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Q9UKP5 (ATS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 6

Short name=ADAM-TS 6
Short name=ADAM-TS6
Short name=ADAMTS-6
EC=3.4.24.-
Gene names
Name:ADAMTS6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1117 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity.

Tissue specificity

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

Induction

Isoform 1 and isoform 2 expressions are up-regulated by TNF in retinal pigment epithelial cells. Ref.2 Ref.6

Domain

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

Post-translational modification

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-X(2)-(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.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Contains 1 PLAC domain.

Contains 5 TSP type-1 domains.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKP5-1)

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.
Isoform 2 (identifier: Q9UKP5-2)

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.
Isoform 3 (identifier: Q9UKP5-3)

Also known as: Variant 3;

The sequence of this isoform differs from the canonical sequence as follows:
     457-468: DSGRGTCLDNEP → EFLKLGDSISGS
     469-1117: Missing.
Isoform 4 (identifier: Q9UKP5-4)

Also known as: Variant 4;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Propeptide22 – 244223 By similarity
PRO_0000029174
Chain245 – 1117873A disintegrin and metalloproteinase with thrombospondin motifs 6
PRO_0000029175

Regions

Domain250 – 468219Peptidase M12B
Domain495 – 55763Disintegrin
Domain558 – 61356TSP type-1 1
Domain840 – 90061TSP type-1 2
Domain902 – 96059TSP type-1 3
Domain962 – 100746TSP type-1 4
Domain1018 – 107356TSP type-1 5
Domain1079 – 111739PLAC
Region717 – 843127Spacer

Sites

Active site4041 By similarity
Metal binding4031Zinc; catalytic By similarity
Metal binding4071Zinc; catalytic By similarity
Metal binding4131Zinc; catalytic By similarity

Amino acid modifications

Glycosylation991N-linked (GlcNAc...) Potential
Glycosylation1721N-linked (GlcNAc...) Potential
Glycosylation2221N-linked (GlcNAc...) Potential
Glycosylation2341N-linked (GlcNAc...) Potential
Glycosylation7241N-linked (GlcNAc...) Potential
Glycosylation9561N-linked (GlcNAc...) Potential
Disulfide bond326 ↔ 387 By similarity
Disulfide bond362 ↔ 369 By similarity
Disulfide bond381 ↔ 463 By similarity
Disulfide bond420 ↔ 447 By similarity
Disulfide bond490 ↔ 512 By similarity
Disulfide bond501 ↔ 519 By similarity
Disulfide bond507 ↔ 542 By similarity
Disulfide bond532 ↔ 547 By similarity
Disulfide bond570 ↔ 607 By similarity
Disulfide bond574 ↔ 612 By similarity
Disulfide bond585 ↔ 597 By similarity
Disulfide bond911 ↔ 954 By similarity
Disulfide bond915 ↔ 959 By similarity
Disulfide bond926 ↔ 943 By similarity

Natural variations

Alternative sequence283 – 29210AKLYRDSSLG → RLPNFTVIPA in isoform 4.
VSP_037093
Alternative sequence293 – 1117825Missing in isoform 4.
VSP_037094
Alternative sequence422 – 50483TKGHE…QCKYG → RKVMKQQNYGSSHYCEYQSF FLVCLQSRFHHQLFR in isoform 2.
VSP_037095
Alternative sequence457 – 46812DSGRG…LDNEP → EFLKLGDSISGS in isoform 3.
VSP_037096
Alternative sequence469 – 1117649Missing in isoform 3.
VSP_037097
Alternative sequence860 – 90849VQRQE…FIGDW → KMPTRQPTQRARWRTKHILS YALCLLKKLIGNISCRFASS CNLAKETLL in isoform 2.
VSP_037098
Alternative sequence909 – 1117209Missing in isoform 2.
VSP_037099

Experimental info

Sequence conflict41L → S in AAW47399. Ref.2
Sequence conflict241D → G in AAW47398. Ref.2
Sequence conflict831S → P in AAW47398. Ref.2
Sequence conflict2291Y → H in AAW47397. Ref.2
Sequence conflict4061G → V in AAD56357. Ref.1
Sequence conflict4261E → G in AAD56357. Ref.1
Sequence conflict4261E → G in AAW47397. Ref.2
Sequence conflict588 – 5892PA → LK in BAD92922. Ref.4
Sequence conflict7121D → G in AAD56357. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Variant 2) [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: 5901E86BC82A9A87

FASTA1,117125,273
        10         20         30         40         50         60 
MEILWKTLTW ILSLIMASSE FHSDHRLSYS SQEEFLTYLE HYQLTIPIRV DQNGAFLSFT 

        70         80         90        100        110        120 
VKNDKHSRRR RSMDPIDPQQ AVSKLFFKLS AYGKHFHLNL TLNTDFVSKH FTVEYWGKDG 

       130        140        150        160        170        180 
PQWKHDFLDN CHYTGYLQDQ RSTTKVALSN CVGLHGVIAT EDEEYFIEPL KNTTEDSKHF 

       190        200        210        220        230        240 
SYENGHPHVI YKKSALQQRH LYDHSHCGVS DFTRSGKPWW LNDTSTVSYS LPINNTHIHH 

       250        260        270        280        290        300 
RQKRSVSIER FVETLVVADK MMVGYHGRKD IEHYILSVMN IVAKLYRDSS LGNVVNIIVA 

       310        320        330        340        350        360 
RLIVLTEDQP NLEINHHADK SLDSFCKWQK SILSHQSDGN TIPENGIAHH DNAVLITRYD 

       370        380        390        400        410        420 
ICTYKNKPCG TLGLASVAGM CEPERSCSIN EDIGLGSAFT IAHEIGHNFG MNHDGIGNSC 

       430        440        450        460        470        480 
GTKGHEAAKL MAAHITANTN PFSWSACSRD YITSFLDSGR GTCLDNEPPK RDFLYPAVAP 

       490        500        510        520        530        540 
GQVYDADEQC RFQYGATSRQ CKYGEVCREL WCLSKSNRCV TNSIPAAEGT LCQTGNIEKG 

       550        560        570        580        590        600 
WCYQGDCVPF GTWPQSIDGG WGPWSLWGEC SRTCGGGVSS SLRHCDSPAP SGGGKYCLGE 

       610        620        630        640        650        660 
RKRYRSCNTD PCPLGSRDFR EKQCADFDNM PFRGKYYNWK PYTGGGVKPC ALNCLAEGYN 

       670        680        690        700        710        720 
FYTERAPAVI DGTQCNADSL DICINGECKH VGCDNILGSD AREDRCRVCG GDGSTCDAIE 

       730        740        750        760        770        780 
GFFNDSLPRG GYMEVVQIPR GSVHIEVREV AMSKNYIALK SEGDDYYING AWTIDWPRKF 

       790        800        810        820        830        840 
DVAGTAFHYK RPTDEPESLE ALGPTSENLI VMVLLQEQNL GIRYKFNVPI TRTGSGDNEV 

       850        860        870        880        890        900 
GFTWNHQPWS ECSATCAGGV QRQEVVCKRL DDNSIVQNNY CDPDSKPPEN QRACNTEPCP 

       910        920        930        940        950        960 
PEWFIGDWLE CSKTCDGGMR TRAVLCIRKI GPSEEETLDY SGCLTHRPVE KEPCNNQSCP 

       970        980        990       1000       1010       1020 
PQWVALDWSE CTPKCGPGFK HRIVLCKSSD LSKTFPAAQC PEESKPPVRI RCSLGRCPPP 

      1030       1040       1050       1060       1070       1080 
RWVTGDWGQC SAQCGLGQQM RTVQCLSYTG QASSDCLETV RPPSMQQCES KCDSTPISNT 

      1090       1100       1110 
EECKDVNKVA YCPLVLKFKF CSRAYFRQMC CKTCQGH 

« Hide

Isoform 2 (Variant 1) [UniParc].

Checksum: EA137275B9A465C2
Show »

FASTA86097,152
Isoform 3 (Variant 3) [UniParc].

Checksum: E8D2E75EF8A1C468
Show »

FASTA46853,165
Isoform 4 (Variant 4) [UniParc].

Checksum: 01A54680DCEFABD7
Show »

FASTA29234,189

References

« Hide 'large scale' references
[1]"ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases."
Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S.
J. Biol. Chem. 274:25555-25563(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"Analysis of full length ADAMTS6 transcript reveals alternative splicing and a role for the 5' untranslated region in translational control."
Bevitt D.J., Li Z., Lindrop J.L., Barker M.D., Clarke M.P., McKie N.
Gene 359:99-110(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), INDUCTION.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 588-1117 (ISOFORM 1).
Tissue: Brain.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 804-1117 (ISOFORM 1).
Tissue: Uterus.
[6]"Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19: transcriptional regulation by TNFalpha."
Bevitt D.J., Mohamed J., Catterall J.B., Li Z., Arris C.E., Hiscott P., Sheridan C., Langton K.P., Barker M.D., Clarke M.P., McKie N.
Biochim. Biophys. Acta 1626:83-91(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3983.2. [Q9UKP5-1]
RefSeqNP_922932.2. NM_197941.2. [Q9UKP5-1]
UniGeneHs.482291.

3D structure databases

ProteinModelPortalQ9UKP5.
SMRQ9UKP5. Positions 247-729.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116345. 2 interactions.

Protein family/group databases

MEROPSM12.230.

PTM databases

PhosphoSiteQ9UKP5.

Polymorphism databases

DMDM229462816.

Proteomic databases

PaxDbQ9UKP5.
PRIDEQ9UKP5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381052; ENSP00000424377; ENSG00000049192. [Q9UKP5-4]
ENST00000381055; ENSP00000370443; ENSG00000049192. [Q9UKP5-1]
ENST00000536360; ENSP00000440995; ENSG00000049192. [Q9UKP5-3]
GeneID11174.
KEGGhsa:11174.
UCSCuc003jto.4. human. [Q9UKP5-1]

Organism-specific databases

CTD11174.
GeneCardsGC05M064526.
HGNCHGNC:222. ADAMTS6.
HPAHPA027216.
MIM605008. gene.
neXtProtNX_Q9UKP5.
PharmGKBPA24550.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237764.
HOGENOMHOG000004800.
HOVERGENHBG004315.
KOK08621.
OMANLIIMVL.
OrthoDBEOG78WKQV.
PhylomeDBQ9UKP5.
TreeFamTF313537.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressQ9UKP5.
BgeeQ9UKP5.
CleanExHS_ADAMTS6.
GenevestigatorQ9UKP5.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF08686. PLAC. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
PRINTSPR01857. ADAMTSFAMILY.
SMARTSM00209. TSP1. 5 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 5 hits.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi11174.
NextBio42521.
PROQ9UKP5.
SOURCESearch...

Entry information

Entry nameATS6_HUMAN
AccessionPrimary (citable) accession number: Q9UKP5
Secondary accession number(s): Q59EX6 expand/collapse secondary AC list , Q5IR87, Q5IR88, Q5IR89, Q68DL1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 5, 2009
Last modified: July 9, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM