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Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

ADAM10

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:10097139). Contributes to the normal cleavage of the cellular prion protein (By similarity). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (By similarity). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (By similarity). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (By similarity). May regulate the EFNA5-EPHA3 signaling (By similarity).By similarity1 Publication

Catalytic activityi

Endopeptidase of broad specificity.

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi173Zinc; in inhibited formBy similarity1
Metal bindingi383Zinc; catalyticBy similarity1
Active sitei3841 Publication1
Metal bindingi387Zinc; catalyticBy similarity1
Metal bindingi393Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processNotch signaling pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-BTA-1474228. Degradation of the extracellular matrix.
R-BTA-1980148. Signaling by NOTCH3.
R-BTA-1980150. Signaling by NOTCH4.
R-BTA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-BTA-6798695. Neutrophil degranulation.
R-BTA-8957275. Post-translational protein phosphorylation.

Protein family/group databases

MEROPSiM12.210.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 10 (EC:3.4.24.81)
Short name:
ADAM 10
Alternative name(s):
Kuzbanian protein homolog
Mammalian disintegrin-metalloprotease
Myelin-associated metalloproteinase
CD_antigen: CD156c
Gene namesi
Name:ADAM10
Synonyms:MADM
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 10

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 672ExtracellularSequence analysisAdd BLAST653
Transmembranei673 – 696HelicalSequence analysisAdd BLAST24
Topological domaini697 – 748CytoplasmicSequence analysisAdd BLAST52

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi384E → A: Decreased stimulated and constitutive secretion of APP. 1 Publication1
Mutagenesisi573E → A: Abrogates EFNA5 cleavage; when associated with Ala-578 and 579. 1 Publication1
Mutagenesisi578E → A: Abrogates EFNA5 cleavage; when associated with Ala-573 and 579. 1 Publication1
Mutagenesisi579E → A: Abrogates EFNA5 cleavage; when associated with Ala-573 and 578. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000002906420 – 2131 PublicationAdd BLAST194
ChainiPRO_0000029065214 – 748Disintegrin and metalloproteinase domain-containing protein 10Add BLAST535

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi222 ↔ 313By similarity
Glycosylationi267N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi278N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi344 ↔ 451By similarity
Disulfide bondi399 ↔ 435By similarity
Glycosylationi439N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi484 ↔ 5151 Publication
Disulfide bondi503 ↔ 5111 Publication
Disulfide bondi524 ↔ 5431 Publication
Disulfide bondi530 ↔ 5621 Publication
Glycosylationi551N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi555 ↔ 5671 Publication
Disulfide bondi572 ↔ 5981 Publication
Disulfide bondi580 ↔ 6071 Publication
Disulfide bondi582 ↔ 5971 Publication
Disulfide bondi594 ↔ 6391 Publication
Disulfide bondi632 ↔ 6451 Publication
Modified residuei719PhosphothreonineBy similarity1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiQ10741.
PeptideAtlasiQ10741.
PRIDEiQ10741.

Expressioni

Tissue specificityi

Expressed at low level in kidney, spleen, lung, adrenal, heart and peripheral nerve.

Inductioni

By interleukin-1 alpha in nasal cartilage.

Gene expression databases

BgeeiENSBTAG00000005481.

Interactioni

Subunit structurei

Interacts with EPHA2 (By similarity). Constitutively associates with EphA3. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells (PubMed:16239146). Interacts with NGF in a divalent cation-dependent manner (By similarity). Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression (PubMed:23035126). Interacts with TSPAN5, TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity (PubMed:23035126).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-48422N.
STRINGi9913.ENSBTAP00000042110.

Structurei

Secondary structure

1748
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni476 – 478Combined sources3
Beta strandi482 – 484Combined sources3
Beta strandi487 – 489Combined sources3
Turni505 – 507Combined sources3
Beta strandi523 – 525Combined sources3
Beta strandi529 – 531Combined sources3
Turni556 – 559Combined sources4
Beta strandi563 – 566Combined sources4
Helixi571 – 574Combined sources4
Beta strandi578 – 580Combined sources3
Helixi591 – 594Combined sources4
Beta strandi597 – 600Combined sources4
Helixi604 – 606Combined sources3
Helixi616 – 619Combined sources4
Turni633 – 636Combined sources4
Beta strandi637 – 639Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AO7X-ray2.90A455-646[»]
5L0QX-ray2.76A/D455-646[»]
ProteinModelPortaliQ10741.
SMRiQ10741.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ10741.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini220 – 456Peptidase M12BPROSITE-ProRule annotationAdd BLAST237
Domaini457 – 551DisintegrinPROSITE-ProRule annotationAdd BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi171 – 178Cysteine switchBy similarity8
Motifi708 – 715SH3-bindingSequence analysis8
Motifi722 – 728SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi555 – 595Cys-richAdd BLAST41

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.
The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins PubMed:16239146. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (By similarity). Stalk region is sufficient for interaction with TSPAN15 (By similarity).By similarity1 Publication

Keywords - Domaini

SH3-binding, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiQ10741.
KOiK06704.
OMAiEGFIQTH.
OrthoDBiEOG091G01J4.
TreeFamiTF352021.

Family and domain databases

CDDicd04270. ZnMc_TACE_like. 1 hit.
Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiView protein in InterPro
IPR034025. ADAM10_ADAM17.
IPR027053. ADAM_10.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
PANTHERiPTHR11905:SF166. PTHR11905:SF166. 1 hit.
PfamiView protein in Pfam
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
SMARTiView protein in SMART
SM00050. DISIN. 1 hit.
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiView protein in PROSITE
PS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q10741-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLLRVLILL LSWVAGLGGQ YGNPLNKYIR HYEGLSYDVD SLHQKHQRAK
60 70 80 90 100
RAVSHEDQFL RLDFHAHGRH FNLRMKRDTS LFSEEFRVET SNAVLDYDTS
110 120 130 140 150
HIYTGHIYGE EGSFSHGSVI DGRFEGFIQT HGGTFYVEPA ERYIKDRTLP
160 170 180 190 200
FHSVIYHEDD IKYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEVTQTPQEK
210 220 230 240 250
HAINGPELLR KKRTTVAEKN TCQLYIQTDH LFFKYYGTRE AVIAQISSHV
260 270 280 290 300
KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF
310 320 330 340 350
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY
360 370 380 390 400
SDGKKKSLNT GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT
410 420 430 440 450
PGESKNLGQK ENGNYIMYAR ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN
460 470 480 490 500
CFVESGQPIC GNGMVEQGEE CDCGYSDQCK DECCYDANQP EGKKCKLKPG
510 520 530 540 550
KQCSPSQGPC CTAHCAFKSK TEKCRDDSDC AKEGICNGIT ALCPASDPKP
560 570 580 590 600
NFTDCNRHTQ VCINGQCAGS ICEKHGLEEC TCASSDGKDD KELCHVCCMK
610 620 630 640 650
KMEPSTCAST GSVQWNKYFL GRTITLQPGS PCNDFRGYCD VFMRCRLVDA
660 670 680 690 700
DGPLARLKKA IFSPELYENI AEWIVAYWWA VLLMGIALIM LMAGFIKICS
710 720 730 740
VHTPSSNPKL PPPKPLPGTL KRRRPPQPIQ QPQRQRPRES YQMGHMRR
Length:748
Mass (Da):84,188
Last modified:November 1, 1996 - v1
Checksum:i202E29830611F9E1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21961 mRNA. Translation: CAA79973.1.
BC153863 mRNA. Translation: AAI53864.1.
PIRiS66129.
RefSeqiNP_776921.1. NM_174496.2.
UniGeneiBt.49218.

Genome annotation databases

EnsembliENSBTAT00000044627; ENSBTAP00000042110; ENSBTAG00000005481.
GeneIDi282132.
KEGGibta:282132.

Similar proteinsi

Entry informationi

Entry nameiADA10_BOVIN
AccessioniPrimary (citable) accession number: Q10741
Secondary accession number(s): A8E663
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1996
Last modified: August 30, 2017
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references