Q86TH1 (ATL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ADAMTS-like protein 2
Short name=ADAMTSL-2

Gene names

Name:	ADAMTSL2
Synonyms:	KIAA0605

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	951 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Interacts with LTBP1. Ref.4
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.
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.4 Ref.5
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.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype Ref.4. Source: BHF-UCL
Cellular_component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 951	929	ADAMTS-like protein 2		PRO_0000249682
Regions
	Domain	47 – 106	60	TSP type-1 1
	Domain	564 – 618	55	TSP type-1 2
	Domain	622 – 686	65	TSP type-1 3
	Domain	688 – 736	49	TSP type-1 4
	Domain	737 – 795	59	TSP type-1 5
	Domain	797 – 851	55	TSP type-1 6
	Domain	853 – 908	56	TSP type-1 7
	Domain	912 – 950	39	PLAC
Amino acid modifications
	Glycosylation	87	1	N-linked (GlcNAc...) Potential
	Glycosylation	367	1	N-linked (GlcNAc...) Potential
	Glycosylation	428	1	N-linked (GlcNAc...) Potential
	Glycosylation	475	1	N-linked (GlcNAc...) Potential
	Glycosylation	511	1	N-linked (GlcNAc...) Potential
	Glycosylation	524	1	N-linked (GlcNAc...) Potential
	Glycosylation	533	1	N-linked (GlcNAc...) Potential
	Glycosylation	544	1	N-linked (GlcNAc...) Potential
	Glycosylation	731	1	N-linked (GlcNAc...) Potential
	Glycosylation	807	1	N-linked (GlcNAc...) Potential
	Disulfide bond	59 ↔ 100		By similarity
	Disulfide bond	63 ↔ 105		By similarity
	Disulfide bond	74 ↔ 90		By similarity
Natural variations
	Natural variant	50	1	W → C in GPHYSD1. Ref.5		VAR_066543
	Natural variant	72	1	R → Q in GPHYSD1. Ref.5		VAR_066544
	Natural variant	113	1	R → H in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.4		VAR_054874
	Natural variant	114	1	E → K in GPHYSD1. Ref.4 Ref.5		VAR_054875
	Natural variant	147	1	P → L in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.4		VAR_054876
	Natural variant	159	1	R → W in GPHYSD1. Ref.5		VAR_066545
	Natural variant	165	1	A → T in GPHYSD1. Ref.5		VAR_066546
	Natural variant	171	1	C → R in GPHYSD1. Ref.5		VAR_066547
	Natural variant	221	1	R → C in GPHYSD1. Ref.5		VAR_066548
	Natural variant	239	1	A → T in GPHYSD1. Ref.5		VAR_066549
	Natural variant	364	1	V → I. Ref.1 Corresponds to variant rs35767802 [ dbSNP | Ensembl ].		VAR_046011
	Natural variant	383 – 392	10	Missing in GPHYSD1.		VAR_066550
	Natural variant	593	1	R → C in GPHYSD1. Ref.5		VAR_066551
	Natural variant	635	1	S → L in GPHYSD1. Ref.5		VAR_066552
	Natural variant	811	1	G → R in GPHYSD1; leads to the reduced secretion of the mutated protein. Ref.4		VAR_054877
	Natural variant	906	1	P → L in GPHYSD1. Ref.5		VAR_066553
Experimental info
	Sequence conflict	59	1	C → F in BAA25531. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q86TH1 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 93A9B0DC5BAB6CC7	FASTA	951	104,621
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[5]	"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. , 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

GeneReviews

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.
IPI	IPI00644346.
PIR	T00260.
RefSeq	NP_001138792.1. NM_001145320.1. NP_055509.2. NM_014694.3.
UniGene	Hs.522543.
3D structure databases
HSSP	HSSP built from PDB template 1LSL based on UniProtKB P07996.
ProteinModelPortal	Q86TH1.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86TH1. 1 interaction.
STRING	9606.ENSP00000346478.
PTM databases
PhosphoSite	Q86TH1.
Polymorphism databases
DMDM	74750384.
Proteomic databases
PaxDb	Q86TH1.
PRIDE	Q86TH1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354484; ENSP00000346478; ENSG00000197859. ENST00000393060; ENSP00000376780; ENSG00000197859.
GeneID	9719.
KEGG	hsa:9719.
UCSC	uc004cei.3. human.
Organism-specific databases
CTD	9719.
GeneCards	GC09P136397.
H-InvDB	HIX0170293.
HGNC	HGNC:14631. ADAMTSL2.
HPA	HPA045634.
MIM	231050. phenotype. 612277. gene.
neXtProt	NX_Q86TH1.
Orphanet	2623. Geleophysic dysplasia.
PharmGKB	PA134920655.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG299441.
HOGENOM	HOG000116076.
HOVERGEN	HBG079685.
InParanoid	Q86TH1.
OrthoDB	EOG4SJ5D6.
PhylomeDB	Q86TH1.
Gene expression databases
ArrayExpress	Q86TH1.
Bgee	Q86TH1.
CleanEx	HS_ADAMTSL2.
Genevestigator	Q86TH1.
GermOnline	ENSG00000197859. Homo sapiens.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. IPR013273. Peptidase_M12B_ADAM-TS. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Pfam	PF05986. ADAM_spacer1. 1 hit. PF08686. PLAC. 1 hit. PF00090. TSP_1. 5 hits. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 7 hits. [Graphical view]
SUPFAM	SSF82895. TSP1. 7 hits.
PROSITE	PS50900. PLAC. 1 hit. PS50092. TSP1. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ADAMTSL2. human.
GenomeRNAi	9719.
NextBio	36549.
SOURCE	Search...

Entry information

Entry name

ATL2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.