ID   SHOX2_HUMAN             Reviewed;         331 AA.
AC   O60902; O60465; O60467; O60903;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 4.
DT   27-MAR-2024, entry version 198.
DE   RecName: Full=Short stature homeobox protein 2;
DE   AltName: Full=Homeobox protein Og12X;
DE   AltName: Full=Paired-related homeobox protein SHOT;
GN   Name=SHOX2; Synonyms=OG12X, SHOT;
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] (ISOFORMS 1 AND 2).
RC   TISSUE=Fibroblast;
RX   PubMed=9482898; DOI=10.1073/pnas.95.5.2406;
RA   Blaschke R.J., Monaghan A.P., Schiller S., Schechinger B., Rao E.,
RA   Padilla-Nash H., Ried T., Rappold G.A.;
RT   "SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain,
RT   heart, and limb development.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:2406-2411(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Muscle;
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 [MRNA] OF 116-331 (ISOFORM 2).
RC   TISSUE=Craniofacial;
RX   PubMed=9466998; DOI=10.1093/hmg/7.3.415;
RA   Semina E.V., Reiter R.S., Murray J.C.;
RT   "A new human homeobox gene OG12X is a member of the most conserved homeobox
RT   gene family and is expressed during heart development in mouse.";
RL   Hum. Mol. Genet. 7:415-422(1998).
RN   [4]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
CC   -!- FUNCTION: May be a growth regulator and have a role in specifying
CC       neural systems involved in processing somatosensory information, as
CC       well as in face and body structure formation.
CC   -!- INTERACTION:
CC       O60902-3; P55212: CASP6; NbExp=3; IntAct=EBI-9092164, EBI-718729;
CC       O60902-3; P48643: CCT5; NbExp=3; IntAct=EBI-9092164, EBI-355710;
CC       O60902-3; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-9092164, EBI-745535;
CC       O60902-3; P22607: FGFR3; NbExp=3; IntAct=EBI-9092164, EBI-348399;
CC       O60902-3; Q14957: GRIN2C; NbExp=3; IntAct=EBI-9092164, EBI-8285963;
CC       O60902-3; P28799: GRN; NbExp=3; IntAct=EBI-9092164, EBI-747754;
CC       O60902-3; O60333-2: KIF1B; NbExp=3; IntAct=EBI-9092164, EBI-10975473;
CC       O60902-3; P13473-2: LAMP2; NbExp=3; IntAct=EBI-9092164, EBI-21591415;
CC       O60902-3; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-9092164, EBI-473160;
CC       O60902-3; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-9092164, EBI-5280197;
CC       O60902-3; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-9092164, EBI-396669;
CC       O60902-3; O76024: WFS1; NbExp=3; IntAct=EBI-9092164, EBI-720609;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=SHOX2A, SHOTA;
CC         IsoId=O60902-1; Sequence=Displayed;
CC       Name=2; Synonyms=SHOX2B, SHOTB, OG12XB;
CC         IsoId=O60902-2; Sequence=VSP_002288;
CC       Name=3;
CC         IsoId=O60902-3; Sequence=VSP_024427;
CC   -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, liver, lung,
CC       bone marrow fibroblast, pancreas and placenta.
CC   -!- DEVELOPMENTAL STAGE: Expressed during cranofacial development as well
CC       as in heart.
CC   -!- MISCELLANEOUS: [Isoform 1]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay.
CC   -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC39662.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA05341.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA05342.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AJ002367; CAA05341.1; ALT_INIT; mRNA.
DR   EMBL; AJ002368; CAA05342.1; ALT_INIT; mRNA.
DR   EMBL; BC008829; AAH08829.1; -; mRNA.
DR   EMBL; AF022654; AAC39662.1; ALT_INIT; mRNA.
DR   EMBL; AF023203; AAC39663.1; -; mRNA.
DR   CCDS; CCDS33884.2; -. [O60902-3]
DR   CCDS; CCDS43164.1; -. [O60902-1]
DR   CCDS; CCDS54664.1; -. [O60902-2]
DR   RefSeq; NP_001157150.1; NM_001163678.1. [O60902-2]
DR   RefSeq; NP_003021.3; NM_003030.4. [O60902-3]
DR   RefSeq; NP_006875.2; NM_006884.3. [O60902-1]
DR   RefSeq; XP_006713791.1; XM_006713728.3.
DR   RefSeq; XP_016862544.1; XM_017007055.1.
DR   AlphaFoldDB; O60902; -.
DR   SMR; O60902; -.
DR   BioGRID; 112370; 8.
DR   IntAct; O60902; 16.
DR   STRING; 9606.ENSP00000374240; -.
DR   iPTMnet; O60902; -.
DR   PhosphoSitePlus; O60902; -.
DR   BioMuta; SHOX2; -.
DR   MassIVE; O60902; -.
DR   PaxDb; 9606-ENSP00000374240; -.
DR   PeptideAtlas; O60902; -.
DR   ProteomicsDB; 49660; -. [O60902-1]
DR   ProteomicsDB; 49661; -. [O60902-2]
DR   ProteomicsDB; 49662; -. [O60902-3]
DR   Antibodypedia; 18427; 167 antibodies from 26 providers.
DR   DNASU; 6474; -.
DR   Ensembl; ENST00000389589.8; ENSP00000374240.4; ENSG00000168779.21. [O60902-3]
DR   Ensembl; ENST00000441443.6; ENSP00000397099.3; ENSG00000168779.21. [O60902-1]
DR   Ensembl; ENST00000483851.7; ENSP00000419362.1; ENSG00000168779.21. [O60902-2]
DR   GeneID; 6474; -.
DR   KEGG; hsa:6474; -.
DR   MANE-Select; ENST00000483851.7; ENSP00000419362.1; NM_001163678.2; NP_001157150.1. [O60902-2]
DR   UCSC; uc003fbr.4; human. [O60902-1]
DR   AGR; HGNC:10854; -.
DR   CTD; 6474; -.
DR   DisGeNET; 6474; -.
DR   GeneCards; SHOX2; -.
DR   HGNC; HGNC:10854; SHOX2.
DR   HPA; ENSG00000168779; Tissue enhanced (adipose tissue, breast, cervix).
DR   MIM; 602504; gene.
DR   neXtProt; NX_O60902; -.
DR   OpenTargets; ENSG00000168779; -.
DR   PharmGKB; PA35756; -.
DR   VEuPathDB; HostDB:ENSG00000168779; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000154287; -.
DR   HOGENOM; CLU_047013_5_0_1; -.
DR   InParanoid; O60902; -.
DR   OMA; PTGCAEP; -.
DR   OrthoDB; 2897127at2759; -.
DR   PhylomeDB; O60902; -.
DR   TreeFam; TF350757; -.
DR   PathwayCommons; O60902; -.
DR   SignaLink; O60902; -.
DR   BioGRID-ORCS; 6474; 20 hits in 1177 CRISPR screens.
DR   GeneWiki; SHOX2; -.
DR   GenomeRNAi; 6474; -.
DR   Pharos; O60902; Tbio.
DR   PRO; PR:O60902; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; O60902; Protein.
DR   Bgee; ENSG00000168779; Expressed in buccal mucosa cell and 113 other cell types or tissues.
DR   ExpressionAtlas; O60902; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IBA:GO_Central.
DR   GO; GO:0060920; P:cardiac pacemaker cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0003213; P:cardiac right atrium morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl.
DR   GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR   GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
DR   GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR   GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IEA:Ensembl.
DR   GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:0060415; P:muscle tissue morphogenesis; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR   GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl.
DR   GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:0048743; P:positive regulation of skeletal muscle fiber development; IEA:Ensembl.
DR   GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR   GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR   GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; IEA:Ensembl.
DR   GO; GO:0032330; P:regulation of chondrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0002027; P:regulation of heart rate; ISS:BHF-UCL.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0060931; P:sinoatrial node cell development; ISS:BHF-UCL.
DR   GO; GO:0003163; P:sinoatrial node development; ISS:BHF-UCL.
DR   GO; GO:0003172; P:sinoatrial valve development; ISS:BHF-UCL.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR   GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR000047; HTH_motif.
DR   InterPro; IPR003654; OAR_dom.
DR   PANTHER; PTHR46255; SHORT STATURE HOMEOBOX; 1.
DR   PANTHER; PTHR46255:SF1; SHORT STATURE HOMEOBOX PROTEIN 2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF03826; OAR; 1.
DR   PRINTS; PR00031; HTHREPRESSR.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS50803; OAR; 1.
DR   Genevisible; O60902; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW   Nucleus; Reference proteome.
FT   CHAIN           1..331
FT                   /note="Short stature homeobox protein 2"
FT                   /id="PRO_0000049292"
FT   DNA_BIND        140..199
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          27..140
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           313..326
FT                   /note="OAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT   COMPBIAS        97..140
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         115
FT                   /note="E -> EGRRKPTKAEVQATLLLPGEAFRFL (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_024427"
FT   VAR_SEQ         235..246
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9466998,
FT                   ECO:0000303|PubMed:9482898"
FT                   /id="VSP_002288"
FT   CONFLICT        125
FT                   /note="E -> D (in Ref. 1; CAA05341)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        244
FT                   /note="S -> P (in Ref. 1; CAA05341)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312
FT                   /note="N -> D (in Ref. 1; CAA05341/CAA05342)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        325
FT                   /note="H -> L (in Ref. 3; AAC39663)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   331 AA;  34953 MW;  06402B3955682252 CRC64;
     MEELTAFVSK SFDQKVKEKK EAITYREVLE SGPLRGAKEP TGCTEAGRDD RSSPAVRAAG
     GGGGGGGGGG GGGGGGGVGG GGAGGGAGGG RSPVRELDMG AAERSREPGS PRLTEVSPEL
     KDRKEDAKGM EDEGQTKIKQ RRSRTNFTLE QLNELERLFD ETHYPDAFMR EELSQRLGLS
     EARVQVWFQN RRAKCRKQEN QLHKGVLIGA ASQFEACRVA PYVNVGALRM PFQQDSHCNV
     TPLSFQVQAQ LQLDSAVAHA HHHLHPHLAA HAPYMMFPAP PFGLPLATLA ADSASAASVV
     AAAAAAKTTS KNSSIADLRL KAKKHAAALG L
//