ID   CRTAP_HUMAN             Reviewed;         401 AA.
AC   O75718; B2RBL6;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   13-FEB-2019, entry version 152.
DE   RecName: Full=Cartilage-associated protein;
DE   Flags: Precursor;
GN   Name=CRTAP; Synonyms=CASP;
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].
RC   TISSUE=Fetal brain;
RX   PubMed=10702664;
RA   Tonachini L., Morello R., Monticone M., Skaug J., Scherer S.W.,
RA   Cancedda R., Castagnola P.;
RT   "cDNA cloning, characterization and chromosome mapping of the gene
RT   encoding human cartilage associated protein (CRTAP).";
RL   Cytogenet. Cell Genet. 87:191-194(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-137.
RC   TISSUE=Kidney;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, AND INVOLVEMENT IN OI7.
RX   PubMed=17055431; DOI=10.1016/j.cell.2006.08.039;
RA   Morello R., Bertin T.K., Chen Y., Hicks J., Tonachini L.,
RA   Monticone M., Castagnola P., Rauch F., Glorieux F.H., Vranka J.,
RA   Baechinger H.P., Pace J.M., Schwarze U., Byers P.H., Weis M.,
RA   Fernandes R.J., Eyre D.R., Yao Z., Boyce B.F., Lee B.;
RT   "CRTAP is required for prolyl 3-hydroxylation and mutations cause
RT   recessive osteogenesis imperfecta.";
RL   Cell 127:291-304(2006).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [6]
RP   INVOLVEMENT IN OI7.
RX   PubMed=21955071; DOI=10.1111/j.1399-0004.2011.01794.x;
RA   Valli M., Barnes A.M., Gallanti A., Cabral W.A., Viglio S., Weis M.A.,
RA   Makareeva E., Eyre D., Leikin S., Antoniazzi F., Marini J.C.,
RA   Mottes M.;
RT   "Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta
RT   reduces collagen deposition into matrix.";
RL   Clin. Genet. 82:453-459(2012).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
RA   Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [8]
RP   VARIANT OI7 PRO-67.
RX   PubMed=18566967; DOI=10.1002/humu.20799;
RA   Baldridge D., Schwarze U., Morello R., Lennington J., Bertin T.K.,
RA   Pace J.M., Pepin M.G., Weis M., Eyre D.R., Walsh J., Lambert D.,
RA   Green A., Robinson H., Michelson M., Houge G., Lindman C., Martin J.,
RA   Ward J., Lemyre E., Mitchell J.J., Krakow D., Rimoin D.L., Cohn D.H.,
RA   Byers P.H., Lee B.;
RT   "CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta.";
RL   Hum. Mutat. 29:1435-1442(2008).
RN   [9]
RP   VARIANTS OI7 GLU-13 AND GLU-157.
RX   PubMed=19550437; DOI=10.1038/ejhg.2009.75;
RA   Van Dijk F.S., Nesbitt I.M., Nikkels P.G.J., Dalton A.,
RA   Bongers E.M.H.F., van de Kamp J.M., Hilhorst-Hofstee Y.,
RA   Den Hollander N.S., Lachmeijer A.M.A., Marcelis C.L.,
RA   Tan-Sindhunata G.M.B., van Rijn R.R., Meijers-Heijboer H.,
RA   Cobben J.M., Pals G.;
RT   "CRTAP mutations in lethal and severe osteogenesis imperfecta: the
RT   importance of combining biochemical and molecular genetic analysis.";
RL   Eur. J. Hum. Genet. 17:1560-1569(2009).
CC   -!- FUNCTION: Necessary for efficient 3-hydroxylation of fibrillar
CC       collagen prolyl residues. {ECO:0000269|PubMed:17055431}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Found in articular chondrocytes. Expressed in
CC       a variety of tissues.
CC   -!- DISEASE: Osteogenesis imperfecta 7 (OI7) [MIM:610682]: A form of
CC       osteogenesis imperfecta, a connective tissue disorder
CC       characterized by low bone mass, bone fragility and susceptibility
CC       to fractures after minimal trauma. Disease severity ranges from
CC       very mild forms without fractures to intrauterine fractures and
CC       perinatal lethality. Extraskeletal manifestations, which affect a
CC       variable number of patients, are dentinogenesis imperfecta,
CC       hearing loss, and blue sclerae. OI7 is an autosomal recessive,
CC       severe form. Multiple fractures are present at birth and patients
CC       have short stature, short humeri and femora, coxa vara, and white
CC       sclera. Dentinogenesis imperfecta is absent. Death can occur in
CC       the perinatal period due to secondary respiratory insufficiency.
CC       {ECO:0000269|PubMed:17055431, ECO:0000269|PubMed:18566967,
CC       ECO:0000269|PubMed:19550437, ECO:0000269|PubMed:21955071}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC       Note=Cartilage-associated protein (CRTAP);
CC       URL="http://oi.gene.le.ac.uk/home.php?select_db=CRTAP";
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DR   EMBL; AJ006470; CAA07054.1; -; mRNA.
DR   EMBL; AK314719; BAG37263.1; -; mRNA.
DR   EMBL; BC008745; AAH08745.1; -; mRNA.
DR   CCDS; CCDS2657.1; -.
DR   RefSeq; NP_006362.1; NM_006371.4.
DR   UniGene; Hs.517888; -.
DR   ProteinModelPortal; O75718; -.
DR   BioGrid; 115754; 69.
DR   IntAct; O75718; 12.
DR   STRING; 9606.ENSP00000323696; -.
DR   GlyConnect; 1074; -.
DR   iPTMnet; O75718; -.
DR   PhosphoSitePlus; O75718; -.
DR   SwissPalm; O75718; -.
DR   BioMuta; CRTAP; -.
DR   EPD; O75718; -.
DR   jPOST; O75718; -.
DR   MaxQB; O75718; -.
DR   PaxDb; O75718; -.
DR   PeptideAtlas; O75718; -.
DR   PRIDE; O75718; -.
DR   ProteomicsDB; 50176; -.
DR   DNASU; 10491; -.
DR   Ensembl; ENST00000320954; ENSP00000323696; ENSG00000170275.
DR   GeneID; 10491; -.
DR   KEGG; hsa:10491; -.
DR   UCSC; uc003cfl.5; human.
DR   CTD; 10491; -.
DR   DisGeNET; 10491; -.
DR   EuPathDB; HostDB:ENSG00000170275.14; -.
DR   GeneCards; CRTAP; -.
DR   HGNC; HGNC:2379; CRTAP.
DR   HPA; HPA043598; -.
DR   HPA; HPA044150; -.
DR   MalaCards; CRTAP; -.
DR   MIM; 605497; gene.
DR   MIM; 610682; phenotype.
DR   neXtProt; NX_O75718; -.
DR   OpenTargets; ENSG00000170275; -.
DR   Orphanet; 216804; Osteogenesis imperfecta type 2.
DR   Orphanet; 216812; Osteogenesis imperfecta type 3.
DR   Orphanet; 216820; Osteogenesis imperfecta type 4.
DR   PharmGKB; PA26900; -.
DR   eggNOG; ENOG410IQZH; Eukaryota.
DR   eggNOG; ENOG410Y7XP; LUCA.
DR   GeneTree; ENSGT00940000153814; -.
DR   HOGENOM; HOG000247068; -.
DR   HOVERGEN; HBG005540; -.
DR   InParanoid; O75718; -.
DR   KO; K19606; -.
DR   OMA; QCLKRCK; -.
DR   OrthoDB; 607176at2759; -.
DR   PhylomeDB; O75718; -.
DR   TreeFam; TF320837; -.
DR   Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR   ChiTaRS; CRTAP; human.
DR   GeneWiki; Cartilage_associated_protein; -.
DR   GenomeRNAi; 10491; -.
DR   PRO; PR:O75718; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000170275; Expressed in 233 organ(s), highest expression level in tendon.
DR   ExpressionAtlas; O75718; baseline and differential.
DR   Genevisible; O75718; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR   GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR   GO; GO:1901874; P:negative regulation of post-translational protein modification; IMP:UniProtKB.
DR   GO; GO:0018400; P:peptidyl-proline hydroxylation to 3-hydroxy-L-proline; IEA:Ensembl.
DR   GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   Gene3D; 1.25.40.10; -; 2.
DR   InterPro; IPR033212; Crtap.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   PANTHER; PTHR13986:SF3; PTHR13986:SF3; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Disease mutation; Dwarfism; Extracellular matrix;
KW   Glycoprotein; Hydroxylation; Osteogenesis imperfecta; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     26       {ECO:0000255}.
FT   CHAIN        27    401       Cartilage-associated protein.
FT                                /FTId=PRO_0000006319.
FT   CARBOHYD     87     87       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    363    363       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VARIANT      13     13       A -> E (in OI7; severe form;
FT                                dbSNP:rs137853938).
FT                                {ECO:0000269|PubMed:19550437}.
FT                                /FTId=VAR_063599.
FT   VARIANT      67     67       L -> P (in OI7; dbSNP:rs72659358).
FT                                {ECO:0000269|PubMed:18566967}.
FT                                /FTId=VAR_054442.
FT   VARIANT     137    137       E -> D (in dbSNP:rs17850371).
FT                                {ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_032846.
FT   VARIANT     157    157       K -> E (in OI7; severe form;
FT                                dbSNP:rs137853942).
FT                                {ECO:0000269|PubMed:19550437}.
FT                                /FTId=VAR_063600.
FT   VARIANT     261    261       L -> V (in dbSNP:rs1135127).
FT                                /FTId=VAR_053050.
SQ   SEQUENCE   401 AA;  46562 MW;  4BEED4089195456F CRC64;
     MEPGRRGAAA LLALLCVACA LRAGRAQYER YSFRSFPRDE LMPLESAYRH ALDKYSGEHW
     AESVGYLEIS LRLHRLLRDS EAFCHRNCSA APQPEPAAGL ASYPELRLFG GLLRRAHCLK
     RCKQGLPAFR QSQPSREVLA DFQRREPYKF LQFAYFKANN LPKAIAAAHT FLLKHPDDEM
     MKRNMAYYKS LPGAEDYIKD LETKSYESLF IRAVRAYNGE NWRTSITDME LALPDFFKAF
     YECLAACEGS REIKDFKDFY LSIADHYVEV LECKIQCEEN LTPVIGGYPV EKFVATMYHY
     LQFAYYKLND LKNAAPCAVS YLLFDQNDKV MQQNLVYYQY HRDTWGLSDE HFQPRPEAVQ
     FFNVTTLQKE LYDFAKENIM DDDEGEVVEY VDDLLELEET S
//