ID TLL2_HUMAN Reviewed; 1015 AA.
AC Q9Y6L7; A6NDK0; Q2M1H1; Q6PJN5; Q9UQ00;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 01-MAY-2013, entry version 105.
DE RecName: Full=Tolloid-like protein 2;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=TLL2; Synonyms=KIAA0932;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 150-154.
RC TISSUE=Placenta;
RX PubMed=10479448; DOI=10.1006/dbio.1999.9383;
RA Scott I.C., Blitz I.L., Pappano W.N., Imamura Y., Clark T.G.,
RA Steiglitz B.M., Thomas C.L., Maas S.A., Takahara K., Cho K.W.,
RA Greenspan D.S.;
RT "Mammalian BMP-1/Tolloid-related metalloproteinases, including novel
RT family member mammalian Tolloid-like 2, have differential enzymatic
RT activities and distributions of expression relevant to patterning and
RT skeletogenesis.";
RL Dev. Biol. 213:283-300(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP CHARACTERIZATION.
RX PubMed=11313359; DOI=10.1074/jbc.M102352200;
RA Uzel M.I., Scott I.C., Babakhanlou-Chase H., Palamakumbura A.H.,
RA Pappano W.N., Hong H.-H., Greenspan D.S., Trackman P.C.;
RT "Multiple bone morphogenetic protein 1-related mammalian
RT metalloproteinases process pro-lysyl oxidase at the correct
RT physiological site and control lysyl oxidase activation in mouse
RT embryo fibroblast cultures.";
RL J. Biol. Chem. 276:22537-22543(2001).
CC -!- FUNCTION: Protease which specifically processes pro-lysyl oxidase.
CC Required for the embryonic development. Predominant protease,
CC which in the development, influences dorsal-ventral patterning and
CC skeletogenesis.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- SUBCELLULAR LOCATION: Secreted (Probable).
CC -!- SIMILARITY: Belongs to the peptidase M12A family.
CC -!- SIMILARITY: Contains 5 CUB domains.
CC -!- SIMILARITY: Contains 2 EGF-like domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA76776.2; Type=Erroneous initiation;
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DR EMBL; AF059516; AAD42979.1; -; mRNA.
DR EMBL; AB023149; BAA76776.2; ALT_INIT; mRNA.
DR EMBL; AL138765; CAI13580.1; -; Genomic_DNA.
DR EMBL; AL136181; CAI13580.1; JOINED; Genomic_DNA.
DR EMBL; AL391136; CAI13580.1; JOINED; Genomic_DNA.
DR EMBL; AL136181; CAH72983.1; -; Genomic_DNA.
DR EMBL; AL138765; CAH72983.1; JOINED; Genomic_DNA.
DR EMBL; AL391136; CAH72983.1; JOINED; Genomic_DNA.
DR EMBL; AL391136; CAH72234.1; -; Genomic_DNA.
DR EMBL; AL136181; CAH72234.1; JOINED; Genomic_DNA.
DR EMBL; AL138765; CAH72234.1; JOINED; Genomic_DNA.
DR EMBL; BC013871; AAH13871.1; -; mRNA.
DR EMBL; BC112341; AAI12342.1; -; mRNA.
DR EMBL; BC112366; AAI12367.1; -; mRNA.
DR EMBL; BC113577; AAI13578.1; -; mRNA.
DR IPI; IPI00465231; -.
DR RefSeq; NP_036597.1; NM_012465.3.
DR UniGene; Hs.154296; -.
DR ProteinModelPortal; Q9Y6L7; -.
DR STRING; 9606.ENSP00000350630; -.
DR MEROPS; M12.018; -.
DR PhosphoSite; Q9Y6L7; -.
DR DMDM; 74762080; -.
DR PaxDb; Q9Y6L7; -.
DR PRIDE; Q9Y6L7; -.
DR DNASU; 7093; -.
DR Ensembl; ENST00000357947; ENSP00000350630; ENSG00000095587.
DR GeneID; 7093; -.
DR KEGG; hsa:7093; -.
DR UCSC; uc001kml.2; human.
DR CTD; 7093; -.
DR GeneCards; GC10M098114; -.
DR H-InvDB; HIX0009074; -.
DR HGNC; HGNC:11844; TLL2.
DR MIM; 606743; gene.
DR neXtProt; NX_Q9Y6L7; -.
DR PharmGKB; PA36546; -.
DR eggNOG; NOG70307; -.
DR HOGENOM; HOG000236339; -.
DR HOVERGEN; HBG004859; -.
DR InParanoid; Q9Y6L7; -.
DR KO; K13047; -.
DR OMA; KFCGSET; -.
DR OrthoDB; EOG4FTVZV; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR GenomeRNAi; 7093; -.
DR NextBio; 27747; -.
DR Bgee; Q9Y6L7; -.
DR CleanEx; HS_TLL2; -.
DR Genevestigator; Q9Y6L7; -.
DR GermOnline; ENSG00000095587; Homo sapiens.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.290; -; 5.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR015446; BMP_1/tolloid-like.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR000742; EG-like_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024079; MetalloPept_cat_dom.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00431; CUB; 5.
DR Pfam; PF07645; EGF_CA; 2.
DR PIRSF; PIRSF001199; BMP_1/tolloid-like; 1.
DR PRINTS; PR00480; ASTACIN.
DR SMART; SM00042; CUB; 5.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF49854; CUB; 5.
DR PROSITE; PS01180; CUB; 5.
DR PROSITE; PS00022; EGF_1; FALSE_NEG.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 2.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cleavage on pair of basic residues; Complete proteome;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1 25 Potential.
FT PROPEP 26 149
FT /FTId=PRO_0000046036.
FT CHAIN 150 1015 Tolloid-like protein 2.
FT /FTId=PRO_0000046037.
FT DOMAIN 351 463 CUB 1.
FT DOMAIN 464 576 CUB 2.
FT DOMAIN 576 617 EGF-like 1; calcium-binding (Potential).
FT DOMAIN 620 732 CUB 3.
FT DOMAIN 732 772 EGF-like 2; calcium-binding (Potential).
FT DOMAIN 776 888 CUB 4.
FT DOMAIN 889 1005 CUB 5.
FT REGION 150 350 Metalloprotease (By similarity).
FT ACT_SITE 243 243 By similarity.
FT METAL 242 242 Zinc; catalytic (By similarity).
FT METAL 246 246 Zinc; catalytic (By similarity).
FT METAL 252 252 Zinc; catalytic (By similarity).
FT CARBOHYD 171 171 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 361 361 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 392 392 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 628 628 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 805 805 N-linked (GlcNAc...) (Potential).
FT DISULFID 351 377 By similarity.
FT DISULFID 404 426 By similarity.
FT DISULFID 464 490 By similarity.
FT DISULFID 517 539 By similarity.
FT DISULFID 580 592 By similarity.
FT DISULFID 588 601 By similarity.
FT DISULFID 603 616 By similarity.
FT DISULFID 620 646 By similarity.
FT DISULFID 673 695 By similarity.
FT DISULFID 736 747 By similarity.
FT DISULFID 743 756 By similarity.
FT DISULFID 758 771 By similarity.
FT DISULFID 776 802 By similarity.
FT DISULFID 829 851 By similarity.
FT DISULFID 889 919 By similarity.
FT DISULFID 946 968 By similarity.
FT CONFLICT 495 495 T -> M (in Ref. 2; BAA76776).
FT CONFLICT 576 593 EVDECSWPDHGGCEHRCV -> GKKKKKKKKKKKKKKKKK
FT (in Ref. 5; AAH13871).
SQ SEQUENCE 1015 AA; 113557 MW; 25F5B23065861593 CRC64;
MPRATALGAL VSLLLLLPLP RGAGGLGERP DATADYSELD GEEGTEQQLE HYHDPCKAAV
FWGDIALDED DLKLFHIDKA RDWTKQTVGA TGHSTGGLEE QASESSPDTT AMDTGTKEAG
KDGRENTTLL HSPGTLHAAA KTFSPRVRRA TTSRTERIWP GGVIPYVIGG NFTGSQRAIF
KQAMRHWEKH TCVTFIERTD EESFIVFSYR TCGCCSYVGR RGGGPQAISI GKNCDKFGIV
AHELGHVVGF WHEHTRPDRD QHVTIIRENI QPGQEYNFLK MEAGEVSSLG ETYDFDSIMH
YARNTFSRGV FLDTILPRQD DNGVRPTIGQ RVRLSQGDIA QARKLYKCPA CGETLQDTTG
NFSAPGFPNG YPSYSHCVWR ISVTPGEKIV LNFTSMDLFK SRLCWYDYVE VRDGYWRKAP
LLGRFCGDKI PEPLVSTDSR LWVEFRSSSN ILGKGFFAAY EATCGGDMNK DAGQIQSPNY
PDDYRPSKEC VWRITVSEGF HVGLTFQAFE IERHDSCAYD YLEVRDGPTE ESALIGHFCG
YEKPEDVKSS SNRLWMKFVS DGSINKAGFA ANFFKEVDEC SWPDHGGCEH RCVNTLGSYK
CACDPGYELA ADKKMCEVAC GGFITKLNGT ITSPGWPKEY PTNKNCVWQV VAPAQYRISL
QFEVFELEGN DVCKYDFVEV RSGLSPDAKL HGRFCGSETP EVITSQSNNM RVEFKSDNTV
SKRGFRAHFF SDKDECAKDN GGCQHECVNT FGSYLCRCRN GYWLHENGHD CKEAGCAHKI
SSVEGTLASP NWPDKYPSRR ECTWNISSTA GHRVKLTFNE FEIEQHQECA YDHLEMYDGP
DSLAPILGRF CGSKKPDPTV ASGSSMFLRF YSDASVQRKG FQAVHSTECG GRLKAEVQTK
ELYSHAQFGD NNYPSEARCD WVIVAEDGYG VELTFRTFEV EEEADCGYDY MEAYDGYDSS
APRLGRFCGS GPLEEIYSAG DSLMIRFRTD DTINKKGFHA RYTSTKFQDA LHMKK
//
