ID   SPP24_HUMAN             Reviewed;         211 AA.
AC   Q13103; A4QMV3; Q3B892; Q546M5;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   24-JAN-2024, entry version 161.
DE   RecName: Full=Secreted phosphoprotein 24;
DE            Short=Spp-24;
DE   AltName: Full=Secreted phosphoprotein 2;
DE   Flags: Precursor;
GN   Name=SPP2; Synonyms=SPP24;
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=Bone;
RA   Coulson L., Hu B., Price P.A.;
RT   "Isolation and molecular cloning of human spp-24, a bone phosphoprotein
RT   related in sequence to the cystatin family of thiol protease inhibitors.";
RL   Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], DEVELOPMENTAL STAGE, TISSUE
RP   SPECIFICITY, AND VARIANT PHE-38.
RC   TISSUE=Liver;
RX   PubMed=15062857; DOI=10.1016/j.matbio.2003.12.001;
RA   Bennett C.S., Khorram Khorshid H.R., Kitchen J.A., Arteta D., Dalgleish R.;
RT   "Characterization of the human secreted phosphoprotein 24 gene (SPP2) and
RT   comparison of the protein sequence in nine species.";
RL   Matrix Biol. 22:641-651(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
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).
RN   [6]
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., Buerckstuemmer T.,
RA   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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Could coordinate an aspect of bone turnover. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Detected in liver and plasma.
CC       {ECO:0000269|PubMed:15062857}.
CC   -!- DEVELOPMENTAL STAGE: Found in fetal liver and kidney.
CC       {ECO:0000269|PubMed:15062857}.
CC   -!- PTM: Phosphorylation sites are present in the extracellular medium.
CC   -!- SIMILARITY: Belongs to the SPP2 family. {ECO:0000305}.
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DR   EMBL; U20530; AAA87905.1; -; mRNA.
DR   EMBL; AJ272265; CAB75571.1; -; Genomic_DNA.
DR   EMBL; AJ308099; CAC87050.1; -; mRNA.
DR   EMBL; AC006037; AAX93090.1; -; Genomic_DNA.
DR   EMBL; CH471063; EAW71070.1; -; Genomic_DNA.
DR   EMBL; BC069401; AAH69401.1; -; mRNA.
DR   EMBL; BC106705; AAI06706.1; -; mRNA.
DR   EMBL; BC112438; AAI12439.1; -; mRNA.
DR   CCDS; CCDS2511.1; -.
DR   PIR; G01654; G01654.
DR   RefSeq; NP_008875.1; NM_006944.2.
DR   RefSeq; XP_005246159.1; XM_005246102.3.
DR   RefSeq; XP_011510000.1; XM_011511698.2.
DR   RefSeq; XP_011510001.1; XM_011511699.2.
DR   RefSeq; XP_011510002.1; XM_011511700.2.
DR   AlphaFoldDB; Q13103; -.
DR   SMR; Q13103; -.
DR   BioGRID; 112572; 1.
DR   IntAct; Q13103; 1.
DR   STRING; 9606.ENSP00000168148; -.
DR   iPTMnet; Q13103; -.
DR   PhosphoSitePlus; Q13103; -.
DR   BioMuta; SPP2; -.
DR   DMDM; 2498939; -.
DR   EPD; Q13103; -.
DR   jPOST; Q13103; -.
DR   MassIVE; Q13103; -.
DR   PaxDb; 9606-ENSP00000168148; -.
DR   PeptideAtlas; Q13103; -.
DR   ProteomicsDB; 59154; -.
DR   Antibodypedia; 34459; 49 antibodies from 7 providers.
DR   DNASU; 6694; -.
DR   Ensembl; ENST00000168148.8; ENSP00000168148.3; ENSG00000072080.11.
DR   Ensembl; ENST00000373368.5; ENSP00000362466.1; ENSG00000072080.11.
DR   GeneID; 6694; -.
DR   KEGG; hsa:6694; -.
DR   MANE-Select; ENST00000168148.8; ENSP00000168148.3; NM_006944.3; NP_008875.1.
DR   UCSC; uc002vvk.2; human.
DR   AGR; HGNC:11256; -.
DR   CTD; 6694; -.
DR   DisGeNET; 6694; -.
DR   GeneCards; SPP2; -.
DR   HGNC; HGNC:11256; SPP2.
DR   HPA; ENSG00000072080; Tissue enriched (liver).
DR   MIM; 602637; gene.
DR   neXtProt; NX_Q13103; -.
DR   OpenTargets; ENSG00000072080; -.
DR   PharmGKB; PA36086; -.
DR   VEuPathDB; HostDB:ENSG00000072080; -.
DR   eggNOG; ENOG502S7TB; Eukaryota.
DR   GeneTree; ENSGT00390000009001; -.
DR   HOGENOM; CLU_115216_0_0_1; -.
DR   InParanoid; Q13103; -.
DR   OMA; CRSTVQM; -.
DR   OrthoDB; 4041620at2759; -.
DR   PhylomeDB; Q13103; -.
DR   TreeFam; TF335972; -.
DR   PathwayCommons; Q13103; -.
DR   Reactome; R-HSA-114608; Platelet degranulation.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   SignaLink; Q13103; -.
DR   BioGRID-ORCS; 6694; 9 hits in 1148 CRISPR screens.
DR   ChiTaRS; SPP2; human.
DR   GenomeRNAi; 6694; -.
DR   Pharos; Q13103; Tbio.
DR   PRO; PR:Q13103; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q13103; Protein.
DR   Bgee; ENSG00000072080; Expressed in right lobe of liver and 62 other cell types or tissues.
DR   ExpressionAtlas; Q13103; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0046849; P:bone remodeling; IEA:InterPro.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   Gene3D; 3.10.450.10; -; 1.
DR   InterPro; IPR046350; Cystatin_sf.
DR   InterPro; IPR010892; Spp-24.
DR   PANTHER; PTHR15444; SECRETED PHOSPHOPROTEIN 24; 1.
DR   PANTHER; PTHR15444:SF4; SECRETED PHOSPHOPROTEIN 24; 1.
DR   Pfam; PF07448; Spp-24; 1.
DR   SUPFAM; SSF54403; Cystatin/monellin; 1.
DR   Genevisible; Q13103; HS.
PE   1: Evidence at protein level;
KW   Disulfide bond; Phosphoprotein; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..211
FT                   /note="Secreted phosphoprotein 24"
FT                   /id="PRO_0000022403"
FT   MOD_RES         96
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         145
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62740"
FT   MOD_RES         146
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62740"
FT   MOD_RES         170
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8K1I3"
FT   MOD_RES         173
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8K1I3"
FT   MOD_RES         182
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62740"
FT   DISULFID        92..103
FT                   /evidence="ECO:0000250"
FT   DISULFID        116..134
FT                   /evidence="ECO:0000250"
FT   VARIANT         38
FT                   /note="S -> F (in dbSNP:rs34347825)"
FT                   /evidence="ECO:0000269|PubMed:15062857"
FT                   /id="VAR_025698"
FT   CONFLICT        124
FT                   /note="A -> V (in Ref. 5; AAI06706)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   211 AA;  24338 MW;  AED049E63464E38D CRC64;
     MISRMEKMTM MMKILIMFAL GMNYWSCSGF PVYDYDPSSL RDALSASVVK VNSQSLSPYL
     FRAFRSSLKR VEVLDENNLV MNLEFSIRET TCRKDSGEDP ATCAFQRDYY VSTAVCRSTV
     KVSAQQVQGV HARCSWSSST SESYSSEEMI FGDMLGSHKW RNNYLFGLIS DESISEQFYD
     RSLGIMRRVL PPGNRRYPNH RHRARINTDF E
//