LOCUS NP_036597 1015 aa linear PRI 14-NOV-2023
DEFINITION tolloid-like protein 2 precursor [Homo sapiens].
ACCESSION NP_036597
VERSION NP_036597.1
DBSOURCE REFSEQ: accession NM_012465.4
KEYWORDS RefSeq; MANE Select.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 1015)
AUTHORS Jiang J, Huang J, Gu J, Cai X, Zhao H and Lu H.
TITLE Genomic analysis of a spinal muscular atrophy (SMA) discordant
family identifies a novel mutation in TLL2, an activator of growth
differentiation factor 8 (myostatin): a case report
JOURNAL BMC Med Genet 20 (1), 204 (2019)
PUBMED 31888525
REMARK GeneRIF: genomic analysis identified compound heterozygous
mutations at TLL2 on the male patient's genome, and compound
heterozygous mutations at VPS13A and the de novo mutation at AGAP5
on female patient's genome
Publication Status: Online-Only
REFERENCE 2 (residues 1 to 1015)
AUTHORS Xu Y, Wang Y, Liu H, Shi Q, Zhu D, Amos CI, Fang S, Lee JE, Hyslop
T, Li X, Han J and Wei Q.
TITLE Genetic variants in the metzincin metallopeptidase family genes
predict melanoma survival
JOURNAL Mol Carcinog 57 (1), 22-31 (2018)
PUBMED 28796414
REMARK GeneRIF: Findings suggest that these MMP16 rs10090371, ADAMTS3
rs788935, TLL2 rs10882807 and MMP9 rs3918251 may be promising
prognostic biomarkers for cutaneous melanoma specific survival
(CMSS).
REFERENCE 3 (residues 1 to 1015)
AUTHORS de Mooij-van Malsen JG, van Lith HA, Laarakker MC, Brandys MK,
Oppelaar H, Collier DA, Olivier B, Breen G and Kas MJ.
TITLE Cross-species genetics converge to TLL2 for mouse avoidance
behavior and human bipolar disorder
JOURNAL Genes Brain Behav 12 (6), 653-657 (2013)
PUBMED 23777486
REMARK GeneRIF: By means of a cross-species comparative genetic strategy
we describe an association for TLL2 with bipolar disorder.
REFERENCE 4 (residues 1 to 1015)
AUTHORS Mac Sweeney A, Gil-Parrado S, Vinzenz D, Bernardi A, Hein A,
Bodendorf U, Erbel P, Logel C and Gerhartz B.
TITLE Structural basis for the substrate specificity of bone
morphogenetic protein 1/tolloid-like metalloproteases
JOURNAL J Mol Biol 384 (1), 228-239 (2008)
PUBMED 18824173
REMARK GeneRIF: The crystal structures of the protease domains of human
BMP-1 and the closely related Tolloid-like protease 1 (TLL-1), are
reported.
REFERENCE 5 (residues 1 to 1015)
AUTHORS Lesch KP, Timmesfeld N, Renner TJ, Halperin R, Roser C, Nguyen TT,
Craig DW, Romanos J, Heine M, Meyer J, Freitag C, Warnke A, Romanos
M, Schafer H, Walitza S, Reif A, Stephan DA and Jacob C.
TITLE Molecular genetics of adult ADHD: converging evidence from
genome-wide association and extended pedigree linkage studies
JOURNAL J Neural Transm (Vienna) 115 (11), 1573-1585 (2008)
PUBMED 18839057
REFERENCE 6 (residues 1 to 1015)
AUTHORS Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L,
Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE,
Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles
J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD,
Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H,
Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J,
Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee
CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner
L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S,
Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E,
Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C,
Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK,
Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird
G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE,
McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson
T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan
S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou
T, Sehra HK, Shownkeen R, Skuce CD, 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 AP, Willey DL, Whitehead
SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK,
Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T,
Doucette-Stamm L, Beck S, Smith DR and Rogers J.
TITLE The DNA sequence and comparative analysis of human chromosome 10
JOURNAL Nature 429 (6990), 375-381 (2004)
PUBMED 15164054
REFERENCE 7 (residues 1 to 1015)
AUTHORS Uzel MI, Scott IC, Babakhanlou-Chase H, Palamakumbura AH, Pappano
WN, Hong HH, Greenspan DS and Trackman PC.
TITLE 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
JOURNAL J Biol Chem 276 (25), 22537-22543 (2001)
PUBMED 11313359
REFERENCE 8 (residues 1 to 1015)
AUTHORS Reynolds SD, Zhang D, Puzas JE, O'Keefe RJ, Rosier RN and Reynolds
PR.
TITLE Cloning of the chick BMP1/Tolloid cDNA and expression in skeletal
tissues
JOURNAL Gene 248 (1-2), 233-243 (2000)
PUBMED 10806368
REFERENCE 9 (residues 1 to 1015)
AUTHORS Scott IC, Blitz IL, Pappano WN, Imamura Y, Clark TG, Steiglitz BM,
Thomas CL, Maas SA, Takahara K, Cho KW and Greenspan DS.
TITLE 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
JOURNAL Dev Biol 213 (2), 283-300 (1999)
PUBMED 10479448
REFERENCE 10 (residues 1 to 1015)
AUTHORS Scott IC, Clark TG, Takahara K, Hoffman GG, Eddy RL, Haley LL,
Shows TB and Greenspan DS.
TITLE Assignment of TLL1 and TLL2, which encode human
BMP-1/Tolloid-related metalloproteases, to chromosomes 4q32-->q33
and 10q23-->q24 and assignment of murine Tll2 to chromosome 19
JOURNAL Cytogenet Cell Genet 86 (1), 64-65 (1999)
PUBMED 10516436
COMMENT VALIDATED REFSEQ: This record has undergone validation or
preliminary review. The reference sequence was derived from
DA716349.1, AB023149.2, BC112341.1, AL136181.13 and AW452288.1.
Summary: This gene encodes an astacin-like zinc-dependent
metalloprotease and is a subfamily member of the metzincin family.
Unlike other family members, a similar protein in mice does not
cleave procollagen C-propeptides or chordin. [provided by RefSeq,
Jul 2008].
Sequence Note: This RefSeq record was created from transcript and
genomic sequence data to make the sequence consistent with the
reference genome assembly. The genomic coordinates used for the
transcript record were based on transcript alignments.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the Gene
record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AB023149.2, BC112341.1 [ECO:0000332]
RNAseq introns :: mixed sample support SAMEA1965299,
SAMEA1966682 [ECO:0006172]
##Evidence-Data-END##
##RefSeq-Attributes-START##
MANE Ensembl match :: ENST00000357947.4/ ENSP00000350630.3
RefSeq Select criteria :: based on single protein-coding transcript
##RefSeq-Attributes-END##
FEATURES Location/Qualifiers
source 1..1015
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="10"
/map="10q24.1"
Protein 1..1015
/product="tolloid-like protein 2 precursor"
/note="tolloid-like protein 2"
/calculated_mol_wt=111117
sig_peptide 1..25
/inference="COORDINATES: ab initio prediction:SignalP:4.0"
/calculated_mol_wt=2458
Region 24..49
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Region 88..130
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (Q9Y6L7.1)"
mat_peptide 150..1015
/product="Tolloid-like protein 2. /id=PRO_0000046037"
/note="propagated from UniProtKB/Swiss-Prot (Q9Y6L7.1)"
/calculated_mol_wt=97639
Region 150..349
/region_name="ZnMc_BMP1_TLD"
/note="Zinc-dependent metalloprotease; BMP1/TLD-like
subfamily. BMP1 (Bone morphogenetic protein 1) and TLD
(tolloid)-like metalloproteases play vital roles in
extracellular matrix formation, by cleaving precursor
proteins such as enzymes, structural proteins; cd04281"
/db_xref="CDD:239808"
Site 171
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Site order(242..243,246,252)
/site_type="active"
/db_xref="CDD:239808"
Region 351..460
/region_name="CUB"
/note="CUB domain; pfam00431"
/db_xref="CDD:395345"
Site order(361,363,390,395,433,457,459,461..462)
/site_type="other"
/note="heterodimerization interface [polypeptide binding]"
/db_xref="CDD:238001"
Site 361
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Site 392
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Region 464..573
/region_name="CUB"
/note="CUB domain; pfam00431"
/db_xref="CDD:395345"
Site order(474,476,503,508,546,570,572,574)
/site_type="other"
/note="heterodimerization interface [polypeptide binding]"
/db_xref="CDD:238001"
Region 580..616
/region_name="FXa_inhibition"
/note="Coagulation Factor Xa inhibitory site; pfam14670"
/db_xref="CDD:434114"
Region 620..729
/region_name="CUB"
/note="CUB domain; pfam00431"
/db_xref="CDD:395345"
Site order(628,630,632,659,664,702,726,728,730..731)
/site_type="other"
/note="heterodimerization interface [polypeptide binding]"
/db_xref="CDD:238001"
Site 628
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Region 736..771
/region_name="FXa_inhibition"
/note="Coagulation Factor Xa inhibitory site; pfam14670"
/db_xref="CDD:434114"
Region 776..885
/region_name="CUB"
/note="CUB domain; pfam00431"
/db_xref="CDD:395345"
Site order(784,786,788,815,820,858,882,884,886..887)
/site_type="other"
/note="heterodimerization interface [polypeptide binding]"
/db_xref="CDD:238001"
Site 805
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Region 889..1002
/region_name="CUB"
/note="CUB domain; pfam00431"
/db_xref="CDD:395345"
Site order(899,901,903,932,937,975,999,1001,1003..1004)
/site_type="other"
/note="heterodimerization interface [polypeptide binding]"
/db_xref="CDD:238001"
Site 963
/site_type="methylation"
/note="Omega-N-methylarginine.
/evidence=ECO:0000250|UniProtKB:Q9WVM6; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
Site 966
/site_type="methylation"
/note="Omega-N-methylarginine.
/evidence=ECO:0000250|UniProtKB:Q9WVM6; propagated from
UniProtKB/Swiss-Prot (Q9Y6L7.1)"
CDS 1..1015
/gene="TLL2"
/coded_by="NM_012465.4:242..3289"
/db_xref="CCDS:CCDS7449.1"
/db_xref="GeneID:7093"
/db_xref="HGNC:HGNC:11844"
/db_xref="MIM:606743"
ORIGIN
1 mpratalgal vslllllplp rgagglgerp datadyseld geegteqqle hyhdpckaav
61 fwgdialded dlklfhidka rdwtkqtvga tghstgglee qasesspdtt amdtgtkeag
121 kdgrenttll hspgtlhaaa ktfsprvrra ttsrteriwp ggvipyvigg nftgsqraif
181 kqamrhwekh tcvtfiertd eesfivfsyr tcgccsyvgr rgggpqaisi gkncdkfgiv
241 ahelghvvgf whehtrpdrd qhvtiireni qpgqeynflk meagevsslg etydfdsimh
301 yarntfsrgv fldtilprqd dngvrptigq rvrlsqgdia qarklykcpa cgetlqdttg
361 nfsapgfpng ypsyshcvwr isvtpgekiv lnftsmdlfk srlcwydyve vrdgywrkap
421 llgrfcgdki peplvstdsr lwvefrsssn ilgkgffaay eatcggdmnk dagqiqspny
481 pddyrpskec vwritvsegf hvgltfqafe ierhdscayd ylevrdgpte esalighfcg
541 yekpedvkss snrlwmkfvs dgsinkagfa anffkevdec swpdhggceh rcvntlgsyk
601 cacdpgyela adkkmcevac ggfitklngt itspgwpkey ptnkncvwqv vapaqyrisl
661 qfevfelegn dvckydfvev rsglspdakl hgrfcgsetp evitsqsnnm rvefksdntv
721 skrgfrahff sdkdecakdn ggcqhecvnt fgsylcrcrn gywlhenghd ckeagcahki
781 ssvegtlasp nwpdkypsrr ectwnissta ghrvkltfne feieqhqeca ydhlemydgp
841 dslapilgrf cgskkpdptv asgssmflrf ysdasvqrkg fqavhstecg grlkaevqtk
901 elyshaqfgd nnypsearcd wvivaedgyg veltfrtfev eeeadcgydy meaydgydss
961 aprlgrfcgs gpleeiysag dslmirfrtd dtinkkgfha rytstkfqda lhmkk
//
