Q9H013 (ADA19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	955 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.6
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 Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heart development Inferred from electronic annotation. Source: Compara membrane protein ectodomain proteolysis Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
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:
     902-955: 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 – 202	177	By similarity		PRO_0000029102
	Chain	203 – 955	753	Disintegrin and metalloproteinase domain-containing protein 19		PRO_0000029103
Regions
	Topological domain	203 – 699	497	Extracellular Potential
	Transmembrane	700 – 720	21	Helical; Potential
	Topological domain	721 – 955	235	Cytoplasmic Potential
	Domain	210 – 408	199	Peptidase M12B
	Domain	416 – 502	87	Disintegrin
	Domain	650 – 682	33	EGF-like
	Motif	130 – 137	8	Cysteine switch By similarity
	Motif	833 – 844	12	SH3-binding Potential
	Compositional bias	434 – 437	4	Poly-Glu
	Compositional bias	502 – 649	148	Cys-rich
Sites
	Active site	346	1	By similarity
	Metal binding	132	1	Zinc; in inhibited form By similarity
	Metal binding	345	1	Zinc; catalytic By similarity
	Metal binding	349	1	Zinc; catalytic By similarity
	Metal binding	355	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
	Glycosylation	447	1	N-linked (GlcNAc...) Potential
	Glycosylation	645	1	N-linked (GlcNAc...) Potential
	Disulfide bond	320 ↔ 403		By similarity
	Disulfide bond	360 ↔ 387		By similarity
	Disulfide bond	361 ↔ 370		By similarity
	Disulfide bond	474 ↔ 494		By similarity
	Disulfide bond	654 ↔ 664		By similarity
	Disulfide bond	658 ↔ 670		By similarity
	Disulfide bond	672 ↔ 681		By similarity
Natural variations
	Alternative sequence	902 – 955	54	VSPRE…FLVPA → FPEYRSQRAGGMISSKI in isoform B.		VSP_005481
	Natural variant	4	1	G → S. Ref.2 Corresponds to variant rs11465228 [ dbSNP | Ensembl ].		VAR_057066
	Natural variant	133	1	R → Q in a colorectal cancer sample; somatic mutation. Ref.7		VAR_036146
	Natural variant	298	1	A → T in a colorectal cancer sample; somatic mutation. Ref.7		VAR_036147
	Natural variant	609	1	H → Q in a pancreatic ductal adenocarcinoma sample; somatic mutation. Ref.8		VAR_062670
Experimental info
	Sequence conflict	32	1	R → SK in AAG50282. Ref.1
	Sequence conflict	557	1	D → V in AAG50282. Ref.1
	Sequence conflict	557	1	D → V in AAF22162. Ref.5
	Sequence conflict	622	1	D → N in AAG50282. Ref.1
	Sequence conflict	622	1	D → N in AAF22162. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified August 10, 2010. Version 3. Checksum: 9C9D42BED18BF7F9	FASTA	955	104,997
	10 20 30 40 50 60 MPGGAGAARL CLLAFALQPL RPRAAREPGW TRGSEEGSPK LQHELIIPQW KTSESPVREK 70 80 90 100 110 120 HPLKAELRVM AEGRELILDL EKNEQLFAPS YTETHYTSSG NPQTTTRKLE DHCFYHGTVR 130 140 150 160 170 180 ETELSSVTLS TCRGIRGLIT VSSNLSYVIE PLPDSKGQHL IYRSEHLKPP PGNCGFEHSK 190 200 210 220 230 240 PTTRDWALQF TQQTKKRPRR MKREDLNSMK YVELYLVADY LEFQKNRRDQ DATKHKLIEI 250 260 270 280 290 300 ANYVDKFYRS LNIRIALVGL EVWTHGNMCE VSENPYSTLW SFLSWRRKLL AQKYHDNAQL 310 320 330 340 350 360 ITGMSFHGTT IGLAPLMAMC SVYQSGGVNM DHSENAIGVA ATMAHEMGHN FGMTHDSADC 370 380 390 400 410 420 CSASAADGGC IMAAATGHPF PKVFNGCNRR ELDRYLQSGG GMCLSNMPDT RMLYGGRRCG 430 440 450 460 470 480 NGYLEDGEEC DCGEEEECNN PCCNASNCTL RPGAECAHGS CCHQCKLLAP GTLCREQARQ 490 500 510 520 530 540 CDLPEFCTGK SPHCPTNFYQ MDGTPCEGGQ AYCYNGMCLT YQEQCQQLWG PGARPAPDLC 550 560 570 580 590 600 FEKVNVAGDT FGNCGKDMNG EHRKCNMRDA KCGKIQCQSS EARPLESNAV PIDTTIIMNG 610 620 630 640 650 660 RQIQCRGTHV YRGPEEEGDM LDPGLVMTGT KCGYNHICFE GQCRNTSFFE TEGCGKKCNG 670 680 690 700 710 720 HGVCNNNQNC HCLPGWAPPF CNTPGHGGSI DSGPMPPESV GPVVAGVLVA ILVLAVLMLM 730 740 750 760 770 780 YYCCRQNNKL GQLKPSALPS KLRQQFSCPF RVSQNSGTGH ANPTFKLQTP QGKRKVINTP 790 800 810 820 830 840 EILRKPSQPP PRPPPDYLRG GSPPAPLPAH LSRAARNSPG PGSQIERTES SRRPPPSRPI 850 860 870 880 890 900 PPAPNCIVSQ DFSRPRPPQK ALPANPVPGR RSLPRPGGAS PLRPPGAGPQ QSRPLAALAP 910 920 930 940 950 KVSPREALKV KAGTRGLQGG RCRVEKTKQF MLLVVWTELP EQKPRAKHSC FLVPA
	Isoform B [UniParc]. Checksum: 048EA0189D3D126A	FASTA	918	100,848
	10 20 30 40 50 60 MPGGAGAARL CLLAFALQPL RPRAAREPGW TRGSEEGSPK LQHELIIPQW KTSESPVREK 70 80 90 100 110 120 HPLKAELRVM AEGRELILDL EKNEQLFAPS YTETHYTSSG NPQTTTRKLE DHCFYHGTVR 130 140 150 160 170 180 ETELSSVTLS TCRGIRGLIT VSSNLSYVIE PLPDSKGQHL IYRSEHLKPP PGNCGFEHSK 190 200 210 220 230 240 PTTRDWALQF TQQTKKRPRR MKREDLNSMK YVELYLVADY LEFQKNRRDQ DATKHKLIEI 250 260 270 280 290 300 ANYVDKFYRS LNIRIALVGL EVWTHGNMCE VSENPYSTLW SFLSWRRKLL AQKYHDNAQL 310 320 330 340 350 360 ITGMSFHGTT IGLAPLMAMC SVYQSGGVNM DHSENAIGVA ATMAHEMGHN FGMTHDSADC 370 380 390 400 410 420 CSASAADGGC IMAAATGHPF PKVFNGCNRR ELDRYLQSGG GMCLSNMPDT RMLYGGRRCG 430 440 450 460 470 480 NGYLEDGEEC DCGEEEECNN PCCNASNCTL RPGAECAHGS CCHQCKLLAP GTLCREQARQ 490 500 510 520 530 540 CDLPEFCTGK SPHCPTNFYQ MDGTPCEGGQ AYCYNGMCLT YQEQCQQLWG PGARPAPDLC 550 560 570 580 590 600 FEKVNVAGDT FGNCGKDMNG EHRKCNMRDA KCGKIQCQSS EARPLESNAV PIDTTIIMNG 610 620 630 640 650 660 RQIQCRGTHV YRGPEEEGDM LDPGLVMTGT KCGYNHICFE GQCRNTSFFE TEGCGKKCNG 670 680 690 700 710 720 HGVCNNNQNC HCLPGWAPPF CNTPGHGGSI DSGPMPPESV GPVVAGVLVA ILVLAVLMLM 730 740 750 760 770 780 YYCCRQNNKL GQLKPSALPS KLRQQFSCPF RVSQNSGTGH ANPTFKLQTP QGKRKVINTP 790 800 810 820 830 840 EILRKPSQPP PRPPPDYLRG GSPPAPLPAH LSRAARNSPG PGSQIERTES SRRPPPSRPI 850 860 870 880 890 900 PPAPNCIVSQ DFSRPRPPQK ALPANPVPGR RSLPRPGGAS PLRPPGAGPQ QSRPLAALAP 910 KFPEYRSQRA GGMISSKI

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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). Tissue: Dendritic cell.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 99-955 (ISOFORM A).
[6]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH3PXD2A.
[7]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-133 AND THR-298.
[8]	"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses." Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y. , Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Science 321:1801-1806(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-609.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF326918 mRNA. Translation: AAG50282.1. Y13786 mRNA. Translation: CAC20585.1. AF311317 mRNA. Translation: AAK07852.1. AC008676 Genomic DNA. No translation available. AC008694 Genomic DNA. No translation available. AC106801 Genomic DNA. No translation available. AF134707 mRNA. Translation: AAF22162.1.
IPI	IPI00249735. IPI00941096.
RefSeq	NP_150377.1. NM_033274.3.
UniGene	Hs.483944.
3D structure databases
ProteinModelPortal	Q9H013.
SMR	Q9H013. Positions 206-684.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-246384.
STRING	9606.ENSP00000257527.
Protein family/group databases
MEROPS	M12.214.
PTM databases
PhosphoSite	Q9H013.
Polymorphism databases
DMDM	302393821.
Proteomic databases
PaxDb	Q9H013.
PRIDE	Q9H013.
Protocols and materials databases
DNASU	8728.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257527; ENSP00000257527; ENSG00000135074. ENST00000517905; ENSP00000428654; ENSG00000135074.
GeneID	8728.
KEGG	hsa:8728.
UCSC	uc003lwy.3. human. uc003lwz.3. human.
Organism-specific databases
CTD	8728.
GeneCards	GC05M156836.
HGNC	HGNC:197. ADAM19.
HPA	HPA055537.
MIM	603640. gene.
neXtProt	NX_Q9H013.
PharmGKB	PA24514.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG294463.
HOGENOM	HOG000230883.
HOVERGEN	HBG006978.
InParanoid	Q9H013.
KO	K08608.
OMA	IYRSEHL.
Enzyme and pathway databases
SABIO-RK	Q9H013.
Gene expression databases
ArrayExpress	Q9H013.
Bgee	Q9H013.
CleanEx	HS_ADAM19.
Genevestigator	Q9H013.
GermOnline	ENSG00000135074. Homo sapiens.
Family and domain databases
Gene3D	3.40.390.10. 1 hit. 4.10.70.10. 1 hit.
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR024079. MetalloPept_cat_dom. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Pfam	PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 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]
SUPFAM	SSF57552. Disintegrin. 1 hit.
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
GenomeRNAi	8728.
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:	August 10, 2010
Last modified:	May 1, 2013
This is version 127 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.