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

A disintegrin and metalloproteinase with thrombospondin motifs 6

Gene

ADAMTS6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi403Zinc; catalyticBy similarity1
Active sitei404PROSITE-ProRule annotation1
Metal bindingi407Zinc; catalyticBy similarity1
Metal bindingi413Zinc; catalyticBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5083635 Defective B3GALTL causes Peters-plus syndrome (PpS)
R-HSA-5173214 O-glycosylation of TSR domain-containing proteins

Protein family/group databases

MEROPSiM12.230

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 6 (EC:3.4.24.-)
Short name:
ADAM-TS 6
Short name:
ADAM-TS6
Short name:
ADAMTS-6
Gene namesi
Name:ADAMTS6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000049192.14
HGNCiHGNC:222 ADAMTS6
MIMi605008 gene
neXtProtiNX_Q9UKP5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi11174
OpenTargetsiENSG00000049192
PharmGKBiPA24550

Polymorphism and mutation databases

BioMutaiADAMTS6
DMDMi229462816

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000002917422 – 244By similarityAdd BLAST223
ChainiPRO_0000029175245 – 1117A disintegrin and metalloproteinase with thrombospondin motifs 6Add BLAST873

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi99N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi222N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi234N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi326 ↔ 387By similarity
Disulfide bondi362 ↔ 369By similarity
Disulfide bondi381 ↔ 463By similarity
Disulfide bondi420 ↔ 447By similarity
Disulfide bondi490 ↔ 512By similarity
Disulfide bondi501 ↔ 519By similarity
Disulfide bondi507 ↔ 542By similarity
Disulfide bondi532 ↔ 547By similarity
Disulfide bondi570 ↔ 607By similarity
Disulfide bondi574 ↔ 612By similarity
Disulfide bondi585 ↔ 597By similarity
Glycosylationi724N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi911 ↔ 954By similarity
Disulfide bondi915 ↔ 959By similarity
Disulfide bondi926 ↔ 943By similarity
Glycosylationi956N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X2-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiQ9UKP5
PeptideAtlasiQ9UKP5
PRIDEiQ9UKP5
ProteomicsDBi84829
84830 [Q9UKP5-2]
84831 [Q9UKP5-3]
84832 [Q9UKP5-4]

PTM databases

iPTMnetiQ9UKP5
PhosphoSitePlusiQ9UKP5

Expressioni

Tissue specificityi

Expressed at low levels in placenta and barely detectable in a number of other tissues.

Inductioni

Isoform 1 and isoform 2 expressions are up-regulated by TNF in retinal pigment epithelial cells.2 Publications

Gene expression databases

BgeeiENSG00000049192 Expressed in 129 organ(s), highest expression level in amniotic fluid
CleanExiHS_ADAMTS6
GenevisibleiQ9UKP5 HS

Organism-specific databases

HPAiHPA043441

Interactioni

Protein-protein interaction databases

BioGridi116345, 2 interactors
STRINGi9606.ENSP00000370443

Structurei

3D structure databases

ProteinModelPortaliQ9UKP5
SMRiQ9UKP5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini250 – 468Peptidase M12BPROSITE-ProRule annotationAdd BLAST219
Domaini495 – 557DisintegrinAdd BLAST63
Domaini558 – 613TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini840 – 900TSP type-1 2PROSITE-ProRule annotationAdd BLAST61
Domaini902 – 960TSP type-1 3PROSITE-ProRule annotationAdd BLAST59
Domaini962 – 1007TSP type-1 4PROSITE-ProRule annotationAdd BLAST46
Domaini1018 – 1073TSP type-1 5PROSITE-ProRule annotationAdd BLAST56
Domaini1079 – 1117PLACPROSITE-ProRule annotationAdd BLAST39

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni717 – 843SpacerAdd BLAST127

Domaini

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3538 Eukaryota
KOG4597 Eukaryota
ENOG410XPKZ LUCA
GeneTreeiENSGT00900000140815
HOGENOMiHOG000004800
HOVERGENiHBG004315
InParanoidiQ9UKP5
KOiK08621
OMAiGWCYQGD
OrthoDBiEOG091G14M8
PhylomeDBiQ9UKP5
TreeFamiTF313537

Family and domain databases

Gene3Di2.20.100.10, 5 hits
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR010294 ADAM_spacer1
IPR013273 ADAMTS/ADAMTS-like
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR010909 PLAC
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
PfamiView protein in Pfam
PF05986 ADAM_spacer1, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF08686 PLAC, 1 hit
PF01421 Reprolysin, 1 hit
PF00090 TSP_1, 5 hits
PRINTSiPR01857 ADAMTSFAMILY
SMARTiView protein in SMART
SM00209 TSP1, 5 hits
SUPFAMiSSF82895 SSF82895, 5 hits
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS50900 PLAC, 1 hit
PS50092 TSP1, 4 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9UKP5-1) [UniParc]FASTAAdd to basket
Also known as: Variant 2

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
MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV
60 70 80 90 100
DQNGAFLSFT VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL
110 120 130 140 150
TLNTDFVSKH FTVEYWGKDG PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN
160 170 180 190 200
CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF SYENGHPHVI YKKSALQQRH
210 220 230 240 250
LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH RQKRSVSIER
260 270 280 290 300
FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA
310 320 330 340 350
RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH
360 370 380 390 400
DNAVLITRYD ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT
410 420 430 440 450
IAHEIGHNFG MNHDGIGNSC GTKGHEAAKL MAAHITANTN PFSWSACSRD
460 470 480 490 500
YITSFLDSGR GTCLDNEPPK RDFLYPAVAP GQVYDADEQC RFQYGATSRQ
510 520 530 540 550
CKYGEVCREL WCLSKSNRCV TNSIPAAEGT LCQTGNIEKG WCYQGDCVPF
560 570 580 590 600
GTWPQSIDGG WGPWSLWGEC SRTCGGGVSS SLRHCDSPAP SGGGKYCLGE
610 620 630 640 650
RKRYRSCNTD PCPLGSRDFR EKQCADFDNM PFRGKYYNWK PYTGGGVKPC
660 670 680 690 700
ALNCLAEGYN FYTERAPAVI DGTQCNADSL DICINGECKH VGCDNILGSD
710 720 730 740 750
AREDRCRVCG GDGSTCDAIE GFFNDSLPRG GYMEVVQIPR GSVHIEVREV
760 770 780 790 800
AMSKNYIALK SEGDDYYING AWTIDWPRKF DVAGTAFHYK RPTDEPESLE
810 820 830 840 850
ALGPTSENLI VMVLLQEQNL GIRYKFNVPI TRTGSGDNEV GFTWNHQPWS
860 870 880 890 900
ECSATCAGGV QRQEVVCKRL DDNSIVQNNY CDPDSKPPEN QRACNTEPCP
910 920 930 940 950
PEWFIGDWLE CSKTCDGGMR TRAVLCIRKI GPSEEETLDY SGCLTHRPVE
960 970 980 990 1000
KEPCNNQSCP PQWVALDWSE CTPKCGPGFK HRIVLCKSSD LSKTFPAAQC
1010 1020 1030 1040 1050
PEESKPPVRI RCSLGRCPPP RWVTGDWGQC SAQCGLGQQM RTVQCLSYTG
1060 1070 1080 1090 1100
QASSDCLETV RPPSMQQCES KCDSTPISNT EECKDVNKVA YCPLVLKFKF
1110
CSRAYFRQMC CKTCQGH
Length:1,117
Mass (Da):125,273
Last modified:May 5, 2009 - v2
Checksum:i5901E86BC82A9A87
GO
Isoform 2 (identifier: Q9UKP5-2) [UniParc]FASTAAdd to basket
Also known as: Variant 1

The sequence of this isoform differs from the canonical sequence as follows:
     422-504: TKGHEAAKLM...GATSRQCKYG → RKVMKQQNYGSSHYCEYQSFFLVCLQSRFHHQLFR
     860-908: VQRQEVVCKR...CPPEWFIGDW → KMPTRQPTQR...SCNLAKETLL
     909-1117: Missing.

Note: Contains critical point mutations in the region encoding the catalytic domain as well as 2 point mutations compared with genomic sequence. May either be a rare polymorphism or may have arisen through a combination of aberrant RNA editing and point mutation/sequencing error.
Show »
Length:860
Mass (Da):97,152
Checksum:iEA137275B9A465C2
GO
Isoform 3 (identifier: Q9UKP5-3) [UniParc]FASTAAdd to basket
Also known as: Variant 3

The sequence of this isoform differs from the canonical sequence as follows:
     457-468: DSGRGTCLDNEP → EFLKLGDSISGS
     469-1117: Missing.

Show »
Length:468
Mass (Da):53,165
Checksum:iE8D2E75EF8A1C468
GO
Isoform 4 (identifier: Q9UKP5-4) [UniParc]FASTAAdd to basket
Also known as: Variant 4

The sequence of this isoform differs from the canonical sequence as follows:
     283-292: AKLYRDSSLG → RLPNFTVIPA
     293-1117: Missing.

Show »
Length:292
Mass (Da):34,189
Checksum:i01A54680DCEFABD7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4L → S in AAW47399 (PubMed:16129570).Curated1
Sequence conflicti24D → G in AAW47398 (PubMed:16129570).Curated1
Sequence conflicti83S → P in AAW47398 (PubMed:16129570).Curated1
Sequence conflicti229Y → H in AAW47397 (PubMed:16129570).Curated1
Sequence conflicti406G → V in AAD56357 (PubMed:10464288).Curated1
Sequence conflicti426E → G in AAD56357 (PubMed:10464288).Curated1
Sequence conflicti426E → G in AAW47397 (PubMed:16129570).Curated1
Sequence conflicti588 – 589PA → LK in BAD92922 (Ref. 4) Curated2
Sequence conflicti712D → G in AAD56357 (PubMed:10464288).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037093283 – 292AKLYRDSSLG → RLPNFTVIPA in isoform 4. 1 Publication10
Alternative sequenceiVSP_037094293 – 1117Missing in isoform 4. 1 PublicationAdd BLAST825
Alternative sequenceiVSP_037095422 – 504TKGHE…QCKYG → RKVMKQQNYGSSHYCEYQSF FLVCLQSRFHHQLFR in isoform 2. 1 PublicationAdd BLAST83
Alternative sequenceiVSP_037096457 – 468DSGRG…LDNEP → EFLKLGDSISGS in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_037097469 – 1117Missing in isoform 3. 1 PublicationAdd BLAST649
Alternative sequenceiVSP_037098860 – 908VQRQE…FIGDW → KMPTRQPTQRARWRTKHILS YALCLLKKLIGNISCRFASS CNLAKETLL in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_037099909 – 1117Missing in isoform 2. 1 PublicationAdd BLAST209

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF140674 mRNA Translation: AAD56357.1
AY692424 mRNA Translation: AAW47397.1
AY692425 mRNA Translation: AAW47398.1
AY692426 mRNA Translation: AAW47399.1
AC008847 Genomic DNA No translation available.
AC008868 Genomic DNA No translation available.
AC025176 Genomic DNA No translation available.
AC025186 Genomic DNA No translation available.
AC099505 Genomic DNA No translation available.
AB209685 mRNA Translation: BAD92922.1
CR749356 mRNA Translation: CAH18209.1
CCDSiCCDS3983.2 [Q9UKP5-1]
RefSeqiNP_922932.2, NM_197941.3 [Q9UKP5-1]
XP_011541415.1, XM_011543113.2 [Q9UKP5-1]
XP_011541416.1, XM_011543114.2 [Q9UKP5-1]
UniGeneiHs.482291

Genome annotation databases

EnsembliENST00000381052; ENSP00000424377; ENSG00000049192 [Q9UKP5-4]
ENST00000381055; ENSP00000370443; ENSG00000049192 [Q9UKP5-1]
GeneIDi11174
KEGGihsa:11174
UCSCiuc003jtp.4 human [Q9UKP5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF140674 mRNA Translation: AAD56357.1
AY692424 mRNA Translation: AAW47397.1
AY692425 mRNA Translation: AAW47398.1
AY692426 mRNA Translation: AAW47399.1
AC008847 Genomic DNA No translation available.
AC008868 Genomic DNA No translation available.
AC025176 Genomic DNA No translation available.
AC025186 Genomic DNA No translation available.
AC099505 Genomic DNA No translation available.
AB209685 mRNA Translation: BAD92922.1
CR749356 mRNA Translation: CAH18209.1
CCDSiCCDS3983.2 [Q9UKP5-1]
RefSeqiNP_922932.2, NM_197941.3 [Q9UKP5-1]
XP_011541415.1, XM_011543113.2 [Q9UKP5-1]
XP_011541416.1, XM_011543114.2 [Q9UKP5-1]
UniGeneiHs.482291

3D structure databases

ProteinModelPortaliQ9UKP5
SMRiQ9UKP5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116345, 2 interactors
STRINGi9606.ENSP00000370443

Protein family/group databases

MEROPSiM12.230

PTM databases

iPTMnetiQ9UKP5
PhosphoSitePlusiQ9UKP5

Polymorphism and mutation databases

BioMutaiADAMTS6
DMDMi229462816

Proteomic databases

PaxDbiQ9UKP5
PeptideAtlasiQ9UKP5
PRIDEiQ9UKP5
ProteomicsDBi84829
84830 [Q9UKP5-2]
84831 [Q9UKP5-3]
84832 [Q9UKP5-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381052; ENSP00000424377; ENSG00000049192 [Q9UKP5-4]
ENST00000381055; ENSP00000370443; ENSG00000049192 [Q9UKP5-1]
GeneIDi11174
KEGGihsa:11174
UCSCiuc003jtp.4 human [Q9UKP5-1]

Organism-specific databases

CTDi11174
DisGeNETi11174
EuPathDBiHostDB:ENSG00000049192.14
GeneCardsiADAMTS6
HGNCiHGNC:222 ADAMTS6
HPAiHPA043441
MIMi605008 gene
neXtProtiNX_Q9UKP5
OpenTargetsiENSG00000049192
PharmGKBiPA24550
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3538 Eukaryota
KOG4597 Eukaryota
ENOG410XPKZ LUCA
GeneTreeiENSGT00900000140815
HOGENOMiHOG000004800
HOVERGENiHBG004315
InParanoidiQ9UKP5
KOiK08621
OMAiGWCYQGD
OrthoDBiEOG091G14M8
PhylomeDBiQ9UKP5
TreeFamiTF313537

Enzyme and pathway databases

ReactomeiR-HSA-5083635 Defective B3GALTL causes Peters-plus syndrome (PpS)
R-HSA-5173214 O-glycosylation of TSR domain-containing proteins

Miscellaneous databases

ChiTaRSiADAMTS6 human
GenomeRNAii11174
PROiPR:Q9UKP5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000049192 Expressed in 129 organ(s), highest expression level in amniotic fluid
CleanExiHS_ADAMTS6
GenevisibleiQ9UKP5 HS

Family and domain databases

Gene3Di2.20.100.10, 5 hits
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR010294 ADAM_spacer1
IPR013273 ADAMTS/ADAMTS-like
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR010909 PLAC
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
PfamiView protein in Pfam
PF05986 ADAM_spacer1, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF08686 PLAC, 1 hit
PF01421 Reprolysin, 1 hit
PF00090 TSP_1, 5 hits
PRINTSiPR01857 ADAMTSFAMILY
SMARTiView protein in SMART
SM00209 TSP1, 5 hits
SUPFAMiSSF82895 SSF82895, 5 hits
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS50900 PLAC, 1 hit
PS50092 TSP1, 4 hits
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiATS6_HUMAN
AccessioniPrimary (citable) accession number: Q9UKP5
Secondary accession number(s): Q59EX6
, Q5IR87, Q5IR88, Q5IR89, Q68DL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: November 7, 2018
This is version 167 of the entry and version 2 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again