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Q9H013

- ADA19_HUMAN

UniProt

Q9H013 - ADA19_HUMAN

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Protein

Disintegrin and metalloproteinase domain-containing protein 19

Gene
ADAM19, MLTNB, FKSG34
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

Cofactori

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi132 – 1321Zinc; in inhibited form By similarity
Metal bindingi345 – 3451Zinc; catalytic By similarity
Active sitei346 – 3461 By similarity
Metal bindingi349 – 3491Zinc; catalytic By similarity
Metal bindingi355 – 3551Zinc; catalytic By similarity

GO - Molecular functioni

  1. metalloendopeptidase activity Source: InterPro
  2. zinc ion binding Source: InterPro

GO - Biological processi

  1. heart development Source: Ensembl
  2. membrane protein ectodomain proteolysis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SABIO-RKQ9H013.

Protein family/group databases

MEROPSiM12.214.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 19 (EC:3.4.24.-)
Short name:
ADAM 19
Alternative name(s):
Meltrin-beta
Metalloprotease and disintegrin dendritic antigen marker
Short name:
MADDAM
Gene namesi
Name:ADAM19
Synonyms:MLTNB
ORF Names:FKSG34
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:197. ADAM19.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini203 – 699497Extracellular Reviewed predictionAdd
BLAST
Transmembranei700 – 72021Helical; Reviewed predictionAdd
BLAST
Topological domaini721 – 955235Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24514.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525 Reviewed predictionAdd
BLAST
Propeptidei26 – 202177 By similarityPRO_0000029102Add
BLAST
Chaini203 – 955753Disintegrin and metalloproteinase domain-containing protein 19PRO_0000029103Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi144 – 1441N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi320 ↔ 403 By similarity
Disulfide bondi360 ↔ 387 By similarity
Disulfide bondi361 ↔ 370 By similarity
Glycosylationi444 – 4441N-linked (GlcNAc...) Reviewed prediction
Glycosylationi447 – 4471N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi474 ↔ 494 By similarity
Glycosylationi645 – 6451N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi654 ↔ 664 By similarity
Disulfide bondi658 ↔ 670 By similarity
Disulfide bondi672 ↔ 681 By similarity

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ9H013.
PaxDbiQ9H013.
PRIDEiQ9H013.

PTM databases

PhosphoSiteiQ9H013.

Expressioni

Tissue specificityi

Expressed in many normal organ tissues and several cancer cell lines.

Inductioni

By 1,25(OH)2VD3 in monocytes.

Gene expression databases

ArrayExpressiQ9H013.
BgeeiQ9H013.
CleanExiHS_ADAM19.
GenevestigatoriQ9H013.

Organism-specific databases

HPAiHPA055537.

Interactioni

Subunit structurei

Interacts with SH3PXD2A.1 Publication

Protein-protein interaction databases

BioGridi114267. 4 interactions.
IntActiQ9H013. 3 interactions.
MINTiMINT-246384.
STRINGi9606.ENSP00000257527.

Structurei

3D structure databases

ProteinModelPortaliQ9H013.
SMRiQ9H013. Positions 206-685.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini210 – 408199Peptidase M12BAdd
BLAST
Domaini416 – 50287DisintegrinAdd
BLAST
Domaini650 – 68233EGF-likeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi130 – 1378Cysteine switch By similarity
Motifi833 – 84412SH3-binding Reviewed predictionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi434 – 4374Poly-Glu
Compositional biasi502 – 649148Cys-richAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 disintegrin domain.
Contains 1 EGF-like domain.

Keywords - Domaini

EGF-like domain, SH3-binding, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG294463.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9H013.
KOiK08608.
OMAiFQKNRRD.
OrthoDBiEOG7F7W89.
PhylomeDBiQ9H013.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. 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]
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform A (identifier: Q9H013-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MPGGAGAARL CLLAFALQPL RPRAAREPGW TRGSEEGSPK LQHELIIPQW    50
KTSESPVREK HPLKAELRVM AEGRELILDL EKNEQLFAPS YTETHYTSSG 100
NPQTTTRKLE DHCFYHGTVR ETELSSVTLS TCRGIRGLIT VSSNLSYVIE 150
PLPDSKGQHL IYRSEHLKPP PGNCGFEHSK PTTRDWALQF TQQTKKRPRR 200
MKREDLNSMK YVELYLVADY LEFQKNRRDQ DATKHKLIEI ANYVDKFYRS 250
LNIRIALVGL EVWTHGNMCE VSENPYSTLW SFLSWRRKLL AQKYHDNAQL 300
ITGMSFHGTT IGLAPLMAMC SVYQSGGVNM DHSENAIGVA ATMAHEMGHN 350
FGMTHDSADC CSASAADGGC IMAAATGHPF PKVFNGCNRR ELDRYLQSGG 400
GMCLSNMPDT RMLYGGRRCG NGYLEDGEEC DCGEEEECNN PCCNASNCTL 450
RPGAECAHGS CCHQCKLLAP GTLCREQARQ CDLPEFCTGK SPHCPTNFYQ 500
MDGTPCEGGQ AYCYNGMCLT YQEQCQQLWG PGARPAPDLC FEKVNVAGDT 550
FGNCGKDMNG EHRKCNMRDA KCGKIQCQSS EARPLESNAV PIDTTIIMNG 600
RQIQCRGTHV YRGPEEEGDM LDPGLVMTGT KCGYNHICFE GQCRNTSFFE 650
TEGCGKKCNG HGVCNNNQNC HCLPGWAPPF CNTPGHGGSI DSGPMPPESV 700
GPVVAGVLVA ILVLAVLMLM YYCCRQNNKL GQLKPSALPS KLRQQFSCPF 750
RVSQNSGTGH ANPTFKLQTP QGKRKVINTP EILRKPSQPP PRPPPDYLRG 800
GSPPAPLPAH LSRAARNSPG PGSQIERTES SRRPPPSRPI PPAPNCIVSQ 850
DFSRPRPPQK ALPANPVPGR RSLPRPGGAS PLRPPGAGPQ QSRPLAALAP 900
KVSPREALKV KAGTRGLQGG RCRVEKTKQF MLLVVWTELP EQKPRAKHSC 950
FLVPA 955
Length:955
Mass (Da):104,997
Last modified:August 10, 2010 - v3
Checksum:i9C9D42BED18BF7F9
GO
Isoform B (identifier: Q9H013-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     902-955: VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQKPRAKHSCFLVPA → FPEYRSQRAGGMISSKI

Show »
Length:918
Mass (Da):100,848
Checksum:i048EA0189D3D126A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti4 – 41G → S.1 Publication
Corresponds to variant rs11465228 [ dbSNP | Ensembl ].
VAR_057066
Natural varianti133 – 1331R → Q in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036146
Natural varianti298 – 2981A → T in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036147
Natural varianti609 – 6091H → Q in a pancreatic ductal adenocarcinoma sample; somatic mutation. 1 Publication
VAR_062670

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei902 – 95554VSPRE…FLVPA → FPEYRSQRAGGMISSKI in isoform B. VSP_005481Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti32 – 321R → SK in AAG50282. 1 Publication
Sequence conflicti557 – 5571D → V in AAG50282. 1 Publication
Sequence conflicti557 – 5571D → V in AAF22162. 1 Publication
Sequence conflicti622 – 6221D → N in AAG50282. 1 Publication
Sequence conflicti622 – 6221D → N in AAF22162. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4338.1. [Q9H013-2]
RefSeqiNP_150377.1. NM_033274.4. [Q9H013-2]
XP_005266060.1. XM_005266003.1. [Q9H013-1]
UniGeneiHs.483944.

Genome annotation databases

EnsembliENST00000257527; ENSP00000257527; ENSG00000135074. [Q9H013-2]
ENST00000517905; ENSP00000428654; ENSG00000135074. [Q9H013-1]
GeneIDi8728.
KEGGihsa:8728.
UCSCiuc003lwy.3. human. [Q9H013-1]
uc003lwz.4. human. [Q9H013-2]

Polymorphism databases

DMDMi302393821.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS4338.1. [Q9H013-2 ]
RefSeqi NP_150377.1. NM_033274.4. [Q9H013-2 ]
XP_005266060.1. XM_005266003.1. [Q9H013-1 ]
UniGenei Hs.483944.

3D structure databases

ProteinModelPortali Q9H013.
SMRi Q9H013. Positions 206-685.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114267. 4 interactions.
IntActi Q9H013. 3 interactions.
MINTi MINT-246384.
STRINGi 9606.ENSP00000257527.

Protein family/group databases

MEROPSi M12.214.

PTM databases

PhosphoSitei Q9H013.

Polymorphism databases

DMDMi 302393821.

Proteomic databases

MaxQBi Q9H013.
PaxDbi Q9H013.
PRIDEi Q9H013.

Protocols and materials databases

DNASUi 8728.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000257527 ; ENSP00000257527 ; ENSG00000135074 . [Q9H013-2 ]
ENST00000517905 ; ENSP00000428654 ; ENSG00000135074 . [Q9H013-1 ]
GeneIDi 8728.
KEGGi hsa:8728.
UCSCi uc003lwy.3. human. [Q9H013-1 ]
uc003lwz.4. human. [Q9H013-2 ]

Organism-specific databases

CTDi 8728.
GeneCardsi GC05M156836.
HGNCi HGNC:197. ADAM19.
HPAi HPA055537.
MIMi 603640. gene.
neXtProti NX_Q9H013.
PharmGKBi PA24514.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG294463.
HOGENOMi HOG000230883.
HOVERGENi HBG006978.
InParanoidi Q9H013.
KOi K08608.
OMAi FQKNRRD.
OrthoDBi EOG7F7W89.
PhylomeDBi Q9H013.
TreeFami TF314733.

Enzyme and pathway databases

SABIO-RK Q9H013.

Miscellaneous databases

GeneWikii ADAM19.
GenomeRNAii 8728.
NextBioi 32743.
PROi Q9H013.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9H013.
Bgeei Q9H013.
CleanExi HS_ADAM19.
Genevestigatori Q9H013.

Family and domain databases

Gene3Di 3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProi 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 ]
Pfami PF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view ]
PRINTSi PR00289. DISINTEGRIN.
SMARTi SM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view ]
SUPFAMi SSF57552. SSF57552. 1 hit.
PROSITEi PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-133 AND THR-298.
  8. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-609.

Entry informationi

Entry nameiADA19_HUMAN
AccessioniPrimary (citable) accession number: Q9H013
Secondary accession number(s): Q9BZL5, Q9UHP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: August 10, 2010
Last modified: July 9, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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