ID SAMN1_HUMAN Reviewed; 373 AA.
AC Q9NSI8; B3KWJ3; F8WAA1; Q8NFF7; Q9C041;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 186.
DE RecName: Full=SAM domain-containing protein SAMSN-1;
DE AltName: Full=Hematopoietic adaptor containing SH3 and SAM domains 1;
DE AltName: Full=Nash1;
DE AltName: Full=SAM domain, SH3 domain and nuclear localization signals protein 1;
DE AltName: Full=SH3-SAM adaptor protein;
GN Name=SAMSN1; Synonyms=HACS1;
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] (ISOFORM 1).
RA Groet J., Blechschmidt K., Yaspo M., Rosenthal A., Nizetic D.;
RT "A novel gene, located on human chromosome 21q11.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=11536050; DOI=10.1038/sj.onc.1204698;
RA Claudio J.O., Zhu Y.X., Benn S.J., Shukla A.H., McGlade C.J., Falcioni N.,
RA Stewart A.K.;
RT "HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in
RT normal and malignant hematopoietic cells.";
RL Oncogene 20:5373-5377(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RA Brun M.-E., Ruault M., Roizes G., De Sario A.;
RT "Transcriptional map of the juxtacentromeric region of human chromosome
RT 21.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11594764; DOI=10.1006/bbrc.2001.5722;
RA Uchida T., Nakao A., Nakano N., Kuramasu A., Saito H., Okumura K., Ra C.,
RA Ogawa H.;
RT "Identification of Nash1, a novel protein containing a nuclear localization
RT signal, a sterile alpha motif, and an SH3 domain preferentially expressed
RT in mast cells.";
RL Biochem. Biophys. Res. Commun. 288:137-141(2001).
RN [8]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=15381729; DOI=10.1084/jem.20031816;
RA Zhu Y.X., Benn S., Li Z.H., Wei E., Masih-Khan E., Trieu Y., Bali M.,
RA McGlade C.J., Claudio J.O., Stewart A.K.;
RT "The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling
RT cascades.";
RL J. Exp. Med. 200:737-747(2004).
RN [9]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-34; SER-74; THR-76;
RP SER-90 AND SER-119, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=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 [12]
RP STRUCTURE BY NMR OF 162-224.
RA Donaldson L.;
RT "NMR solution structure of the HACS1 SH3 domain.";
RL Submitted (FEB-2010) to the PDB data bank.
CC -!- FUNCTION: Negative regulator of B-cell activation. Down-regulates cell
CC proliferation (in vitro). Promotes RAC1-dependent membrane ruffle
CC formation and reorganization of the actin cytoskeleton. Regulates cell
CC spreading and cell polarization. Stimulates HDAC1 activity. Regulates
CC LYN activity by modulating its tyrosine phosphorylation (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:15381729}.
CC -!- SUBUNIT: Interacts with FASLG. Interacts with phosphotyrosine
CC containing proteins. Interacts (via SH3 domain) with CTTN. Interacts
CC (phosphorylated at Ser-23) with YWHAB, YWHAE, YWHAG, YWHAH, YWHAZ and
CC SFN. Interacts directly with SAP30 and HDAC1. Identified in a complex
CC with SAP30 and HDAC1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11594764}. Cytoplasm
CC {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Note=Shuttles
CC between cytoplasm and nucleus. Colocalizes with the actin cytoskeleton
CC and actin-rich membrane ruffles (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NSI8-1; Sequence=Displayed;
CC Name=2; Synonyms=b;
CC IsoId=Q9NSI8-2; Sequence=VSP_008119;
CC Name=3;
CC IsoId=Q9NSI8-3; Sequence=VSP_008120;
CC -!- TISSUE SPECIFICITY: Detected in peripheral blood B-cells (at protein
CC level). Detected in spleen, liver and peripheral blood.
CC {ECO:0000269|PubMed:11594764, ECO:0000269|PubMed:15381729}.
CC -!- INDUCTION: Up-regulated in peripheral blood B-cells by IL4, IL13 and by
CC CD40 stimulation. {ECO:0000269|PubMed:15381729}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK07746.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF222927; AAG23355.1; -; mRNA.
DR EMBL; AF218085; AAK07746.1; ALT_INIT; mRNA.
DR EMBL; AF519621; AAM75349.1; -; mRNA.
DR EMBL; AK125144; BAG54155.1; -; mRNA.
DR EMBL; AL163206; CAB90391.1; -; Genomic_DNA.
DR EMBL; AF165138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029112; AAH29112.1; -; mRNA.
DR CCDS; CCDS42906.1; -. [Q9NSI8-1]
DR CCDS; CCDS58786.1; -. [Q9NSI8-3]
DR RefSeq; NP_001243299.1; NM_001256370.1. [Q9NSI8-3]
DR RefSeq; NP_001273452.1; NM_001286523.1.
DR RefSeq; NP_071419.3; NM_022136.4. [Q9NSI8-1]
DR PDB; 6UZJ; NMR; -; A=151-224.
DR PDBsum; 6UZJ; -.
DR AlphaFoldDB; Q9NSI8; -.
DR BMRB; Q9NSI8; -.
DR SMR; Q9NSI8; -.
DR BioGRID; 122054; 16.
DR IntAct; Q9NSI8; 2.
DR STRING; 9606.ENSP00000285670; -.
DR iPTMnet; Q9NSI8; -.
DR PhosphoSitePlus; Q9NSI8; -.
DR BioMuta; SAMSN1; -.
DR DMDM; 12230638; -.
DR EPD; Q9NSI8; -.
DR jPOST; Q9NSI8; -.
DR MassIVE; Q9NSI8; -.
DR MaxQB; Q9NSI8; -.
DR PaxDb; 9606-ENSP00000285670; -.
DR PeptideAtlas; Q9NSI8; -.
DR ProteomicsDB; 30460; -.
DR ProteomicsDB; 82558; -. [Q9NSI8-1]
DR ProteomicsDB; 82559; -. [Q9NSI8-2]
DR ProteomicsDB; 82560; -. [Q9NSI8-3]
DR Pumba; Q9NSI8; -.
DR Antibodypedia; 2139; 322 antibodies from 31 providers.
DR DNASU; 64092; -.
DR Ensembl; ENST00000285670.7; ENSP00000285670.2; ENSG00000155307.19. [Q9NSI8-3]
DR Ensembl; ENST00000400564.5; ENSP00000383409.1; ENSG00000155307.19. [Q9NSI8-2]
DR Ensembl; ENST00000400566.6; ENSP00000383411.2; ENSG00000155307.19. [Q9NSI8-1]
DR GeneID; 64092; -.
DR KEGG; hsa:64092; -.
DR MANE-Select; ENST00000400566.6; ENSP00000383411.2; NM_022136.5; NP_071419.3.
DR UCSC; uc002yju.3; human. [Q9NSI8-1]
DR AGR; HGNC:10528; -.
DR CTD; 64092; -.
DR DisGeNET; 64092; -.
DR GeneCards; SAMSN1; -.
DR HGNC; HGNC:10528; SAMSN1.
DR HPA; ENSG00000155307; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 607978; gene.
DR neXtProt; NX_Q9NSI8; -.
DR OpenTargets; ENSG00000155307; -.
DR PharmGKB; PA34939; -.
DR VEuPathDB; HostDB:ENSG00000155307; -.
DR eggNOG; KOG4384; Eukaryota.
DR GeneTree; ENSGT00940000157806; -.
DR HOGENOM; CLU_027875_1_0_1; -.
DR InParanoid; Q9NSI8; -.
DR OMA; TDMDLPH; -.
DR OrthoDB; 5403637at2759; -.
DR PhylomeDB; Q9NSI8; -.
DR TreeFam; TF350709; -.
DR PathwayCommons; Q9NSI8; -.
DR SignaLink; Q9NSI8; -.
DR BioGRID-ORCS; 64092; 11 hits in 1163 CRISPR screens.
DR ChiTaRS; SAMSN1; human.
DR EvolutionaryTrace; Q9NSI8; -.
DR GenomeRNAi; 64092; -.
DR Pharos; Q9NSI8; Tbio.
DR PRO; PR:Q9NSI8; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q9NSI8; Protein.
DR Bgee; ENSG00000155307; Expressed in bone marrow and 175 other cell types or tissues.
DR ExpressionAtlas; Q9NSI8; baseline and differential.
DR Genevisible; Q9NSI8; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0002820; P:negative regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0050869; P:negative regulation of B cell activation; ISS:UniProtKB.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR CDD; cd09561; SAM_SAMSN1; 1.
DR Gene3D; 2.30.30.40; SH3 Domains; 1.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR037623; SAMSN1_SAM.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR021090; SPIDER.
DR PANTHER; PTHR12301:SF4; SAM DOMAIN-CONTAINING PROTEIN SAMSN-1; 1.
DR PANTHER; PTHR12301; SAM-DOMAIN, SH3 AND NUCLEAR LOCALIZATION SIGNALS PROTEIN RELATED; 1.
DR Pfam; PF07647; SAM_2; 1.
DR Pfam; PF07653; SH3_2; 1.
DR Pfam; PF12485; SLY; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR SUPFAM; SSF50044; SH3-domain; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..373
FT /note="SAM domain-containing protein SAMSN-1"
FT /id="PRO_0000097574"
FT DOMAIN 163..224
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 241..305
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 20..25
FT /note="Important for interaction with 14-3-3 proteins"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 76
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 160
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P57725"
FT VAR_SEQ 1..19
FT /note="MLKRKPSNVSEKEKHQKPK -> MEIRLDTLSASLGRSSTLNNCNLEDKLAW
FT YEGEAYMWHHWKPFPENPLWTCLDFQIAQVGPWDHCSSCIRHTRLKSSCSDMDLLHSW
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11536050"
FT /id="VSP_008120"
FT VAR_SEQ 19..186
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_008119"
FT VARIANT 63
FT /note="G -> A (in dbSNP:rs34607574)"
FT /id="VAR_051331"
FT CONFLICT 105
FT /note="R -> G (in Ref. 4; BAG54155)"
FT /evidence="ECO:0000305"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:6UZJ"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:6UZJ"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6UZJ"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:6UZJ"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:6UZJ"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:6UZJ"
FT CONFLICT Q9NSI8-3:20
FT /note="N -> D (in Ref. 2; AAK07746)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9NSI8-3:64
FT /note="H -> Y (in Ref. 2; AAK07746)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 373 AA; 41708 MW; 964B852ADBA2D777 CRC64;
MLKRKPSNVS EKEKHQKPKR SSSFGNFDRF RNNSLSKPDD STEAHEGDPT NGSGEQSKTS
NNGGGLGKKM RAISWTMKKK VGKKYIKALS EEKDEEDGEN AHPYRNSDPV IGTHTEKVSL
KASDSMDSLY SGQSSSSGIT SCSDGTSNRD SFRLDDDGPY SGPFCGRARV HTDFTPSPYD
TDSLKIKKGD IIDIICKTPM GMWTGMLNNK VGNFKFIYVD VISEEEAAPK KIKANRRSNS
KKSKTLQEFL ERIHLQEYTS TLLLNGYETL EDLKDIKESH LIELNIENPD DRRRLLSAAE
NFLEEEIIQE QENEPEPLSL SSDISLNKSQ LDDCPRDSGC YISSGNSDNG KEDLESENLS
DMVHKIIITE PSD
//
