SHOX2_HUMAN
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 03-AUG-2022, entry version 190.
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; 7.
DR IntAct; O60902; 16.
DR STRING; 9606.ENSP00000374240; -.
DR iPTMnet; O60902; -.
DR PhosphoSitePlus; O60902; -.
DR BioMuta; SHOX2; -.
DR MassIVE; O60902; -.
DR PaxDb; O60902; -.
DR PeptideAtlas; O60902; -.
DR PRIDE; O60902; -.
DR ProteomicsDB; 49660; -. [O60902-1]
DR ProteomicsDB; 49661; -. [O60902-2]
DR ProteomicsDB; 49662; -. [O60902-3]
DR Antibodypedia; 18427; 153 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 CTD; 6474; -.
DR DisGeNET; 6474; -.
DR GeneCards; SHOX2; -.
DR HGNC; HGNC:10854; SHOX2.
DR HPA; ENSG00000168779; Tissue enriched (brain).
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; 1367513at2759; -.
DR PhylomeDB; O60902; -.
DR TreeFam; TF350757; -.
DR PathwayCommons; O60902; -.
DR SignaLink; O60902; -.
DR BioGRID-ORCS; 6474; 18 hits in 1098 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 111 other tissues.
DR ExpressionAtlas; O60902; baseline and differential.
DR Genevisible; O60902; HS.
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 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 Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
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
