Reviewed, UniProtKB/Swiss-Prot Q9H013 (ADA19_HUMAN)

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
    Metalloprotease and disintegrin dendritic antigen marker
      Short name=MADDAM

Gene names

Name:	ADAM19
Synonyms:	MLTNB
ORF Names:	FKSG34

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	956 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	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. Ref.5
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in many normal organ tissues and several cancer cell lines.
Induction	By 1,25(OH)2VD3 in monocytes.
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
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain SH3-binding Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	integral to 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 zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: Q9H013-1)

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 B (identifier: Q9H013-2)

The sequence of this isoform differs from the canonical sequence as follows:
     903-956: VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQKPRAKHSCFLVPA → FPEYRSQRAGGMISSKI

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Propeptide	26 – 203	178	By similarity		PRO_0000029102
	Chain	204 – 956	753	Disintegrin and metalloproteinase domain-containing protein 19		PRO_0000029103
Regions
	Topological domain	204 – 700	497	Extracellular Potential
	Transmembrane	701 – 721	21	Potential
	Topological domain	722 – 956	235	Cytoplasmic Potential
	Domain	211 – 409	199	Peptidase M12B
	Domain	417 – 503	87	Disintegrin
	Domain	651 – 683	33	EGF-like
	Motif	131 – 138	8	Cysteine switch By similarity
	Motif	834 – 840	7	SH3-binding Potential
	Motif	839 – 845	7	SH3-binding Potential
	Compositional bias	435 – 438	4	Poly-Glu
	Compositional bias	503 – 650	148	Cys-rich
Sites
	Active site	347	1	By similarity
	Metal binding	133	1	Zinc; in inhibited form By similarity
	Metal binding	346	1	Zinc; catalytic By similarity
	Metal binding	350	1	Zinc; catalytic By similarity
	Metal binding	356	1	Zinc; catalytic By similarity
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	646	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	655 ↔ 665		By similarity
	Disulfide bond	659 ↔ 671		By similarity
	Disulfide bond	673 ↔ 682		By similarity
Natural variations
	Alternative sequence	903 – 956	54	VSPRE…FLVPA → FPEYRSQRAGGMISSKI in isoform B.		VSP_005481
	Natural variant	4	1	G → S: dbSNP rs11465228. Ref.2		VAR_057066
	Natural variant	134	1	R → Q in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036146
	Natural variant	299	1	A → T in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036147
Experimental info
	Sequence conflict	32 – 33	2	SK → R Ref.2
	Sequence conflict	32 – 33	2	SK → R Ref.3
	Sequence conflict	558	1	V → D Ref.2
	Sequence conflict	558	1	V → D Ref.3
	Sequence conflict	623	1	N → D Ref.2
	Sequence conflict	623	1	N → D Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified January 31, 2002. Version 2. Checksum: 8373F10FA0418B12	FASTA	956	105,039
	10 20 30 40 50 60 MPGGAGAARL CLLAFALQPL RPRAAREPGW TSKGSEEGSP KLQHELIIPQ WKTSESPVRE 70 80 90 100 110 120 KHPLKAELRV MAEGRELILD LEKNEQLFAP SYTETHYTSS GNPQTTTRKL EDHCFYHGTV 130 140 150 160 170 180 RETELSSVTL STCRGIRGLI TVSSNLSYVI EPLPDSKGQH LIYRSEHLKP PPGNCGFEHS 190 200 210 220 230 240 KPTTRDWALQ FTQQTKKRPR RMKREDLNSM KYVELYLVAD YLEFQKNRRD QDATKHKLIE 250 260 270 280 290 300 IANYVDKFYR SLNIRIALVG LEVWTHGNMC EVSENPYSTL WSFLSWRRKL LAQKYHDNAQ 310 320 330 340 350 360 LITGMSFHGT TIGLAPLMAM CSVYQSGGVN MDHSENAIGV AATMAHEMGH NFGMTHDSAD 370 380 390 400 410 420 CCSASAADGG CIMAAATGHP FPKVFNGCNR RELDRYLQSG GGMCLSNMPD TRMLYGGRRC 430 440 450 460 470 480 GNGYLEDGEE CDCGEEEECN NPCCNASNCT LRPGAECAHG SCCHQCKLLA PGTLCREQAR 490 500 510 520 530 540 QCDLPEFCTG KSPHCPTNFY QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPAPDL 550 560 570 580 590 600 CFEKVNVAGD TFGNCGKVMN GEHRKCNMRD AKCGKIQCQS SEARPLESNA VPIDTTIIMN 610 620 630 640 650 660 GRQIQCRGTH VYRGPEEEGD MLNPGLVMTG TKCGYNHICF EGQCRNTSFF ETEGCGKKCN 670 680 690 700 710 720 GHGVCNNNQN CHCLPGWAPP FCNTPGHGGS IDSGPMPPES VGPVVAGVLV AILVLAVLML 730 740 750 760 770 780 MYYCCRQNNK LGQLKPSALP SKLRQQFSCP FRVSQNSGTG HANPTFKLQT PQGKRKVINT 790 800 810 820 830 840 PEILRKPSQP PPRPPPDYLR GGSPPAPLPA HLSRAARNSP GPGSQIERTE SSRRPPPSRP 850 860 870 880 890 900 IPPAPNCIVS QDFSRPRPPQ KALPANPVPG RRSLPRPGGA SPLRPPGAGP QQSRPLAALA 910 920 930 940 950 PKVSPREALK VKAGTRGLQG GRCRVEKTKQ FMLLVVWTEL PEQKPRAKHS CFLVPA
	Isoform B. Checksum: 4D44FBDC87A573AE	FASTA	919	100,890
	10 20 30 40 50 60 MPGGAGAARL CLLAFALQPL RPRAAREPGW TSKGSEEGSP KLQHELIIPQ WKTSESPVRE 70 80 90 100 110 120 KHPLKAELRV MAEGRELILD LEKNEQLFAP SYTETHYTSS GNPQTTTRKL EDHCFYHGTV 130 140 150 160 170 180 RETELSSVTL STCRGIRGLI TVSSNLSYVI EPLPDSKGQH LIYRSEHLKP PPGNCGFEHS 190 200 210 220 230 240 KPTTRDWALQ FTQQTKKRPR RMKREDLNSM KYVELYLVAD YLEFQKNRRD QDATKHKLIE 250 260 270 280 290 300 IANYVDKFYR SLNIRIALVG LEVWTHGNMC EVSENPYSTL WSFLSWRRKL LAQKYHDNAQ 310 320 330 340 350 360 LITGMSFHGT TIGLAPLMAM CSVYQSGGVN MDHSENAIGV AATMAHEMGH NFGMTHDSAD 370 380 390 400 410 420 CCSASAADGG CIMAAATGHP FPKVFNGCNR RELDRYLQSG GGMCLSNMPD TRMLYGGRRC 430 440 450 460 470 480 GNGYLEDGEE CDCGEEEECN NPCCNASNCT LRPGAECAHG SCCHQCKLLA PGTLCREQAR 490 500 510 520 530 540 QCDLPEFCTG KSPHCPTNFY QMDGTPCEGG QAYCYNGMCL TYQEQCQQLW GPGARPAPDL 550 560 570 580 590 600 CFEKVNVAGD TFGNCGKVMN GEHRKCNMRD AKCGKIQCQS SEARPLESNA VPIDTTIIMN 610 620 630 640 650 660 GRQIQCRGTH VYRGPEEEGD MLNPGLVMTG TKCGYNHICF EGQCRNTSFF ETEGCGKKCN 670 680 690 700 710 720 GHGVCNNNQN CHCLPGWAPP FCNTPGHGGS IDSGPMPPES VGPVVAGVLV AILVLAVLML 730 740 750 760 770 780 MYYCCRQNNK LGQLKPSALP SKLRQQFSCP FRVSQNSGTG HANPTFKLQT PQGKRKVINT 790 800 810 820 830 840 PEILRKPSQP PPRPPPDYLR GGSPPAPLPA HLSRAARNSP GPGSQIERTE SSRRPPPSRP 850 860 870 880 890 900 IPPAPNCIVS QDFSRPRPPQ KALPANPVPG RRSLPRPGGA SPLRPPGAGP QQSRPLAALA 910 PKFPEYRSQR AGGMISSKI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of FKSG34, a novel human gene encoding for metalloprotease-disintegrin meltrin beta." Wang Y.-G., Gong L. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"Molecular cloning and characterization of a human metalloprotease disintegrin a novel marker for dendritic cell differentiation." Fritsche J., Moser M., Faust S., Peuker A., Buettner R., Andreesen R., Kreutz M. Blood 96:732-739(2000) [PubMed: 10887142] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT SER-4. Tissue: Lymph node.
[3]	"Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta." Wei P., Zhao Y.-G., Zhuang L., Ruben S., Sang Q.-X.A. Biochem. Biophys. Res. Commun. 280:744-755(2001) [PubMed: 11162584] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). Tissue: Dendritic cell.
[4]	"Partial sequence of Homo sapiens ADAM19." Xu R., Cai J., Ying B., Wang F., Xu T., Zhao S., Li C. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 100-956 (ISOFORM A).
[5]	"The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells." Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., Courtneidge S.A. J. Biol. Chem. 278:16844-16851(2003) [PubMed: 12615925] [Abstract] Cited for: INTERACTION WITH SH3PXD2A.
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-134 AND THR-299.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF326918 mRNA. Translation: AAG50282.1. Y13786 mRNA. Translation: CAC20585.1. AF311317 mRNA. Translation: AAK07852.1. AF134707 mRNA. Translation: AAF22162.1.
IPI	IPI00011901. IPI00249735.
RefSeq	NP_150377.1.
UniGene	Hs.483944
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H013.
Protein family/group databases
MEROPS	M12.214.
Proteomic databases
PRIDE	Q9H013.
Genome annotation databases
Ensembl	ENST00000432888; ENSP00000410266; ENSG00000135074; Homo sapiens. [Genome view]
GeneID	8728.
KEGG	hsa:8728.
UCSC	uc003lwz.1. human.
Organism-specific databases
CTD	8728.
GeneCards	GC05M156836.
HGNC	HGNC:197. ADAM19.
MIM	603640. gene.
PharmGKB	PA24514.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9H013.
InParanoid	Q9H013.
Gene expression databases
ArrayExpress	Q9H013.
Bgee	Q9H013.
CleanEx	HS_ADAM19.
Genevestigator	Q9H013.
GermOnline	ENSG00000135074. Homo sapiens.
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. 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.
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	32743.
SOURCE	Search...

Entry information

Entry name

ADA19_HUMAN

Accession

Primary (citable) accession number: Q9H013
Secondary accession number(s): Q9BZL5, Q9UHP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	January 31, 2002
Last modified:	December 15, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.