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Q86TH1 (ATL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADAMTS-like protein 2

Short name=ADAMTSL-2
Gene names
Name:ADAMTSL2
Synonyms:KIAA0605
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length951 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Subunit structure

Interacts with LTBP1. Ref.5

Subcellular location

Secreted Potential.

Post-translational modification

Glycosylated By similarity. 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. Ref.4

Involvement in disease

Geleophysic dysplasia 1 (GPHYSD1) [MIM:231050]: An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Miscellaneous

There is a significant increase in total and active TGFB1 in the culture medium as well as nuclear localization of phosphorylated SMAD2 in fibroblasts from individuals with geleophysic dysplasia.

Sequence similarities

Contains 1 PLAC domain.

Contains 7 TSP type-1 domains.

Caution

Although strongly similar to members of the ADAMTS family it lacks the metalloprotease and disintegrin-like domains which are typical of that family.

Sequence caution

The sequence BAA25531.2 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 951929ADAMTS-like protein 2
PRO_0000249682

Regions

Domain47 – 10660TSP type-1 1
Domain564 – 61855TSP type-1 2
Domain622 – 68665TSP type-1 3
Domain688 – 73649TSP type-1 4
Domain737 – 79559TSP type-1 5
Domain797 – 85155TSP type-1 6
Domain853 – 90856TSP type-1 7
Domain912 – 95039PLAC

Amino acid modifications

Glycosylation871N-linked (GlcNAc...) Potential
Glycosylation3671N-linked (GlcNAc...) Potential
Glycosylation4281N-linked (GlcNAc...) (complex) Ref.4
Glycosylation4751N-linked (GlcNAc...) Potential
Glycosylation5111N-linked (GlcNAc...) Potential
Glycosylation5241N-linked (GlcNAc...) Potential
Glycosylation5331N-linked (GlcNAc...) Potential
Glycosylation5441N-linked (GlcNAc...) Potential
Glycosylation7311N-linked (GlcNAc...) Potential
Glycosylation8071N-linked (GlcNAc...) Potential
Disulfide bond59 ↔ 100 By similarity
Disulfide bond63 ↔ 105 By similarity
Disulfide bond74 ↔ 90 By similarity

Natural variations

Natural variant501W → C in GPHYSD1. Ref.6
VAR_066543
Natural variant721R → Q in GPHYSD1. Ref.6
VAR_066544
Natural variant1131R → H in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.5
VAR_054874
Natural variant1141E → K in GPHYSD1. Ref.5 Ref.6
VAR_054875
Natural variant1471P → L in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.5
VAR_054876
Natural variant1591R → W in GPHYSD1. Ref.6
VAR_066545
Natural variant1651A → T in GPHYSD1. Ref.6
VAR_066546
Natural variant1711C → R in GPHYSD1. Ref.6
VAR_066547
Natural variant2211R → C in GPHYSD1. Ref.6
VAR_066548
Natural variant2391A → T in GPHYSD1. Ref.6
VAR_066549
Natural variant3641V → I. Ref.1
Corresponds to variant rs35767802 [ dbSNP | Ensembl ].
VAR_046011
Natural variant383 – 39210Missing in GPHYSD1.
VAR_066550
Natural variant5931R → C in GPHYSD1. Ref.6
VAR_066551
Natural variant6351S → L in GPHYSD1. Ref.6
VAR_066552
Natural variant8111G → R in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.5
VAR_054877
Natural variant9061P → L in GPHYSD1. Ref.6
VAR_066553

Experimental info

Sequence conflict591C → F in BAA25531. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q86TH1 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 93A9B0DC5BAB6CC7

FASTA951104,621
        10         20         30         40         50         60 
MDGRWQCSCW AWFLLVLAVV AGDTVSTGST DNSPTSNSLE GGTDATAFWW GEWTKWTACS 

        70         80         90        100        110        120 
RSCGGGVTSQ ERHCLQQRRK SVPGPGNRTC TGTSKRYQLC RVQECPPDGR SFREEQCVSF 

       130        140        150        160        170        180 
NSHVYNGRTH QWKPLYPDDY VHISSKPCDL HCTTVDGQRQ LMVPARDGTS CKLTDLRGVC 

       190        200        210        220        230        240 
VSGKCEPIGC DGVLFSTHTL DKCGICQGDG SSCTHVTGNY RKGNAHLGYS LVTHIPAGAR 

       250        260        270        280        290        300 
DIQIVERKKS ADVLALADEA GYYFFNGNYK VDSPKNFNIA GTVVKYRRPM DVYETGIEYI 

       310        320        330        340        350        360 
VAQGPTNQGL NVMVWNQNGK SPSITFEYTL LQPPHESRPQ PIYYGFSESA ESQGLDGAGL 

       370        380        390        400        410        420 
MGFVPHNGSL YGQASSERLG LDNRLFGHPG LDMELGPSQG QETNEVCEQA GGGACEGPPR 

       430        440        450        460        470        480 
GKGFRDRNVT GTPLTGDKDD EEVDTHFASQ EFFSANAISD QLLGAGSDLK DFTLNETVNS 

       490        500        510        520        530        540 
IFAQGAPRSS LAESFFVDYE ENEGAGPYLL NGSYLELSSD RVANSSSEAP FPNVSTSLLT 

       550        560        570        580        590        600 
SAGNRTHKAR TRPKARKQGV SPADMYRWKL SSHEPCSATC TTGVMSAYAM CVRYDGVEVD 

       610        620        630        640        650        660 
DSYCDALTRP EPVHEFCAGR ECQPRWETSS WSECSRTCGE GYQFRVVRCW KMLSPGFDSS 

       670        680        690        700        710        720 
VYSDLCEAAE AVRPEERKTC RNPACGPQWE MSEWSECTAK CGERSVVTRD IRCSEDEKLC 

       730        740        750        760        770        780 
DPNTRPVGEK NCTGPPCDRQ WTVSDWGPCS GSCGQGRTIR HVYCKTSDGR VVPESQCQME 

       790        800        810        820        830        840 
TKPLAIHPCG DKNCPAHWLA QDWERCNTTC GRGVKKRLVL CMELANGKPQ TRSGPECGLA 

       850        860        870        880        890        900 
KKPPEESTCF ERPCFKWYTS PWSECTKTCG VGVRMRDVKC YQGTDIVRGC DPLVKPVGRQ 

       910        920        930        940        950 
ACDLQPCPTE PPDDSCQDQP GTNCALAIKV NLCGHWYYSK ACCRSCRPPH S 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-364.
Tissue: Brain.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: PNS.
[4]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-428.
[5]"ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation."
Le Goff C., Morice-Picard F., Dagoneau N., Wang L.W., Perrot C., Crow Y.J., Bauer F., Flori E., Prost-Squarcioni C., Krakow D., Ge G., Greenspan D.S., Bonnet D., Le Merrer M., Munnich A., Apte S.S., Cormier-Daire V.
Nat. Genet. 40:1119-1123(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GPHYSD1 HIS-113; LYS-114; LEU-147 AND ARG-811, CHARACTERIZATION OF VARIANTS HIS-113; LEU-147 AND ARG-811, INTERACTION WITH LTBP1.
[6]"Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia."
Allali S., Le Goff C., Pressac-Diebold I., Pfennig G., Mahaut C., Dagoneau N., Alanay Y., Brady A.F., Crow Y.J., Devriendt K., Drouin-Garraud V., Flori E., Genevieve D., Hennekam R.C., Hurst J., Krakow D., Le Merrer M., Lichtenbelt K.D. expand/collapse author list , Lynch S.A., Lyonnet S., MacDermot K., Mansour S., Megarbane A., Santos H.G., Splitt M., Superti-Furga A., Unger S., Williams D., Munnich A., Cormier-Daire V.
J. Med. Genet. 48:417-421(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GPHYSD1 CYS-50; GLN-72; LYS-114; TRP-159; THR-165; ARG-171; CYS-221; THR-239; 383-ASN--ASP-392 DEL; CYS-593; LEU-635 AND LEU-906.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB011177 mRNA. Translation: BAA25531.2. Different initiation.
BX324209, BX629352, BX649571 Genomic DNA. Translation: CAI17317.1.
BX649571, BX324209, BX629352 Genomic DNA. Translation: CAI18773.1.
BX629352, BX324209, BX649571 Genomic DNA. Translation: CAI23592.1.
BC050544 mRNA. Translation: AAH50544.1.
PIRT00260.
RefSeqNP_001138792.1. NM_001145320.1.
NP_055509.2. NM_014694.3.
XP_005272296.1. XM_005272239.1.
UniGeneHs.522543.

3D structure databases

ProteinModelPortalQ86TH1.
SMRQ86TH1. Positions 18-333, 564-737, 742-911.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115068. 1 interaction.
IntActQ86TH1. 2 interactions.
MINTMINT-8417703.
STRING9606.ENSP00000346478.

PTM databases

PhosphoSiteQ86TH1.

Polymorphism databases

DMDM74750384.

Proteomic databases

PaxDbQ86TH1.
PRIDEQ86TH1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354484; ENSP00000346478; ENSG00000197859.
ENST00000393060; ENSP00000376780; ENSG00000197859.
GeneID9719.
KEGGhsa:9719.
UCSCuc004cei.3. human.

Organism-specific databases

CTD9719.
GeneCardsGC09P136397.
H-InvDBHIX0170293.
HGNCHGNC:14631. ADAMTSL2.
HPAHPA045634.
MIM231050. phenotype.
612277. gene.
neXtProtNX_Q86TH1.
Orphanet2623. Geleophysic dysplasia.
PharmGKBPA134920655.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299441.
HOGENOMHOG000116076.
HOVERGENHBG079685.
InParanoidQ86TH1.
OrthoDBEOG74N5FZ.
PhylomeDBQ86TH1.
TreeFamTF316874.

Enzyme and pathway databases

SignaLinkQ86TH1.

Gene expression databases

ArrayExpressQ86TH1.
BgeeQ86TH1.
CleanExHS_ADAMTSL2.
GenevestigatorQ86TH1.

Family and domain databases

InterProIPR010294. ADAM_spacer1.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR010909. PLAC.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF08686. PLAC. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
PRINTSPR01857. ADAMTSFAMILY.
SMARTSM00209. TSP1. 7 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 7 hits.
PROSITEPS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAMTSL2. human.
GenomeRNAi9719.
NextBio36549.
PROQ86TH1.
SOURCESearch...

Entry information

Entry nameATL2_HUMAN
AccessionPrimary (citable) accession number: Q86TH1
Secondary accession number(s): B1B0D5, O60345
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: June 1, 2003
Last modified: April 16, 2014
This is version 91 of the entry and version 1 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM