ID   HPLN4_HUMAN             Reviewed;         402 AA.
AC   Q86UW8; A5PKW5; Q96PW2;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Hyaluronan and proteoglycan link protein 4;
DE   AltName: Full=Brain link protein 2;
DE   Flags: Precursor;
GN   Name=HAPLN4; Synonyms=BRAL2, KIAA1926;
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 {ECO:0000312|EMBL:AAP22048.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND 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   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=14550776; DOI=10.1016/s1044-7431(03)00133-7;
RA   Bekku Y., Su W.-D., Hirakawa S., Faessler R., Ohtsuka A., Kang J.S.,
RA   Sanders J., Murakami T., Ninomiya Y., Oohashi T.;
RT   "Molecular cloning of Bral2, a novel brain-specific link protein, and
RT   immunohistochemical colocalization with brevican in perineuronal nets.";
RL   Mol. Cell. Neurosci. 24:148-159(2003).
RN   [3] {ECO:0000312|EMBL:BAB67819.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain {ECO:0000312|EMBL:BAB67819.1};
RX   PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA   Nagase T., Kikuno R., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XXI. The
RT   complete sequences of 60 new cDNA clones from brain which code for large
RT   proteins.";
RL   DNA Res. 8:179-187(2001).
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
CC   -!- FUNCTION: Essential for the proper localization of brevican (BCAN),
CC       mainly as a perineuronal nets (PNNs)-type deposition in the brainstem
CC       and cerebellum thereby playing a key role in the formation and
CC       structural organization of PNNs (By similarity). Contributes to the
CC       formation and transmission of inhibitory GABAergic synapses between
CC       Purkinje cells and deep cerebellar nuclei neurons (By similarity).
CC       {ECO:0000250|UniProtKB:Q80WM4}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250|UniProtKB:Q9ESM3}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in brain.
CC       {ECO:0000269|PubMed:12663660}.
CC   -!- SIMILARITY: Belongs to the HAPLN family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB67819.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AY262756; AAP22048.1; -; mRNA.
DR   EMBL; AB107883; BAC79077.1; -; mRNA.
DR   EMBL; AB067513; BAB67819.1; ALT_INIT; mRNA.
DR   EMBL; CH471106; EAW84804.1; -; Genomic_DNA.
DR   EMBL; BC142644; AAI42645.1; -; mRNA.
DR   EMBL; BC142698; AAI42699.1; -; mRNA.
DR   CCDS; CCDS12398.1; -.
DR   RefSeq; NP_075378.1; NM_023002.2.
DR   AlphaFoldDB; Q86UW8; -.
DR   SMR; Q86UW8; -.
DR   BioGRID; 135639; 2.
DR   STRING; 9606.ENSP00000291481; -.
DR   GlyCosmos; Q86UW8; 1 site, No reported glycans.
DR   GlyGen; Q86UW8; 1 site.
DR   iPTMnet; Q86UW8; -.
DR   PhosphoSitePlus; Q86UW8; -.
DR   BioMuta; HAPLN4; -.
DR   DMDM; 47605684; -.
DR   jPOST; Q86UW8; -.
DR   MassIVE; Q86UW8; -.
DR   MaxQB; Q86UW8; -.
DR   PaxDb; 9606-ENSP00000291481; -.
DR   PeptideAtlas; Q86UW8; -.
DR   ProteomicsDB; 69922; -.
DR   Antibodypedia; 28414; 217 antibodies from 28 providers.
DR   DNASU; 404037; -.
DR   Ensembl; ENST00000291481.8; ENSP00000291481.5; ENSG00000187664.9.
DR   GeneID; 404037; -.
DR   KEGG; hsa:404037; -.
DR   MANE-Select; ENST00000291481.8; ENSP00000291481.5; NM_023002.3; NP_075378.1.
DR   UCSC; uc002nmb.5; human.
DR   AGR; HGNC:31357; -.
DR   CTD; 404037; -.
DR   DisGeNET; 404037; -.
DR   GeneCards; HAPLN4; -.
DR   HGNC; HGNC:31357; HAPLN4.
DR   HPA; ENSG00000187664; Group enriched (brain, intestine, liver).
DR   MIM; 619710; gene.
DR   neXtProt; NX_Q86UW8; -.
DR   PharmGKB; PA134886721; -.
DR   VEuPathDB; HostDB:ENSG00000187664; -.
DR   eggNOG; ENOG502QRG1; Eukaryota.
DR   GeneTree; ENSGT00940000160926; -.
DR   HOGENOM; CLU_052285_1_0_1; -.
DR   InParanoid; Q86UW8; -.
DR   OMA; QACLQQD; -.
DR   OrthoDB; 5402504at2759; -.
DR   PhylomeDB; Q86UW8; -.
DR   TreeFam; TF332134; -.
DR   PathwayCommons; Q86UW8; -.
DR   BioGRID-ORCS; 404037; 12 hits in 1138 CRISPR screens.
DR   GenomeRNAi; 404037; -.
DR   Pharos; Q86UW8; Tbio.
DR   PRO; PR:Q86UW8; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q86UW8; Protein.
DR   Bgee; ENSG00000187664; Expressed in primary visual cortex and 77 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0072534; C:perineuronal net; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005540; F:hyaluronic acid binding; IEA:UniProtKB-KW.
DR   GO; GO:0150043; F:structural constituent of synapse-associated extracellular matrix; ISS:UniProtKB.
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:1904862; P:inhibitory synapse assembly; ISS:UniProtKB.
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   GO; GO:0051932; P:synaptic transmission, GABAergic; ISS:UniProtKB.
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; IPR003598; Ig_sub2.
DR   InterPro; IPR013106; Ig_V-set.
DR   InterPro; IPR000538; Link_dom.
DR   PANTHER; PTHR22804; AGGRECAN/VERSICAN PROTEOGLYCAN; 1.
DR   PANTHER; PTHR22804:SF11; HYALURONAN AND PROTEOGLYCAN LINK PROTEIN 4; 1.
DR   Pfam; PF07686; V-set; 1.
DR   Pfam; PF00193; Xlink; 2.
DR   PRINTS; PR01265; LINKMODULE.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 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; 1.
DR   PROSITE; PS50963; LINK_2; 2.
DR   Genevisible; Q86UW8; HS.
PE   2: Evidence at transcript level;
KW   Disulfide bond; Extracellular matrix; Glycoprotein; Hyaluronic acid;
KW   Immunoglobulin domain; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..402
FT                   /note="Hyaluronan and proteoglycan link protein 4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000013192"
FT   DOMAIN          46..161
FT                   /note="Ig-like C2-type"
FT   DOMAIN          163..268
FT                   /note="Link 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT                   ECO:0000305"
FT   DOMAIN          273..365
FT                   /note="Link 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00323,
FT                   ECO:0000305"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305"
FT   DISULFID        68..143
FT                   /evidence="ECO:0000250|UniProtKB:P03994"
FT   DISULFID        185..266
FT                   /evidence="ECO:0000250|UniProtKB:P03994"
FT   DISULFID        209..230
FT                   /evidence="ECO:0000250|UniProtKB:P03994"
FT   DISULFID        293..363
FT                   /evidence="ECO:0000250|UniProtKB:P03994"
FT   DISULFID        318..339
FT                   /evidence="ECO:0000250|UniProtKB:P03994"
SQ   SEQUENCE   402 AA;  42801 MW;  B1B6CE2098244124 CRC64;
     MVCARAALGP GALWAAAWGV LLLTAPAGAQ RGRKKVVHVL EGESGSVVVQ TAPGQVVSHR
     GGTIVLPCRY HYEAAAHGHD GVRLKWTKVV DPLAFTDVFV ALGPQHRAFG SYRGRAELQG
     DGPGDASLVL RNVTLQDYGR YECEVTNELE DDAGMVKLDL EGVVFPYHPR GGRYKLTFAE
     AQRACAEQDG ILASAEQLHA AWRDGLDWCN AGWLRDGSVQ YPVNRPREPC GGLGGTGSAG
     GGGDANGGLR NYGYRHNAEE RYDAFCFTSN LPGRVFFLKP LRPVPFSGAA RACAARGAAV
     AKVGQLFAAW KLQLLDRCTA GWLADGSARY PIVNPRARCG GRRPGVRSLG FPDATRRLFG
     VYCYRAPGAP DPAPGGWGWG WAGGGGWAGG ARDPAAWTPL HV
//