQ QPQRQRPRES YQMGHMRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types." Howard L., Mitchell S., Lu X., Griffiths S., Glynn P. Biochem. J. 317:45-50(1996) [PubMed: 8694785] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease." Lammich S., Kojro E., Postina R., Gilbert S., Pfeiffer R., Jasionowski M., Haass C., Fahrenholz F. Proc. Natl. Acad. Sci. U.S.A. 96:3922-3927(1999) [PubMed: 10097139] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-233, FUNCTION, MUTAGENESIS OF GLU-384.
[3]	NIH - Mammalian Gene Collection (MGC) project Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Basal ganglia.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z21961 mRNA. Translation: CAA79973.1.
BC153863 mRNA. Translation: AAI53864.1.

IPI

IPI00705810.

PIR

S66129.

RefSeq

NP_776921.1. NM_174496.2.

UniGene

Bt.49218.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AO7	X-ray	2.90	A	455-646	[»]

ProteinModelPortal

Q10741.

SMR

Q10741. Positions 483-646.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48422N.

STRING

Q10741.

Protein family/group databases

MEROPS

M12.210.

Proteomic databases

PRIDE

Q10741.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSBTAT00000044627; ENSBTAP00000042110; ENSBTAG00000005481.

GeneID

282132.

KEGG

bta:282132.

Organism-specific databases

CTD

102.

Phylogenomic databases

eggNOG

maNOG08909.

GeneTree

ENSGT00530000063304.

HOVERGEN

HBG050455.

InParanoid

Q10741.

Family and domain databases

InterPro

IPR001762. Blood-coag_inhib_Disintegrin.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]

Gene3D

G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.

KO

K06704.

Pfam

PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]

SMART

SM00050. DISIN. 1 hit.
[Graphical view]

SUPFAM

SSF57552. Disintegrin. 1 hit.

PROSITE

PS50215. ADAM_MEPRO. 1 hit.
PS00546. CYSTEINE_SWITCH. False negative.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

ADA10_BOVIN

Accession

Primary (citable) accession number: Q10741
Secondary accession number(s): A8E663

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	November 1, 1996
Last modified:	November 16, 2011
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program