SC65_MOUSE
ID SC65_MOUSE Reviewed; 443 AA.
AC Q8K2B0;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Endoplasmic reticulum protein SC65 {ECO:0000303|PubMed:23959653};
DE AltName: Full=Leprecan-like protein 4;
DE AltName: Full=Prolyl 3-hydroxylase family member 4 {ECO:0000312|MGI:MGI:1913430};
DE AltName: Full=Synaptonemal complex protein SC65 {ECO:0000250|UniProtKB:Q64375};
DE Flags: Precursor;
GN Name=P3h4 {ECO:0000312|MGI:MGI:1913430};
GN Synonyms=Leprel4, Sc65 {ECO:0000250|UniProtKB:Q64375};
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].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23959653; DOI=10.1002/jbmr.2075;
RA Gruenwald K., Castagnola P., Besio R., Dimori M., Chen Y., Akel N.S.,
RA Swain F.L., Skinner R.A., Eyre D.R., Gaddy D., Suva L.J., Morello R.;
RT "Sc65 is a novel endoplasmic reticulum protein that regulates bone mass
RT homeostasis.";
RL J. Bone Miner. Res. 29:666-675(2014).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, INTERACTION WITH PLOD1;
RP P3H3 AND PPIB, AND IDENTIFICATION IN A COMPLEX WITH PLOD1 AND P3H3.
RX PubMed=27119146; DOI=10.1371/journal.pgen.1006002;
RA Heard M.E., Besio R., Weis M., Rai J., Hudson D.M., Dimori M.,
RA Zimmerman S.M., Kamykowski J.A., Hogue W.R., Swain F.L., Burdine M.S.,
RA Mackintosh S.G., Tackett A.J., Suva L.J., Eyre D.R., Morello R.;
RT "Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex
RT Regulating Collagen Lysyl Hydroxylation.";
RL PLoS Genet. 12:E1006002-E1006002(2016).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=28115524; DOI=10.1074/jbc.m116.762245;
RA Hudson D.M., Weis M., Rai J., Joeng K.S., Dimori M., Lee B.H., Morello R.,
RA Eyre D.R.;
RT "P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-
RT hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type
RT VIA.";
RL J. Biol. Chem. 292:3877-3887(2017).
CC -!- FUNCTION: Part of a complex composed of PLOD1, P3H3 and P3H4 that
CC catalyzes hydroxylation of lysine residues in collagen alpha chains and
CC is required for normal assembly and cross-linking of collagen fibrils
CC (PubMed:27119146). Required for normal bone density and normal skin
CC stability via its role in hydroxylation of lysine residues in collagen
CC alpha chains and in collagen fibril assembly (PubMed:23959653,
CC PubMed:27119146, PubMed:28115524). {ECO:0000269|PubMed:23959653,
CC ECO:0000269|PubMed:27119146, ECO:0000269|PubMed:28115524}.
CC -!- SUBUNIT: Interacts with PLOD1, P3H3 and PPIB. Identified in a complex
CC with PLOD1 and P3H3. {ECO:0000269|PubMed:27119146}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q92791}.
CC -!- TISSUE SPECIFICITY: Detected in calvaria, cartilage, kidney, ribs, and
CC at lower levels in tail (PubMed:23959653, PubMed:27119146). Detected in
CC proliferating and prehypertrophic chondrocytes in the growth plate of
CC long bones and in mineralizing chondro-osseus bone collar and cortical
CC bone (PubMed:23959653). Detected on osteoblasts in long bones
CC (PubMed:23959653, PubMed:27119146). Detected in skin fibroblasts (at
CC protein level) (PubMed:27119146). Detected in fetal ribs, and in tibia
CC and metatarsus from neonates (PubMed:23959653).
CC {ECO:0000269|PubMed:23959653, ECO:0000269|PubMed:27119146}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth (PubMed:23959653,
CC PubMed:27119146, PubMed:28115524). Mice are born at the expected
CC Mendelian rate (PubMed:23959653, PubMed:27119146). Two and six month
CC old mutant mice display a decreased ratio between trabecular bone
CC volume and tissue volume in tibia and femur, plus decreased
CC connectivity density in femur and tibia (PubMed:23959653,
CC PubMed:27119146). Osteoblast number is not affected, while osteoclast
CC numbers are increased, suggesting that increased bone resorption is the
CC cause for the low bone mass phenotype (PubMed:23959653). Lysine
CC hydroxylation of skin and bone collagen alpha chains is strongly
CC reduced (PubMed:27119146, PubMed:28115524). In contrast, prolyl 3-
CC hydroxylation is not affected (PubMed:23959653, PubMed:27119146).
CC Dorsal skin displays impaired packing of collagen fibrils, decreased
CC skin tensile strength, decreased skin stiffness and increased skin
CC fragility (PubMed:27119146, PubMed:28115524). Likewise, mice deficient
CC for both P3h3 and P3h4 display decreased lysine hydroxylation of
CC collagen alpha chains, but normal collagen prolyl 3-hydroxylation
CC (PubMed:28115524). {ECO:0000269|PubMed:23959653,
CC ECO:0000269|PubMed:27119146, ECO:0000269|PubMed:28115524}.
CC -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
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DR EMBL; AL590968; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC031856; AAH31856.1; -; mRNA.
DR CCDS; CCDS25421.1; -.
DR RefSeq; NP_789800.1; NM_176830.2.
DR AlphaFoldDB; Q8K2B0; -.
DR BioGRID; 211276; 2.
DR STRING; 10090.ENSMUSP00000065278; -.
DR GlyConnect; 2748; 1 N-Linked glycan (1 site).
DR GlyGen; Q8K2B0; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; Q8K2B0; -.
DR PhosphoSitePlus; Q8K2B0; -.
DR MaxQB; Q8K2B0; -.
DR PaxDb; Q8K2B0; -.
DR PeptideAtlas; Q8K2B0; -.
DR PRIDE; Q8K2B0; -.
DR ProteomicsDB; 256736; -.
DR Antibodypedia; 28941; 136 antibodies from 24 providers.
DR DNASU; 66180; -.
DR Ensembl; ENSMUST00000066489; ENSMUSP00000065278; ENSMUSG00000006931.
DR GeneID; 66180; -.
DR KEGG; mmu:66180; -.
DR UCSC; uc007lla.1; mouse.
DR CTD; 10609; -.
DR MGI; MGI:1913430; P3h4.
DR VEuPathDB; HostDB:ENSMUSG00000006931; -.
DR eggNOG; KOG4459; Eukaryota.
DR GeneTree; ENSGT00940000153814; -.
DR HOGENOM; CLU_029887_0_0_1; -.
DR InParanoid; Q8K2B0; -.
DR OMA; EAFCGRN; -.
DR OrthoDB; 607176at2759; -.
DR PhylomeDB; Q8K2B0; -.
DR TreeFam; TF320837; -.
DR BioGRID-ORCS; 66180; 4 hits in 73 CRISPR screens.
DR ChiTaRS; P3h4; mouse.
DR PRO; PR:Q8K2B0; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8K2B0; protein.
DR Bgee; ENSMUSG00000006931; Expressed in vault of skull and 249 other tissues.
DR ExpressionAtlas; Q8K2B0; baseline and differential.
DR Genevisible; Q8K2B0; MM.
DR GO; GO:1902494; C:catalytic complex; IMP:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0000795; C:synaptonemal complex; ISO:MGI.
DR GO; GO:0046849; P:bone remodeling; IMP:UniProtKB.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; IMP:UniProtKB.
DR GO; GO:0017185; P:peptidyl-lysine hydroxylation; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR033213; SC65.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR13986:SF4; PTHR13986:SF4; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Reference proteome; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..443
FT /note="Endoplasmic reticulum protein SC65"
FT /evidence="ECO:0000255"
FT /id="PRO_0000320294"
FT REGION 81..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..421
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 443 AA; 51132 MW; 99FA2B03344F15B1 CRC64;
MARGAWGLLW LLLGSAGAQY EKYSFRGFPP EDLMPLATAY GHALEQYEGE SWRESARYLE
AALRLHRLLR DSEAFCHANC SGPATSQPRP ASGPDGDHDG DGEDWARELR LFGHVLERAA
CLRRCKKTLP AFQVPYPPRQ LLRDFQSRLP YQYLHYAHFK ANRLEKAVAA AYTFLQRNPK
HELTAKYLNY YRGMLDIGDE SLTDLEAQPY EAVFLRAVKL YNSGDFRSST EDMERALAEY
MTVFARCLAG CEGAHEQVDF KDFYPAIADL FAESLQCKVD CETNLTPNVG GFFVDKFVAT
MYHYLQFAYY KLNDVRQAAR SAASYMLFDP KDSVMQQNLV YYRFHRARWG LEDEDFQPRE
EAMLYHNQTS ELRELLDFTH MYLQSDDEME LEETESLPEP EEPLSDAEFE GEGDYEEGLY
ADWWQEPEAK GDEAEAEPEP ELT
