ATL2_HUMAN
ID ATL2_HUMAN Reviewed; 951 AA.
AC Q86TH1; B1B0D5; O60345;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=ADAMTS-like protein 2;
DE Short=ADAMTSL-2;
DE Flags: Precursor;
GN Name=ADAMTSL2; Synonyms=KIAA0605;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-364.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP GLYCOSYLATION AT ASN-428.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [5]
RP VARIANTS GPHYSD1 HIS-113; LYS-114; LEU-147 AND ARG-811, CHARACTERIZATION OF
RP VARIANTS HIS-113; LEU-147 AND ARG-811, AND INTERACTION WITH LTBP1.
RX PubMed=18677313; DOI=10.1038/ng.199;
RA Le Goff C., Morice-Picard F., Dagoneau N., Wang L.W., Perrot C., Crow Y.J.,
RA Bauer F., Flori E., Prost-Squarcioni C., Krakow D., Ge G., Greenspan D.S.,
RA Bonnet D., Le Merrer M., Munnich A., Apte S.S., Cormier-Daire V.;
RT "ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-
RT like proteins in TGF-beta bioavailability regulation.";
RL Nat. Genet. 40:1119-1123(2008).
RN [6]
RP VARIANTS GPHYSD1 CYS-50; GLN-72; LYS-114; TRP-159; THR-165; ARG-171;
RP CYS-221; THR-239; 383-ASN--ASP-392 DEL; CYS-593; LEU-635 AND LEU-906.
RX PubMed=21415077; DOI=10.1136/jmg.2010.087544;
RA Allali S., Le Goff C., Pressac-Diebold I., Pfennig G., Mahaut C.,
RA Dagoneau N., Alanay Y., Brady A.F., Crow Y.J., Devriendt K.,
RA Drouin-Garraud V., Flori E., Genevieve D., Hennekam R.C., Hurst J.,
RA Krakow D., Le Merrer M., Lichtenbelt K.D., Lynch S.A., Lyonnet S.,
RA MacDermot K., Mansour S., Megarbane A., Santos H.G., Splitt M.,
RA Superti-Furga A., Unger S., Williams D., Munnich A., Cormier-Daire V.;
RT "Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic
RT heterogeneity of geleophysic dysplasia.";
RL J. Med. Genet. 48:417-421(2011).
CC -!- SUBUNIT: Interacts with LTBP1. {ECO:0000269|PubMed:18677313}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- PTM: Glycosylated (By similarity). Can be O-fucosylated by POFUT2 on a
CC serine or a threonine residue found within the consensus sequence C1-
CC X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are
CC the first and second cysteine residue of the repeat, respectively.
CC Fucosylated repeats can then be further glycosylated by the addition of
CC a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL.
CC Fucosylation mediates the efficient secretion of ADAMTS family members.
CC Can also be C-glycosylated with one or two mannose molecules on
CC tryptophan residues within the consensus sequence W-X-X-W of the TPRs,
CC and N-glycosylated. These other glycosylations can also facilitate
CC secretion (By similarity). {ECO:0000250}.
CC -!- DISEASE: Geleophysic dysplasia 1 (GPHYSD1) [MIM:231050]: An autosomal
CC recessive disorder characterized by severe short stature, short hands
CC and feet, joint limitations, and skin thickening. Radiologic features
CC include delayed bone age, cone-shaped epiphyses, shortened long tubular
CC bones, and ovoid vertebral bodies. Affected individuals have
CC characteristic facial features including a 'happy' face with full
CC cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin
CC upper lip. Other distinctive features include progressive cardiac
CC valvular thickening often leading to an early death, toe walking,
CC tracheal stenosis, respiratory insufficiency, and lysosomal-like
CC storage vacuoles in various tissues. {ECO:0000269|PubMed:18677313,
CC ECO:0000269|PubMed:21415077}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: There is a significant increase in total and active
CC TGFB1 in the culture medium as well as nuclear localization of
CC phosphorylated SMAD2 in fibroblasts from individuals with geleophysic
CC dysplasia.
CC -!- CAUTION: Although strongly similar to members of the ADAMTS family it
CC lacks the metalloprotease and disintegrin-like domains which are
CC typical of that family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25531.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB011177; BAA25531.2; ALT_INIT; mRNA.
DR EMBL; BX324209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX649571; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX629352; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050544; AAH50544.1; -; mRNA.
DR CCDS; CCDS6976.1; -.
DR PIR; T00260; T00260.
DR RefSeq; NP_001138792.1; NM_001145320.1.
DR RefSeq; NP_055509.2; NM_014694.3.
DR RefSeq; XP_005272296.1; XM_005272239.2.
DR AlphaFoldDB; Q86TH1; -.
DR SMR; Q86TH1; -.
DR BioGRID; 115068; 2.
DR IntAct; Q86TH1; 3.
DR MINT; Q86TH1; -.
DR STRING; 9606.ENSP00000346478; -.
DR GlyConnect; 1911; 5 N-Linked glycans (4 sites).
DR GlyGen; Q86TH1; 15 sites, 6 N-linked glycans (4 sites), 2 O-linked glycans (4 sites).
DR iPTMnet; Q86TH1; -.
DR PhosphoSitePlus; Q86TH1; -.
DR BioMuta; ADAMTSL2; -.
DR DMDM; 74750384; -.
DR jPOST; Q86TH1; -.
DR MassIVE; Q86TH1; -.
DR PaxDb; Q86TH1; -.
DR PeptideAtlas; Q86TH1; -.
DR PRIDE; Q86TH1; -.
DR ProteomicsDB; 69695; -.
DR Antibodypedia; 45302; 87 antibodies from 24 providers.
DR DNASU; 9719; -.
DR Ensembl; ENST00000354484.8; ENSP00000346478.4; ENSG00000197859.11.
DR Ensembl; ENST00000393060.1; ENSP00000376780.1; ENSG00000197859.11.
DR Ensembl; ENST00000651351.2; ENSP00000498961.2; ENSG00000197859.11.
DR GeneID; 9719; -.
DR KEGG; hsa:9719; -.
DR MANE-Select; ENST00000651351.2; ENSP00000498961.2; NM_014694.4; NP_055509.2.
DR UCSC; uc011mdl.2; human.
DR CTD; 9719; -.
DR DisGeNET; 9719; -.
DR GeneCards; ADAMTSL2; -.
DR GeneReviews; ADAMTSL2; -.
DR HGNC; HGNC:14631; ADAMTSL2.
DR HPA; ENSG00000197859; Tissue enhanced (heart muscle, liver).
DR MalaCards; ADAMTSL2; -.
DR MIM; 231050; phenotype.
DR MIM; 612277; gene.
DR neXtProt; NX_Q86TH1; -.
DR OpenTargets; ENSG00000197859; -.
DR Orphanet; 1901; Dermatosparaxis Ehlers-Danlos syndrome.
DR Orphanet; 2623; Geleophysic dysplasia.
DR PharmGKB; PA134920655; -.
DR VEuPathDB; HostDB:ENSG00000197859; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000159447; -.
DR HOGENOM; CLU_000660_6_1_1; -.
DR InParanoid; Q86TH1; -.
DR OrthoDB; 807790at2759; -.
DR PhylomeDB; Q86TH1; -.
DR TreeFam; TF316874; -.
DR PathwayCommons; Q86TH1; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q86TH1; -.
DR BioGRID-ORCS; 9719; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; ADAMTSL2; human.
DR GenomeRNAi; 9719; -.
DR Pharos; Q86TH1; Tbio.
DR PRO; PR:Q86TH1; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q86TH1; protein.
DR Bgee; ENSG00000197859; Expressed in right atrium auricular region and 92 other tissues.
DR ExpressionAtlas; Q86TH1; baseline and differential.
DR Genevisible; Q86TH1; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0050436; F:microfibril binding; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0060481; P:lobar bronchus epithelium development; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL.
DR Gene3D; 2.20.100.10; -; 5.
DR InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR010909; PLAC.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF08686; PLAC; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR01857; ADAMTSFAMILY.
DR SMART; SM00209; TSP1; 7.
DR SUPFAM; SSF82895; SSF82895; 7.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS50092; TSP1; 4.
PE 1: Evidence at protein level;
KW Disease variant; Disulfide bond; Dwarfism; Glycoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..951
FT /note="ADAMTS-like protein 2"
FT /id="PRO_0000249682"
FT DOMAIN 47..106
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 564..618
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 622..686
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 688..736
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 737..795
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 797..851
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 853..908
FT /note="TSP type-1 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 912..950
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 414..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 807
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 63..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 74..90
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT VARIANT 50
FT /note="W -> C (in GPHYSD1; dbSNP:rs1395219766)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066543"
FT VARIANT 72
FT /note="R -> Q (in GPHYSD1; dbSNP:rs387907064)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066544"
FT VARIANT 113
FT /note="R -> H (in GPHYSD1; leads to the reduced secretion
FT of the mutated protein; dbSNP:rs113994122)"
FT /evidence="ECO:0000269|PubMed:18677313"
FT /id="VAR_054874"
FT VARIANT 114
FT /note="E -> K (in GPHYSD1; dbSNP:rs113994123)"
FT /evidence="ECO:0000269|PubMed:18677313,
FT ECO:0000269|PubMed:21415077"
FT /id="VAR_054875"
FT VARIANT 147
FT /note="P -> L (in GPHYSD1; leads to the reduced secretion
FT of the mutated protein; dbSNP:rs113994121)"
FT /evidence="ECO:0000269|PubMed:18677313"
FT /id="VAR_054876"
FT VARIANT 159
FT /note="R -> W (in GPHYSD1; dbSNP:rs776178041)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066545"
FT VARIANT 165
FT /note="A -> T (in GPHYSD1; dbSNP:rs764516811)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066546"
FT VARIANT 171
FT /note="C -> R (in GPHYSD1)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066547"
FT VARIANT 221
FT /note="R -> C (in GPHYSD1; dbSNP:rs387907065)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066548"
FT VARIANT 239
FT /note="A -> T (in GPHYSD1)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066549"
FT VARIANT 364
FT /note="V -> I (in dbSNP:rs35767802)"
FT /evidence="ECO:0000269|PubMed:9628581"
FT /id="VAR_046011"
FT VARIANT 383..392
FT /note="Missing (in GPHYSD1)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066550"
FT VARIANT 593
FT /note="R -> C (in GPHYSD1)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066551"
FT VARIANT 635
FT /note="S -> L (in GPHYSD1)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066552"
FT VARIANT 811
FT /note="G -> R (in GPHYSD1; leads to the reduced secretion
FT of the mutated protein; dbSNP:rs113994124)"
FT /evidence="ECO:0000269|PubMed:18677313"
FT /id="VAR_054877"
FT VARIANT 906
FT /note="P -> L (in GPHYSD1; dbSNP:rs969732840)"
FT /evidence="ECO:0000269|PubMed:21415077"
FT /id="VAR_066553"
FT CONFLICT 59
FT /note="C -> F (in Ref. 1; BAA25531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 951 AA; 104621 MW; 93A9B0DC5BAB6CC7 CRC64;
MDGRWQCSCW AWFLLVLAVV AGDTVSTGST DNSPTSNSLE GGTDATAFWW GEWTKWTACS
RSCGGGVTSQ ERHCLQQRRK SVPGPGNRTC TGTSKRYQLC RVQECPPDGR SFREEQCVSF
NSHVYNGRTH QWKPLYPDDY VHISSKPCDL HCTTVDGQRQ LMVPARDGTS CKLTDLRGVC
VSGKCEPIGC DGVLFSTHTL DKCGICQGDG SSCTHVTGNY RKGNAHLGYS LVTHIPAGAR
DIQIVERKKS ADVLALADEA GYYFFNGNYK VDSPKNFNIA GTVVKYRRPM DVYETGIEYI
VAQGPTNQGL NVMVWNQNGK SPSITFEYTL LQPPHESRPQ PIYYGFSESA ESQGLDGAGL
MGFVPHNGSL YGQASSERLG LDNRLFGHPG LDMELGPSQG QETNEVCEQA GGGACEGPPR
GKGFRDRNVT GTPLTGDKDD EEVDTHFASQ EFFSANAISD QLLGAGSDLK DFTLNETVNS
IFAQGAPRSS LAESFFVDYE ENEGAGPYLL NGSYLELSSD RVANSSSEAP FPNVSTSLLT
SAGNRTHKAR TRPKARKQGV SPADMYRWKL SSHEPCSATC TTGVMSAYAM CVRYDGVEVD
DSYCDALTRP EPVHEFCAGR ECQPRWETSS WSECSRTCGE GYQFRVVRCW KMLSPGFDSS
VYSDLCEAAE AVRPEERKTC RNPACGPQWE MSEWSECTAK CGERSVVTRD IRCSEDEKLC
DPNTRPVGEK NCTGPPCDRQ WTVSDWGPCS GSCGQGRTIR HVYCKTSDGR VVPESQCQME
TKPLAIHPCG DKNCPAHWLA QDWERCNTTC GRGVKKRLVL CMELANGKPQ TRSGPECGLA
KKPPEESTCF ERPCFKWYTS PWSECTKTCG VGVRMRDVKC YQGTDIVRGC DPLVKPVGRQ
ACDLQPCPTE PPDDSCQDQP GTNCALAIKV NLCGHWYYSK ACCRSCRPPH S