SASH1_HUMAN
ID SASH1_HUMAN Reviewed; 1247 AA.
AC O94885; Q5TGN5; Q8TAI0; Q9H7R7;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=SAM and SH3 domain-containing protein 1;
DE AltName: Full=Proline-glutamate repeat-containing protein;
GN Name=SASH1; Synonyms=KIAA0790, PEPE1;
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], TISSUE SPECIFICITY, AND VARIANT ARG-884.
RX PubMed=12771949; DOI=10.1038/sj.onc.1206474;
RA Zeller C., Hinzmann B., Seitz S., Prokoph H., Burkhardt-Goettges E.,
RA Fischer J., Jandrig B., Estevez-Schwarz L., Rosenthal A., Scherneck S.;
RT "SASH1 - a candidate tumour suppressor gene on chromosome 6q24.3 is
RT downregulated in breast cancer.";
RL Oncogene 22:2972-2983(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT ARG-884.
RA Rice A.J., Shpak M., Fountain J.W., Dubeau L.;
RT "PEPE1 is a candidate tumor suppressor gene on chromosome 6q24.3 involved
RT in melanoma and ovarian cancer.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-884.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 181-1247.
RC TISSUE=Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1006-1247.
RC TISSUE=Placenta;
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP FUNCTION, INVOLVEMENT IN DUH1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP INTERACTION WITH GNAS AND IQGAP1, VARIANTS DUH1 LYS-509; PRO-515 AND
RP ASP-551, AND CHARACTERIZATION OF VARIANTS DUH1 LYS-509; PRO-515 AND
RP ASP-551.
RX PubMed=23333244; DOI=10.1016/j.cellsig.2012.12.025;
RA Zhou D., Wei Z., Deng S., Wang T., Zai M., Wang H., Guo L., Zhang J.,
RA Zhong H., He L., Xing Q.;
RT "SASH1 regulates melanocyte transepithelial migration through a novel
RT Galphas-SASH1-IQGAP1-E-cadherin dependent pathway.";
RL Cell. Signal. 25:1526-1538(2013).
RN [12]
RP FUNCTION, INTERACTION WITH TRAF6; MAP3K7; CHUK AND IKBKB, AND MUTAGENESIS
RP OF 852-ASP--PRO-860.
RX PubMed=23776175; DOI=10.4049/jimmunol.1200583;
RA Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J.,
RA Fuller M.E., Blonder J., Veenstra T.D., Karsan A.;
RT "SASH1 is a scaffold molecule in endothelial TLR4 signaling.";
RL J. Immunol. 191:892-901(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407; SER-614 AND THR-858, AND
RP IDENTIFICATION BY 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).
RN [15]
RP FUNCTION, INVOLVEMENT IN CAPOK, VARIANT CAPOK LYS-617, AND CHARACTERIZATION
RP OF VARIANT CAPOK LYS-617.
RX PubMed=25315659; DOI=10.1038/ejhg.2014.213;
RA Courcet J.B., Elalaoui S.C., Duplomb L., Tajir M., Riviere J.B.,
RA Thevenon J., Gigot N., Marle N., Aral B., Duffourd Y., Sarasin A., Naim V.,
RA Courcet-Degrolard E., Aubriot-Lorton M.H., Martin L., Abrid J.E.,
RA Thauvin C., Sefiani A., Vabres P., Faivre L.;
RT "Autosomal-recessive SASH1 variants associated with a new genodermatosis
RT with pigmentation defects, palmoplantar keratoderma and skin carcinoma.";
RL Eur. J. Hum. Genet. 23:957-962(2015).
RN [16]
RP TISSUE SPECIFICITY, INVOLVEMENT IN DUH1, AND VARIANT DUH1 ASN-519.
RX PubMed=26203640; DOI=10.1038/jid.2015.292;
RA Shellman Y.G., Lambert K.A., Brauweiler A., Fain P., Spritz R.A.,
RA Martini M., Janssen K.P., Box N.F., Terzian T., Rewers M., Horvath A.,
RA Stratakis C.A., Robinson W.A., Robinson S.E., Norris D.A., Artinger K.B.,
RA Pacheco T.R.;
RT "SASH1 is involved in an autosomal dominant lentiginous phenotype.";
RL J. Invest. Dermatol. 135:3192-3194(2015).
RN [17]
RP STRUCTURE BY NMR OF 555-614 AND 1164-1247.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3 and SAM-domains from human SAM and SH3
RT domain-containing protein 1.";
RL Submitted (AUG-2007) to the PDB data bank.
RN [18]
RP VARIANT DUH1 ARG-513.
RX PubMed=27659786; DOI=10.1111/cge.12728;
RA Zhang J., Cheng R., Liang J., Ni C., Li M., Yao Z.;
RT "Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and
RT PTPN11): clinical and molecular discrimination.";
RL Clin. Genet. 90:372-377(2016).
RN [19]
RP VARIANT DUH1 ALA-507.
RX PubMed=27840890; DOI=10.2340/00015555-2575;
RA Wang J., Zhang J., Li X., Wang Z., Lei D., Wang G., Li J., Zhang S., Li Z.,
RA Li M.;
RT "A novel de novo mutation of the SASH1 gene in a chinese family with
RT multiple lentigines.";
RL Acta Derm. Venereol. 97:530-531(2017).
RN [20]
RP VARIANTS DUH1 LYS-509; PRO-515 AND ASP-551.
RX PubMed=27885802; DOI=10.1111/jcmm.13022;
RA Zhou D., Wei Z., Kuang Z., Luo H., Ma J., Zeng X., Wang K., Liu B.,
RA Gong F., Wang J., Lei S., Wang D., Zeng J., Wang T., He Y., Yuan Y.,
RA Dai H., He L., Xing Q.;
RT "A novel P53/POMC/Galphas/SASH1 autoregulatory feedback loop activates
RT mutated SASH1 to cause pathologic hyperpigmentation.";
RL J. Cell. Mol. Med. 21:802-815(2017).
RN [21]
RP VARIANTS DUH1 HIS-551 AND THR-595.
RX PubMed=29956681; DOI=10.4103/ijdvl.ijdvl_360_17;
RA Zhong W.L., Wang H.J., Lin Z.M., Yang Y.;
RT "Novel mutations in SASH1 associated with dyschromatosis universalis
RT hereditaria.";
RL Indian J. Dermatol. Venereol. Leprol. 85:440-440(2019).
CC -!- FUNCTION: Is a positive regulator of NF-kappa-B signaling downstream of
CC TLR4 activation. It acts as a scaffold molecule to assemble a molecular
CC complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby
CC facilitating NF-kappa-B signaling activation (PubMed:23776175).
CC Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved
CC in the regulation of cell mobility (PubMed:23333244, PubMed:23776175,
CC PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial
CC cell migration (PubMed:23776175). Is involved in the regulation of skin
CC pigmentation through the control of melanocyte migration in the
CC epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244,
CC ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}.
CC -!- SUBUNIT: Interacts with GNAS (PubMed:23333244). Interacts with IQGAP1
CC (PubMed:23333244). Interacts with TRAF6 (via C-terminus); the
CC interaction is LPS-dependent (PubMed:23776175). Interacts with MAP3K7,
CC CHUK and IKBKB (PubMed:23776175). {ECO:0000269|PubMed:23333244,
CC ECO:0000269|PubMed:23776175}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23333244}.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously, with highest levels in
CC lung, placenta, spleen and thymus. Down-regulated in the majority (74%)
CC of breast tumors in comparison with corresponding normal breast
CC epithelial tissues. Expressed in the epidermis, epidermal
CC keratinocytes, dermal fibroblasts and melanocytes (PubMed:23333244,
CC PubMed:26203640). {ECO:0000269|PubMed:12771949,
CC ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:26203640}.
CC -!- DISEASE: Dyschromatosis universalis hereditaria 1 (DUH1) [MIM:127500]:
CC A form of dyschromatosis universalis, an autosomal dominant pigmentary
CC genodermatosis characterized by a mixture of hyperpigmented and
CC hypopigmented macules distributed randomly over the body, that appear
CC in infancy or early childhood. The trunk and extremities are the
CC dominant sites of abnormal pigmentation. Facial lesions can be seen in
CC 50% of affected individuals, but involvement of palms and soles is
CC unusual. Abnormalities of hair and nails have also been reported.
CC Dyschromatosis universalis hereditaria may be associated with
CC abnormalities of dermal connective tissue, nerve tissue, or other
CC systemic complications. {ECO:0000269|PubMed:23333244,
CC ECO:0000269|PubMed:26203640, ECO:0000269|PubMed:27659786,
CC ECO:0000269|PubMed:27840890, ECO:0000269|PubMed:27885802,
CC ECO:0000269|PubMed:29956681}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cancer, alopecia, pigment dyscrasia, onychodystrophy, and
CC keratoderma (CAPOK) [MIM:618373]: An autosomal recessive genodermatosis
CC characterized by hypo- and hyperpigmented macular skin lesions,
CC progressive alopecia, palmoplantar keratoderma, dystrophic nails, teeth
CC abnormalities and a predisposition to squamous cell carcinoma.
CC {ECO:0000269|PubMed:25315659}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34510.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB14909.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ507735; CAD47811.1; -; mRNA.
DR EMBL; BN000088; CAD92036.1; -; mRNA.
DR EMBL; AY351979; AAQ55463.1; -; Genomic_DNA.
DR EMBL; AY351960; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351961; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351962; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351963; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351964; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351965; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351966; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351967; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351968; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351969; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351970; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351971; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351972; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351973; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351974; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351975; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351976; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351977; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AY351978; AAQ55463.1; JOINED; Genomic_DNA.
DR EMBL; AB018333; BAA34510.1; ALT_INIT; mRNA.
DR EMBL; AL513164; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL033378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK024403; BAB14909.1; ALT_INIT; mRNA.
DR EMBL; CH471051; EAW47815.1; -; Genomic_DNA.
DR EMBL; BC028303; AAH28303.1; -; mRNA.
DR CCDS; CCDS5212.1; -.
DR RefSeq; NP_056093.3; NM_015278.4.
DR PDB; 2DL0; NMR; -; A=1164-1247.
DR PDB; 2EBP; NMR; -; A=555-614.
DR PDBsum; 2DL0; -.
DR PDBsum; 2EBP; -.
DR AlphaFoldDB; O94885; -.
DR SMR; O94885; -.
DR BioGRID; 116916; 51.
DR IntAct; O94885; 20.
DR MINT; O94885; -.
DR STRING; 9606.ENSP00000356437; -.
DR iPTMnet; O94885; -.
DR PhosphoSitePlus; O94885; -.
DR BioMuta; SASH1; -.
DR EPD; O94885; -.
DR jPOST; O94885; -.
DR MassIVE; O94885; -.
DR MaxQB; O94885; -.
DR PaxDb; O94885; -.
DR PeptideAtlas; O94885; -.
DR PRIDE; O94885; -.
DR ProteomicsDB; 50522; -.
DR Antibodypedia; 33257; 236 antibodies from 23 providers.
DR DNASU; 23328; -.
DR Ensembl; ENST00000367467.8; ENSP00000356437.3; ENSG00000111961.19.
DR GeneID; 23328; -.
DR KEGG; hsa:23328; -.
DR MANE-Select; ENST00000367467.8; ENSP00000356437.3; NM_015278.5; NP_056093.3.
DR UCSC; uc003qme.2; human.
DR CTD; 23328; -.
DR DisGeNET; 23328; -.
DR GeneCards; SASH1; -.
DR HGNC; HGNC:19182; SASH1.
DR HPA; ENSG00000111961; Low tissue specificity.
DR MalaCards; SASH1; -.
DR MIM; 127500; phenotype.
DR MIM; 607955; gene.
DR MIM; 618373; phenotype.
DR neXtProt; NX_O94885; -.
DR OpenTargets; ENSG00000111961; -.
DR Orphanet; 231040; Familial generalized lentiginosis.
DR Orphanet; 447961; Pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome.
DR PharmGKB; PA134984521; -.
DR VEuPathDB; HostDB:ENSG00000111961; -.
DR eggNOG; KOG4384; Eukaryota.
DR GeneTree; ENSGT00940000156778; -.
DR HOGENOM; CLU_281404_0_0_1; -.
DR InParanoid; O94885; -.
DR OMA; VESWPRS; -.
DR OrthoDB; 949260at2759; -.
DR PhylomeDB; O94885; -.
DR TreeFam; TF350709; -.
DR PathwayCommons; O94885; -.
DR SignaLink; O94885; -.
DR BioGRID-ORCS; 23328; 8 hits in 1077 CRISPR screens.
DR ChiTaRS; SASH1; human.
DR EvolutionaryTrace; O94885; -.
DR GeneWiki; SASH1; -.
DR GenomeRNAi; 23328; -.
DR Pharos; O94885; Tbio.
DR PRO; PR:O94885; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O94885; protein.
DR Bgee; ENSG00000111961; Expressed in synovial joint and 213 other tissues.
DR ExpressionAtlas; O94885; baseline and differential.
DR Genevisible; O94885; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IMP:MGI.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:UniProtKB.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IDA:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IDA:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IMP:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0010632; P:regulation of epithelial cell migration; IMP:UniProtKB.
DR GO; GO:1902498; P:regulation of protein autoubiquitination; IDA:MGI.
DR GO; GO:1900044; P:regulation of protein K63-linked ubiquitination; IDA:MGI.
DR CDD; cd09559; SAM_SASH1_repeat1; 1.
DR CDD; cd09492; SAM_SASH1_repeat2; 1.
DR CDD; cd11967; SH3_SASH1; 1.
DR Gene3D; 1.10.150.50; -; 2.
DR InterPro; IPR021090; rSAM/SH3_domain-containing.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR037627; SASH1_SAM_repeat1.
DR InterPro; IPR037630; SASH1_SAM_repeat2.
DR InterPro; IPR035720; SASH1_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF07647; SAM_2; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF12485; SLY; 1.
DR SMART; SM00454; SAM; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SSF47769; 2.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disease variant; Hypotrichosis;
KW Palmoplantar keratoderma; Phosphoprotein; Reference proteome; Repeat;
KW SH3 domain; Tumor suppressor.
FT CHAIN 1..1247
FT /note="SAM and SH3 domain-containing protein 1"
FT /id="PRO_0000097597"
FT DOMAIN 554..615
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 633..697
FT /note="SAM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 1177..1241
FT /note="SAM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 316..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 616..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 846..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 852..860
FT /note="Required for interaction with TRAF6"
FT /evidence="ECO:0000269|PubMed:23776175"
FT REGION 903..946
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 971..1065
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..145
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 509..535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 536..553
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 868..884
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1030..1060
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59808"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 821
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59808"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59808"
FT MOD_RES 858
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 298
FT /note="P -> Q (in dbSNP:rs35078400)"
FT /id="VAR_031714"
FT VARIANT 507
FT /note="S -> A (in DUH1; dbSNP:rs1562489143)"
FT /evidence="ECO:0000269|PubMed:27840890"
FT /id="VAR_082102"
FT VARIANT 509
FT /note="E -> K (in DUH1; increased interaction with GNAS;
FT increased interaction with IQGAP1; increased protein
FT levels; increased protein stability; dbSNP:rs1562489156)"
FT /evidence="ECO:0000269|PubMed:23333244,
FT ECO:0000269|PubMed:27885802"
FT /id="VAR_082103"
FT VARIANT 513
FT /note="S -> R (in DUH1; unknown pathological significance;
FT dbSNP:rs1237876014)"
FT /evidence="ECO:0000269|PubMed:27659786"
FT /id="VAR_082104"
FT VARIANT 515
FT /note="L -> P (in DUH1; affects the regulation of cell
FT mobility resulting in increased melanocyte migration;
FT increased interaction with GNAS; increased interaction with
FT IQGAP1; increased protein levels; increased protein
FT stability; dbSNP:rs1562489224)"
FT /evidence="ECO:0000269|PubMed:23333244,
FT ECO:0000269|PubMed:27885802"
FT /id="VAR_082105"
FT VARIANT 519
FT /note="S -> N (in DUH1; dbSNP:rs1562489240)"
FT /evidence="ECO:0000269|PubMed:26203640"
FT /id="VAR_082106"
FT VARIANT 551
FT /note="Y -> D (in DUH1; affects the regulation of cell
FT mobility resulting in increased melanocyte migration;
FT increased interaction with GNAS; increased interaction with
FT IQGAP1; increased protein levels; increased protein
FT stability; dbSNP:rs1562490566)"
FT /evidence="ECO:0000269|PubMed:23333244,
FT ECO:0000269|PubMed:27885802"
FT /id="VAR_082107"
FT VARIANT 551
FT /note="Y -> H (in DUH1; dbSNP:rs1562490566)"
FT /evidence="ECO:0000269|PubMed:29956681"
FT /id="VAR_082108"
FT VARIANT 595
FT /note="M -> T (in DUH1; unknown pathological significance;
FT dbSNP:rs1562491501)"
FT /evidence="ECO:0000269|PubMed:29956681"
FT /id="VAR_082109"
FT VARIANT 617
FT /note="E -> K (in CAPOK; affects the regulation of cell
FT mobility; patient fibroblasts migrate better than control
FT fibroblasts; dbSNP:rs587781245)"
FT /evidence="ECO:0000269|PubMed:25315659"
FT /id="VAR_082110"
FT VARIANT 884
FT /note="Q -> R (in dbSNP:rs208696)"
FT /evidence="ECO:0000269|PubMed:12771949,
FT ECO:0000269|PubMed:9872452, ECO:0000269|Ref.2"
FT /id="VAR_031715"
FT MUTAGEN 852..860
FT /note="Missing: Abolishes interaction with TRAF6."
FT /evidence="ECO:0000269|PubMed:23776175"
FT CONFLICT 751
FT /note="T -> A (in Ref. 6; BAB14909)"
FT /evidence="ECO:0000305"
FT CONFLICT 1157
FT /note="H -> R (in Ref. 6; BAB14909)"
FT /evidence="ECO:0000305"
FT STRAND 556..561
FT /evidence="ECO:0007829|PDB:2EBP"
FT STRAND 582..587
FT /evidence="ECO:0007829|PDB:2EBP"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:2EBP"
FT STRAND 594..597
FT /evidence="ECO:0007829|PDB:2EBP"
FT STRAND 602..605
FT /evidence="ECO:0007829|PDB:2EBP"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:2EBP"
SQ SEQUENCE 1247 AA; 136653 MW; 48A806B3AE32E563 CRC64;
MEDAGAAGPG PEPEPEPEPE PEPAPEPEPE PKPGAGTSEA FSRLWTDVMG ILDGSLGNID
DLAQQYADYY NTCFSDVCER MEELRKRRVS QDLEVEKPDA SPTSLQLRSQ IEESLGFCSA
VSTPEVERKN PLHKSNSEDS SVGKGDWKKK NKYFWQNFRK NQKGIMRQTS KGEDVGYVAS
EITMSDEERI QLMMMVKEKM ITIEEALARL KEYEAQHRQS AALDPADWPD GSYPTFDGSS
NCNSREQSDD ETEESVKFKR LHKLVNSTRR VRKKLIRVEE MKKPSTEGGE EHVFENSPVL
DERSALYSGV HKKPLFFDGS PEKPPEDDSD SLTTSPSSSS LDTWGAGRKL VKTFSKGESR
GLIKPPKKMG TFFSYPEEEK AQKVSRSLTE GEMKKGLGSL SHGRTCSFGG FDLTNRSLHV
GSNNSDPMGK EGDFVYKEVI KSPTASRISL GKKVKSVKET MRKRMSKKYS SSVSEQDSGL
DGMPGSPPPS QPDPEHLDKP KLKAGGSVES LRSSLSGQSS MSGQTVSTTD SSTSNRESVK
SEDGDDEEPP YRGPFCGRAR VHTDFTPSPY DTDSLKLKKG DIIDIISKPP MGTWMGLLNN
KVGTFKFIYV DVLSEDEEKP KRPTRRRRKG RPPQPKSVED LLDRINLKEH MPTFLFNGYE
DLDTFKLLEE EDLDELNIRD PEHRAVLLTA VELLQEYDSN SDQSGSQEKL LVDSQGLSGC
SPRDSGCYES SENLENGKTR KASLLSAKSS TEPSLKSFSR NQLGNYPTLP LMKSGDALKQ
GQEEGRLGGG LAPDTSKSCD PPGVTGLNKN RRSLPVSICR SCETLEGPQT VDTWPRSHSL
DDLQVEPGAE QDVPTEVTEP PPQIVPEVPQ KTTASSTKAQ PLEQDSAVDN ALLLTQSKRF
SEPQKLTTKK LEGSIAASGR GLSPPQCLPR NYDAQPPGAK HGLARTPLEG HRKGHEFEGT
HHPLGTKEGV DAEQRMQPKI PSQPPPVPAK KSRERLANGL HPVPMGPSGA LPSPDAPCLP
VKRGSPASPT SPSDCPPALA PRPLSGQAPG SPPSTRPPPW LSELPENTSL QEHGVKLGPA
LTRKVSCARG VDLETLTENK LHAEGIDLTE EPYSDKHGRC GIPEALVQRY AEDLDQPERD
VAANMDQIRV KQLRKQHRMA IPSGGLTEIC RKPVSPGCIS SVSDWLISIG LPMYAGTLST
AGFSTLSQVP SLSHTCLQEA GITEERHIRK LLSAARLFKL PPGPEAM
