ID   CILP2_HUMAN             Reviewed;        1156 AA.
AC   Q8IUL8; Q6NV88; Q8N4A6; Q8WV21;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 2.
DT   24-JAN-2024, entry version 157.
DE   RecName: Full=Cartilage intermediate layer protein 2;
DE            Short=CILP-2;
DE   Contains:
DE     RecName: Full=Cartilage intermediate layer protein 2 C1;
DE   Contains:
DE     RecName: Full=Cartilage intermediate layer protein 2 C2;
DE   Flags: Precursor;
GN   Name=CILP2;
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], AND TISSUE SPECIFICITY.
RC   TISSUE=Osteoarthritic cartilage;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [3]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=21880736; DOI=10.1074/jbc.m111.248039;
RA   Bernardo B.C., Belluoccio D., Rowley L., Little C.B., Hansen U.,
RA   Bateman J.F.;
RT   "Cartilage intermediate layer protein 2 (CILP-2) is expressed in articular
RT   and meniscal cartilage and down-regulated in experimental osteoarthritis.";
RL   J. Biol. Chem. 286:37758-37767(2011).
CC   -!- FUNCTION: May play a role in cartilage scaffolding.
CC       {ECO:0000250|UniProtKB:O75339}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000269|PubMed:21880736}.
CC   -!- TISSUE SPECIFICITY: Expressed in articular chondrocytes but not in knee
CC       meniscal cartilage cells (PubMed:12746903). Localizes to the
CC       intermediate to deep zone of articular cartilage (PubMed:21880736).
CC       {ECO:0000269|PubMed:12746903, ECO:0000269|PubMed:21880736}.
CC   -!- PTM: May be cleaved into 2 chains possibly by a furin-like protease
CC       upon or preceding secretion. {ECO:0000250}.
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DR   EMBL; AF542080; AAN17826.1; -; mRNA.
DR   EMBL; BC018939; AAH18939.2; -; mRNA.
DR   EMBL; BC034926; AAH34926.2; -; mRNA.
DR   CCDS; CCDS12405.1; -.
DR   RefSeq; NP_694953.2; NM_153221.2.
DR   AlphaFoldDB; Q8IUL8; -.
DR   BioGRID; 127119; 47.
DR   IntAct; Q8IUL8; 4.
DR   STRING; 9606.ENSP00000291495; -.
DR   GlyCosmos; Q8IUL8; 3 sites, No reported glycans.
DR   GlyGen; Q8IUL8; 5 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q8IUL8; -.
DR   PhosphoSitePlus; Q8IUL8; -.
DR   BioMuta; CILP2; -.
DR   DMDM; 68565198; -.
DR   EPD; Q8IUL8; -.
DR   jPOST; Q8IUL8; -.
DR   MassIVE; Q8IUL8; -.
DR   PaxDb; 9606-ENSP00000291495; -.
DR   PeptideAtlas; Q8IUL8; -.
DR   ProteomicsDB; 70584; -.
DR   Antibodypedia; 48010; 95 antibodies from 19 providers.
DR   DNASU; 148113; -.
DR   Ensembl; ENST00000291495.5; ENSP00000291495.3; ENSG00000160161.9.
DR   GeneID; 148113; -.
DR   KEGG; hsa:148113; -.
DR   MANE-Select; ENST00000291495.5; ENSP00000291495.3; NM_153221.2; NP_694953.2.
DR   UCSC; uc002nmv.4; human.
DR   AGR; HGNC:24213; -.
DR   CTD; 148113; -.
DR   DisGeNET; 148113; -.
DR   GeneCards; CILP2; -.
DR   HGNC; HGNC:24213; CILP2.
DR   HPA; ENSG00000160161; Tissue enhanced (ovary, testis).
DR   MIM; 612419; gene.
DR   neXtProt; NX_Q8IUL8; -.
DR   OpenTargets; ENSG00000160161; -.
DR   PharmGKB; PA134970563; -.
DR   VEuPathDB; HostDB:ENSG00000160161; -.
DR   eggNOG; ENOG502QQ8H; Eukaryota.
DR   GeneTree; ENSGT00390000008152; -.
DR   InParanoid; Q8IUL8; -.
DR   OMA; CGVRRME; -.
DR   OrthoDB; 5383253at2759; -.
DR   PhylomeDB; Q8IUL8; -.
DR   TreeFam; TF330132; -.
DR   PathwayCommons; Q8IUL8; -.
DR   SignaLink; Q8IUL8; -.
DR   BioGRID-ORCS; 148113; 19 hits in 1146 CRISPR screens.
DR   GenomeRNAi; 148113; -.
DR   Pharos; Q8IUL8; Tbio.
DR   PRO; PR:Q8IUL8; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8IUL8; Protein.
DR   Bgee; ENSG00000160161; Expressed in cartilage tissue and 98 other cell types or tissues.
DR   ExpressionAtlas; Q8IUL8; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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:SF0; CARTILAGE INTERMEDIATE LAYER PROTEIN 2; 1.
DR   PANTHER; PTHR15031; CARTILAGE INTERMEDIATE LAYER PROTEIN CLIP; 1.
DR   Pfam; PF13620; CarboxypepD_reg; 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; Q8IUL8; HS.
PE   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Immunoglobulin domain; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..1156
FT                   /note="Cartilage intermediate layer protein 2"
FT                   /id="PRO_0000014678"
FT   CHAIN           21..?709
FT                   /note="Cartilage intermediate layer protein 2 C1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000014679"
FT   CHAIN           ?710..1156
FT                   /note="Cartilage intermediate layer protein 2 C2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000014680"
FT   DOMAIN          146..197
FT                   /note="TSP type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT   DOMAIN          292..376
FT                   /note="Ig-like C2-type"
FT   REGION          1134..1156
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        158..191
FT                   /evidence="ECO:0000250"
FT   DISULFID        162..196
FT                   /evidence="ECO:0000250"
FT   DISULFID        173..181
FT                   /evidence="ECO:0000250"
FT   DISULFID        313..359
FT                   /evidence="ECO:0000250"
FT   CONFLICT        768
FT                   /note="A -> G (in Ref. 1; AAN17826)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1156 AA;  126291 MW;  CE4AAB47841C07F9 CRC64;
     MASLLPLLCL CVVAAHLAGA RDATPTEEPM ATALGLERRS VYTGQPSPAL EDWEEASEWT
     SWFNVDHPGG DGDFESLAAI RFYYGPARVC PRPLALEART TDWALPSAVG ERVHLNPTRG
     FWCLNREQPR GRRCSNYHVR FRCPLEASWG AWGPWGPCSG SCGPGRRLRR RHCPSPAGDA
     CPGRPLEAQK CVRPRCPGCS LDTCECPDHI LLGSVVTPSG QPLLGARVSL RDQPGTVATS
     DAHGTFRVPG VCADSRANIR AQMDGFSAGE AQAQANGSIS VVTIILDKLE KPYLVKHPES
     RVREAGQNVT FCCKASGTPM PKKYSWFHNG TLLDRRAHGY GAHLELRGLR PDQAGIYHCK
     AWNEAGAVRS GTARLTVLAP GQPACDPRPR EYLIKLPEDC GQPGSGPAYL DVGLCPDTRC
     PSLAGSSPRC GDASSRCCSV RRLERREIHC PGYVLPVKVV AECGCQKCLP PRGLVRGRVV
     AADSGEPLRF ARILLGQEPI GFTAYQGDFT IEVPPSTQRL VVTFVDPSGE FMDAVRVLPF
     DPRGAGVYHE VKAMRKKAPV ILHTSQSNTI PLGELEDEAP LGELVLPSGA FRRADGKPYS
     GPVEARVTFV DPRDLTSAAS APSDLRFVDS DGELAPLRTY GMFSVDLRAP GSAEQLQVGP
     VAVRVAASQI HMPGHVEALK LWSLNPETGL WEEESGFRRE GSSGPRVRRE ERVFLVGNVE
     IRERRLFNLD VPERRRCFVK VRAYANDKFT PSEQVEGVVV TLVNLEPAPG FSANPRAWGR
     FDSAVTGPNG ACLPAFCDAD RPDAYTALVT ATLGGEELEP APSLPRPLPA TVGVTQPYLD
     RLGYRRTDHD DPAFKRNGFR INLAKPRPGD PAEANGPVYP WRSLRECQGA PVTASHFRFA
     RVEADKYEYN VVPFREGTPA SWTGDLLAWW PNPQEFRACF LKVKIQGPQE YMVRSHNAGG
     SHPRTRGQLY GLRDARSVRD PERPGTSAAC VEFKCSGMLF DQRQVDRTLV TIMPQGSCRR
     VAVNGLLRDY LTRHPPPVPA EDPAAFSMLA PLDPLGHNYG VYTVTDQSPR LAKEIAIGRC
     FDGSSDGFSR EMKADAGTAV TFQCREPPAG RPSLFQRLLE SPATALGDIR REMSEAAQAQ
     ARASGPLRTR RGRVRQ
//