Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

Adam10

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. 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). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B. May regulate the EFNA5-EPHA3 signaling.By similarity

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 bindingi179Zinc; catalyticBy similarity1
Active sitei180PROSITE-ProRule annotation1
Metal bindingi183Zinc; catalyticBy similarity1
Metal bindingi189Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Notch signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

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
CD_antigen: CD156c
Gene namesi
Name:Adam10
Synonyms:Madm
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2032. Adam10.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein
  • Golgi apparatus membrane By similarity; Single-pass type I membrane protein Curated

  • Note: Is localized in the plasma membrane but is predominantly expressed in the Golgi apparatus and in released membrane vesicles derived likely from the Golgi.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini10 – 468ExtracellularSequence analysisAdd BLAST459
Transmembranei469 – 492HelicalSequence analysisAdd BLAST24
Topological domaini493 – 544CytoplasmicSequence analysisAdd BLAST52

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • Golgi-associated vesicle Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: RGD
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
  • trans-Golgi network Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000029070‹1 – 9Sequence analysis›9
ChainiPRO_000002907110 – 544Disintegrin and metalloproteinase domain-containing protein 10Add BLAST535

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi18 ↔ 109By similarity
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Glycosylationi74N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi140 ↔ 247By similarity
Disulfide bondi195 ↔ 231By similarity
Glycosylationi235N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi280 ↔ 311By similarity
Disulfide bondi299 ↔ 307By similarity
Disulfide bondi320 ↔ 339By similarity
Disulfide bondi326 ↔ 358By similarity
Glycosylationi347N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi351 ↔ 363By similarity
Disulfide bondi368 ↔ 394By similarity
Disulfide bondi376 ↔ 403By similarity
Disulfide bondi378 ↔ 393By similarity
Disulfide bondi390 ↔ 435By similarity
Disulfide bondi428 ↔ 441By similarity
Modified residuei515PhosphothreonineBy 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

PaxDbiQ10743.
PRIDEiQ10743.

PTM databases

iPTMnetiQ10743.
PhosphoSitePlusiQ10743.
SwissPalmiQ10743.
UniCarbKBiQ10743.

Expressioni

Tissue specificityi

Expressed in brain, kidney, lung, spleen, ovary and testis.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021066.

Structurei

3D structure databases

ProteinModelPortaliQ10743.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 252Peptidase M12BPROSITE-ProRule annotationAdd BLAST237
Domaini253 – 347DisintegrinPROSITE-ProRule annotationAdd BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi504 – 511SH3-bindingSequence analysis8
Motifi518 – 524SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi347 – 468Cys-richAdd BLAST122

Domaini

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. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33. Stalk region is sufficient for interaction with TSPAN15.By similarity

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
HOVERGENiHBG050455.
InParanoidiQ10743.
PhylomeDBiQ10743.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
[Graphical view]
PANTHERiPTHR11905:SF4. PTHR11905:SF4. 1 hit.
PfamiPF00200. Disintegrin. 1 hit.
[Graphical view]
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

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

Q10743-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
GPELLRKKRT TLPERNTCQL YIQTDHLFFK SYGTREAVIA QISSHVKAID
60 70 80 90 100
AIYQTTDFSG IRNISFMVKR IRINTTSDEK DPTNPFRFPN IGVEKFLELN
110 120 130 140 150
SEQNHDDYCL AYVFTDRDFD DGVLGLAWVG APSGSSGGIC EKSKLYSDGK
160 170 180 190 200
KKSLNTGIIT VQNYGSHVPP KVSHITFAHE VGHNFGSPHD SGTECTPGES
210 220 230 240 250
KNLGQKENGN YIMYARATSG DKLNNNKFSL CSIRNISQVL EKKRNNCFVE
260 270 280 290 300
SGQPICGNGM VEQGEECDCG YSDQCKDECC FDANQPEGKK CKLKPGKQCS
310 320 330 340 350
PSQGPCCTAQ CAFKSKSEKC RDDSDCAKEG ICNGFTALCP ASDPKPNFTD
360 370 380 390 400
CNRHTQVCIN GQCAGSICEK YDLEECTCAS SDGKDDKELC HVCCMKKMAP
410 420 430 440 450
STCASTGSLQ WNKQFTGRTI TLQPGSPCND FRGYCDVFMR CRLVDADGPL
460 470 480 490 500
ARLKKAIFSP QLYENIAEWI VAHWWAVLLM GIALIMLMAG FIKICSVHTP
510 520 530 540
SSNPKLPPPK PLPGTLKRRR PPQPIQQPQR QRPRESYQMG HMRR
Length:544
Mass (Da):60,445
Last modified:November 1, 1996 - v1
Checksum:iF75E0E8D6C88A7DD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z48444 mRNA. Translation: CAA88359.1.
PIRiS52477.
UniGeneiRn.42924.

Genome annotation databases

UCSCiRGD:2032. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z48444 mRNA. Translation: CAA88359.1.
PIRiS52477.
UniGeneiRn.42924.

3D structure databases

ProteinModelPortaliQ10743.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021066.

Protein family/group databases

MEROPSiM12.210.

PTM databases

iPTMnetiQ10743.
PhosphoSitePlusiQ10743.
SwissPalmiQ10743.
UniCarbKBiQ10743.

Proteomic databases

PaxDbiQ10743.
PRIDEiQ10743.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2032. rat.

Organism-specific databases

RGDi2032. Adam10.

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
HOVERGENiHBG050455.
InParanoidiQ10743.
PhylomeDBiQ10743.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
[Graphical view]
PANTHERiPTHR11905:SF4. PTHR11905:SF4. 1 hit.
PfamiPF00200. Disintegrin. 1 hit.
[Graphical view]
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADA10_RAT
AccessioniPrimary (citable) accession number: Q10743
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.