ID   HPLN1_HUMAN             Reviewed;         354 AA.
AC   P10915; B2R9A9;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 2.
DT   24-JAN-2024, entry version 206.
DE   RecName: Full=Hyaluronan and proteoglycan link protein 1;
DE   AltName: Full=Cartilage-linking protein 1;
DE            Short=Cartilage-link protein;
DE   AltName: Full=Proteoglycan link protein;
DE   Flags: Precursor;
GN   Name=HAPLN1; Synonyms=CRTL1;
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].
RC   TISSUE=Articular chondrocyte;
RX   PubMed=2320422; DOI=10.1093/nar/18.5.1292;
RA   Dudhia J., Hardingham T.E.;
RT   "The primary structure of human cartilage link protein.";
RL   Nucleic Acids Res. 18:1292-1292(1990).
RN   [2]
RP   ERRATUM OF PUBMED:2320422.
RX   PubMed=2336413; DOI=10.1093/nar/18.8.2214;
RA   Dudhia J., Hardingham T.E.;
RL   Nucleic Acids Res. 18:2214-2214(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2286376; DOI=10.1016/0888-7543(90)90044-u;
RA   Osborne-Lawrence S.L., Sinclair A.K., Hicks R.C., Lacey S.W.,
RA   Eddy R.L. Jr., Byers M.G., Shows T.B., Duby A.D.;
RT   "Complete amino acid sequence of human cartilage link protein (CRTL1)
RT   deduced from cDNA clones and chromosomal assignment of the gene.";
RL   Genomics 8:562-567(1990).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2030970; DOI=10.1093/nar/19.8.1933;
RA   Rhodes C., Savagner P., Line S., Sasaki M., Chirigos M., Doege K.,
RA   Yamada Y.;
RT   "Characterization of the promoter for the rat and human link protein
RT   gene.";
RL   Nucleic Acids Res. 19:1933-1939(1991).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   TISSUE SPECIFICITY.
RX   PubMed=11027579; DOI=10.1006/bbrc.2000.3583;
RA   Hirakawa S., Oohashi T., Su W.-D., Yoshioka H., Murakami T., Arata J.,
RA   Ninomiya Y.;
RT   "The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and
RT   characterization as a novel link protein expressed in adult brain.";
RL   Biochem. Biophys. Res. Commun. 276:982-989(2000).
RN   [9]
RP   TISSUE SPECIFICITY.
RX   PubMed=12663660; DOI=10.1074/jbc.m213100200;
RA   Spicer A.P., Joo A., Bowling R.A. Jr.;
RT   "A hyaluronan binding link protein gene family whose members are physically
RT   linked adjacent to chondroitin sulfate proteoglycan core protein genes: the
RT   missing links.";
RL   J. Biol. Chem. 278:21083-21091(2003).
RN   [10]
RP   VARIANT [LARGE SCALE ANALYSIS] HIS-333.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Stabilizes the aggregates of proteoglycan monomers with
CC       hyaluronic acid in the extracellular cartilage matrix.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Weakly expressed in the brain.
CC       {ECO:0000269|PubMed:11027579, ECO:0000269|PubMed:12663660}.
CC   -!- SIMILARITY: Belongs to the HAPLN family. {ECO:0000305}.
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DR   EMBL; X17405; CAA35462.1; -; mRNA.
DR   EMBL; U43328; AAA85216.1; -; mRNA.
DR   EMBL; AK313713; BAG36456.1; -; mRNA.
DR   EMBL; CH471084; EAW95912.1; -; Genomic_DNA.
DR   EMBL; BC057808; AAH57808.1; -; mRNA.
DR   CCDS; CCDS4061.1; -.
DR   PIR; S14914; LKHU.
DR   RefSeq; NP_001875.1; NM_001884.3.
DR   RefSeq; XP_011541470.1; XM_011543168.2.
DR   RefSeq; XP_016864540.1; XM_017009051.1.
DR   RefSeq; XP_016864541.1; XM_017009052.1.
DR   AlphaFoldDB; P10915; -.
DR   SMR; P10915; -.
DR   BioGRID; 107794; 5.
DR   IntAct; P10915; 2.
DR   STRING; 9606.ENSP00000274341; -.
DR   DrugBank; DB08818; Hyaluronic acid.
DR   GlyConnect; 1380; 1 N-Linked glycan (1 site).
DR   GlyCosmos; P10915; 2 sites, 1 glycan.
DR   GlyGen; P10915; 2 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; P10915; -.
DR   PhosphoSitePlus; P10915; -.
DR   BioMuta; HAPLN1; -.
DR   DMDM; 130310; -.
DR   EPD; P10915; -.
DR   jPOST; P10915; -.
DR   MassIVE; P10915; -.
DR   MaxQB; P10915; -.
DR   PaxDb; 9606-ENSP00000274341; -.
DR   PeptideAtlas; P10915; -.
DR   ProteomicsDB; 52677; -.
DR   Antibodypedia; 12888; 266 antibodies from 29 providers.
DR   DNASU; 1404; -.
DR   Ensembl; ENST00000274341.9; ENSP00000274341.4; ENSG00000145681.11.
DR   GeneID; 1404; -.
DR   KEGG; hsa:1404; -.
DR   MANE-Select; ENST00000274341.9; ENSP00000274341.4; NM_001884.4; NP_001875.1.
DR   UCSC; uc003kin.4; human.
DR   AGR; HGNC:2380; -.
DR   CTD; 1404; -.
DR   DisGeNET; 1404; -.
DR   GeneCards; HAPLN1; -.
DR   HGNC; HGNC:2380; HAPLN1.
DR   HPA; ENSG00000145681; Tissue enriched (placenta).
DR   MIM; 115435; gene.
DR   neXtProt; NX_P10915; -.
DR   OpenTargets; ENSG00000145681; -.
DR   PharmGKB; PA26901; -.
DR   VEuPathDB; HostDB:ENSG00000145681; -.
DR   eggNOG; ENOG502QRAR; Eukaryota.
DR   GeneTree; ENSGT00940000159267; -.
DR   HOGENOM; CLU_052285_1_0_1; -.
DR   InParanoid; P10915; -.
DR   OMA; ERACHDQ; -.
DR   OrthoDB; 5402504at2759; -.
DR   PhylomeDB; P10915; -.
DR   TreeFam; TF332134; -.
DR   PathwayCommons; P10915; -.
DR   Reactome; R-HSA-3000178; ECM proteoglycans.
DR   SignaLink; P10915; -.
DR   SIGNOR; P10915; -.
DR   BioGRID-ORCS; 1404; 10 hits in 1153 CRISPR screens.
DR   ChiTaRS; HAPLN1; human.
DR   GeneWiki; HAPLN1; -.
DR   GenomeRNAi; 1404; -.
DR   Pharos; P10915; Tbio.
DR   PRO; PR:P10915; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P10915; Protein.
DR   Bgee; ENSG00000145681; Expressed in tibia and 127 other cell types or tissues.
DR   ExpressionAtlas; P10915; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0072534; C:perineuronal net; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005540; F:hyaluronic acid binding; IEA:UniProtKB-KW.
DR   GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0010001; P:glial cell differentiation; IBA:GO_Central.
DR   GO; GO:0002052; P:positive regulation of neuroblast proliferation; IBA:GO_Central.
DR   GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR   CDD; cd05877; Ig_LP_like; 1.
DR   CDD; cd03518; Link_domain_HAPLN_module_1; 1.
DR   CDD; cd03519; Link_domain_HAPLN_module_2; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 2.
DR   InterPro; IPR016186; C-type_lectin-like/link_sf.
DR   InterPro; IPR016187; CTDL_fold.
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; IPR013106; Ig_V-set.
DR   InterPro; IPR000538; Link_dom.
DR   PANTHER; PTHR22804; AGGRECAN/VERSICAN PROTEOGLYCAN; 1.
DR   PANTHER; PTHR22804:SF10; HYALURONAN AND PROTEOGLYCAN LINK PROTEIN 1; 1.
DR   Pfam; PF07686; V-set; 1.
DR   Pfam; PF00193; Xlink; 2.
DR   PRINTS; PR01265; LINKMODULE.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00406; IGv; 1.
DR   SMART; SM00445; LINK; 2.
DR   SUPFAM; SSF56436; C-type lectin-like; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS01241; LINK_1; 2.
DR   PROSITE; PS50963; LINK_2; 2.
DR   Genevisible; P10915; HS.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Extracellular matrix; Glycoprotein; Hyaluronic acid;
KW   Immunoglobulin domain; Reference proteome; Repeat; Secreted.
FT   PROPEP          1..15
FT                   /id="PRO_0000013177"
FT   CHAIN           16..354
FT                   /note="Hyaluronan and proteoglycan link protein 1"
FT                   /id="PRO_0000013178"
FT   DOMAIN          38..152
FT                   /note="Ig-like V-type"
FT   DOMAIN          159..254
FT                   /note="Link 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT   DOMAIN          259..351
FT                   /note="Link 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT   CARBOHYD        21
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        56
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        61..139
FT                   /evidence="ECO:0000250"
FT   DISULFID        181..252
FT                   /evidence="ECO:0000250"
FT   DISULFID        205..226
FT                   /evidence="ECO:0000250"
FT   DISULFID        279..349
FT                   /evidence="ECO:0000250"
FT   DISULFID        304..325
FT                   /evidence="ECO:0000250"
FT   VARIANT         281
FT                   /note="N -> S (in dbSNP:rs6864342)"
FT                   /id="VAR_049316"
FT   VARIANT         333
FT                   /note="R -> H (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036168"
FT   CONFLICT        274
FT                   /note="E -> V (in Ref. 7; AAH57808)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   354 AA;  40166 MW;  315C96EC3AC2626A CRC64;
     MKSLLLLVLI SICWADHLSD NYTLDHDRAI HIQAENGPHL LVEAEQAKVF SHRGGNVTLP
     CKFYRDPTAF GSGIHKIRIK WTKLTSDYLK EVDVFVSMGY HKKTYGGYQG RVFLKGGSDS
     DASLVITDLT LEDYGRYKCE VIEGLEDDTV VVALDLQGVV FPYFPRLGRY NLNFHEAQQA
     CLDQDAVIAS FDQLYDAWRG GLDWCNAGWL SDGSVQYPIT KPREPCGGQN TVPGVRNYGF
     WDKDKSRYDV FCFTSNFNGR FYYLIHPTKL TYDEAVQACL NDGAQIAKVG QIFAAWKILG
     YDRCDAGWLA DGSVRYPISR PRRRCSPTEA AVRFVGFPDK KHKLYGVYCF RAYN
//