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   24-JAN-2024, entry version 175.
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}.
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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   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; 169 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.
DR   Genevisible; O75339; HS.
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   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
//