Reviewed, UniProtKB/Swiss-Prot O35674 (ADA19_MOUSE)

Names and origin

Protein names

Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 19
      Short name=ADAM 19
    EC=3.4.24.-
Alternative name(s):
    Meltrin-beta

Gene names

Name:	Adam19
Synonyms:	Mltnb

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

Protein attributes

Sequence length	920 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell. Also cleaves alpha-2 macroglobulin. May be involved in osteoblast differentiation and/or osteoblast activity in bone By similarity.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with SH3PXD2A By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed, with the highest expression in bone, heart and lung, followed by brain and spleen and relatively low expression in liver, skeletal muscle, kidney and testis. In bone, primarily expressed in cell of the osteoblast lineage and not detected in mature osteoclasts.
Developmental stage	Expressed in the heart and in the tail bud at 8.0 dpc, and then in the cranial and dorsal root ganglia. Also expressed weakly and transiently in the intestine, lung and in bone marrow. Ref.2
Induction	By calcitriol and during osteoblast differentiation.
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 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	EGF-like domain SH3-binding Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	heart development Inferred from mutant phenotype. Source: MGI membrane protein ectodomain proteolysis Inferred from mutant phenotype. Source: MGI
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Propeptide	27 – 204	178	By similarity		PRO_0000029104
	Chain	205 – 920	716	Disintegrin and metalloproteinase domain-containing protein 19		PRO_0000029105
Regions
	Topological domain	27 – 703	677	Extracellular Potential
	Transmembrane	704 – 724	21	Potential
	Topological domain	725 – 920	196	Cytoplasmic Potential
	Domain	211 – 409	199	Peptidase M12B
	Domain	417 – 503	87	Disintegrin
	Domain	654 – 686	33	EGF-like
	Motif	131 – 138	8	Cysteine switch By similarity
	Motif	835 – 841	7	SH3-binding Potential
	Motif	840 – 846	7	SH3-binding Potential
	Compositional bias	435 – 438	4	Poly-Glu
	Compositional bias	504 – 653	150	Cys-rich
	Compositional bias	616 – 621	6	Poly-Glu
Sites
	Active site	347	1
	Metal binding	133	1	Zinc; in inhibited form By similarity
	Metal binding	346	1	Zinc; catalytic
	Metal binding	350	1	Zinc; catalytic
	Metal binding	356	1	Zinc; catalytic
Amino acid modifications
	Glycosylation	145	1	N-linked (GlcNAc...) Potential
	Glycosylation	445	1	N-linked (GlcNAc...) Potential
	Glycosylation	448	1	N-linked (GlcNAc...) Potential
	Glycosylation	649	1	N-linked (GlcNAc...) Potential
	Disulfide bond	321 ↔ 404		By similarity
	Disulfide bond	361 ↔ 388		By similarity
	Disulfide bond	362 ↔ 371		By similarity
	Disulfide bond	475 ↔ 495		By similarity
	Disulfide bond	658 ↔ 668		By similarity
	Disulfide bond	662 ↔ 674		By similarity
	Disulfide bond	676 ↔ 685		By similarity

Sequences

	Sequence		Length	Mass (Da)
	O35674-1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 7094FDD4EE547382	FASTA	920	100,860
	10 20 30 40 50 60 MPGRAGVARF CLLALALQLH WPLAACEPGW TTRGSQEGSP PLQHELIIPQ WRTSESPGRG 70 80 90 100 110 120 KHPLRAELRV MAEGRELILD LEKNEHLFAP AYTETCYTAS GNPQTSTLKS EDHCFYHGTV 130 140 150 160 170 180 RDVDESSVTL STCRGIRGLI IVRSNLSYII EPVPNSDSQH RIYRSEHLTL PPGNCGFEHS 190 200 210 220 230 240 GPTSKDWALQ FTHQTKKQPR RMKREDLHSM KYVELYLVAD YAEFQKNRHD QDATKRKLME 250 260 270 280 290 300 IANYVDKFYR SLNIRIALVG LEVWTHGDKC EVSENPYSTL WSFLSWRRKL LAQKSHDNAQ 310 320 330 340 350 360 LITGRSFQGT TIGLAPLMAM CSVYQSGGVS MDHSENAIGV ASTVAHEIGH NFGMSHDSAH 370 380 390 400 410 420 CCSASAADGG CIMAAATGHP FPKVFSWCNR KELDRYLQTG GGMCLSNMPD TRTLYGGRRC 430 440 450 460 470 480 GNGYLEDGEE CDCGEEEECK NPCCNASNCT LKEGAECAHG SCCHQCKLVA PGTQCREQVR 490 500 510 520 530 540 QCDLPEFCTG KSPHCPTNYY QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPALDL 550 560 570 580 590 600 CFERVNAAGD TYGNCGKGLN GQYRKCSPRD AKCGKIQCQS TQARPLESNA VSIDTTITLN 610 620 630 640 650 660 GRRIHCRGTH VYRGPEEEEG EGDMLDPGLV MTGTKCGHNH ICFEGQCRNT SFFETEGCGK 670 680 690 700 710 720 KCNGHGVCNN NKNCHCFPGW SPPFCNTPGD GGSVDSGPLP PKSVGPVIAG VFSALFVLAV 730 740 750 760 770 780 LVLLCHCYRQ SHKLGKPSAL PFKLRHQFSC PFRVSQSGGT GHANPTFKLQ TPQGKRKVTN 790 800 810 820 830 840 TPESLRKPSH PPPRPPPDYL RVESPPAPLP AHLNRAAGSS PEAGARIERK ESARRPPPSR 850 860 870 880 890 900 PMPPAPNCLL SQDFSRPRPP QKALPANPVP GQRTGPRSGG TSLLQPPTSG PQPPRPPAVP 910 920 VPKLPEYRSQ RVGAIISSKI

References

[1]	"Cloning and initial characterization of mouse meltrin beta and analysis of the expression of four metalloprotease-disintegrins in bone cells." Inoue D., Reid M.S., Lum L., Kraetzschmar J., Weskamp G., Myung Y.M., Baron R., Blobel C.P. J. Biol. Chem. 273:4180-4187(1998) [PubMed: 9461614] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Myoblast.
[2]	"Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo." Kurisaki T., Masuda A., Osumi N., Nabeshima Y., Fujisawa-Sehara A. Mech. Dev. 73:211-215(1998) [PubMed: 9622634] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE. Tissue: Myoblast.
[3]	"A metalloprotease-disintegrin participating in myoblast fusion." Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y., Fujisawa-Sehara A. Nature 377:652-656(1995) [PubMed: 7566181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 429-578. Tissue: Embryonic fibroblast.
[4]	"Roles of Meltrin beta /ADAM19 in the processing of neuregulin." Shirakabe K., Wakatsuki S., Kurisaki T., Fujisawa-Sehara A. J. Biol. Chem. 276:9352-9358(2001) [PubMed: 11116142] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF019887 mRNA. Translation: AAC40037.1. D50410 mRNA. Translation: BAA18923.2.
IPI	IPI00132872.
PIR	PC7067.
RefSeq	NP_033746.1. XP_001475069.1.
UniGene	Mm.89940
3D structure databases
HSSP	HSSP built from PDB template 1FVL based on UniProtKB P18619.
ModBase	Search...
Protein family/group databases
MEROPS	M12.214.
Genome annotation databases
Ensembl	ENSMUSG00000011256. Mus musculus. [Contig view]
GeneID	100045780. 11492.
KEGG	mmu:100045780. mmu:11492.
Organism-specific databases
MGI	MGI:105377. Adam19.
Phylogenomic databases
HOVERGEN	O35674.
OMA	O35674. IYRSEHL.
Gene expression databases
ArrayExpress	O35674.
Bgee	O35674.
GermOnline	ENSMUSG00000011256. Mus musculus.
Family and domain databases
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR013111. EGF_extracell. IPR001818. Pept_M10A_M12B. IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Gene3D	G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
Pfam	PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF07974. EGF_2. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view]
PRINTS	PR00289. DISINTEGRIN.
ProDom	PD000664. Disintegrin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	459238.
SOURCE	Search...

Entry information

Entry name

ADA19_MOUSE

Accession

Primary (citable) accession number: O35674

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)