ID LTBP4_HUMAN Reviewed; 1624 AA. AC Q8N2S1; O00508; O75412; O75413; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 2. DT 22-JUL-2008, entry version 51. DE RecName: Full=Latent-transforming growth factor beta-binding protein 4; DE Short=LTBP-4; DE Flags: Precursor; GN Name=LTBP4; 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] (ISOFORM 3), TISSUE SPECIFICITY, AND RP VARIANT MET-1141. RX MEDLINE=97415399; PubMed=9271198; DOI=10.1016/S0014-5793(97)00685-6; RA Giltay R., Kostka G., Timpl R.; RT "Sequence and expression of a novel member (LTBP-4) of the family of RT latent transforming growth factor-beta binding proteins."; RL FEBS Lett. 411:164-168(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP INTERACTION WITH LTBP1 AND TGFB1, AND VARIANTS ILE-194; ALA-787; RP ALA-820 AND MET-1141. RC TISSUE=Heart; RX MEDLINE=98325059; PubMed=9660815; DOI=10.1074/jbc.273.29.18459; RA Saharinen J., Taipale J., Monni O., Keski-Oja J.; RT "Identification and characterization of a new latent transforming RT growth factor-beta-binding protein, LTBP-4."; RL J. Biol. Chem. 273:18459-18469(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP SUBCELLULAR LOCATION. RX PubMed=16157329; DOI=10.1016/j.yexcr.2005.08.008; RA Koli K., Hyytieainen M., Ryynanen M.J., Keski-Oja J.; RT "Sequential deposition of latent TGF-beta binding proteins (LTBPs) RT during formation of the extracellular matrix in human lung RT fibroblasts."; RL Exp. Cell Res. 310:370-382(2005). CC -!- FUNCTION: May be involved in the assembly, secretion and targeting CC of TGFB1 to sites at which it is stored and/or activated. May play CC critical roles in controlling and directing the activity of TGFB1. CC May have a structural role in the extra cellular matrix (ECM) (By CC similarity). CC -!- SUBUNIT: Forms part of the large latent transforming growth factor CC beta precursor complex; removal is essential for activation of CC complex. Interacts with LTBP1 and TGFB1. Binds to FBN1 (By CC similarity). CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=LTBP-4L; CC IsoId=Q8N2S1-1; Sequence=Displayed; CC Name=2; Synonyms=LTBP-4S; CC IsoId=Q8N2S1-2; Sequence=VSP_029364, VSP_029365; CC Name=3; CC IsoId=Q8N2S1-3; Sequence=VSP_029363; CC Name=4; CC IsoId=Q8N2S1-4; Sequence=VSP_029362, VSP_029366, VSP_029367; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, CC pancreas, uterus, and small intestine. Weakly expressed in CC placenta and lung,. CC -!- DEVELOPMENTAL STAGE: Very low expression in fetal brain, liver, CC heart, spleen and thymus. CC -!- PTM: Contains hydroxylated asparagine residues (By similarity). CC -!- SIMILARITY: Belongs to the LTBP family. CC -!- SIMILARITY: Contains 16 EGF-like domains. CC -!- SIMILARITY: Contains 4 TB (TGF-beta binding) domains. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y13622; CAA73944.1; -; mRNA. DR EMBL; AF051344; AAC39879.2; -; mRNA. DR EMBL; AF051345; AAC39880.2; -; mRNA. DR EMBL; AK074499; BAC11024.1; -; mRNA. DR RefSeq; NP_001036009.1; -. DR RefSeq; NP_001036010.1; -. DR RefSeq; NP_003564.2; -. DR UniGene; Hs.466766; -. DR HSSP; P22064; 1KSQ. DR PhosphoSite; Q8N2S1; -. DR Ensembl; ENSG00000090006; Homo sapiens. DR GeneID; 8425; -. DR KEGG; hsa:8425; -. DR HGNC; HGNC:6717; LTBP4. DR HPA; CAB015194; -. DR MIM; 604710; gene. DR PharmGKB; PA30480; -. DR HOVERGEN; Q8N2S1; -. DR ArrayExpress; Q8N2S1; -. DR CleanEx; HS_LTBP4; -. DR GO; GO:0005578; C:proteinaceous extracellular matrix; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB. DR GO; GO:0005539; F:glycosaminoglycan binding; NAS:UniProtKB. DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB. DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:UniProtKB. DR GO; GO:0005024; F:transforming growth factor beta receptor ac...; NAS:UniProtKB. DR GO; GO:0030252; P:growth hormone secretion; TAS:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; TAS:UniProtKB. DR GO; GO:0006457; P:protein folding; TAS:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB. DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB. DR GO; GO:0030162; P:regulation of proteolysis; IDA:UniProtKB. DR GO; GO:0017015; P:regulation of transforming growth factor be...; TAS:UniProtKB. DR InterPro; IPR006210; EGF. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_CS. DR InterPro; IPR000742; EGF_3. DR InterPro; IPR001881; EGF_Ca_bd. DR InterPro; IPR013091; EGF_Ca_bd_2. DR InterPro; IPR013111; EGF_extracell. DR InterPro; IPR006209; EGF_like. DR InterPro; IPR013032; EGF_like_reg_CS. DR InterPro; IPR002212; Fibril-assoc. DR Gene3D; G3DSA:3.90.290.10; Fibril-assoc; 3. DR Pfam; PF00008; EGF; 2. DR Pfam; PF07974; EGF_2; 1. DR Pfam; PF07645; EGF_CA; 16. DR Pfam; PF00683; TB; 4. DR SMART; SM00181; EGF; 3. DR SMART; SM00179; EGF_CA; 16. DR PROSITE; PS00010; ASX_HYDROXYL; 14. DR PROSITE; PS00022; EGF_1; 2. DR PROSITE; PS01186; EGF_2; 12. DR PROSITE; PS50026; EGF_3; 15. DR PROSITE; PS01187; EGF_CA; 17. DR PROSITE; PS51364; TB; 4. PE 1: Evidence at protein level; KW Alternative splicing; EGF-like domain; Extracellular matrix; KW Glycoprotein; Growth factor binding; Polymorphism; Repeat; Secreted; KW Signal. FT SIGNAL 1 27 Potential. FT CHAIN 28 1624 Latent-transforming growth factor beta- FT binding protein 4. FT /FTId=PRO_0000310964. FT DOMAIN 149 181 EGF-like 1. FT DOMAIN 287 339 TB 1. FT DOMAIN 357 397 EGF-like 2; calcium-binding (Potential). FT DOMAIN 407 459 TB 2. FT DOMAIN 545 586 EGF-like 3. FT DOMAIN 587 628 EGF-like 4; calcium-binding (Potential). FT DOMAIN 629 670 EGF-like 5; calcium-binding (Potential). FT DOMAIN 671 708 EGF-like 6; calcium-binding (Potential). FT DOMAIN 710 751 EGF-like 7; calcium-binding (Potential). FT DOMAIN 752 793 EGF-like 8; calcium-binding (Potential). FT DOMAIN 834 877 EGF-like 9; calcium-binding (Potential). FT DOMAIN 878 919 EGF-like 10; calcium-binding (Potential). FT DOMAIN 920 960 EGF-like 11; calcium-binding (Potential). FT DOMAIN 1049 1090 EGF-like 12; calcium-binding (Potential). FT DOMAIN 1181 1235 TB 3. FT DOMAIN 1253 1295 EGF-like 13; calcium-binding (Potential). FT DOMAIN 1296 1337 EGF-like 14; calcium-binding (Potential). FT DOMAIN 1349 1402 TB 4. FT DOMAIN 1533 1573 EGF-like 15. FT DOMAIN 1574 1618 EGF-like 16. FT COMPBIAS 478 565 Pro-rich. FT COMPBIAS 549 1118 Cys-rich. FT COMPBIAS 1119 1175 Pro-rich. FT COMPBIAS 1407 1492 Pro-rich. FT CARBOHYD 352 352 N-linked (GlcNAc...) (Potential). FT CARBOHYD 425 425 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1055 1055 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1200 1200 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1339 1339 N-linked (GlcNAc...) (Potential). FT DISULFID 153 163 By similarity. FT DISULFID 157 169 By similarity. FT DISULFID 171 180 By similarity. FT DISULFID 361 372 By similarity. FT DISULFID 367 381 By similarity. FT DISULFID 383 396 By similarity. FT DISULFID 549 561 By similarity. FT DISULFID 556 570 By similarity. FT DISULFID 572 585 By similarity. FT DISULFID 591 603 By similarity. FT DISULFID 598 612 By similarity. FT DISULFID 614 627 By similarity. FT DISULFID 633 645 By similarity. FT DISULFID 640 654 By similarity. FT DISULFID 656 669 By similarity. FT DISULFID 675 687 By similarity. FT DISULFID 682 696 By similarity. FT DISULFID 698 707 By similarity. FT DISULFID 714 726 By similarity. FT DISULFID 721 735 By similarity. FT DISULFID 737 750 By similarity. FT DISULFID 756 768 By similarity. FT DISULFID 763 777 By similarity. FT DISULFID 779 792 By similarity. FT DISULFID 838 851 By similarity. FT DISULFID 845 860 By similarity. FT DISULFID 862 876 By similarity. FT DISULFID 882 894 By similarity. FT DISULFID 888 903 By similarity. FT DISULFID 905 918 By similarity. FT DISULFID 924 935 By similarity. FT DISULFID 930 944 By similarity. FT DISULFID 946 959 By similarity. FT DISULFID 1053 1065 By similarity. FT DISULFID 1059 1074 By similarity. FT DISULFID 1076 1089 By similarity. FT DISULFID 1257 1270 By similarity. FT DISULFID 1265 1279 By similarity. FT DISULFID 1281 1294 By similarity. FT DISULFID 1300 1312 By similarity. FT DISULFID 1307 1321 By similarity. FT DISULFID 1323 1336 By similarity. FT DISULFID 1537 1548 By similarity. FT DISULFID 1543 1557 By similarity. FT DISULFID 1559 1572 By similarity. FT DISULFID 1578 1593 By similarity. FT DISULFID 1588 1602 By similarity. FT DISULFID 1604 1617 By similarity. FT VAR_SEQ 1 902 Missing (in isoform 4). FT /FTId=VSP_029362. FT VAR_SEQ 1 68 MPRPGTSGRRPLLLVLLLPLFAAATSAASPSPSPSQVVEVP FT GVPSRPASVAVCRCCPGQTSRRSRCIR -> MGDVKALLFV FT VAARARRLGGAAASESLAVSE (in isoform 3). FT /FTId=VSP_029363. FT VAR_SEQ 1 67 Missing (in isoform 2). FT /FTId=VSP_029364. FT VAR_SEQ 68 151 RAFCRVRSCQPKKCAGPQRCLNPVPAVPSPSPSVRKRQVSL FT NWQPLTLQEARALLKRRRPRGPGGRGLLRRRPPQRAPAGKA FT PV -> MAGGVRLLWVSLLVLLAQLGPQPGLGRLGERLRVR FT FTPVVCGLRCVHGPTGSRCTPTCAPRNATSVDSGAPGGAAP FT GGPGFRAF (in isoform 2). FT /FTId=VSP_029365. FT VAR_SEQ 903 919 CTCAPGYRPGPRGASCL -> MLGGAGGGPGLRTPCPA FT (in isoform 4). FT /FTId=VSP_029366. FT VAR_SEQ 1007 1092 Missing (in isoform 4). FT /FTId=VSP_029367. FT VARIANT 194 194 V -> I (in dbSNP:rs2303729). FT /FTId=VAR_037119. FT VARIANT 635 635 R -> G (in dbSNP:rs33937741). FT /FTId=VAR_037120. FT VARIANT 679 679 P -> A (in dbSNP:rs34299942). FT /FTId=VAR_037121. FT VARIANT 787 787 T -> A (in dbSNP:rs1131620). FT /FTId=VAR_037122. FT VARIANT 820 820 T -> A (in dbSNP:rs1051303). FT /FTId=VAR_037123. FT VARIANT 1141 1141 T -> M (in dbSNP:rs11668767). FT /FTId=VAR_037124. FT CONFLICT 170 170 L -> F (in Ref. 1; CAA73944). FT CONFLICT 346 346 T -> A (in Ref. 3; BAC11024). FT CONFLICT 526 526 L -> F (in Ref. 2; AAC39879/AAC39880). FT CONFLICT 686 686 A -> G (in Ref. 1; CAA73944). FT CONFLICT 974 974 G -> R (in Ref. 3; BAC11024). FT CONFLICT 1139 1139 A -> V (in Ref. 1; CAA73944). FT CONFLICT 1142 1142 F -> S (in Ref. 1; CAA73944). FT CONFLICT 1151 1151 A -> V (in Ref. 1; CAA73944). FT CONFLICT 1165 1165 P -> S (in Ref. 1; CAA73944). FT CONFLICT 1169 1170 ST -> RK (in Ref. 1; CAA73944). FT CONFLICT 1173 1173 Q -> K (in Ref. 1; CAA73944). FT CONFLICT 1180 1180 R -> C (in Ref. 1; CAA73944). FT CONFLICT 1402 1402 C -> R (in Ref. 3; BAC11024). FT CONFLICT 1512 1512 P -> S (in Ref. 3; BAC11024). FT CONFLICT 1546 1546 G -> D (in Ref. 1; CAA73944). SQ SEQUENCE 1624 AA; 173435 MW; 75682D1F6E40657A CRC64; MPRPGTSGRR PLLLVLLLPL FAAATSAASP SPSPSQVVEV PGVPSRPASV AVCRCCPGQT SRRSRCIRAF CRVRSCQPKK CAGPQRCLNP VPAVPSPSPS VRKRQVSLNW QPLTLQEARA LLKRRRPRGP GGRGLLRRRP PQRAPAGKAP VLCPLICHNG GVCVKPDRCL CPPDFAGKFC QLHSSGARPP APAVPGLTRS VYTMPLANHR DDEHGVASMV SVHVEHPQEA SVVVHQVERV SGPWEEADAE AVARAEAAAR AEAAAPYTVL AQSAPREDGY SDASGFGYCF RELRGGECAS PLPGLRTQEV CCRGAGLAWG VHDCQLCSER LGNSERVSAP DGPCPTGFER VNGSCEDVDE CATGGRCQHG ECANTRGGYT CVCPDGFLLD SSRSSCISQH VISEAKGPCF RVLRDGGCSL PILRNITKQI CCCSRVGKAW GRGCQLCPPF GSEGFREICP AGPGYHYSAS DLRYNTRPLG QEPPRVSLSQ PRTLPATSRP SAGFLPTHRL EPRPEPRPDP RPGPELPLPS IPAWTGPEIP ESGPSSGMCQ RNPQVCGPGR CISRPSGYTC ACDSGFRLSP QGTRCIDVDE CRRVPPPCAP GRCENSPGSF RCVCGPGFRA GPRAAECLDV DECHRVPPPC DLGRCENTPG SFLCVCPAGY QAAPHGASCQ DVDECTQSPG LCGRGACKNL PGSFRCVCPA GFRGSACEED VDECAQEPPP CGPGRCDNTA GSFHCACPAG FRSRGPGAPC QDVDECARSP PPCTYGRCEN TEGSFQCVCP MGFQPNTAGS ECEDVDECEN HLACPGQECV NSPGSFQCRT CPSGHHLHRG RCTDVDECSS GAPPCGPHGH CTNTEGSFRC SCAPGYRAPS GRPGPCADVN ECLEGDFCFP HGECLNTDGS FACTCAPGYR PGPRGASCLD VDECSEEDLC QSGICTNTDG SFECICPPGH RAGPDLASCL DVDECRERGP ALCGSQRCEN SPGSYRCVRD CDPGYHAGPE GTCDDVDECQ EYGPEICGAQ RCENTPGSYR CTPACDPGYQ PTPGGGCQDV DECRNRSFCG AHAVCQNLPG SFQCLCDQGY EGARDGRHCV DVNECETLQG VCGAALCENV EGSFLCVCPN SPEEFDPMTG RCVPPRTSAG TFPGSQPQAP ASPVLPARPP PPPLPRRPST PRQGPVGSGR RECYFDTAAP DACDNILARN VTWQECCCTV GEGWGSGCRI QQCPGTETAE YQSLCPHGRG YLAPSGDLSL RRDVDECQLF RDQVCKSGVC VNTAPGYSCY CSNGYYYHTQ RLECIDNDEC ADEEPACEGG RCVNTVGSYH CTCEPPLVLD GSQRRCVSNE SQSLDDNLGV CWQEVGADLV CSHPRLDRQA TYTECCCLYG EAWGMDCALC PAQDSDDFEA LCNVLRPPAY SPPRPGGFGL PYEYGPDLGP PYQGLPYGPE LYPPPALPYD PYPPPPGPFA RREAPYGAPR FDMPDFEDDG GPYGESEAPA PPGPGTRWPY RSRDTRRSFP EPEEPPEGGS YAGSLAEPYE ELEAEECGIL DGCTNGRCVR VPEGFTCRCF DGYRLDMTRM ACVDINECDE AEAASPLCVN ARCLNTDGSF RCICRPGFAP THQPHHCAPA RPRA //