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Q6UY14 (ATL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADAMTS-like protein 4

Short name=ADAMTSL-4
Alternative name(s):
Thrombospondin repeat-containing protein 1
Gene names
Name:ADAMTSL4
Synonyms:TSRC1
ORF Names:PP1396, UNQ2803/PRO34012
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1074 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Positive regulation of apoptosis. May facilitate FBN1 microfibril biogenesis. Ref.5 Ref.7 Ref.11

Subunit structure

Interacts with CTSB. Interacts with FBN1. Ref.5 Ref.7 Ref.11

Subcellular location

Secretedextracellular spaceextracellular matrix. Note: Colocalizes with FMN1 microfibrils in the eye ECM. Ref.11

Tissue specificity

Expressed in colon, heart, leukocyte, liver, lung, skeletal muscle, spleen, testis and placenta. Weaker expression in bone marrow, brain tissue, kidney and pancreas. Expression studies in fetal tissues reveal strong expression in heart, kidney, liver, lung and skeletal muscle, but weaker expression in fetal brain and skin. Ref.8

Post-translational modification

N-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. N- and C-glycosylations can also facilitate secretion By similarity. Ref.9 Ref.11

Involvement in disease

Ectopia lentis 2, isolated, autosomal recessive (ECTOL2) [MIM:225200]: An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Ectopia lentis et pupillae (ECTOLP) [MIM:225200]: An ocular abnormality characterized by displacement of the lenses and the pupils, associated with other ocular anomalies, but without systemic manifestations. The condition is usually bilateral, with the lenses and pupils displaced in opposite directions. Additional signs include enlarged corneal diameter, increased corneal astigmatism, increased anterior chamber depth, thinning and flattening of the iris with loss of crypts, angle malformation caused by enlarged iris processes, persistent pupillary membrane, loss of zonular fibers, tilted disk, and increased axial length. Secondary manifestations include refractive errors, glaucoma, early cataract development, and retinal detachment. Membrane formation on the posterior aspect of the iris has been observed both in histologic sections and on ultrasound biomicroscopy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Contains 1 PLAC domain.

Contains 6 TSP type-1 domains.

Caution

Although 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 AAG17217.1 differs from that shown. Reason: Frameshift at position 719.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CTSBP078583EBI-742002,EBI-715062
Hoxa1P090223EBI-742002,EBI-3957603From a different organism.
STK16O757163EBI-742002,EBI-749295

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.5 (identifier: Q6UY14-1)

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.
Note: Gene prediction confirmed by EST data.
Isoform 2 Ref.1 (identifier: Q6UY14-2)

The sequence of this isoform differs from the canonical sequence as follows:
     854-877: CSAECGTGIQRRSVVCLGSGAALG → VSPEPPAISCILGNHAQDTSAFPA
     878-1074: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 10741050ADAMTS-like protein 4
PRO_0000257966

Regions

Domain48 – 9346TSP type-1 1
Domain723 – 78260TSP type-1 2
Domain783 – 84260TSP type-1 3
Domain845 – 90965TSP type-1 4
Domain910 – 96960TSP type-1 5
Domain970 – 102657TSP type-1 6
Domain1029 – 106638PLAC
Compositional bias602 – 66463Pro-rich

Amino acid modifications

Glycosylation31N-linked (GlcNAc...) Potential
Glycosylation4901N-linked (GlcNAc...) (complex) Ref.6 Ref.9
Glycosylation7731N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence854 – 87724CSAEC…GAALG → VSPEPPAISCILGNHAQDTS AFPA in isoform 2. Ref.1
VSP_052183
Alternative sequence878 – 1074197Missing in isoform 2. Ref.1
VSP_052184
Natural variant1931A → P.
Corresponds to variant rs41317515 [ dbSNP | Ensembl ].
VAR_061918
Natural variant10281R → H.
Corresponds to variant rs56411234 [ dbSNP | Ensembl ].
VAR_061919

Sequences

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

Last modified October 31, 2006. Version 2.
Checksum: 79AE0E5DF5488CA1

FASTA1,074116,545
        10         20         30         40         50         60 
MENWTGRPWL YLLLLLSLPQ LCLDQEVLSG HSLQTPTEEG QGPEGVWGPW VQWASCSQPC 

        70         80         90        100        110        120 
GVGVQRRSRT CQLPTVQLHP SLPLPPRPPR HPEALLPRGQ GPRPQTSPET LPLYRTQSRG 

       130        140        150        160        170        180 
RGGPLRGPAS HLGREETQEI RAARRSRLRD PIKPGMFGYG RVPFALPLHR NRRHPRSPPR 

       190        200        210        220        230        240 
SELSLISSRG EEAIPSPTPR AEPFSANGSP QTELPPTELS VHTPSPQAEP LSPETAQTEV 

       250        260        270        280        290        300 
APRTRPAPLR HHPRAQASGT EPPSPTHSLG EGGFFRASPQ PRRPSSQGWA SPQVAGRRPD 

       310        320        330        340        350        360 
PFPSVPRGRG QQGQGPWGTG GTPHGPRLEP DPQHPGAWLP LLSNGPHASS LWSLFAPSSP 

       370        380        390        400        410        420 
IPRCSGESEQ LRACSQAPCP PEQPDPRALQ CAAFNSQEFM GQLYQWEPFT EVQGSQRCEL 

       430        440        450        460        470        480 
NCRPRGFRFY VRHTEKVQDG TLCQPGAPDI CVAGRCLSPG CDGILGSGRR PDGCGVCGGD 

       490        500        510        520        530        540 
DSTCRLVSGN LTDRGGPLGY QKILWIPAGA LRLQIAQLRP SSNYLALRGP GGRSIINGNW 

       550        560        570        580        590        600 
AVDPPGSYRA GGTVFRYNRP PREEGKGESL SAEGPTTQPV DVYMIFQEEN PGVFYQYVIS 

       610        620        630        640        650        660 
SPPPILENPT PEPPVPQLQP EILRVEPPLA PAPRPARTPG TLQRQVRIPQ MPAPPHPRTP 

       670        680        690        700        710        720 
LGSPAAYWKR VGHSACSASC GKGVWRPIFL CISRESGEEL DERSCAAGAR PPASPEPCHG 

       730        740        750        760        770        780 
TPCPPYWEAG EWTSCSRSCG PGTQHRQLQC RQEFGGGGSS VPPERCGHLP RPNITQSCQL 

       790        800        810        820        830        840 
RLCGHWEVGS PWSQCSVRCG RGQRSRQVRC VGNNGDEVSE QECASGPPQP PSREACDMGP 

       850        860        870        880        890        900 
CTTAWFHSDW SSKCSAECGT GIQRRSVVCL GSGAALGPGQ GEAGAGTGQS CPTGSRPPDM 

       910        920        930        940        950        960 
RACSLGPCER TWRWYTGPWG ECSSECGSGT QRRDIICVSK LGTEFNVTSP SNCSHLPRPP 

       970        980        990       1000       1010       1020 
ALQPCQGQAC QDRWFSTPWS PCSRSCQGGT QTREVQCLST NQTLSTRCPP QLRPSRKRPC 

      1030       1040       1050       1060       1070 
NSQPCSQRPD DQCKDSSPHC PLVVQARLCV YPYYTATCCR SCAHVLERSP QDPS 

« Hide

Isoform 2 [UniParc].

Checksum: B778D79DB24E4EA9
Show »

FASTA87795,132

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [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] OF 425-1074.
Tissue: Lung and Placenta.
[4]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 638-1074.
[5]"TSRC1, a widely expressed gene containing seven thrombospondin type I repeats."
Buchner D.A., Meisler M.H.
Gene 307:23-30(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 1).
[6]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-490.
Tissue: Plasma.
[7]"Cathepsin B and its interacting proteins, bikunin and TSRC1, correlate with TNF-induced apoptosis of ovarian cancer cells OV-90."
Liu J., Guo Q., Chen B., Yu Y., Lu H., Li Y.-Y.
FEBS Lett. 580:245-250(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CTSB.
[8]"A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis."
Ahram D., Sato T.S., Kohilan A., Tayeh M., Chen S., Leal S., Al-Salem M., El-Shanti H.
Am. J. Hum. Genet. 84:274-278(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN ECTOL2.
[9]"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-490.
[10]"A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae."
Christensen A.E., Fiskerstrand T., Knappskog P.M., Boman H., Roedahl E.
Invest. Ophthalmol. Vis. Sci. 51:6369-6373(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ECTOLP.
[11]"ADAMTSL4, a secreted glycoprotein widely distributed in the eye, binds Fibrillin-1 microfibrils and accelerates microfibril biogenesis."
Gabriel L.A., Wang L.W., Bader H., Ho J.C., Majors A.K., Hollyfield J.G., Traboulsi E.I., Apte S.S.
Invest. Ophthalmol. Vis. Sci. 53:461-469(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBN1, GLYCOSYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY358122 mRNA. Translation: AAQ88489.1.
AL356356 Genomic DNA. Translation: CAI15499.1.
AL356356 Genomic DNA. Translation: CAI15500.2.
BC027478 mRNA. Translation: AAH27478.2.
BC071852 mRNA. Translation: AAH71852.1.
BC094811 mRNA. Translation: AAH94811.1.
AF217974 mRNA. Translation: AAG17217.1. Frameshift.
CCDSCCDS30852.1. [Q6UY14-2]
CCDS955.1. [Q6UY14-1]
RefSeqNP_001275536.1. NM_001288607.1.
NP_001275537.1. NM_001288608.1.
NP_061905.2. NM_019032.5. [Q6UY14-1]
NP_079284.2. NM_025008.4. [Q6UY14-2]
UniGeneHs.516243.

3D structure databases

ProteinModelPortalQ6UY14.
SMRQ6UY14. Positions 364-548.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120002. 19 interactions.
IntActQ6UY14. 22 interactions.
MINTMINT-1445070.
STRING9606.ENSP00000271643.

PTM databases

PhosphoSiteQ6UY14.

Polymorphism databases

DMDM118573317.

Proteomic databases

PaxDbQ6UY14.
PRIDEQ6UY14.

Protocols and materials databases

DNASU54507.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000271643; ENSP00000271643; ENSG00000143382. [Q6UY14-1]
ENST00000369038; ENSP00000358034; ENSG00000143382. [Q6UY14-1]
ENST00000369041; ENSP00000358037; ENSG00000143382. [Q6UY14-2]
GeneID54507.
KEGGhsa:54507.
UCSCuc001euw.3. human. [Q6UY14-2]
uc001eux.3. human. [Q6UY14-1]

Organism-specific databases

CTD54507.
GeneCardsGC01P150522.
GeneReviewsADAMTSL4.
HGNCHGNC:19706. ADAMTSL4.
HPAHPA006279.
MIM225200. phenotype.
610113. gene.
neXtProtNX_Q6UY14.
Orphanet1885. Isolated ectopia lentis.
PharmGKBPA134879921.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG242665.
HOGENOMHOG000034174.
HOVERGENHBG080879.
InParanoidQ6UY14.
OrthoDBEOG73FQKT.
PhylomeDBQ6UY14.
TreeFamTF316874.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressQ6UY14.
BgeeQ6UY14.
CleanExHS_ADAMTSL4.
GenevestigatorQ6UY14.

Family and domain databases

InterProIPR010294. ADAM_spacer1.
IPR010909. PLAC.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF08686. PLAC. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
SMARTSM00209. TSP1. 6 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 6 hits.
PROSITEPS50900. PLAC. 1 hit.
PS50092. TSP1. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAMTSL4. human.
GeneWikiADAMTSL4.
GenomeRNAi54507.
NextBio56873.
PROQ6UY14.
SOURCESearch...

Entry information

Entry nameATL4_HUMAN
AccessionPrimary (citable) accession number: Q6UY14
Secondary accession number(s): Q5T5F7 expand/collapse secondary AC list , Q6IPM6, Q8N643, Q9HBS6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 31, 2006
Last modified: July 9, 2014
This is version 98 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

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 1

Human chromosome 1: entries, gene names and cross-references to MIM