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Protein

Src-like-adapter

Gene

Sla

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins.3 Publications

Names & Taxonomyi

Protein namesi
Recommended name:
Src-like-adapter
Alternative name(s):
Src-like-adapter protein 1
Short name:
SLAP-1
Short name:
mSLAP
Gene namesi
Name:Sla
Synonyms:Slap, Slap1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:104295. Sla.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Endosome 1 Publication

  • Note: Colocalizes with endosomes.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Abolishes myristoylation and localization to endosomes. 1 Publication
Mutagenesisi73 – 731P → L: Slightly affects inhibitory function. Abolishes inhibitory function; when associated with E-111. 1 Publication
Mutagenesisi111 – 1111R → E: Abolishes localization to endosomes. Strongly affects inhibitory function. Abolishes inhibitory function; when associated with L-73. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 281280Src-like-adapterPRO_0000071947Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei258 – 2581PhosphoserineBy similarity
Modified residuei278 – 2781PhosphotyrosineCombined sources

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ60898.
MaxQBiQ60898.
PaxDbiQ60898.
PRIDEiQ60898.

PTM databases

iPTMnetiQ60898.
PhosphoSiteiQ60898.

Expressioni

Tissue specificityi

Predominantly expressed in lymphoid tissues. Highly expressed in spleen, thymus and lymph nodes. Weakly expressed in lung and brain. Expressed in T-cells and at low level in B-cells.1 Publication

Developmental stagei

Expressed during thymocyte maturation. Weakly expressed in CD4- CD8- thymocytes, strongly expressed in CD4+ CD8+ thymocytes, while expression decreases in more mature cells.1 Publication

Gene expression databases

BgeeiQ60898.
CleanExiMM_SLA.
ExpressionAtlasiQ60898. baseline and differential.
GenevisibleiQ60898. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with phosphorylated CBL, SYK and LAT. Homodimerization and interaction with phosphorylated CBL occurs via its C-terminal domain (By similarity). Interacts with PDGFRB and EPHA2. Interacts with phosphorylated proteins ZAP70; CD3Z; VAV1 and LCP2 via its SH2 domain.By similarity3 Publications

Protein-protein interaction databases

BioGridi203272. 3 interactions.
DIPiDIP-292N.
IntActiQ60898. 1 interaction.
STRINGi10090.ENSMUSP00000131865.

Structurei

3D structure databases

ProteinModelPortaliQ60898.
SMRiQ60898. Positions 9-176.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 8261SH3PROSITE-ProRule annotationAdd
BLAST
Domaini84 – 17592SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni190 – 28192SLA C-terminalAdd
BLAST

Domaini

The C-terminal domain is essential for the homodimerization and the interaction with CBL. While the interaction with CBL is apparently mediated via the hydrophobic region of this domain, the highly charged region is apparently required for the homodimerization (By similarity).By similarity

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiENOG410IFZ7. Eukaryota.
ENOG4111KT3. LUCA.
GeneTreeiENSGT00390000001681.
HOGENOMiHOG000234240.
HOVERGENiHBG054908.
InParanoidiQ60898.
OrthoDBiEOG7DVDBX.
PhylomeDBiQ60898.
TreeFamiTF354288.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q60898-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGNSMKSTSP PSERPLSSSE GLESDFLAVL TDYPSPDISP PIFRRGEKLR
60 70 80 90 100
VISDEGGWWK AISLSTGRES YIPGICVARV YHGWLFEGLG RDKAEELLQL
110 120 130 140 150
PDTKIGSFMI RESETKKGFY SLSVRHRQVK HYRIFRLPNN WYYISPRLTF
160 170 180 190 200
QCLEDLVTHY SEVADGLCCV LTTPCLAQNI PAPTSHPSPC TSPGSPVTLR
210 220 230 240 250
QKTFDWKRVS RLQEGSEGAE NPLRVDESLF SYGLRESIAS YLSLTGDDSS
260 270 280
SFDRKKKSLS LMYTGSKRKS SFFSAPQYFE D
Length:281
Mass (Da):31,681
Last modified:January 23, 2007 - v3
Checksum:iB347921656A74DA1
GO
Isoform 2 (identifier: Q60898-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MG → MLCRLRVPSTAQGEKEM

Show »
Length:296
Mass (Da):33,424
Checksum:i99F2DEEED7E9D19A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti162 – 1621Missing in BAC29896 (PubMed:16141072).Curated
Sequence conflicti179 – 1791N → S in BAC30988 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 22MG → MLCRLRVPSTAQGEKEM in isoform 2. 1 PublicationVSP_007239

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U29056 mRNA. Translation: AAA82756.1.
AJ131777 mRNA. Translation: CAB66139.1.
AY079449 Genomic DNA. Translation: AAL87537.1.
AY079450 Genomic DNA. Translation: AAL87538.1.
AK036167 mRNA. Translation: BAC29328.1.
AK037901 mRNA. Translation: BAC29896.1.
AK041565 mRNA. Translation: BAC30988.1.
BC032922 mRNA. Translation: AAH32922.1.
CCDSiCCDS27509.1. [Q60898-1]
PIRiA57152.
RefSeqiNP_001025012.1. NM_001029841.4.
NP_033218.1. NM_009192.3. [Q60898-1]
XP_011243832.1. XM_011245530.1. [Q60898-1]
UniGeneiMm.7601.

Genome annotation databases

EnsembliENSMUST00000100572; ENSMUSP00000098138; ENSMUSG00000022372. [Q60898-1]
ENSMUST00000164163; ENSMUSP00000127901; ENSMUSG00000022372. [Q60898-1]
ENSMUST00000168589; ENSMUSP00000130222; ENSMUSG00000022372. [Q60898-1]
GeneIDi20491.
KEGGimmu:20491.
UCSCiuc007war.2. mouse. [Q60898-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U29056 mRNA. Translation: AAA82756.1.
AJ131777 mRNA. Translation: CAB66139.1.
AY079449 Genomic DNA. Translation: AAL87537.1.
AY079450 Genomic DNA. Translation: AAL87538.1.
AK036167 mRNA. Translation: BAC29328.1.
AK037901 mRNA. Translation: BAC29896.1.
AK041565 mRNA. Translation: BAC30988.1.
BC032922 mRNA. Translation: AAH32922.1.
CCDSiCCDS27509.1. [Q60898-1]
PIRiA57152.
RefSeqiNP_001025012.1. NM_001029841.4.
NP_033218.1. NM_009192.3. [Q60898-1]
XP_011243832.1. XM_011245530.1. [Q60898-1]
UniGeneiMm.7601.

3D structure databases

ProteinModelPortaliQ60898.
SMRiQ60898. Positions 9-176.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203272. 3 interactions.
DIPiDIP-292N.
IntActiQ60898. 1 interaction.
STRINGi10090.ENSMUSP00000131865.

PTM databases

iPTMnetiQ60898.
PhosphoSiteiQ60898.

Proteomic databases

EPDiQ60898.
MaxQBiQ60898.
PaxDbiQ60898.
PRIDEiQ60898.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000100572; ENSMUSP00000098138; ENSMUSG00000022372. [Q60898-1]
ENSMUST00000164163; ENSMUSP00000127901; ENSMUSG00000022372. [Q60898-1]
ENSMUST00000168589; ENSMUSP00000130222; ENSMUSG00000022372. [Q60898-1]
GeneIDi20491.
KEGGimmu:20491.
UCSCiuc007war.2. mouse. [Q60898-1]

Organism-specific databases

CTDi6503.
MGIiMGI:104295. Sla.

Phylogenomic databases

eggNOGiENOG410IFZ7. Eukaryota.
ENOG4111KT3. LUCA.
GeneTreeiENSGT00390000001681.
HOGENOMiHOG000234240.
HOVERGENiHBG054908.
InParanoidiQ60898.
OrthoDBiEOG7DVDBX.
PhylomeDBiQ60898.
TreeFamiTF354288.

Miscellaneous databases

NextBioi298627.
PROiQ60898.
SOURCEiSearch...

Gene expression databases

BgeeiQ60898.
CleanExiMM_SLA.
ExpressionAtlasiQ60898. baseline and differential.
GenevisibleiQ60898. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase."
    Pandey A., Duan H., Dixit V.M.
    J. Biol. Chem. 270:19201-19204(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH EPHA2.
    Tissue: Embryonic brain.
  2. "Differential gene expression in CD3epsilon- and RAG1-deficient thymuses: definition of a set of genes potentially involved in thymocyte maturation."
    Carrier A., Nguyen C., Victorero G., Granjeaud S., Rocha D., Bernard K., Miazek A., Ferrier P., Malissen M., Naquet P., Malissen B., Jordan B.R.
    Immunogenetics 50:255-270(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "High-throughput sequence identification of gene coding variants within alcohol-related QTLs."
    Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.
    Mamm. Genome 12:657-663(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    Strain: ILS and ISS.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Cerebellum and Thymus.
  5. "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: Mammary gland.
  6. "Src-like adaptor protein (Slap) is a negative regulator of mitogenesis."
    Roche S., Alonso G., Kazlauskas A., Dixit V.M., Courtneidge S.A., Pandey A.
    Curr. Biol. 8:975-978(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PDGFRB.
  7. "Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling."
    Sosinowski T., Pandey A., Dixit V.M., Weiss A.
    J. Exp. Med. 191:463-474(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, FUNCTION, INTERACTION WITH ZAP70; CD3Z; VAV1 AND LCP2, MUTAGENESIS OF PRO-73 AND ARG-111.
  8. "Slap negatively regulates Src mitogenic function but does not revert Src-induced cell morphology changes."
    Manes G., Bello P., Roche S.
    Mol. Cell. Biol. 20:3396-3406(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2.
  9. "The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection."
    Sosinowski T., Killeen N., Weiss A.
    Immunity 15:457-466(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  10. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-278, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Lung and Spleen.

Entry informationi

Entry nameiSLAP1_MOUSE
AccessioniPrimary (citable) accession number: Q60898
Secondary accession number(s): Q8C9Q8
, Q8CAT0, Q8CBE9, Q8QZX8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: January 23, 2007
Last modified: March 16, 2016
This is version 132 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

SLA deficient mice show a strong up-regulation of TCR and CD5 at the CD4+ CD8+ stage, and an enhanced positive selection in T-cells.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.