Q9NS15 (LTBP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Latent-transforming growth factor beta-binding protein 3
Short name=LTBP-3

Gene names

Name:

LTBP3

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	1303 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	May be involved in the assembly, secretion and targeting of TGFB1 to sites at which it is stored and/or activated. May play critical roles in controlling and directing the activity of TGFB1. May have a structural role in the extra cellular matrix (ECM).
Subunit structure	Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex.
Subcellular location	Secreted By similarity. Note: Secretion occurs after coexpression with TGFB1 and requires complexing with 'Cys-33' of the TGFB1 propeptide By similarity.
Tissue specificity	Isoform 2 is expressed prominently in heart, skeletal muscle, prostate, testis, small intestine and ovary. Isoform 1 is strongly expressed in pancreas and liver.
Post-translational modification	Contains hydroxylated asparagine residues By similarity. Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.
Involvement in disease	Tooth agenesis selective 6 (STHAG6) [MIM:613097]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). In tooth agenesis selective type 6, alveolar bone is absent where the teeth are missing. Some individuals have short stature. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the LTBP family. Contains 13 EGF-like domains. Contains 4 TB (TGF-beta binding) domains.
Sequence caution	The sequence BAB15767.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	EGF-like domain Repeat Signal
Ligand	Growth factor binding
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone morphogenesis Inferred from electronic annotation. Source: Compara bone remodeling Inferred from electronic annotation. Source: Compara lung saccule development Inferred from electronic annotation. Source: Compara negative regulation of bone mineralization Inferred from electronic annotation. Source: Compara negative regulation of chondrocyte differentiation Inferred from electronic annotation. Source: Compara positive regulation of bone resorption Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NS15-1)

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.

Isoform 2 (identifier: Q9NS15-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1082-1128: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 43	43	Potential
	Chain	44 – 1303	1260	Latent-transforming growth factor beta-binding protein 3		PRO_0000007646
Regions
	Domain	109 – 141	33	EGF-like 1
	Domain	277 – 331	55	TB 1
	Domain	355 – 395	41	EGF-like 2; calcium-binding Potential
	Domain	403 – 455	53	TB 2
	Domain	574 – 615	42	EGF-like 3
	Domain	616 – 659	44	EGF-like 4; calcium-binding Potential
	Domain	660 – 702	43	EGF-like 5; calcium-binding Potential
	Domain	744 – 784	41	EGF-like 6; calcium-binding Potential
	Domain	785 – 825	41	EGF-like 7; calcium-binding Potential
	Domain	826 – 865	40	EGF-like 8; calcium-binding Potential
	Domain	866 – 908	43	EGF-like 9; calcium-binding Potential
	Domain	917 – 971	55	TB 3
	Domain	993 – 1035	43	EGF-like 10; calcium-binding Potential
	Domain	1036 – 1076	41	EGF-like 11; calcium-binding Potential
	Domain	1082 – 1122	41	EGF-like 12; calcium-binding Potential
	Domain	1136 – 1186	51	TB 4
	Domain	1254 – 1298	45	EGF-like 13; calcium-binding Potential
	Compositional bias	3 – 167	165	Gly-rich
	Compositional bias	578 – 894	317	Cys-rich
Amino acid modifications
	Glycosylation	89	1	N-linked (GlcNAc...) Potential
	Glycosylation	349	1	N-linked (GlcNAc...) Potential
	Glycosylation	845	1	N-linked (GlcNAc...) Potential
	Glycosylation	936	1	N-linked (GlcNAc...) Potential
	Glycosylation	1275	1	N-linked (GlcNAc...) Potential
	Disulfide bond	113 ↔ 123		By similarity
	Disulfide bond	117 ↔ 129		By similarity
	Disulfide bond	131 ↔ 140		By similarity
	Disulfide bond	359 ↔ 370		By similarity
	Disulfide bond	365 ↔ 379		By similarity
	Disulfide bond	381 ↔ 394		By similarity
	Disulfide bond	578 ↔ 590		By similarity
	Disulfide bond	585 ↔ 599		By similarity
	Disulfide bond	601 ↔ 614		By similarity
	Disulfide bond	620 ↔ 632		By similarity
	Disulfide bond	625 ↔ 641		By similarity
	Disulfide bond	643 ↔ 658		By similarity
	Disulfide bond	664 ↔ 676		By similarity
	Disulfide bond	670 ↔ 685		By similarity
	Disulfide bond	687 ↔ 701		By similarity
	Disulfide bond	748 ↔ 759		By similarity
	Disulfide bond	754 ↔ 768		By similarity
	Disulfide bond	770 ↔ 783		By similarity
	Disulfide bond	789 ↔ 800		By similarity
	Disulfide bond	795 ↔ 809		By similarity
	Disulfide bond	811 ↔ 824		By similarity
	Disulfide bond	830 ↔ 841		By similarity
	Disulfide bond	836 ↔ 850		By similarity
	Disulfide bond	852 ↔ 864		By similarity
	Disulfide bond	870 ↔ 883		By similarity
	Disulfide bond	877 ↔ 892		By similarity
	Disulfide bond	894 ↔ 907		By similarity
	Disulfide bond	997 ↔ 1010		By similarity
	Disulfide bond	1005 ↔ 1019		By similarity
	Disulfide bond	1021 ↔ 1034		By similarity
	Disulfide bond	1040 ↔ 1051		By similarity
	Disulfide bond	1046 ↔ 1060		By similarity
	Disulfide bond	1062 ↔ 1075		By similarity
	Disulfide bond	1086 ↔ 1097		By similarity
	Disulfide bond	1092 ↔ 1106		By similarity
	Disulfide bond	1108 ↔ 1121		By similarity
	Disulfide bond	1258 ↔ 1273		By similarity
	Disulfide bond	1268 ↔ 1282		By similarity
	Disulfide bond	1284 ↔ 1297		By similarity
Natural variations
	Alternative sequence	1082 – 1128	47	Missing in isoform 2.		VSP_009241
Experimental info
	Sequence conflict	35	1	Missing in BAB15767. Ref.2
	Sequence conflict	477	1	D → H in AAB64201. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 4. Checksum: 3BC6B1EE19198414	FASTA	1,303	139,359
	10 20 30 40 50 60 MPGPRGAAGG LAPEMRGAGA AGLLALLLLL LLLLLGLGGR VEGGPAGERG AGGGGALARE 70 80 90 100 110 120 RFKVVFAPVI CKRTCLKGQC RDSCQQGSNM TLIGENGHST DTLTGSGFRV VVCPLPCMNG 130 140 150 160 170 180 GQCSSRNQCL CPPDFTGRFC QVPAGGAGGG TGGSGPGLSR TGALSTGALP PLAPEGDSVA 190 200 210 220 230 240 SKHAIYAVQV IADPPGPGEG PPAQHAAFLV PLGPGQISAE VQAPPPVVNV RVHHPPEASV 250 260 270 280 290 300 QVHRIESSNA ESAAPSQHLL PHPKPSHPRP PTQKPLGRCF QDTLPKQPCG SNPLPGLTKQ 310 320 330 340 350 360 EDCCGSIGTA WGQSKCHKCP QLQYTGVQKP GPVRGEVGAD CPQGYKRLNS THCQDINECA 370 380 390 400 410 420 MPGVCRHGDC LNNPGSYRCV CPPGHSLGPS RTQCIADKPE EKSLCFRLVS PEHQCQHPLT 430 440 450 460 470 480 TRLTRQLCCC SVGKAWGARC QRCPTDGTAA FKEICPAGKG YHILTSHQTL TIQGESDFSL 490 500 510 520 530 540 FLHPDGPPKP QQLPESPSQA PPPEDTEEER GVTTDSPVSE ERSVQQSHPT ATTTPARPYP 550 560 570 580 590 600 ELISRPSPPT MRWFLPDLPP SRSAVEIAPT QVTETDECRL NQNICGHGEC VPGPPDYSCH 610 620 630 640 650 660 CNPGYRSHPQ HRYCVDVNEC EAEPCGPGRG ICMNTGGSYN CHCNRGYRLH VGAGGRSCVD 670 680 690 700 710 720 LNECAKPHLC GDGGFCINFP GHYKCNCYPG YRLKASRPPV CEDIDECRDP SSCPDGKCEN 730 740 750 760 770 780 KPGSFKCIAC QPGYRSQGGG ACRDVNECAE GSPCSPGWCE NLPGSFRCTC AQGYAPAPDG 790 800 810 820 830 840 RSCLDVDECE AGDVCDNGIC SNTPGSFQCQ CLSGYHLSRD RSHCEDIDEC DFPAACIGGD 850 860 870 880 890 900 CINTNGSYRC LCPQGHRLVG GRKCQDIDEC SQDPSLCLPH GACKNLQGSY VCVCDEGFTP 910 920 930 940 950 960 TQDQHGCEEV EQPHHKKECY LNFDDTVFCD SVLATNVTQQ ECCCSLGAGW GDHCEIYPCP 970 980 990 1000 1010 1020 VYSSAEFHSL CPDGKGYTQD NNIVNYGIPA HRDIDECMLF GSEICKEGKC VNTQPGYECY 1030 1040 1050 1060 1070 1080 CKQGFYYDGN LLECVDVDEC LDESNCRNGV CENTRGGYRC ACTPPAEYSP AQRQCLSPEE 1090 1100 1110 1120 1130 1140 MDVDECQDPA ACRPGRCVNL PGSYRCECRP PWVPGPSGRD CQLPESPAER APERRDVCWS 1150 1160 1170 1180 1190 1200 QRGEDGMCAG PLAGPALTFD DCCCRQGRGW GAQCRPCPPR GAGSHCPTSQ SESNSFWDTS 1210 1220 1230 1240 1250 1260 PLLLGKPPRD EDSSEEDSDE CRCVSGRCVP RPGGAVCECP GGFQLDASRA RCVDIDECRE 1270 1280 1290 1300 LNQRGLLCKS ERCVNTSGSF RCVCKAGFAR SRPHGACVPQ RRR
	Isoform 2 [UniParc]. Checksum: 1D930E5D208601E2	FASTA	1,256	134,292
	10 20 30 40 50 60 MPGPRGAAGG LAPEMRGAGA AGLLALLLLL LLLLLGLGGR VEGGPAGERG AGGGGALARE 70 80 90 100 110 120 RFKVVFAPVI CKRTCLKGQC RDSCQQGSNM TLIGENGHST DTLTGSGFRV VVCPLPCMNG 130 140 150 160 170 180 GQCSSRNQCL CPPDFTGRFC QVPAGGAGGG TGGSGPGLSR TGALSTGALP PLAPEGDSVA 190 200 210 220 230 240 SKHAIYAVQV IADPPGPGEG PPAQHAAFLV PLGPGQISAE VQAPPPVVNV RVHHPPEASV 250 260 270 280 290 300 QVHRIESSNA ESAAPSQHLL PHPKPSHPRP PTQKPLGRCF QDTLPKQPCG SNPLPGLTKQ 310 320 330 340 350 360 EDCCGSIGTA WGQSKCHKCP QLQYTGVQKP GPVRGEVGAD CPQGYKRLNS THCQDINECA 370 380 390 400 410 420 MPGVCRHGDC LNNPGSYRCV CPPGHSLGPS RTQCIADKPE EKSLCFRLVS PEHQCQHPLT 430 440 450 460 470 480 TRLTRQLCCC SVGKAWGARC QRCPTDGTAA FKEICPAGKG YHILTSHQTL TIQGESDFSL 490 500 510 520 530 540 FLHPDGPPKP QQLPESPSQA PPPEDTEEER GVTTDSPVSE ERSVQQSHPT ATTTPARPYP 550 560 570 580 590 600 ELISRPSPPT MRWFLPDLPP SRSAVEIAPT QVTETDECRL NQNICGHGEC VPGPPDYSCH 610 620 630 640 650 660 CNPGYRSHPQ HRYCVDVNEC EAEPCGPGRG ICMNTGGSYN CHCNRGYRLH VGAGGRSCVD 670 680 690 700 710 720 LNECAKPHLC GDGGFCINFP GHYKCNCYPG YRLKASRPPV CEDIDECRDP SSCPDGKCEN 730 740 750 760 770 780 KPGSFKCIAC QPGYRSQGGG ACRDVNECAE GSPCSPGWCE NLPGSFRCTC AQGYAPAPDG 790 800 810 820 830 840 RSCLDVDECE AGDVCDNGIC SNTPGSFQCQ CLSGYHLSRD RSHCEDIDEC DFPAACIGGD 850 860 870 880 890 900 CINTNGSYRC LCPQGHRLVG GRKCQDIDEC SQDPSLCLPH GACKNLQGSY VCVCDEGFTP 910 920 930 940 950 960 TQDQHGCEEV EQPHHKKECY LNFDDTVFCD SVLATNVTQQ ECCCSLGAGW GDHCEIYPCP 970 980 990 1000 1010 1020 VYSSAEFHSL CPDGKGYTQD NNIVNYGIPA HRDIDECMLF GSEICKEGKC VNTQPGYECY 1030 1040 1050 1060 1070 1080 CKQGFYYDGN LLECVDVDEC LDESNCRNGV CENTRGGYRC ACTPPAEYSP AQRQCLSPEE 1090 1100 1110 1120 1130 1140 MERAPERRDV CWSQRGEDGM CAGPLAGPAL TFDDCCCRQG RGWGAQCRPC PPRGAGSHCP 1150 1160 1170 1180 1190 1200 TSQSESNSFW DTSPLLLGKP PRDEDSSEED SDECRCVSGR CVPRPGGAVC ECPGGFQLDA 1210 1220 1230 1240 1250 SRARCVDIDE CRELNQRGLL CKSERCVNTS GSFRCVCKAG FARSRPHGAC VPQRRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Secretion of human latent TGF-beta-binding protein-3 (LTBP-3) is dependent on co-expression of TGF-beta." Penttinen C., Saharinen J., Weikkolainen K., Hyytiainen M., Keski-Oja J. J. Cell Sci. 115:3457-3468(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION (ISOFORM 2).
[2]	"The nucleotide sequence of a long cDNA clone isolated from human spleen." Ohara O., Nagase T., Kikuno R., Okumura K. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Spleen.
[3]	"Analysis of the expression pattern of the latent transforming growth factor beta binding protein isoforms in normal and diseased human liver reveals a new splice variant missing the proteinase-sensitive hinge region." Michel K., Roth S., Trautwein C., Gong W., Flemming P., Gressner A.M. Hepatology 27:1592-1599(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 394-573. Tissue: Liver.
[4]	"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 514-1303 (ISOFORM 2). Tissue: Colon.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 793-1303. Tissue: Uterus.
[6]	"Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta." Saharinen J., Keski-Oja J. Mol. Biol. Cell 11:2691-2704(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TGFB1.
[7]	"Latent transforming growth factor-beta binding proteins (LTBPs) --structural extracellular matrix proteins for targeting TGF-beta action." Saharinen J., Hyytiainen M., Taipale J., Keski-Oja J. Cytokine Growth Factor Rev. 10:99-117(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[8]	"The latent transforming growth factor beta binding protein (LTBP) family." Oklu R., Hesketh R. Biochem. J. 352:601-610(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3." Noor A., Windpassinger C., Vitcu I., Orlic M., Rafiq M.A., Khalid M., Malik M.N., Ayub M., Alman B., Vincent J.B. Am. J. Hum. Genet. 84:519-523(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN STHAG6.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF135960 mRNA. Translation: AAF62352.3. AK024477 mRNA. Translation: BAB15767.1. Different initiation. AF011407 mRNA. Translation: AAB64201.1. BC008761 mRNA. Translation: AAH08761.2. AL117551 mRNA. Translation: CAB55988.1.
IPI	IPI00073196. IPI00398794.
PIR	T17298.
RefSeq	NP_001123616.1. NM_001130144.2. NP_001157738.1. NM_001164266.1. NP_066548.2. NM_021070.4.
UniGene	Hs.289019.
3D structure databases
ProteinModelPortal	Q9NS15.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NS15. 5 interactions.
MINT	MINT-1184940.
STRING	9606.ENSP00000301873.
PTM databases
PhosphoSite	Q9NS15.
Polymorphism databases
DMDM	116242623.
Proteomic databases
PaxDb	Q9NS15.
PRIDE	Q9NS15.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000301873; ENSP00000301873; ENSG00000168056. ENST00000322147; ENSP00000326647; ENSG00000168056.
GeneID	4054.
KEGG	hsa:4054.
UCSC	uc001oei.3. human. uc001oej.3. human.
Organism-specific databases
CTD	4054.
GeneCards	GC11M065306.
HGNC	HGNC:6716. LTBP3.
MIM	602090. gene. 613097. phenotype.
neXtProt	NX_Q9NS15.
Orphanet	99798. Oligodontia.
PharmGKB	PA30479.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG261244.
HOGENOM	HOG000293153.
HOVERGEN	HBG052370.
InParanoid	Q9NS15.
KO	K08023.
OMA	MRWFLPD.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q9NS15.
Bgee	Q9NS15.
CleanEx	HS_LTBP3.
Genevestigator	Q9NS15.
GermOnline	ENSG00000168056. Homo sapiens.
Family and domain databases
Gene3D	3.90.290.10. 5 hits.
InterPro	IPR026823. cEGF. 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. IPR017878. TB_dom. [Graphical view]
Pfam	PF12662. cEGF. 1 hit. PF07645. EGF_CA. 10 hits. PF00683. TB. 4 hits. [Graphical view]
SMART	SM00181. EGF. 3 hits. SM00179. EGF_CA. 12 hits. [Graphical view]
SUPFAM	SSF57581. Fibril-assoc. 4 hits.
PROSITE	PS00010. ASX_HYDROXYL. 11 hits. PS00022. EGF_1. 1 hit. PS01186. EGF_2. 8 hits. PS50026. EGF_3. 13 hits. PS01187. EGF_CA. 12 hits. PS51364. TB. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LTBP3. human.
GenomeRNAi	4054.
NextBio	15884.
SOURCE	Search...

Entry information

Entry name

LTBP3_HUMAN

Accession

Primary (citable) accession number: Q9NS15
Secondary accession number(s): O15107 , Q96HB9, Q9H7K2, Q9UFN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 16, 2004
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 115 of the entry and version 4 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.