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Protein

Disintegrin and metalloproteinase domain-containing protein 19

Gene

ADAM19

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi132Zinc; in inhibited formBy similarity1
Metal bindingi345Zinc; catalyticBy similarity1
Active sitei346PROSITE-ProRule annotation1
Metal bindingi349Zinc; catalyticBy similarity1
Metal bindingi355Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135074-MONOMER.
SABIO-RKQ9H013.
SIGNORiQ9H013.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:197. ADAM19.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini203 – 699ExtracellularSequence analysisAdd BLAST497
Transmembranei700 – 720HelicalSequence analysisAdd BLAST21
Topological domaini721 – 955CytoplasmicSequence analysisAdd BLAST235

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8728.
OpenTargetsiENSG00000135074.
PharmGKBiPA24514.

Polymorphism and mutation databases

DMDMi302393821.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000002910226 – 202By similarityAdd BLAST177
ChainiPRO_0000029103203 – 955Disintegrin and metalloproteinase domain-containing protein 19Add BLAST753

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi144N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi320 ↔ 403By similarity
Disulfide bondi360 ↔ 387By similarity
Disulfide bondi361 ↔ 370By similarity
Glycosylationi444N-linked (GlcNAc...)Sequence analysis1
Glycosylationi447N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi474 ↔ 494By similarity
Glycosylationi645N-linked (GlcNAc...)Sequence analysis1
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.
PeptideAtlasiQ9H013.
PRIDEiQ9H013.

PTM databases

iPTMnetiQ9H013.
PhosphoSitePlusiQ9H013.

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

BgeeiENSG00000135074.
CleanExiHS_ADAM19.
ExpressionAtlasiQ9H013. baseline and differential.
GenevisibleiQ9H013. HS.

Organism-specific databases

HPAiHPA055537.

Interactioni

Subunit structurei

Interacts with SH3PXD2A.1 Publication

Protein-protein interaction databases

BioGridi114267. 3 interactors.
IntActiQ9H013. 3 interactors.
MINTiMINT-246384.
STRINGi9606.ENSP00000257527.

Structurei

3D structure databases

ProteinModelPortaliQ9H013.
SMRiQ9H013.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini210 – 408Peptidase M12BPROSITE-ProRule annotationAdd BLAST199
Domaini416 – 502DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini650 – 682EGF-likePROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi130 – 137Cysteine switchBy similarity8
Motifi833 – 844SH3-bindingSequence analysisAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi434 – 437Poly-Glu4
Compositional biasi502 – 649Cys-richAdd BLAST148

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

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9H013.
KOiK08608.
OMAiLEVWTHG.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9H013.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR033596. ADAM19.
IPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF19. PTHR11905:SF19. 2 hits.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti32R → SK in AAG50282 (Ref. 1) Curated1
Sequence conflicti557D → V in AAG50282 (Ref. 1) Curated1
Sequence conflicti557D → V in AAF22162 (Ref. 5) Curated1
Sequence conflicti622D → N in AAG50282 (Ref. 1) Curated1
Sequence conflicti622D → N in AAF22162 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0570664G → S.1 PublicationCorresponds to variant rs11465228dbSNPEnsembl.1
Natural variantiVAR_036146133R → Q in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs200894535dbSNPEnsembl.1
Natural variantiVAR_036147298A → T in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_062670609H → Q in a pancreatic ductal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005481902 – 955VSPRE…FLVPA → FPEYRSQRAGGMISSKI in isoform B. 2 PublicationsAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005266003.2. [Q9H013-1]
UniGeneiHs.483944.

Genome annotation databases

EnsembliENST00000257527; ENSP00000257527; ENSG00000135074. [Q9H013-2]
ENST00000517905; ENSP00000428654; ENSG00000135074. [Q9H013-1]
GeneIDi8728.
KEGGihsa:8728.
UCSCiuc003lwz.5. human. [Q9H013-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_005266003.2. [Q9H013-1]
UniGeneiHs.483944.

3D structure databases

ProteinModelPortaliQ9H013.
SMRiQ9H013.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114267. 3 interactors.
IntActiQ9H013. 3 interactors.
MINTiMINT-246384.
STRINGi9606.ENSP00000257527.

Protein family/group databases

MEROPSiM12.214.

PTM databases

iPTMnetiQ9H013.
PhosphoSitePlusiQ9H013.

Polymorphism and mutation databases

DMDMi302393821.

Proteomic databases

MaxQBiQ9H013.
PaxDbiQ9H013.
PeptideAtlasiQ9H013.
PRIDEiQ9H013.

Protocols and materials databases

DNASUi8728.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257527; ENSP00000257527; ENSG00000135074. [Q9H013-2]
ENST00000517905; ENSP00000428654; ENSG00000135074. [Q9H013-1]
GeneIDi8728.
KEGGihsa:8728.
UCSCiuc003lwz.5. human. [Q9H013-1]

Organism-specific databases

CTDi8728.
DisGeNETi8728.
GeneCardsiADAM19.
HGNCiHGNC:197. ADAM19.
HPAiHPA055537.
MIMi603640. gene.
neXtProtiNX_Q9H013.
OpenTargetsiENSG00000135074.
PharmGKBiPA24514.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9H013.
KOiK08608.
OMAiLEVWTHG.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9H013.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135074-MONOMER.
SABIO-RKQ9H013.
SIGNORiQ9H013.

Miscellaneous databases

ChiTaRSiADAM19. human.
GeneWikiiADAM19.
GenomeRNAii8728.
PROiQ9H013.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135074.
CleanExiHS_ADAM19.
ExpressionAtlasiQ9H013. baseline and differential.
GenevisibleiQ9H013. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR033596. ADAM19.
IPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF19. PTHR11905:SF19. 2 hits.
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]
ProtoNetiSearch...

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: November 2, 2016
This is version 158 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.