Q6UY14 (ATL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1074 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)

Function	Positive regulation of apoptosis. Ref.7
Subunit structure	Interacts with CTSB. Ref.7
Subcellular location	Secreted Potential.
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
Involvement in disease	Defects in ADAMTSL4 are a cause of autosomal recessive isolated ectopia lentis (ARI-EL) [MIM:225100]. ARI-EL is a rare condition characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation. Ref.8
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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of apoptotic process Inferred from direct assay Ref.7. Source: UniProtKB
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro protease binding Inferred from physical interaction Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STK16	O75716	3	EBI-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.5 (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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 1074	1050	ADAMTS-like protein 4		PRO_0000257966
Regions
	Domain	48 – 93	46	TSP type-1 1
	Domain	723 – 782	60	TSP type-1 2
	Domain	783 – 842	60	TSP type-1 3
	Domain	845 – 909	65	TSP type-1 4
	Domain	910 – 969	60	TSP type-1 5
	Domain	970 – 1026	57	TSP type-1 6
	Domain	1029 – 1066	38	PLAC
	Compositional bias	602 – 664	63	Pro-rich
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Glycosylation	490	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	773	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	854 – 877	24	CSAEC…GAALG → VSPEPPAISCILGNHAQDTS AFPA in isoform 2. Ref.5		VSP_052183
	Alternative sequence	878 – 1074	197	Missing in isoform 2. Ref.5		VSP_052184
	Natural variant	193	1	A → P. Corresponds to variant rs41317515 [ dbSNP | Ensembl ].		VAR_061918
	Natural variant	1028	1	R → H. Corresponds to variant rs56411234 [ dbSNP | Ensembl ].		VAR_061919

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 31, 2006. Version 2. Checksum: 79AE0E5DF5488CA1	FASTA	1,074	116,545
	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
	Isoform 2 [UniParc]. Checksum: B778D79DB24E4EA9	FASTA	877	95,132
	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 CTTAWFHSDW SSKVSPEPPA ISCILGNHAQ DTSAFPA

References

	« Hide 'large scale' referencesShow '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. , 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: 12975309] [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. , 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: 16710414] [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: 15489334] [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. , 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: 15498874] [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: 12706885] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-490, MASS SPECTROMETRY. 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: 16364318] [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: 19200529] [Abstract] Cited for: TISSUE SPECIFICITY, INVOLVEMENT IN ARI-EL.
+	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.
IPI	IPI00374068. IPI00550741.
RefSeq	NP_061905.2. NM_019032.4. NP_079284.2. NM_025008.3.
UniGene	Hs.516243.
3D structure databases
ProteinModelPortal	Q6UY14.
SMR	Q6UY14. Positions 351-602, 666-1027.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6UY14. 16 interactions.
MINT	MINT-1445070.
STRING	Q6UY14.
PTM databases
PhosphoSite	Q6UY14.
Polymorphism databases
DMDM	118573317.
Proteomic databases
PRIDE	Q6UY14.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000271643; ENSP00000271643; ENSG00000143382. ENST00000369038; ENSP00000358034; ENSG00000143382.
GeneID	54507.
KEGG	hsa:54507.
UCSC	uc001euw.1. human. uc001eux.1. human.
Organism-specific databases
CTD	54507.
GeneCards	GC01P150522.
HGNC	HGNC:19706. ADAMTSL4.
HPA	HPA006279.
MIM	225100. phenotype. 610113. gene.
neXtProt	NX_Q6UY14.
Orphanet	1885. Isolated ectopia lentis.
PharmGKB	PA134879921.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17714.
HOVERGEN	HBG080879.
InParanoid	Q6UY14.
PhylomeDB	Q6UY14.
Gene expression databases
ArrayExpress	Q6UY14.
Bgee	Q6UY14.
CleanEx	HS_ADAMTSL4.
Genevestigator	Q6UY14.
GermOnline	ENSG00000143382. Homo sapiens.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. 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]
SMART	SM00209. TSP1. 6 hits. [Graphical view]
SUPFAM	SSF82895. TSP1. 7 hits.
PROSITE	PS50900. PLAC. 1 hit. PS50092. TSP1. 6 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	56873.
SOURCE	Search...

Entry information

Entry name

ATL4_HUMAN

Accession

Primary (citable) accession number: Q6UY14
Secondary accession number(s): Q5T5F7 , Q6IPM6, Q8N643, Q9HBS6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 31, 2006
Last modified:	January 25, 2012
This is version 71 of the entry and version 2 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.