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Q13239 (SLAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Src-like-adapter
Alternative name(s):
Src-like-adapter protein 1
Short name=SLAP-1
Short name=hSLAP
Gene names
Name:SLA
Synonyms:SLAP, SLAP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length276 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.11

Subunit structure

Interacts with EPHA2, VAV1, LCP2 and PDGFRB By similarity. Homodimer. Homodimerization and interaction with phosphorylated CBL occurs via its C-terminal domain. Interacts with phosphorylated proteins ZAP70, CD3Z, SYK and LAT via its SH2 domain. Ref.11

Subcellular location

Cytoplasm By similarity. Endosome By similarity. Note: Colocalizes with endosomes By similarity.

Tissue specificity

Expressed in lung and fetal brain. Weakly expressed in heart, adult brain, placenta, liver, skeletal muscle, kidney and pancreas. Ref.3

Induction

By all-trans retinoic acid (ATRA). Induction is indirect and is mediated through other proteins. Ref.2

Domain

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.

Sequence similarities

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Sequence caution

The sequence AAH07042.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG35478.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDGFRBP096194EBI-726214,EBI-641237

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13239-1)

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: Q13239-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q13239-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLHRLWASPAAPGKKKEM
Note: No experimental confirmation available.
Isoform 4 (identifier: Q13239-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLHRLWASPAAPGKKKEM
     118-161: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q13239-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLSKLGHSPLGGLRARLTFPVCLLYHRLWASPAAPGKKKEM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 276275Src-like-adapter
PRO_0000071946

Regions

Domain22 – 8261SH3
Domain84 – 17592SH2
Region212 – 27665SLA C-terminal

Amino acid modifications

Modified residue2731Phosphotyrosine By similarity
Lipidation21N-myristoyl glycine By similarity

Natural variations

Alternative sequence1 – 108108Missing in isoform 2.
VSP_055122
Alternative sequence11M → MLHRLWASPAAPGKKKEM in isoform 3 and isoform 4.
VSP_055123
Alternative sequence11M → MLSKLGHSPLGGLRARLTFP VCLLYHRLWASPAAPGKKKE M in isoform 5.
VSP_055124
Alternative sequence118 – 16144Missing in isoform 4.
VSP_055125
Natural variant151P → T.
Corresponds to variant rs4486183 [ dbSNP | Ensembl ].
VAR_061706

Experimental info

Mutagenesis1111R → K: Strongly reduces interaction with ZAP70, CD3Z, SYK and LAT. Ref.11
Mutagenesis2181L → S: Abolishes interaction with CBL. Does not affect dimerization; when associated with S-224 and S-229. Ref.11
Mutagenesis2241L → S: Abolishes interaction with CBL. Does not affect dimerization; when associated with S-218 and S-229. Ref.11
Mutagenesis2291L → S: Abolishes interaction with CBL. Does not affect dimerization; when associated with S-218 and S-224. Ref.11
Mutagenesis237 – 2393LSL → QSQ: Abolishes interaction with CBL. Slightly affects dimerization. Ref.11
Sequence conflict711Y → D in CAB53536. Ref.10

Secondary structure

................ 276
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: B0FCC7D7B2ECA378

FASTA27631,156
        10         20         30         40         50         60 
MGNSMKSTPA PAERPLPNPE GLDSDFLAVL SDYPSPDISP PIFRRGEKLR VISDEGGWWK 

        70         80         90        100        110        120 
AISLSTGRES YIPGICVARV YHGWLFEGLG RDKAEELLQL PDTKVGSFMI RESETKKGFY 

       130        140        150        160        170        180 
SLSVRHRQVK HYRIFRLPNN WYYISPRLTF QCLEDLVNHY SEVADGLCCV LTTPCLTQST 

       190        200        210        220        230        240 
AAPAVRASSS PVTLRQKTVD WRRVSRLQED PEGTENPLGV DESLFSYGLR ESIASYLSLT 

       250        260        270 
SEDNTSFDRK KKSISLMYGG SKRKSSFFSS PPYFED 

« Hide

Isoform 2 [UniParc].

Checksum: 0BC12A843F32869D
Show »

FASTA16819,285
Isoform 3 [UniParc].

Checksum: 6721FE5A9562C6DC
Show »

FASTA29333,059
Isoform 4 [UniParc].

Checksum: D072FF483DAA2778
Show »

FASTA24927,558
Isoform 5 [UniParc].

Checksum: 93C3155474168A96
Show »

FASTA31635,540

References

« Hide 'large scale' references
[1]"Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA."
Angrist M., Wells D.E., Chakravarti A., Pandey A.
Genomics 30:623-625(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid."
Ohtsuki T., Hatake K., Ikeda M., Tomizuka H., Terui Y., Uwai M., Miura Y.
Biochem. Biophys. Res. Commun. 230:81-84(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION BY ATRA.
Tissue: Histiocytic lymphoma.
[3]"The gene for the human Src-like adaptor protein (hSLAP) is located within the 64-kb intron of the thyroglobulin gene."
Meijerink P.H.S., Yanakiev P., Zorn I., Grierson A.J., Bikker H., Dye D., Kalaydjieva L., Baas F.
Eur. J. Biochem. 254:297-303(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Fetal brain.
[4]"Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling."
Holland S.J., Liao X.C., Mendenhall M.K., Zhou X., Pardo J., Chu P., Spencer C., Fu A.C., Sheng N., Yu P., Pali E., Nagin A., Shen M., Yu S., Chan E., Wu X., Li C., Woisetschlager M. expand/collapse author list , Aversa G., Kolbinger F., Bennett M.K., Molineaux S., Luo Y., Payan D.G., Mancebo H.S.Y., Wu J.
J. Exp. Med. 194:1263-1276(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"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. expand/collapse author list , 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] (ISOFORMS 2; 3 AND 4).
Tissue: Brain.
[7]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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 5).
Tissue: Bone marrow.
[10]"Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein."
Kratchmarova I., Sosinowski T., Weiss A., Witter K., Vincenz C., Pandey A.
Gene 262:267-273(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-72.
[11]"SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling."
Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.
Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HOMODIMERIZATION, PHOSPHORYLATION, INTERACTION WITH CBL; ZAP70; CD3Z; SYK AND LAT, MUTAGENESIS OF ARG-111; LEU-218; LEU-224; LEU-229 AND 237-LEU--LEU-239.
[12]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Solution structure of the SH3 domain of the human Src-like adapter protein (SLAP)."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 15-80.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U30473 mRNA. Translation: AAC50357.1.
D89077 mRNA. Translation: BAA13758.1.
U44403 mRNA. Translation: AAC27662.1.
CR536537 mRNA. Translation: CAG38774.1.
AK297423 mRNA. Translation: BAH12578.1.
AK297519 mRNA. Translation: BAH12602.1.
AK312584 mRNA. Translation: BAG35478.1. Different initiation.
AF235100 Genomic DNA. No translation available.
AF305872 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW92159.1.
BC007042 mRNA. Translation: AAH07042.1. Different initiation.
AJ238591 mRNA. Translation: CAB53536.1.
CCDSCCDS6370.1.
RefSeqNP_001039021.1. NM_001045556.2.
NP_001039022.2. NM_001045557.2.
NP_006739.2. NM_006748.3.
UniGeneHs.75367.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CUDNMR-A15-80[»]
ProteinModelPortalQ13239.
SMRQ13239. Positions 13-212.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112394. 14 interactions.
IntActQ13239. 6 interactions.
MINTMINT-1404565.
STRING9606.ENSP00000394049.

PTM databases

PhosphoSiteQ13239.

Polymorphism databases

DMDM30173237.

Proteomic databases

MaxQBQ13239.
PaxDbQ13239.
PRIDEQ13239.

Protocols and materials databases

DNASU6503.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338087; ENSP00000337548; ENSG00000155926.
ENST00000517648; ENSP00000428559; ENSG00000155926.
ENST00000524345; ENSP00000427928; ENSG00000155926.
GeneID6503.
KEGGhsa:6503.
UCSCuc003ytz.3. human.

Organism-specific databases

CTD6503.
GeneCardsGC08M134118.
HGNCHGNC:10902. SLA.
HPAHPA012296.
MIM601099. gene.
neXtProtNX_Q13239.
PharmGKBPA35802.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG151065.
HOGENOMHOG000234240.
HOVERGENHBG054908.
InParanoidQ13239.
OrthoDBEOG7DVDBX.
PhylomeDBQ13239.

Enzyme and pathway databases

SignaLinkQ13239.

Gene expression databases

ArrayExpressQ13239.
BgeeQ13239.
CleanExHS_SLA.
GenevestigatorQ13239.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13239.
GenomeRNAi6503.
NextBio25281.
PROQ13239.
SOURCESearch...

Entry information

Entry nameSLAP1_HUMAN
AccessionPrimary (citable) accession number: Q13239
Secondary accession number(s): B7Z4J2 expand/collapse secondary AC list , B7Z4L6, Q6FI01, Q9UMQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM