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Protein

Disintegrin and metalloproteinase domain-containing protein 8

Gene

ADAM8

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

Functioni

Possible involvement in extravasation of leukocytes.

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi334Zinc; catalytic1 Publication1
Active sitei335PROSITE-ProRule annotation1
Metal bindingi338Zinc; catalytic1 Publication1
Metal bindingi344Zinc; catalytic1 Publication1

GO - Molecular functioni

  • calcium ion binding Source: BHF-UCL
  • cell adhesion molecule binding Source: BHF-UCL
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: BHF-UCL
  • protein self-association Source: BHF-UCL
  • serine-type endopeptidase activity Source: Reactome
  • zinc ion binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151651-MONOMER.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiM12.208.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 8 (EC:3.4.24.-)
Short name:
ADAM 8
Alternative name(s):
Cell surface antigen MS2
CD_antigen: CD156a
Gene namesi
Name:ADAM8
Synonyms:MS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:215. ADAM8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 655ExtracellularSequence analysisAdd BLAST639
Transmembranei656 – 676HelicalSequence analysisAdd BLAST21
Topological domaini677 – 824CytoplasmicSequence analysisAdd BLAST148

GO - Cellular componenti

  • alpha9-beta1 integrin-ADAM8 complex Source: BHF-UCL
  • cell surface Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • dense core granule membrane Source: BHF-UCL
  • integral component of plasma membrane Source: BHF-UCL
  • phagolysosome Source: BHF-UCL
  • plasma membrane Source: BHF-UCL
  • podosome Source: BHF-UCL
  • specific granule Source: BHF-UCL
  • tertiary granule Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi101.
OpenTargetsiENSG00000151651.

Chemistry databases

ChEMBLiCHEMBL5665.
GuidetoPHARMACOLOGYi1656.

Polymorphism and mutation databases

BioMutaiADAM8.
DMDMi408359955.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000002906017 – 824Disintegrin and metalloproteinase domain-containing protein 8Add BLAST808

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi67N-linked (GlcNAc...)Sequence analysis1
Glycosylationi91N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi310 ↔ 395By similarity
Disulfide bondi351 ↔ 379By similarity
Disulfide bondi353 ↔ 362By similarity
Disulfide bondi435 ↔ 457By similarity
Glycosylationi436N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi448 ↔ 454By similarity
Disulfide bondi466 ↔ 486By similarity
Disulfide bondi473 ↔ 503By similarity
Disulfide bondi498 ↔ 508By similarity
Disulfide bondi566 ↔ 613By similarity
Glycosylationi612N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi613 ↔ 623By similarity
Disulfide bondi617 ↔ 629By similarity
Disulfide bondi631 ↔ 640By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP78325.
PaxDbiP78325.
PeptideAtlasiP78325.
PRIDEiP78325.

PTM databases

iPTMnetiP78325.
PhosphoSitePlusiP78325.

Expressioni

Tissue specificityi

Expressed on neutrophils and monocytes.

Gene expression databases

BgeeiENSG00000151651.
CleanExiHS_ADAM8.
ExpressionAtlasiP78325. baseline and differential.
GenevisibleiP78325. HS.

Organism-specific databases

HPAiHPA064637.

Interactioni

Subunit structurei

Interacts with FST3.1 Publication

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • protein self-association Source: BHF-UCL

Protein-protein interaction databases

BioGridi106615. 1 interactor.
IntActiP78325. 2 interactors.
STRINGi9606.ENSP00000453302.

Chemistry databases

BindingDBiP78325.

Structurei

Secondary structure

1824
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi200 – 208Combined sources9
Helixi210 – 216Combined sources7
Helixi219 – 237Combined sources19
Helixi238 – 240Combined sources3
Beta strandi242 – 251Combined sources10
Helixi264 – 276Combined sources13
Turni279 – 281Combined sources3
Beta strandi286 – 292Combined sources7
Beta strandi302 – 304Combined sources3
Beta strandi315 – 319Combined sources5
Helixi325 – 339Combined sources15
Helixi345 – 347Combined sources3
Helixi378 – 387Combined sources10
Helixi391 – 396Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DD8X-ray2.10A/B/C/D196-403[»]
ProteinModelPortaliP78325.
SMRiP78325.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini200 – 400Peptidase M12BPROSITE-ProRule annotationAdd BLAST201
Domaini408 – 494DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini609 – 641EGF-likePROSITE-ProRule annotationAdd BLAST33

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, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOVERGENiHBG006978.
InParanoidiP78325.
KOiK06540.
OMAiCYNGACP.
OrthoDBiEOG091G01NX.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. 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]
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P78325-1) [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
MRGLGLWLLG AMMLPAIAPS RPWALMEQYE VVLPWRLPGP RVRRALPSHL
60 70 80 90 100
GLHPERVSYV LGATGHNFTL HLRKNRDLLG SGYTETYTAA NGSEVTEQPR
110 120 130 140 150
GQDHCFYQGH VEGYPDSAAS LSTCAGLRGF FQVGSDLHLI EPLDEGGEGG
160 170 180 190 200
RHAVYQAEHL LQTAGTCGVS DDSLGSLLGP RTAAVFRPRP GDSLPSRETR
210 220 230 240 250
YVELYVVVDN AEFQMLGSEA AVRHRVLEVV NHVDKLYQKL NFRVVLVGLE
260 270 280 290 300
IWNSQDRFHV SPDPSVTLEN LLTWQARQRT RRHLHDNVQL ITGVDFTGTT
310 320 330 340 350
VGFARVSAMC SHSSGAVNQD HSKNPVGVAC TMAHEMGHNL GMDHDENVQG
360 370 380 390 400
CRCQERFEAG RCIMAGSIGS SFPRMFSDCS QAYLESFLER PQSVCLANAP
410 420 430 440 450
DLSHLVGGPV CGNLFVERGE QCDCGPPEDC RNRCCNSTTC QLAEGAQCAH
460 470 480 490 500
GTCCQECKVK PAGELCRPKK DMCDLEEFCD GRHPECPEDA FQENGTPCSG
510 520 530 540 550
GYCYNGACPT LAQQCQAFWG PGGQAAEESC FSYDILPGCK ASRYRADMCG
560 570 580 590 600
VLQCKGGQQP LGRAICIVDV CHALTTEDGT AYEPVPEGTR CGPEKVCWKG
610 620 630 640 650
RCQDLHVYRS SNCSAQCHNH GVCNHKQECH CHAGWAPPHC AKLLTEVHAA
660 670 680 690 700
SGSLPVFVVV VLVLLAVVLV TLAGIIVYRK ARSRILSRNV APKTTMGRSN
710 720 730 740 750
PLFHQAASRV PAKGGAPAPS RGPQELVPTT HPGQPARHPA SSVALKRPPP
760 770 780 790 800
APPVTVSSPP FPVPVYTRQA PKQVIKPTFA PPVPPVKPGA GAANPGPAEG
810 820
AVGPKVALKP PIQRKQGAGA PTAP
Length:824
Mass (Da):88,771
Last modified:October 3, 2012 - v2
Checksum:iCE3D31330E153DB8
GO
Isoform 2 (identifier: P78325-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     16-92: AIAPSRPWAL...YTETYTAANG → GPAPREGELR...SRQPQHLCRP
     93-131: Missing.
     596-621: Missing.
     774-799: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:733
Mass (Da):78,850
Checksum:i56F70752E92C2FE4
GO
Isoform 3 (identifier: P78325-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     650-742: ASGSLPVFVV...GQPARHPASS → GCQPRAGQGR...RGWCGQPWSS
     743-824: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:742
Mass (Da):80,262
Checksum:iF02B705D4AA89ED3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106F → L in BAA05626 (PubMed:9126482).Curated1
Sequence conflicti372F → L in BAG62738 (PubMed:14702039).Curated1
Sequence conflicti648H → D in BAG62738 (PubMed:14702039).Curated1
Isoform 2 (identifier: P78325-2)
Sequence conflicti46L → F in BAG62738 (PubMed:14702039).Curated1
Isoform 3 (identifier: P78325-3)
Sequence conflicti693A → S in BC064500 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06914435W → R.2 PublicationsCorresponds to variant rs2275725dbSNPEnsembl.1
Natural variantiVAR_059760101G → R.Corresponds to variant rs11101675dbSNPEnsembl.1
Natural variantiVAR_061735189R → W.Corresponds to variant rs45451297dbSNPEnsembl.1
Natural variantiVAR_061736433R → C.Corresponds to variant rs12257830dbSNPEnsembl.1
Natural variantiVAR_069145657F → L.1 PublicationCorresponds to variant rs2275720dbSNPEnsembl.1
Natural variantiVAR_061737775I → T.Corresponds to variant rs3008319dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04615416 – 92AIAPS…TAANG → GPAPREGELRPWGHRAQLHP PPAEEQGPAGLRLHRDLYGC QWLRGDGAASRAGPLLLPGP RRGVPGLSRQPQHLCRP in isoform 2. 1 PublicationAdd BLAST77
Alternative sequenceiVSP_04615593 – 131Missing in isoform 2. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_046156596 – 621Missing in isoform 2. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_046157650 – 742ASGSL…HPASS → GCQPRAGQGRGSSPIQGPPR AGPHHPPGPARPTPGLLGGS EEAAPCSSGHCVQPTLPSSC LHPAGTKAGHQANVRTPSAP SQTRGWCGQPWSS in isoform 3. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_046158743 – 824Missing in isoform 3. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_046159774 – 799Missing in isoform 2. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D26579 mRNA. Translation: BAA05626.1.
AK301147 mRNA. Translation: BAG62738.1.
AL592071 Genomic DNA. No translation available.
BC064500 mRNA. No translation available.
CCDSiCCDS31319.2. [P78325-1]
CCDS58102.1. [P78325-2]
CCDS58103.1. [P78325-3]
RefSeqiNP_001100.3. NM_001109.4. [P78325-1]
NP_001157961.1. NM_001164489.1. [P78325-3]
NP_001157962.1. NM_001164490.1. [P78325-2]
UniGeneiHs.501574.

Genome annotation databases

EnsembliENST00000415217; ENSP00000453855; ENSG00000151651. [P78325-3]
ENST00000445355; ENSP00000453302; ENSG00000151651. [P78325-1]
ENST00000485491; ENSP00000453043; ENSG00000151651. [P78325-2]
GeneIDi101.
KEGGihsa:101.
UCSCiuc009ybi.4. human. [P78325-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D26579 mRNA. Translation: BAA05626.1.
AK301147 mRNA. Translation: BAG62738.1.
AL592071 Genomic DNA. No translation available.
BC064500 mRNA. No translation available.
CCDSiCCDS31319.2. [P78325-1]
CCDS58102.1. [P78325-2]
CCDS58103.1. [P78325-3]
RefSeqiNP_001100.3. NM_001109.4. [P78325-1]
NP_001157961.1. NM_001164489.1. [P78325-3]
NP_001157962.1. NM_001164490.1. [P78325-2]
UniGeneiHs.501574.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4DD8X-ray2.10A/B/C/D196-403[»]
ProteinModelPortaliP78325.
SMRiP78325.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106615. 1 interactor.
IntActiP78325. 2 interactors.
STRINGi9606.ENSP00000453302.

Chemistry databases

BindingDBiP78325.
ChEMBLiCHEMBL5665.
GuidetoPHARMACOLOGYi1656.

Protein family/group databases

MEROPSiM12.208.

PTM databases

iPTMnetiP78325.
PhosphoSitePlusiP78325.

Polymorphism and mutation databases

BioMutaiADAM8.
DMDMi408359955.

Proteomic databases

MaxQBiP78325.
PaxDbiP78325.
PeptideAtlasiP78325.
PRIDEiP78325.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000415217; ENSP00000453855; ENSG00000151651. [P78325-3]
ENST00000445355; ENSP00000453302; ENSG00000151651. [P78325-1]
ENST00000485491; ENSP00000453043; ENSG00000151651. [P78325-2]
GeneIDi101.
KEGGihsa:101.
UCSCiuc009ybi.4. human. [P78325-1]

Organism-specific databases

CTDi101.
DisGeNETi101.
GeneCardsiADAM8.
H-InvDBHIX0035404.
HGNCiHGNC:215. ADAM8.
HPAiHPA064637.
MIMi602267. gene.
neXtProtiNX_P78325.
OpenTargetsiENSG00000151651.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOVERGENiHBG006978.
InParanoidiP78325.
KOiK06540.
OMAiCYNGACP.
OrthoDBiEOG091G01NX.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151651-MONOMER.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiADAM8. human.
GeneWikiiADAM8.
GenomeRNAii101.
PROiP78325.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151651.
CleanExiHS_ADAM8.
ExpressionAtlasiP78325. baseline and differential.
GenevisibleiP78325. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. 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]
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 nameiADAM8_HUMAN
AccessioniPrimary (citable) accession number: P78325
Secondary accession number(s): B4DVM6
, H0YL36, H0YLR0, H0YN39
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 164 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Peptidase families
    Classification of peptidase families and list of entries
  8. 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.