ID   CO8A2_MOUSE             Reviewed;         699 AA.
AC   P25318; A3KFY2; Q68ED0; Q6KAQ4; Q6P1C4;
DT   01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2005, sequence version 2.
DT   27-MAR-2024, entry version 166.
DE   RecName: Full=Collagen alpha-2(VIII) chain;
DE   AltName: Full=Endothelial collagen;
DE   Flags: Precursor;
GN   Name=Col8a2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; 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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 60-699 (ISOFORM 1).
RC   TISSUE=Embryonic tail;
RX   PubMed=15449545; DOI=10.1093/dnares/11.2.127;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of FLJ genes: the
RT   complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified
RT   by screening of terminal sequences of cDNA clones randomly sampled from
RT   size-fractionated libraries.";
RL   DNA Res. 11:127-135(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 530-699.
RX   PubMed=2019595; DOI=10.1016/s0021-9258(20)89508-8;
RA   Muragaki Y., Jacenko O., Apte S., Mattei M.-G., Ninomiya Y., Olsen B.R.;
RT   "The alpha 2(VIII) collagen gene. A novel member of the short chain
RT   collagen family located on the human chromosome 1.";
RL   J. Biol. Chem. 266:7721-7727(1991).
RN   [5]
RP   TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=19401424; DOI=10.2337/db08-0183;
RA   Hopfer U., Hopfer H., Meyer-Schwesinger C., Loeffler I., Fukai N.,
RA   Olsen B.R., Stahl R.A., Wolf G.;
RT   "Lack of type VIII collagen in mice ameliorates diabetic nephropathy.";
RL   Diabetes 58:1672-1681(2009).
CC   -!- FUNCTION: Macromolecular component of the subendothelium. Major
CC       component of the Descemet's membrane (basement membrane) of corneal
CC       endothelial cells. Also a component of the endothelia of blood vessels.
CC       Necessary for migration and proliferation of vascular smooth muscle
CC       cells and thus, has a potential role in the maintenance of vessel wall
CC       integrity and structure, in particular in atherogenesis (By
CC       similarity). {ECO:0000250, ECO:0000269|PubMed:19401424}.
CC   -!- SUBUNIT: Homotrimers, or heterotrimers in association with alpha
CC       2(VIII) type collagens. Four homotrimers can form a tetrahedron
CC       stabilized by central interacting C-terminal NC1 trimers (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix, basement membrane.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P25318-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P25318-2; Sequence=VSP_014975;
CC   -!- TISSUE SPECIFICITY: In the kidney, expressed in mesangial cells,
CC       glomerular endothelial cells, and tubular epithelial cells.
CC       {ECO:0000269|PubMed:19401424}.
CC   -!- PTM: Proteolytically cleaved by neutrophil elastase, in vitro.
CC       {ECO:0000250}.
CC   -!- PTM: Prolines at the third position of the tripeptide repeating unit
CC       (G-X-Y) are hydroxylated in some or all of the chains.
CC   -!- DISRUPTION PHENOTYPE: COL8A1(-)/COL8A2(-) mice exhibit decreased
CC       proliferation of mesangial cells, reduced phosphorylation of ERK1/2 and
CC       increased p27(KIP1) expression. Diabetic COL8A1(-)/COL8A2(-) mice
CC       reveal reduced mesangial expansion and cellularity and extracellular
CC       matrix expansion. {ECO:0000269|PubMed:19401424}.
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DR   EMBL; AL606976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC065148; AAH65148.1; -; mRNA.
DR   EMBL; BC080317; AAH80317.1; -; mRNA.
DR   EMBL; AK131153; BAD21403.1; -; mRNA.
DR   EMBL; M60833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS18649.1; -. [P25318-1]
DR   PIR; B57131; B57131.
DR   RefSeq; NP_955767.1; NM_199473.2. [P25318-1]
DR   AlphaFoldDB; P25318; -.
DR   SMR; P25318; -.
DR   ComplexPortal; CPX-2967; Collagen type VIII trimer variant I.
DR   ComplexPortal; CPX-2969; Collagen type VIII trimer variant 3.
DR   STRING; 10090.ENSMUSP00000070270; -.
DR   iPTMnet; P25318; -.
DR   PhosphoSitePlus; P25318; -.
DR   MaxQB; P25318; -.
DR   PaxDb; 10090-ENSMUSP00000070270; -.
DR   ProteomicsDB; 283413; -. [P25318-1]
DR   ProteomicsDB; 283414; -. [P25318-2]
DR   Antibodypedia; 56213; 180 antibodies from 24 providers.
DR   DNASU; 329941; -.
DR   Ensembl; ENSMUST00000070132.7; ENSMUSP00000070270.7; ENSMUSG00000056174.9. [P25318-1]
DR   GeneID; 329941; -.
DR   KEGG; mmu:329941; -.
DR   UCSC; uc008utd.1; mouse. [P25318-1]
DR   AGR; MGI:88464; -.
DR   CTD; 1296; -.
DR   MGI; MGI:88464; Col8a2.
DR   VEuPathDB; HostDB:ENSMUSG00000056174; -.
DR   eggNOG; ENOG502QRST; Eukaryota.
DR   GeneTree; ENSGT00940000154317; -.
DR   HOGENOM; CLU_001074_21_0_1; -.
DR   InParanoid; P25318; -.
DR   OMA; IPHMKYM; -.
DR   OrthoDB; 4272636at2759; -.
DR   PhylomeDB; P25318; -.
DR   TreeFam; TF334029; -.
DR   Reactome; R-MMU-1442490; Collagen degradation.
DR   Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR   Reactome; R-MMU-2022090; Assembly of collagen fibrils and other multimeric structures.
DR   Reactome; R-MMU-216083; Integrin cell surface interactions.
DR   Reactome; R-MMU-8948216; Collagen chain trimerization.
DR   BioGRID-ORCS; 329941; 4 hits in 77 CRISPR screens.
DR   ChiTaRS; Col8a2; mouse.
DR   PRO; PR:P25318; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; P25318; Protein.
DR   Bgee; ENSMUSG00000056174; Expressed in humerus cartilage element and 138 other cell types or tissues.
DR   ExpressionAtlas; P25318; baseline and differential.
DR   GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR   GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IBA:GO_Central.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0048593; P:camera-type eye morphogenesis; IGI:MGI.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0001935; P:endothelial cell proliferation; IGI:MGI.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   Gene3D; 2.60.120.40; -; 1.
DR   InterPro; IPR001073; C1q_dom.
DR   InterPro; IPR008160; Collagen.
DR   InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR   PANTHER; PTHR15427:SF33; EMI DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR15427; EMILIN ELASTIN MICROFIBRIL INTERFACE-LOCATED PROTEIN ELASTIN MICROFIBRIL INTERFACER; 1.
DR   Pfam; PF00386; C1q; 1.
DR   Pfam; PF01391; Collagen; 3.
DR   PRINTS; PR00007; COMPLEMNTC1Q.
DR   SMART; SM00110; C1Q; 1.
DR   SUPFAM; SSF49842; TNF-like; 1.
DR   PROSITE; PS50871; C1Q; 1.
DR   Genevisible; P25318; MM.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Angiogenesis; Basement membrane; Cell adhesion;
KW   Collagen; Extracellular matrix; Hydroxylation; Reference proteome; Repeat;
KW   Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..699
FT                   /note="Collagen alpha-2(VIII) chain"
FT                   /id="PRO_0000005836"
FT   DOMAIN          566..699
FT                   /note="C1q"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT   REGION          25..72
FT                   /note="Nonhelical region (NC2)"
FT   REGION          66..542
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          73..532
FT                   /note="Triple-helical region (COL1)"
FT   REGION          533..699
FT                   /note="Nonhelical region (NC1)"
FT   COMPBIAS        70..96
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        216..230
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        501..529
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         168..223
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_014975"
FT   CONFLICT        609
FT                   /note="T -> S (in Ref. 4; M60833)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   699 AA;  66943 MW;  FCBD4FBB44642646 CRC64;
     MQGALMPLPS LLLLLLGCGP RVSSGGGAGG AAGYAPVKYV QPMQKGPVGP PFREGKGQYL
     EMPLPMLPMD LKGEPGPPGK PGPRGPPGPP GFPGKPGTGK PGVHGQPGPA GPPGFSRMGK
     AGPPGLPGKV GPPGQPGLRG EPGIRGDQGL RGPPGPPGLP GPSGITVPGK PGAQGAPGPP
     GFRGEPGPQG EPGPRGDRGL KGDNGVGQPG LPGAPGQAGA PGPPGLPGPA GLGKPGLDGI
     PGAPGDKGDS GPPGVPGSRG EPGAVGPKGP PGVDGVGIPG AAGVPGPQGP VGAKGEPGLR
     GPPGLIGPVG YGMPGKPGPK GDRGPVGAPG LLGDRGEPGE DGKPGEQGPQ GLGGPPGLPG
     SAGLPGRRGP PGSKGEVGPG GPPGVPGIRG DQGPNGLAGK PGLPGERGLP GAHGPPGPTG
     PKGEPGFTGR PGGPGVAGAL GQKGDLGLPG QPGLRGPSGI PGLQGPAGPI GPQGLPGLKG
     EPGLPGPPGE GKVGEPGSAG PTGPPGVPGS PGLTGPPGPP GPPGPPGAPG ALDETGIAGL
     HLPNGGVEGA VLGKGGKPQF GLGELSAHAT PAFTAVLTSP FPASGMPVRF DRTLYNGHSG
     YNPATGIFTC PVGGVYYFAY HVHVKGTNVW VALYKNNVPA TYTYDEYKKG YLDQASGGAV
     LQLRPNDQVW VQMPSDQANG LYSTEYIHSS FSGFLLCPT
//