ID CILP1_HUMAN Reviewed; 1184 AA. AC O75339; B2R8F7; Q6UW99; Q8IYI5; DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 02-OCT-2024, entry version 178. DE RecName: Full=Cartilage intermediate layer protein 1; DE Short=CILP-1; DE AltName: Full=Cartilage intermediate-layer protein; DE Contains: DE RecName: Full=Cartilage intermediate layer protein 1 C1; DE Contains: DE RecName: Full=Cartilage intermediate layer protein 1 C2; DE Flags: Precursor; GN Name=CILP; ORFNames=UNQ602/PRO1188; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 39-58; 282-291; 301-317; RP 332-338; 341-356; 361-365; 524-547; 575-594; 680-690 AND 698-707, RP GLYCOSYLATION AT ASN-346, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY, AND RP VARIANTS LEU-59; THR-395; GLU-575; ARG-979 AND SER-1166. RC TISSUE=Articular cartilage; RX PubMed=9722584; DOI=10.1074/jbc.273.36.23469; RA Lorenzo P., Neame P., Sommarin Y., Heinegaerd D.; RT "Cloning and deduced amino acid sequence of a novel cartilage protein RT (CILP) identifies a proform including a nucleotide pyrophosphohydrolase."; RL J. Biol. Chem. 273:23469-23475(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-59; PHE-327; THR-395; RP GLU-575; VAL-895; ARG-979; ASN-1101; SER-1166 AND ALA-1168. RX PubMed=10319588; DOI=10.1007/s100380050143; RA Nakamura I., Okawa A., Ikegawa S., Takaoka K., Nakamura Y.; RT "Genomic organization, mapping, and polymorphisms of the gene encoding RT human cartilage intermediate layer protein (CILP)."; RL J. Hum. Genet. 44:203-205(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-59; THR-395; GLU-575; RP ARG-979 AND SER-1166. RX PubMed=10601732; DOI=10.1016/s0945-053x(99)00035-9; RA Lorenzo P., Aman P., Sommarin Y., Heinegaerd D.; RT "The human CILP gene: exon/intron organization and chromosomal mapping."; RL Matrix Biol. 18:445-454(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-395; GLU-575 AND RP ARG-979. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-395; GLU-575; RP ARG-979 AND SER-1166. RC TISSUE=Testis; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLU-575; ARG-979 AND RP SER-1166. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP SUBUNIT, GLYCOSYLATION, AND TISSUE SPECIFICITY. RX PubMed=9722583; DOI=10.1074/jbc.273.36.23463; RA Lorenzo P., Bayliss M.T., Heinegaerd D.; RT "A novel cartilage protein (CILP) present in the mid-zone of human RT articular cartilage increases with age."; RL J. Biol. Chem. 273:23463-23468(1998). RN [9] RP TISSUE SPECIFICITY. RX PubMed=12483726; DOI=10.1002/art.10632; RA Hirose J., Ryan L.M., Masuda I.; RT "Up-regulated expression of cartilage intermediate-layer protein and ANK in RT articular hyaline cartilage from patients with calcium pyrophosphate RT dihydrate crystal deposition disease."; RL Arthritis Rheum. 46:3218-3229(2002). RN [10] RP INVOLVEMENT IN OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS. RX PubMed=11315923; RX DOI=10.1002/1529-0131(200104)44:4<838::aid-anr140>3.0.co;2-c; RA Tsuruha J., Masuko-Hongo K., Kato T., Sakata M., Nakamura H., Nishioka K.; RT "Implication of cartilage intermediate layer protein in cartilage RT destruction in subsets of patients with osteoarthritis and rheumatoid RT arthritis."; RL Arthritis Rheum. 44:838-845(2001). RN [11] RP FUNCTION. RX PubMed=12746903; DOI=10.1002/art.10927; RA Johnson K., Farley D., Hu S.-I., Terkeltaub R.; RT "One of two chondrocyte-expressed isoforms of cartilage intermediate-layer RT protein functions as an insulin-like growth factor 1 antagonist."; RL Arthritis Rheum. 48:1302-1314(2003). RN [12] RP IMMUNIZATION. RX PubMed=14962958; DOI=10.1136/ard.2003.008045; RA Yao Z., Nakamura H., Masuko-Hongo K., Suzuki-Kurokawa M., Nishioka K., RA Kato T.; RT "Characterisation of cartilage intermediate layer protein (CILP)-induced RT arthropathy in mice."; RL Ann. Rheum. Dis. 63:252-258(2004). RN [13] RP INVOLVEMENT IN OSTEOARTHRITIS. RX PubMed=15378262; DOI=10.1007/s00296-004-0497-2; RA Du H., Masuko-Hongo K., Nakamura H., Xiang Y., Bao C.-D., Wang X.-D., RA Chen S.-L., Nishioka K., Kato T.; RT "The prevalence of autoantibodies against cartilage intermediate layer RT protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients RT with early-stage knee osteoarthritis: evidence of a variety of autoimmune RT processes."; RL Rheumatol. Int. 26:35-41(2005). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH TGFB1, RP INVOLVEMENT IN IDD, AND VARIANT THR-395. RX PubMed=15864306; DOI=10.1038/ng1557; RA Seki S., Kawaguchi Y., Chiba K., Mikami Y., Kizawa H., Oya T., Mio F., RA Mori M., Miyamoto Y., Masuda I., Tsunoda T., Kamata M., Kubo T., Toyama Y., RA Kimura T., Nakamura Y., Ikegawa S.; RT "A functional SNP in CILP, encoding cartilage intermediate layer protein, RT is associated with susceptibility to lumbar disc disease."; RL Nat. Genet. 37:607-612(2005). RN [15] RP VARIANTS HIS-495 AND THR-1032. RX PubMed=23033978; DOI=10.1056/nejmoa1206524; RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., RA Veltman J.A., Vissers L.E.; RT "Diagnostic exome sequencing in persons with severe intellectual RT disability."; RL N. Engl. J. Med. 367:1921-1929(2012). CC -!- FUNCTION: Probably plays a role in cartilage scaffolding. May act by CC antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to CC suppress IGF1-induced proliferation and sulfated proteoglycan CC synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May CC inhibit TGFB1-mediated induction of cartilage matrix genes via its CC interaction with TGFB1. Overexpression may lead to impair chondrocyte CC growth and matrix repair and indirectly promote inorganic pyrophosphate CC (PPi) supersaturation in aging and osteoarthritis cartilage. CC {ECO:0000269|PubMed:12746903, ECO:0000269|PubMed:15864306}. CC -!- SUBUNIT: Monomer. Interacts with TGFB1. {ECO:0000269|PubMed:15864306, CC ECO:0000269|PubMed:9722583}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000269|PubMed:15864306}. CC -!- TISSUE SPECIFICITY: Specifically expressed in cartilage. Localizes in CC the intermediates layer of articular cartilage but neither in the CC superficial nor in the deepest regions. Specifically and highly CC expressed in intervertebral disk tissue. Expression increases with CC aging in hip articular cartilage. Overexpressed in articular hyaline CC cartilage from patients with calcium pyrophosphate dihydrate crystal CC deposition disease (CPPD). Expression in intervertebral disk tissue CC from individuals with lumbar disk disease increases as disk CC degeneration progresses. {ECO:0000269|PubMed:12483726, CC ECO:0000269|PubMed:15864306, ECO:0000269|PubMed:9722583, CC ECO:0000269|PubMed:9722584}. CC -!- PTM: Cleaved into 2 chains possibly by a furin-like protease upon or CC preceding secretion. CC -!- DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common CC musculo-skeletal disorder caused by degeneration of intervertebral CC disks of the lumbar spine. It results in low-back pain and unilateral CC leg pain. {ECO:0000269|PubMed:15864306}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Antibodies against CILP are detected in patients with CC early-stage knee osteoarthritis and rheumatoid arthritis. CC -!- CAUTION: Was originally thought to constitute the ATP pyrophosphatase CC enzyme (NTPPH). However, it was later shown (PubMed:12746903, CC PubMed:15864306) that it is not the case. {ECO:0000305}. 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; AF035408; AAC33838.1; -; mRNA. DR EMBL; AB022430; BAA76692.1; -; Genomic_DNA. DR EMBL; AF035455; AAF14689.1; -; Genomic_DNA. DR EMBL; AF035448; AAF14689.1; JOINED; Genomic_DNA. DR EMBL; AF035451; AAF14689.1; JOINED; Genomic_DNA. DR EMBL; AF035453; AAF14689.1; JOINED; Genomic_DNA. DR EMBL; AF035449; AAF14689.1; JOINED; Genomic_DNA. DR EMBL; AY358904; AAQ89263.1; -; mRNA. DR EMBL; AK313352; BAG36154.1; -; mRNA. DR EMBL; AC068213; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035776; AAH35776.1; -; mRNA. DR CCDS; CCDS10203.1; -. DR PIR; T09484; T09484. DR RefSeq; NP_003604.3; NM_003613.3. DR AlphaFoldDB; O75339; -. DR SMR; O75339; -. DR BioGRID; 114057; 2. DR IntAct; O75339; 1. DR STRING; 9606.ENSP00000261883; -. DR GlyConnect; 1075; 15 N-Linked glycans (5 sites). DR GlyCosmos; O75339; 11 sites, 15 glycans. DR GlyGen; O75339; 16 sites, 13 N-linked glycans (5 sites), 3 O-linked glycans (8 sites). DR iPTMnet; O75339; -. DR PhosphoSitePlus; O75339; -. DR BioMuta; CILP; -. DR jPOST; O75339; -. DR MassIVE; O75339; -. DR PaxDb; 9606-ENSP00000261883; -. DR PeptideAtlas; O75339; -. DR ProteomicsDB; 49908; -. DR Antibodypedia; 760; 165 antibodies from 30 providers. DR DNASU; 8483; -. DR Ensembl; ENST00000261883.6; ENSP00000261883.4; ENSG00000138615.6. DR GeneID; 8483; -. DR KEGG; hsa:8483; -. DR MANE-Select; ENST00000261883.6; ENSP00000261883.4; NM_003613.4; NP_003604.4. DR UCSC; uc002aon.3; human. DR AGR; HGNC:1980; -. DR CTD; 8483; -. DR DisGeNET; 8483; -. DR GeneCards; CILP; -. DR HGNC; HGNC:1980; CILP. DR HPA; ENSG00000138615; Low tissue specificity. DR MalaCards; CILP; -. DR MIM; 603489; gene. DR MIM; 603932; phenotype. DR neXtProt; NX_O75339; -. DR OpenTargets; ENSG00000138615; -. DR PharmGKB; PA26518; -. DR VEuPathDB; HostDB:ENSG00000138615; -. DR eggNOG; ENOG502QQ8H; Eukaryota. DR GeneTree; ENSGT00390000008152; -. DR HOGENOM; CLU_008073_0_0_1; -. DR InParanoid; O75339; -. DR OMA; RAETPYM; -. DR OrthoDB; 5383253at2759; -. DR PhylomeDB; O75339; -. DR TreeFam; TF330132; -. DR PathwayCommons; O75339; -. DR Reactome; R-HSA-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R). DR SignaLink; O75339; -. DR BioGRID-ORCS; 8483; 15 hits in 1137 CRISPR screens. DR ChiTaRS; CILP; human. DR GeneWiki; CILP; -. DR GenomeRNAi; 8483; -. DR Pharos; O75339; Tbio. DR PRO; PR:O75339; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O75339; protein. DR Bgee; ENSG00000138615; Expressed in calcaneal tendon and 155 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; IGI:BHF-UCL. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR CDD; cd00096; Ig; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 1. DR InterPro; IPR008969; CarboxyPept-like_regulatory. DR InterPro; IPR039675; CILP1/CILP2. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR000884; TSP1_rpt. DR InterPro; IPR036383; TSP1_rpt_sf. DR InterPro; IPR025155; WxxW_domain. DR PANTHER; PTHR15031:SF3; CARTILAGE INTERMEDIATE LAYER PROTEIN 1; 1. DR PANTHER; PTHR15031; CARTILAGE INTERMEDIATE LAYER PROTEIN CLIP; 1. DR Pfam; PF13927; Ig_3; 1. DR Pfam; PF13330; Mucin2_WxxW; 1. DR Pfam; PF00090; TSP_1; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00408; IGc2; 1. DR SMART; SM00209; TSP1; 1. DR SUPFAM; SSF49464; Carboxypeptidase regulatory domain-like; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS50092; TSP1; 1. PE 1: Evidence at protein level; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disulfide bond; Extracellular matrix; Glycoprotein; Immunoglobulin domain; KW Proteomics identification; Reference proteome; Secreted; Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..1184 FT /note="Cartilage intermediate layer protein 1" FT /id="PRO_0000014671" FT CHAIN 22..?724 FT /note="Cartilage intermediate layer protein 1 C1" FT /id="PRO_0000014672" FT CHAIN ?725..1184 FT /note="Cartilage intermediate layer protein 1 C2" FT /id="PRO_0000014673" FT DOMAIN 149..201 FT /note="TSP type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210" FT DOMAIN 309..395 FT /note="Ig-like C2-type" FT REGION 1136..1170 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1136..1162 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 129 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 132 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 346 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:9722584" FT CARBOHYD 420 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 550 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1000 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1056 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 161..195 FT /evidence="ECO:0000250" FT DISULFID 165..200 FT /evidence="ECO:0000250" FT DISULFID 177..185 FT /evidence="ECO:0000250" FT DISULFID 330..376 FT /evidence="ECO:0000250" FT VARIANT 59 FT /note="W -> L (in dbSNP:rs2585033)" FT /evidence="ECO:0000269|PubMed:10319588, FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:9722584" FT /id="VAR_022768" FT VARIANT 327 FT /note="S -> F" FT /evidence="ECO:0000269|PubMed:10319588" FT /id="VAR_022769" FT VARIANT 395 FT /note="I -> T (risk factor for lumbar disk disease in FT Japanese; increases binding and inhibition of TGFB1; FT dbSNP:rs2073711)" FT /evidence="ECO:0000269|PubMed:10319588, FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9722584" FT /id="VAR_022770" FT VARIANT 495 FT /note="R -> H (in dbSNP:rs149286218)" FT /evidence="ECO:0000269|PubMed:23033978" FT /id="VAR_069430" FT VARIANT 575 FT /note="K -> E (in dbSNP:rs2679118)" FT /evidence="ECO:0000269|PubMed:10319588, FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9722584" FT /id="VAR_022771" FT VARIANT 895 FT /note="A -> V (in dbSNP:rs771628304)" FT /evidence="ECO:0000269|PubMed:10319588" FT /id="VAR_022772" FT VARIANT 979 FT /note="Q -> R (in dbSNP:rs2679117)" FT /evidence="ECO:0000269|PubMed:10319588, FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:12975309, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9722584" FT /id="VAR_022773" FT VARIANT 1032 FT /note="S -> T (in dbSNP:rs768702821)" FT /evidence="ECO:0000269|PubMed:23033978" FT /id="VAR_069431" FT VARIANT 1101 FT /note="D -> N (in dbSNP:rs769023414)" FT /evidence="ECO:0000269|PubMed:10319588" FT /id="VAR_022774" FT VARIANT 1166 FT /note="G -> S (in dbSNP:rs938952)" FT /evidence="ECO:0000269|PubMed:10319588, FT ECO:0000269|PubMed:10601732, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9722584" FT /id="VAR_022775" FT VARIANT 1168 FT /note="V -> A (in dbSNP:rs747702148)" FT /evidence="ECO:0000269|PubMed:10319588" FT /id="VAR_022776" FT CONFLICT 54 FT /note="G -> M (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 288 FT /note="T -> D (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="R -> D (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 347 FT /note="D -> T (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 1184 AA; 132565 MW; 190B0316404D3B84 CRC64; MVGTKAWVFS FLVLEVTSVL GRQTMLTQSV RRVQPGKKNP SIFAKPADTL ESPGEWTTWF NIDYPGGKGD YERLDAIRFY YGDRVCARPL RLEARTTDWT PAGSTGQVVH GSPREGFWCL NREQRPGQNC SNYTVRFLCP PGSLRRDTER IWSPWSPWSK CSAACGQTGV QTRTRICLAE MVSLCSEASE EGQHCMGQDC TACDLTCPMG QVNADCDACM CQDFMLHGAV SLPGGAPASG AAIYLLTKTP KLLTQTDSDG RFRIPGLCPD GKSILKITKV KFAPIVLTMP KTSLKAATIK AEFVRAETPY MVMNPETKAR RAGQSVSLCC KATGKPRPDK YFWYHNDTLL DPSLYKHESK LVLRKLQQHQ AGEYFCKAQS DAGAVKSKVA QLIVIASDET PCNPVPESYL IRLPHDCFQN ATNSFYYDVG RCPVKTCAGQ QDNGIRCRDA VQNCCGISKT EEREIQCSGY TLPTKVAKEC SCQRCTETRS IVRGRVSAAD NGEPMRFGHV YMGNSRVSMT GYKGTFTLHV PQDTERLVLT FVDRLQKFVN TTKVLPFNKK GSAVFHEIKM LRRKKPITLE AMETNIIPLG EVVGEDPMAE LEIPSRSFYR QNGEPYIGKV KASVTFLDPR NISTATAAQT DLNFINDEGD TFPLRTYGMF SVDFRDEVTS EPLNAGKVKV HLDSTQVKMP EHISTVKLWS LNPDTGLWEE EGDFKFENQR RNKREDRTFL VGNLEIRERR LFNLDVPESR RCFVKVRAYR SERFLPSEQI QGVVISVINL EPRTGFLSNP RAWGRFDSVI TGPNGACVPA FCDDQSPDAY SAYVLASLAG EELQAVESSP KFNPNAIGVP QPYLNKLNYR RTDHEDPRVK KTAFQISMAK PRPNSAEESN GPIYAFENLR ACEEAPPSAA HFRFYQIEGD RYDYNTVPFN EDDPMSWTED YLAWWPKPME FRACYIKVKI VGPLEVNVRS RNMGGTHRQT VGKLYGIRDV RSTRDRDQPN VSAACLEFKC SGMLYDQDRV DRTLVKVIPQ GSCRRASVNP MLHEYLVNHL PLAVNNDTSE YTMLAPLDPL GHNYGIYTVT DQDPRTAKEI ALGRCFDGTS DGSSRIMKSN VGVALTFNCV ERQVGRQSAF QYLQSTPAQS PAAGTVQGRV PSRRQQRASR GGQRQGGVVA SLRFPRVAQQ PLIN //