O35598 (ADA10_MOUSE) 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
CD_antigen=CD156c

Gene names

Name:	Adam10
Synonyms:	Kuz, Madm

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	749 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 proteolytical release of soluble JAM3 from endothelial cells surface By similarity. 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) at '687-Lys-|-Leu-688'. 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.
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 By similarity. Interacts with EPHA2. Ref.5
Subcellular location	Membrane; Single-pass type I membrane protein.
Developmental stage	Widely expressed in the nervous system at 18 dpc, with high expression in the posterior midbrain, which diminished toward the anterior midbrain.
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	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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch receptor processing Non-traceable author statement. Source: UniProtKB Notch signaling pathway Inferred from mutant phenotype. Source: UniProtKB in utero embryonic development Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB nucleocytoplasmic transport Non-traceable author statement. Source: UniProtKB protein phosphorylation Inferred from direct assay. Source: UniProtKB
Cellular component	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 direct assay. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome postsynaptic density Inferred from direct assay. Source: MGI
Molecular function	SH2 domain binding Non-traceable author statement. Source: UniProtKB SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Traceable author statement. Source: Reactome protein homodimerization activity Inferred from physical interaction. Source: UniProtKB protein kinase binding Inferred from direct assay. 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 – 214	195	By similarity		PRO_0000029068
	Chain	215 – 749	535	Disintegrin and metalloproteinase domain-containing protein 10		PRO_0000029069
Regions
	Topological domain	20 – 673	654	Extracellular Potential
	Transmembrane	674 – 694	21	Helical; Potential
	Topological domain	695 – 749	55	Cytoplasmic Potential
	Domain	221 – 457	237	Peptidase M12B
	Domain	458 – 552	95	Disintegrin
	Motif	171 – 178	8	Cysteine switch By similarity
	Motif	709 – 716	8	SH3-binding Potential
	Motif	723 – 729	7	SH3-binding Potential
	Compositional bias	553 – 673	121	Cys-rich
Sites
	Active site	385	1	By similarity
	Metal binding	173	1	Zinc; in inhibited form By similarity
	Metal binding	384	1	Zinc; catalytic
	Metal binding	388	1	Zinc; catalytic
	Metal binding	394	1	Zinc; catalytic
Amino acid modifications
	Glycosylation	268	1	N-linked (GlcNAc...) Potential
	Glycosylation	279	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	440	1	N-linked (GlcNAc...) Potential
	Glycosylation	552	1	N-linked (GlcNAc...) Potential
	Disulfide bond	223 ↔ 314		By similarity
	Disulfide bond	345 ↔ 452		By similarity
	Disulfide bond	400 ↔ 436		By similarity
	Disulfide bond	504 ↔ 512		By similarity
	Disulfide bond	525 ↔ 544		By similarity
	Disulfide bond	531 ↔ 563		By similarity
	Disulfide bond	556 ↔ 568		By similarity
	Disulfide bond	573 ↔ 599		By similarity
	Disulfide bond	581 ↔ 608		By similarity
	Disulfide bond	583 ↔ 598		By similarity
Experimental info
	Sequence conflict	591	1	D → N in AAC53303. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O35598 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 6AA2230B2251ABDA	FASTA	749	83,968
	10 20 30 40 50 60 MVLPTVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL 70 80 90 100 110 120 LLDFHAHGRQ FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI 130 140 150 160 170 180 DGRFEGFIKT RGGTFYIEPA ERYIKDRILP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE 190 200 210 220 230 240 RMRKYQMTGV EEGARAHPEK HAASSGPELL RKKRTTLAER NTCQLYIQTD HLFFKYYGTR 250 260 270 280 290 300 EAVIAQISSH VKAIDTIYQT TDFSGIRNIS FMVKRIRINT TSDEKDPTNP FRFPNIGVEK 310 320 330 340 350 360 FLELNSEQNH DDYCLAYVFT DRDFDDGVLG LAWVGAPSGS SGGICEKSKL YSDGKKKSLN 370 380 390 400 410 420 TGIITVQNYG SHVPPKVSHI TFAHEVGHNF GSPHDSGTEC TPGESKNLGQ KENGNYIMYA 430 440 450 460 470 480 RATSGDKLNN NKFSLCSIRN ISQVLEKKRN NCFVESGQPI CGNGMVEQGE ECDCGYSDQC 490 500 510 520 530 540 KDDCCFDANQ PEGKKCKLKP GKQCSPSQGP CCTAQCAFKS KSEKCRDDSD CAKEGICNGF 550 560 570 580 590 600 TALCPASDPK PNFTDCNRHT QVCINGQCAG SICEKYDLEE CTCASSDGKD DKELCHVCCM 610 620 630 640 650 660 KKMAPSTCAS TGSLQWSKQF SGRTITLQPG SPCNDFRGYC DVFMRCRLVD ADGPLARLKK 670 680 690 700 710 720 AIFSPQLYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC SVHTPSSNPK LPPPKPLPGT 730 740 LKRRRPPQPI QQPPRQRPRE SYQMGHMRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis." Pan D., Rubin G.M. Cell 90:271-280(1997) [PubMed: 9244301] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 252-749. Strain: C57BL/6J. Tissue: Bone and Vagina.
[5]	"Regulated cleavage of a contact-mediated axon repellent." Hattori M., Osterfield M., Flanagan J.G. Science 289:1360-1365(2000) [PubMed: 10958785] [Abstract] Cited for: INTERACTION WITH EPHA2.
[6]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-279, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF011379 mRNA. Translation: AAC53303.1. CT025701, AC091263, AC160636 Genomic DNA. Translation: CAX15709.1. CH466522 Genomic DNA. Translation: EDL26211.1. AK036883 mRNA. Translation: BAC29620.1. AK036599 mRNA. Translation: BAC29502.1.
IPI	IPI00131881.
RefSeq	NP_031425.2. NM_007399.3.
UniGene	Mm.3037.
3D structure databases
ProteinModelPortal	O35598.
SMR	O35598. Positions 212-652.
ModBase	Search...
Protein-protein interaction databases
STRING	O35598.
Protein family/group databases
MEROPS	M12.210.
PTM databases
PhosphoSite	O35598.
Proteomic databases
PRIDE	O35598.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000067880; ENSMUSP00000063839; ENSMUSG00000054693.
GeneID	11487.
KEGG	mmu:11487.
Organism-specific databases
CTD	102.
MGI	MGI:109548. Adam10.
Phylogenomic databases
eggNOG	roNOG06502.
HOGENOM	HBG445763.
HOVERGEN	HBG050455.
InParanoid	O35598.
OrthoDB	EOG457562.
Enzyme and pathway databases
Reactome	REACT_115202. Signal Transduction.
Gene expression databases
ArrayExpress	O35598.
Bgee	O35598.
CleanEx	MM_ADAM10.
Genevestigator	O35598.
GermOnline	ENSMUSG00000054693. Mus musculus.
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...
Other
SOURCE	Search...

Entry information

Entry name

ADA10_MOUSE

Accession

Primary (citable) accession number: O35598
Secondary accession number(s): B8JJJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	July 27, 2011
Last modified:	November 16, 2011
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program