Q9NSI8 (SAMN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SAM domain-containing protein SAMSN-1

Alternative name(s):
Hematopoietic adaptor containing SH3 and SAM domains 1
Nash1
SAM domain, SH3 domain and nuclear localization signals protein 1
SH3-SAM adaptor protein

Gene names

Name:	SAMSN1
Synonyms:	HACS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negative regulator of B-cell activation. Down-regulates cell proliferation (in vitro). Promotes RAC1-dependent membrane ruffle formation and reorganization of the actin cytoskeleton. Regulates cell spreading and cell polarization. Stimulates HDAC1 activity. Regulates LYN activity by modulating its tyrosine phosphorylation By similarity. Ref.8
Subunit structure	Interacts with FASLG. Interacts with phosphotyrosine containing proteins. Interacts (via SH3 domain) with CTTN. Interacts (phosphorylated at Ser-23) with YWHAB, YWHAE, YWHAG, YWHAH, YWHAZ and SFN. Interacts directly with SAP30 and HDAC1. Identified in a complex with SAP30 and HDAC1 By similarity. Ref.9
Subcellular location	Nucleus. Cytoplasm By similarity. Cell projection › ruffle By similarity. Note: Shuttles between cytoplasm and nucleus. Colocalizes with the actin cytoskeleton and actin-rich membrane ruffles By similarity. Ref.7
Tissue specificity	Detected in peripheral blood B-cells (at protein level). Detected in spleen, liver and peripheral blood. Ref.7 Ref.8
Induction	Up-regulated in peripheral blood B-cells by IL4, IL13 and by CD40 stimulation. Ref.8
Sequence similarities	Contains 1 SAM (sterile alpha motif) domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of B cell activation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of adaptive immune response Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.7. Source: UniProtKB ruffle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	phosphotyrosine binding Inferred from direct assay Ref.8. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NSI8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NSI8-2)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     19-186: Missing.

Isoform 3 (identifier: Q9NSI8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MLKRKPSNVSEKEKHQKPK → MDLLHSW

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 373

373

SAM domain-containing protein SAMSN-1

PRO_0000097574

Regions

Domain

166 – 222

57

SH3

Domain

241 – 305

65

SAM

Motif

20 – 25

6

Important for interaction with 14-3-3 proteins By similarity

Amino acid modifications

Modified residue

90

1

Phosphoserine By similarity

Modified residue

160

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

1 – 19

19

MLKRK…HQKPK → MDLLHSW in isoform 3.

VSP_008120

Alternative sequence

19 – 186

168

Missing in isoform 2.

VSP_008119

Natural variant

63

1

G → A.
Corresponds to variant rs34607574 [ dbSNP | Ensembl ].

VAR_051331

Experimental info

Sequence conflict

105

1

R → G in BAG54155. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

373

Helix Strand Turn

Details...

Beta strand

167 – 170

4

Beta strand

181 – 183

3

Beta strand

191 – 196

6

Beta strand

203 – 207

5

Beta strand

210 – 214

5

Helix

216 – 218

3

Beta strand

219 – 221

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 964B852ADBA2D777	FASTA	373	41,708
	10 20 30 40 50 60 MLKRKPSNVS EKEKHQKPKR SSSFGNFDRF RNNSLSKPDD STEAHEGDPT NGSGEQSKTS 70 80 90 100 110 120 NNGGGLGKKM RAISWTMKKK VGKKYIKALS EEKDEEDGEN AHPYRNSDPV IGTHTEKVSL 130 140 150 160 170 180 KASDSMDSLY SGQSSSSGIT SCSDGTSNRD SFRLDDDGPY SGPFCGRARV HTDFTPSPYD 190 200 210 220 230 240 TDSLKIKKGD IIDIICKTPM GMWTGMLNNK VGNFKFIYVD VISEEEAAPK KIKANRRSNS 250 260 270 280 290 300 KKSKTLQEFL ERIHLQEYTS TLLLNGYETL EDLKDIKESH LIELNIENPD DRRRLLSAAE 310 320 330 340 350 360 NFLEEEIIQE QENEPEPLSL SSDISLNKSQ LDDCPRDSGC YISSGNSDNG KEDLESENLS 370 DMVHKIIITE PSD
	Isoform 2 (b) [UniParc]. Checksum: 362B2FB490B972BE	FASTA	205	23,466
	10 20 30 40 50 60 MLKRKPSNVS EKEKHQKPKK GDIIDIICKT PMGMWTGMLN NKVGNFKFIY VDVISEEEAA 70 80 90 100 110 120 PKKIKANRRS NSKKSKTLQE FLERIHLQEY TSTLLLNGYE TLEDLKDIKE SHLIELNIEN 130 140 150 160 170 180 PDDRRRLLSA AENFLEEEII QEQENEPEPL SLSSDISLNK SQLDDCPRDS GCYISSGNSD 190 200 NGKEDLESEN LSDMVHKIII TEPSD
	Isoform 3 [UniParc]. Checksum: 75BEEFB08EE51C3D	FASTA	361	40,316
	10 20 30 40 50 60 MDLLHSWRSS SFGNFDRFRN NSLSKPDDST EAHEGDPTNG SGEQSKTSNN GGGLGKKMRA 70 80 90 100 110 120 ISWTMKKKVG KKYIKALSEE KDEEDGENAH PYRNSDPVIG THTEKVSLKA SDSMDSLYSG 130 140 150 160 170 180 QSSSSGITSC SDGTSNRDSF RLDDDGPYSG PFCGRARVHT DFTPSPYDTD SLKIKKGDII 190 200 210 220 230 240 DIICKTPMGM WTGMLNNKVG NFKFIYVDVI SEEEAAPKKI KANRRSNSKK SKTLQEFLER 250 260 270 280 290 300 IHLQEYTSTL LLNGYETLED LKDIKESHLI ELNIENPDDR RRLLSAAENF LEEEIIQEQE 310 320 330 340 350 360 NEPEPLSLSS DISLNKSQLD DCPRDSGCYI SSGNSDNGKE DLESENLSDM VHKIIITEPS D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene, located on human chromosome 21q11." Groet J., Blechschmidt K., Yaspo M., Rosenthal A., Nizetic D. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells." Claudio J.O., Zhu Y.X., Benn S.J., Shukla A.H., McGlade C.J., Falcioni N., Stewart A.K. Oncogene 20:5373-5377(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[3]	"Transcriptional map of the juxtacentromeric region of human chromosome 21." Brun M.-E., Ruault M., Roizes G., De Sario A. Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thymus.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph.
[7]	"Identification of Nash1, a novel protein containing a nuclear localization signal, a sterile alpha motif, and an SH3 domain preferentially expressed in mast cells." Uchida T., Nakao A., Nakano N., Kuramasu A., Saito H., Okumura K., Ra C., Ogawa H. Biochem. Biophys. Res. Commun. 288:137-141(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades." Zhu Y.X., Benn S., Li Z.H., Wei E., Masih-Khan E., Trieu Y., Bali M., McGlade C.J., Claudio J.O., Stewart A.K. J. Exp. Med. 200:737-747(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[9]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"NMR solution structure of the HACS1 SH3 domain." Donaldson L. Submitted (FEB-2010) to the PDB data bank Cited for: STRUCTURE BY NMR OF 162-224.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF222927 mRNA. Translation: AAG23355.1.
AF218085 mRNA. Translation: AAK07746.1.
AF519621 mRNA. Translation: AAM75349.1.
AK125144 mRNA. Translation: BAG54155.1.
AL163206 Genomic DNA. Translation: CAB90391.1.
BC029112 mRNA. Translation: AAH29112.1.

IPI

IPI00168831.
IPI00339277.
IPI00854619.

RefSeq

NP_001243299.1. NM_001256370.1.
NP_071419.3. NM_022136.4.

UniGene

Hs.473341.
Hs.719474.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KEA	NMR	-	A	162-224	[»]

ProteinModelPortal

Q9NSI8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NSI8. 2 interactions.

STRING

9606.ENSP00000383411.

PTM databases

PhosphoSite

Q9NSI8.

Polymorphism databases

DMDM

12230638.

Proteomic databases

PaxDb

Q9NSI8.

PRIDE

Q9NSI8.

Protocols and materials databases

DNASU

64092.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000400564; ENSP00000383409; ENSG00000155307.
ENST00000400566; ENSP00000383411; ENSG00000155307.

GeneID

64092.

KEGG

hsa:64092.

UCSC

uc002yju.1. human.
uc010gky.1. human.

Organism-specific databases

CTD

64092.

GeneCards

GC21M015857.

H-InvDB

HIX0016027.

HGNC

HGNC:10528. SAMSN1.

HPA

HPA010645.
HPA017055.

MIM

607978. gene.

neXtProt

NX_Q9NSI8.

PharmGKB

PA34939.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG293245.

HOGENOM

HOG000049202.

HOVERGEN

HBG000461.

Gene expression databases

ArrayExpress

Q9NSI8.

Bgee

Q9NSI8.

CleanEx

HS_SAMSN1.

Genevestigator

Q9NSI8.

GermOnline

ENSG00000155307. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.

InterPro

IPR021090. rSAM/SH3_domain-containing.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF07647. SAM_2. 1 hit.
PF07653. SH3_2. 1 hit.
PF12485. SLY. 1 hit.
[Graphical view]

SMART

SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF47769. SAM_homology. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NSI8.

GenomeRNAi

64092.

NextBio

65904.

SOURCE

Search...

Entry information

Entry name

SAMN1_HUMAN

Accession

Primary (citable) accession number: Q9NSI8
Secondary accession number(s): B3KWJ3, Q8NFF7, Q9C041

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.