Q9Y6L7 (TLL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tolloid-like protein 2
EC=3.4.24.-

Gene names

Name:	TLL2
Synonyms:	KIAA0932

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	1015 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	Protease which specifically processes pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted Probable.
Sequence similarities	Belongs to the peptidase M12A family. Contains 5 CUB domains. Contains 2 EGF-like domains.
Sequence caution	The sequence BAA76776.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Secreted
Domain	EGF-like domain Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Developmental protein Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro 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 – 25	25	Potential
	Propeptide	26 – 149	124			PRO_0000046036
	Chain	150 – 1015	866	Tolloid-like protein 2		PRO_0000046037
Regions
	Domain	351 – 463	113	CUB 1
	Domain	464 – 576	113	CUB 2
	Domain	576 – 617	42	EGF-like 1; calcium-binding Potential
	Domain	620 – 732	113	CUB 3
	Domain	732 – 772	41	EGF-like 2; calcium-binding Potential
	Domain	776 – 888	113	CUB 4
	Domain	889 – 1005	117	CUB 5
	Region	150 – 350	201	Metalloprotease By similarity
Sites
	Active site	243	1	By similarity
	Metal binding	242	1	Zinc; catalytic By similarity
	Metal binding	246	1	Zinc; catalytic By similarity
	Metal binding	252	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	171	1	N-linked (GlcNAc...) Potential
	Glycosylation	361	1	N-linked (GlcNAc...) Potential
	Glycosylation	392	1	N-linked (GlcNAc...) Potential
	Glycosylation	628	1	N-linked (GlcNAc...) Potential
	Glycosylation	805	1	N-linked (GlcNAc...) Potential
	Disulfide bond	351 ↔ 377		By similarity
	Disulfide bond	404 ↔ 426		By similarity
	Disulfide bond	464 ↔ 490		By similarity
	Disulfide bond	517 ↔ 539		By similarity
	Disulfide bond	580 ↔ 592		By similarity
	Disulfide bond	588 ↔ 601		By similarity
	Disulfide bond	603 ↔ 616		By similarity
	Disulfide bond	620 ↔ 646		By similarity
	Disulfide bond	673 ↔ 695		By similarity
	Disulfide bond	736 ↔ 747		By similarity
	Disulfide bond	743 ↔ 756		By similarity
	Disulfide bond	758 ↔ 771		By similarity
	Disulfide bond	776 ↔ 802		By similarity
	Disulfide bond	829 ↔ 851		By similarity
	Disulfide bond	889 ↔ 919		By similarity
	Disulfide bond	946 ↔ 968		By similarity
Experimental info
	Sequence conflict	495	1	T → M in BAA76776. Ref.2
	Sequence conflict	576 – 593	18	EVDEC…EHRCV → GKKKKKKKKKKKKKKKKK in AAH13871. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6L7 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 25F5B23065861593	FASTA	1,015	113,557
	10 20 30 40 50 60 MPRATALGAL VSLLLLLPLP RGAGGLGERP DATADYSELD GEEGTEQQLE HYHDPCKAAV 70 80 90 100 110 120 FWGDIALDED DLKLFHIDKA RDWTKQTVGA TGHSTGGLEE QASESSPDTT AMDTGTKEAG 130 140 150 160 170 180 KDGRENTTLL HSPGTLHAAA KTFSPRVRRA TTSRTERIWP GGVIPYVIGG NFTGSQRAIF 190 200 210 220 230 240 KQAMRHWEKH TCVTFIERTD EESFIVFSYR TCGCCSYVGR RGGGPQAISI GKNCDKFGIV 250 260 270 280 290 300 AHELGHVVGF WHEHTRPDRD QHVTIIRENI QPGQEYNFLK MEAGEVSSLG ETYDFDSIMH 310 320 330 340 350 360 YARNTFSRGV FLDTILPRQD DNGVRPTIGQ RVRLSQGDIA QARKLYKCPA CGETLQDTTG 370 380 390 400 410 420 NFSAPGFPNG YPSYSHCVWR ISVTPGEKIV LNFTSMDLFK SRLCWYDYVE VRDGYWRKAP 430 440 450 460 470 480 LLGRFCGDKI PEPLVSTDSR LWVEFRSSSN ILGKGFFAAY EATCGGDMNK DAGQIQSPNY 490 500 510 520 530 540 PDDYRPSKEC VWRITVSEGF HVGLTFQAFE IERHDSCAYD YLEVRDGPTE ESALIGHFCG 550 560 570 580 590 600 YEKPEDVKSS SNRLWMKFVS DGSINKAGFA ANFFKEVDEC SWPDHGGCEH RCVNTLGSYK 610 620 630 640 650 660 CACDPGYELA ADKKMCEVAC GGFITKLNGT ITSPGWPKEY PTNKNCVWQV VAPAQYRISL 670 680 690 700 710 720 QFEVFELEGN DVCKYDFVEV RSGLSPDAKL HGRFCGSETP EVITSQSNNM RVEFKSDNTV 730 740 750 760 770 780 SKRGFRAHFF SDKDECAKDN GGCQHECVNT FGSYLCRCRN GYWLHENGHD CKEAGCAHKI 790 800 810 820 830 840 SSVEGTLASP NWPDKYPSRR ECTWNISSTA GHRVKLTFNE FEIEQHQECA YDHLEMYDGP 850 860 870 880 890 900 DSLAPILGRF CGSKKPDPTV ASGSSMFLRF YSDASVQRKG FQAVHSTECG GRLKAEVQTK 910 920 930 940 950 960 ELYSHAQFGD NNYPSEARCD WVIVAEDGYG VELTFRTFEV EEEADCGYDY MEAYDGYDSS 970 980 990 1000 1010 APRLGRFCGS GPLEEIYSAG DSLMIRFRTD DTINKKGFHA RYTSTKFQDA LHMKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis." Scott I.C., Blitz I.L., Pappano W.N., Imamura Y., Clark T.G., Steiglitz B.M., Thomas C.L., Maas S.A., Takahara K., Cho K.W., Greenspan D.S. Dev. Biol. 213:283-300(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 150-154. Tissue: Placenta.
[2]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	Ohara O., Nagase T., Kikuno R. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Ovary.
[6]	"Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures." Uzel M.I., Scott I.C., Babakhanlou-Chase H., Palamakumbura A.H., Pappano W.N., Hong H.-H., Greenspan D.S., Trackman P.C. J. Biol. Chem. 276:22537-22543(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF059516 mRNA. Translation: AAD42979.1. AB023149 mRNA. Translation: BAA76776.2. Different initiation. AL138765, AL136181, AL391136 Genomic DNA. Translation: CAI13580.1. AL136181, AL138765, AL391136 Genomic DNA. Translation: CAH72983.1. AL391136, AL136181, AL138765 Genomic DNA. Translation: CAH72234.1. BC013871 mRNA. Translation: AAH13871.1. BC112341 mRNA. Translation: AAI12342.1. BC112366 mRNA. Translation: AAI12367.1. BC113577 mRNA. Translation: AAI13578.1.
IPI	IPI00465231.
RefSeq	NP_036597.1. NM_012465.3.
UniGene	Hs.154296.
3D structure databases
ProteinModelPortal	Q9Y6L7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000350630.
Protein family/group databases
MEROPS	M12.018.
PTM databases
PhosphoSite	Q9Y6L7.
Polymorphism databases
DMDM	74762080.
Proteomic databases
PaxDb	Q9Y6L7.
PRIDE	Q9Y6L7.
Protocols and materials databases
DNASU	7093.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357947; ENSP00000350630; ENSG00000095587.
GeneID	7093.
KEGG	hsa:7093.
UCSC	uc001kml.2. human.
Organism-specific databases
CTD	7093.
GeneCards	GC10M098114.
H-InvDB	HIX0009074.
HGNC	HGNC:11844. TLL2.
MIM	606743. gene.
neXtProt	NX_Q9Y6L7.
PharmGKB	PA36546.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG70307.
HOGENOM	HOG000236339.
HOVERGEN	HBG004859.
InParanoid	Q9Y6L7.
KO	K13047.
OMA	KFCGSET.
OrthoDB	EOG4FTVZV.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
Bgee	Q9Y6L7.
CleanEx	HS_TLL2.
Genevestigator	Q9Y6L7.
GermOnline	ENSG00000095587. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.290. 5 hits. 3.40.390.10. 1 hit.
InterPro	IPR015446. BMP_1/tolloid-like. IPR000859. CUB_dom. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR024079. MetalloPept_cat_dom. IPR001506. Peptidase_M12A. IPR006026. Peptidase_Metallo. [Graphical view]
Pfam	PF01400. Astacin. 1 hit. PF00431. CUB. 5 hits. PF07645. EGF_CA. 2 hits. [Graphical view]
PIRSF	PIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTS	PR00480. ASTACIN.
SMART	SM00042. CUB. 5 hits. SM00179. EGF_CA. 2 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 5 hits.
PROSITE	PS01180. CUB. 5 hits. PS00022. EGF_1. False negative. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 2 hits. PS01187. EGF_CA. 2 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7093.
NextBio	27747.
SOURCE	Search...

Entry information

Entry name

TLL2_HUMAN

Accession

Primary (citable) accession number: Q9Y6L7
Secondary accession number(s): A6NDK0 , Q2M1H1, Q6PJN5, Q9UQ00

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 7, 2006
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 105 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.