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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

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.By similarity

Cofactori

Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi132 – 1321Zinc; in inhibited formBy similarity
Metal bindingi345 – 3451Zinc; catalyticBy similarity
Active sitei346 – 3461PROSITE-ProRule annotation
Metal bindingi349 – 3491Zinc; catalyticBy similarity
Metal bindingi355 – 3551Zinc; catalyticBy 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

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 – 2525Sequence AnalysisAdd
BLAST
Propeptidei26 – 202177By 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...)Sequence Analysis
Disulfide bondi320 ↔ 403By similarity
Disulfide bondi360 ↔ 387By similarity
Disulfide bondi361 ↔ 370By similarity
Glycosylationi444 – 4441N-linked (GlcNAc...)Sequence Analysis
Glycosylationi447 – 4471N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi474 ↔ 494By similarity
Glycosylationi645 – 6451N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi654 ↔ 664By similarity
Disulfide bondi658 ↔ 670By similarity
Disulfide bondi672 ↔ 681By 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

BgeeiQ9H013.
CleanExiHS_ADAM19.
ExpressionAtlasiQ9H013. baseline and differential.
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 206-647, 657-686.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini203 – 699497ExtracellularSequence AnalysisAdd
BLAST
Topological domaini721 – 955235CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei700 – 72021HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini210 – 408199Peptidase M12BPROSITE-ProRule annotationAdd
BLAST
Domaini416 – 50287DisintegrinPROSITE-ProRule annotationAdd
BLAST
Domaini650 – 68233EGF-likePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi130 – 1378Cysteine switchBy similarity
Motifi833 – 84412SH3-bindingSequence AnalysisAdd
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.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiNOG294463.
GeneTreeiENSGT00760000118888.
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

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

FLVPA
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

Experimental Info

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

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. 2 PublicationsVSP_005481Add
BLAST

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 206-647, 657-686.
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.
GeneTreei ENSGT00760000118888.
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

Bgeei Q9H013.
CleanExi HS_ADAM19.
ExpressionAtlasi Q9H013. baseline and differential.
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: October 29, 2014
This is version 140 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