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Protein

Src-like-adapter 2

Gene

SLA2

Organism
Homo sapiens (Human)
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. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins.1 Publication

GO - Molecular functioni

  • protein N-terminus binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB

GO - Biological processi

  • antigen receptor-mediated signaling pathway Source: UniProtKB
  • B cell mediated immunity Source: UniProtKB
  • intracellular receptor signaling pathway Source: UniProtKB
  • negative regulation of B cell activation Source: UniProtKB
  • negative regulation of calcium-mediated signaling Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of immune response Source: UniProtKB
  • T cell activation Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

SignaLinkiQ9H6Q3.

Names & Taxonomyi

Protein namesi
Recommended name:
Src-like-adapter 2
Alternative name(s):
Modulator of antigen receptor signaling
Short name:
MARS
Src-like adapter protein 2
Short name:
SLAP-2
Gene namesi
Name:SLA2
Synonyms:C20orf156, SLAP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:17329. SLA2.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Cytoplasm Curated

  • Note: May be cytoplasmic and is not localized to membranes.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • endosome membrane Source: UniProtKB
  • late endosome Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Abolishes localization to membranes. 1 Publication

Organism-specific databases

PharmGKBiPA38231.

Polymorphism and mutation databases

BioMutaiSLA2.
DMDMi30173374.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 261260Src-like-adapter 2PRO_0000022351Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication

Post-translational modificationi

Phosphorylated by CSF1R.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

MaxQBiQ9H6Q3.
PaxDbiQ9H6Q3.
PeptideAtlasiQ9H6Q3.
PRIDEiQ9H6Q3.

PTM databases

iPTMnetiQ9H6Q3.
PhosphoSiteiQ9H6Q3.

Expressioni

Tissue specificityi

Predominantly expressed in immune system, with highest levels in peripheral blood leukocytes. Expressed in spleen, thymus and lymph nodes. Expressed in T-cells as well as in monocytes, and at low level in B-cells. Also detected in placenta, prostate, skin, retina and colon.

Gene expression databases

BgeeiENSG00000101082.
CleanExiHS_SLA2.
GenevisibleiQ9H6Q3. HS.

Organism-specific databases

HPAiCAB013260.
CAB013305.

Interactioni

Subunit structurei

Interacts (via SH2 domain) with ZAP70 (phosphorylated) and CD3Z (phosphorylated). Interacts (via SH2 domain) with CSF1R (phosphorylated) (By similarity). Interacts (via its C-terminal domain) with CBL (phosphorylated).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ERBB2P046262EBI-1222854,EBI-641062
GAB1Q134804EBI-1222854,EBI-517684
KITP107212EBI-1222854,EBI-1379503
METP085814EBI-1222854,EBI-1039152

GO - Molecular functioni

  • protein N-terminus binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi123928. 8 interactions.
IntActiQ9H6Q3. 6 interactions.
MINTiMINT-1493503.
STRINGi9606.ENSP00000262866.

Structurei

Secondary structure

1
261
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi37 – 393Combined sources
Beta strandi58 – 658Combined sources
Beta strandi68 – 736Combined sources
Turni74 – 763Combined sources
Beta strandi79 – 835Combined sources
Helixi84 – 863Combined sources
Beta strandi87 – 915Combined sources
Turni92 – 943Combined sources
Beta strandi95 – 984Combined sources
Helixi101 – 1088Combined sources
Beta strandi118 – 1225Combined sources
Beta strandi124 – 1285Combined sources
Beta strandi130 – 1356Combined sources
Beta strandi145 – 1528Combined sources
Beta strandi158 – 1614Combined sources
Beta strandi164 – 1685Combined sources
Helixi169 – 1768Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4M4ZX-ray2.10A29-193[»]
ProteinModelPortaliQ9H6Q3.
SMRiQ9H6Q3. Positions 36-240.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 9261SH3PROSITE-ProRule annotationAdd
BLAST
Domaini94 – 19198SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni195 – 26167SLA C-terminalAdd
BLAST

Domaini

The loss of the C-terminal domain partially abolishes the inhibitory function, but can be partially compensated by higher level of protein expression.

Sequence similaritiesi

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

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiENOG410IKI6. Eukaryota.
ENOG4111GMN. LUCA.
GeneTreeiENSGT00390000001681.
HOVERGENiHBG054908.
InParanoidiQ9H6Q3.
OMAiWLYEGLS.
OrthoDBiEOG091G0GB0.
PhylomeDBiQ9H6Q3.
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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q9H6Q3-1) [UniParc]FASTAAdd to basket
Also known as: p28

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
MGSLPSRRKS LPSPSLSSSV QGQGPVTMEA ERSKATAVAL GSFPAGGPAE
60 70 80 90 100
LSLRLGEPLT IVSEDGDWWT VLSEVSGREY NIPSVHVAKV SHGWLYEGLS
110 120 130 140 150
REKAEELLLL PGNPGGAFLI RESQTRRGSY SLSVRLSRPA SWDRIRHYRI
160 170 180 190 200
HCLDNGWLYI SPRLTFPSLQ ALVDHYSELA DDICCLLKEP CVLQRAGPLP
210 220 230 240 250
GKDIPLPVTV QRTPLNWKEL DSSLLFSEAA TGEESLLSEG LRESLSFYIS
260
LNDEAVSLDD A
Length:261
Mass (Da):28,585
Last modified:January 23, 2007 - v3
Checksum:i858AF03451672B3D
GO
Isoform 2 (identifier: Q9H6Q3-2) [UniParc]FASTAAdd to basket
Also known as: p23, SLAP-2-v, MARS-v

The sequence of this isoform differs from the canonical sequence as follows:
     179-210: LADDICCLLKEPCVLQRAGPLPGKDIPLPVTV → GWPAPWQGYTPTCDCAEDTTQLERAGQLPPVF
     211-261: Missing.

Show »
Length:210
Mass (Da):23,103
Checksum:iBED62208E53A472E
GO
Isoform 3 (identifier: Q9H6Q3-3) [UniParc]FASTAAdd to basket
Also known as: p25

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.

Note: Produced by alternative initiation at Met-28 of isoform 1.
Show »
Length:234
Mass (Da):25,862
Checksum:iB8DC7A16BCBC3F9F
GO
Isoform 4 (identifier: Q9H6Q3-4) [UniParc]FASTAAdd to basket
Also known as: p20

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.
     179-210: LADDICCLLKEPCVLQRAGPLPGKDIPLPVTV → GWPAPWQGYTPTCDCAEDTTQLERAGQLPPVF
     211-261: Missing.

Note: Produced by alternative initiation at Met-28 of isoform 2.
Show »
Length:183
Mass (Da):20,380
Checksum:i6B4D8B535C3C31CC
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti210 – 2101V → M.
Corresponds to variant rs34834764 [ dbSNP | Ensembl ].
VAR_051361

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727Missing in isoform 3 and isoform 4. CuratedVSP_018794Add
BLAST
Alternative sequencei179 – 21032LADDI…LPVTV → GWPAPWQGYTPTCDCAEDTT QLERAGQLPPVF in isoform 2 and isoform 4. CuratedVSP_007240Add
BLAST
Alternative sequencei211 – 26151Missing in isoform 2 and isoform 4. CuratedVSP_007241Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF326353 mRNA. Translation: AAL29204.1.
AF290985 mRNA. Translation: AAL38197.1.
AF290986 mRNA. Translation: AAL38198.1.
AK025645 mRNA. Translation: BAB15201.1.
AK291513 mRNA. Translation: BAF84202.1.
AL031662, AL050318 Genomic DNA. Translation: CAI21397.1.
AL031662, AL050318 Genomic DNA. Translation: CAI21398.1.
AL050318, AL031662 Genomic DNA. Translation: CAI23504.1.
AL050318, AL031662 Genomic DNA. Translation: CAI23505.1.
CH471077 Genomic DNA. Translation: EAW76116.1.
CH471077 Genomic DNA. Translation: EAW76117.1.
CH471077 Genomic DNA. Translation: EAW76118.1.
CH471077 Genomic DNA. Translation: EAW76119.1.
BC042041 mRNA. Translation: AAH42041.1.
CCDSiCCDS13282.1. [Q9H6Q3-1]
CCDS13283.1. [Q9H6Q3-2]
RefSeqiNP_115590.1. NM_032214.3. [Q9H6Q3-1]
NP_778252.1. NM_175077.2. [Q9H6Q3-2]
UniGeneiHs.713578.

Genome annotation databases

EnsembliENST00000262866; ENSP00000262866; ENSG00000101082. [Q9H6Q3-1]
ENST00000360672; ENSP00000353890; ENSG00000101082. [Q9H6Q3-2]
GeneIDi84174.
KEGGihsa:84174.
UCSCiuc002xfu.4. human. [Q9H6Q3-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF326353 mRNA. Translation: AAL29204.1.
AF290985 mRNA. Translation: AAL38197.1.
AF290986 mRNA. Translation: AAL38198.1.
AK025645 mRNA. Translation: BAB15201.1.
AK291513 mRNA. Translation: BAF84202.1.
AL031662, AL050318 Genomic DNA. Translation: CAI21397.1.
AL031662, AL050318 Genomic DNA. Translation: CAI21398.1.
AL050318, AL031662 Genomic DNA. Translation: CAI23504.1.
AL050318, AL031662 Genomic DNA. Translation: CAI23505.1.
CH471077 Genomic DNA. Translation: EAW76116.1.
CH471077 Genomic DNA. Translation: EAW76117.1.
CH471077 Genomic DNA. Translation: EAW76118.1.
CH471077 Genomic DNA. Translation: EAW76119.1.
BC042041 mRNA. Translation: AAH42041.1.
CCDSiCCDS13282.1. [Q9H6Q3-1]
CCDS13283.1. [Q9H6Q3-2]
RefSeqiNP_115590.1. NM_032214.3. [Q9H6Q3-1]
NP_778252.1. NM_175077.2. [Q9H6Q3-2]
UniGeneiHs.713578.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4M4ZX-ray2.10A29-193[»]
ProteinModelPortaliQ9H6Q3.
SMRiQ9H6Q3. Positions 36-240.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123928. 8 interactions.
IntActiQ9H6Q3. 6 interactions.
MINTiMINT-1493503.
STRINGi9606.ENSP00000262866.

PTM databases

iPTMnetiQ9H6Q3.
PhosphoSiteiQ9H6Q3.

Polymorphism and mutation databases

BioMutaiSLA2.
DMDMi30173374.

Proteomic databases

MaxQBiQ9H6Q3.
PaxDbiQ9H6Q3.
PeptideAtlasiQ9H6Q3.
PRIDEiQ9H6Q3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262866; ENSP00000262866; ENSG00000101082. [Q9H6Q3-1]
ENST00000360672; ENSP00000353890; ENSG00000101082. [Q9H6Q3-2]
GeneIDi84174.
KEGGihsa:84174.
UCSCiuc002xfu.4. human. [Q9H6Q3-1]

Organism-specific databases

CTDi84174.
GeneCardsiSLA2.
HGNCiHGNC:17329. SLA2.
HPAiCAB013260.
CAB013305.
MIMi606577. gene.
neXtProtiNX_Q9H6Q3.
PharmGKBiPA38231.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKI6. Eukaryota.
ENOG4111GMN. LUCA.
GeneTreeiENSGT00390000001681.
HOVERGENiHBG054908.
InParanoidiQ9H6Q3.
OMAiWLYEGLS.
OrthoDBiEOG091G0GB0.
PhylomeDBiQ9H6Q3.
TreeFamiTF354288.

Enzyme and pathway databases

SignaLinkiQ9H6Q3.

Miscellaneous databases

GeneWikiiSLA2.
GenomeRNAii84174.
PROiQ9H6Q3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101082.
CleanExiHS_SLA2.
GenevisibleiQ9H6Q3. HS.

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...

Entry informationi

Entry nameiSLAP2_HUMAN
AccessioniPrimary (citable) accession number: Q9H6Q3
Secondary accession number(s): A8K648
, E1P5U1, E1P5U2, Q5TH27, Q5TH28, Q8WY18, Q96QI4, Q9H135
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.