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Q96JZ2 (HSH2D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
Hematopoietic SH2 domain-containing protein

Short name=Hematopoietic SH2 protein
Alternative name(s):
Adaptor in lymphocytes of unknown function X
Gene names
Name:HSH2D
Synonyms:ALX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be a modulator of the apoptotic response through its ability to affect mitochondrial stability By similarity. Adapter protein involved in tyrosine kinase and CD28 signaling. Seems to affect CD28-mediated activation of the RE/AP element of the interleukin-2 promoter. Ref.1 Ref.2 Ref.7

Subunit structure

Interacts with FES and TNK2. Ref.1

Subcellular location

Cytoplasm. Nucleus Ref.1 Ref.2 Ref.7 Ref.8.

Tissue specificity

Predominantly expressed in spleen and hematopoietic cells such as peripheral blood leukocytes and weakly expressed in prostate, thymus, heart, small intestine and placenta. Ref.1 Ref.2

Post-translational modification

May be phosphorylated by FES and ACK1. Ref.1 Ref.7

Sequence similarities

Contains 1 SH2 domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainSH2 domain
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 24728074. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KITP107215EBI-3919324,EBI-1379503

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96JZ2-1)

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: Q96JZ2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: MTEAGKLPLP...SHVGYTLSYK → MRGSRMSQPPQCLRR
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 352352Hematopoietic SH2 domain-containing protein
PRO_0000233129

Regions

Domain34 – 12592SH2

Natural variations

Alternative sequence1 – 7272MTEAG…TLSYK → MRGSRMSQPPQCLRR in isoform 2.
VSP_018052

Experimental info

Mutagenesis10 – 134PLPP → ALPA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Mutagenesis591R → K: Loss of the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
Mutagenesis1161P → A: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Mutagenesis1351Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Mutagenesis192 – 1954PKSP → AKSA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Mutagenesis3411Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Mutagenesis346 – 3494PFAP → AFAA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7
Sequence conflict1801R → G in BAD18408. Ref.3

Secondary structure

.................. 352
Helix Strand Turn

Details...

Sequences

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

Last modified December 1, 2001. Version 1.
Checksum: CB6B7EAE424A08C3

FASTA35239,002
        10         20         30         40         50         60 
MTEAGKLPLP LPPRLDWFVH TQMGQLAQDG VPEWFHGAIS REDAENLLES QPLGSFLIRV 

        70         80         90        100        110        120 
SHSHVGYTLS YKAQSSCCHF MVKLLDDGTF MIPGEKVAHT SLDALVTFHQ QKPIEPRREL 

       130        140        150        160        170        180 
LTQPCRQKDP ANVDYEDLFL YSNAVAEEAA CPVSAPEEAS PKPVLCHQSK ERKPSAEMNR 

       190        200        210        220        230        240 
ITTKEATSSC PPKSPLGETR QKLWRSLKML PERGQRVRQQ LKSHLATVNL SSLLDVRRST 

       250        260        270        280        290        300 
VISGPGTGKG SQDHSGDPTS GDRGYTDPCV ATSLKSPSQP QAPKDRKVPT RKAERSVSCI 

       310        320        330        340        350 
EVTPGDRSWH QMVVRALSSQ ESKPEHQGLA EPENDQLPEE YQQPPPFAPG YC 

« Hide

Isoform 2 [UniParc].

Checksum: 75269E0DC3046849
Show »

FASTA29532,704

References

« Hide 'large scale' references
[1]"HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine kinase signaling in hematopoietic cells."
Oda T., Muramatsu M.-A., Isogai T., Masuho Y., Asano S., Yamashita T.
Biochem. Biophys. Res. Commun. 288:1078-1086(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH FES AND TNK2, SUBCELLULAR LOCATION, PHOSPHORYLATION, FUNCTION.
[2]"Cloning and characterization of ALX, an adaptor downstream of CD28."
Greene T.A., Powell P., Nzerem C., Shapiro M.J., Shapiro V.S.
J. Biol. Chem. 278:45128-45134(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION.
Tissue: Spleen.
[3]"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 1 AND 2).
Tissue: Placenta and Urinary bladder.
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton 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].
[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: B-cell.
[7]"The ALX Src homology 2 domain is both necessary and sufficient to inhibit T cell receptor/CD28-mediated up-regulation of RE/AP."
Shapiro M.J., Powell P., Ndubuizu A., Nzerem C., Shapiro V.S.
J. Biol. Chem. 279:40647-40652(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 10-PRO--PRO-13; PRO-116; TYR-135; 192-PRO--PRO-195; TYR-341 AND 346-PRO--PRO-349, FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[8]"The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation."
Shapiro M.J., Chen Y.-Y., Shapiro V.S.
J. Biol. Chem. 280:38242-38246(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"Solution structure of the SH2 domain of human HSH2D protein."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 24-129.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY319652 mRNA. Translation: AAQ81285.1.
AK027792 mRNA. Translation: BAB55372.1.
AK131222 mRNA. Translation: BAD18408.1.
AC008894 Genomic DNA. No translation available.
AC020911 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84529.1.
BC025237 mRNA. Translation: AAH25237.1.
PIRJC7781.
RefSeqNP_001278203.1. NM_001291274.1. [Q96JZ2-2]
NP_116244.1. NM_032855.3. [Q96JZ2-1]
UniGeneHs.631617.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CS0NMR-A24-129[»]
ProteinModelPortalQ96JZ2.
SMRQ96JZ2. Positions 13-164.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124375. 3 interactions.
IntActQ96JZ2. 5 interactions.
STRING9606.ENSP00000253680.

PTM databases

PhosphoSiteQ96JZ2.

Polymorphism databases

DMDM74732160.

Proteomic databases

MaxQBQ96JZ2.
PaxDbQ96JZ2.
PRIDEQ96JZ2.

Protocols and materials databases

DNASU84941.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000253680; ENSP00000253680; ENSG00000196684. [Q96JZ2-1]
GeneID84941.
KEGGhsa:84941.
UCSCuc002ndp.4. human. [Q96JZ2-1]
uc002ndr.3. human. [Q96JZ2-2]

Organism-specific databases

CTD84941.
GeneCardsGC19P016244.
HGNCHGNC:24920. HSH2D.
HPAHPA036616.
MIM608349. gene.
neXtProtNX_Q96JZ2.
PharmGKBPA134927763.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70356.
HOGENOMHOG000112961.
HOVERGENHBG081611.
InParanoidQ96JZ2.
OMAKLWRNLK.
OrthoDBEOG751NG5.
PhylomeDBQ96JZ2.
TreeFamTF336893.

Enzyme and pathway databases

SignaLinkQ96JZ2.

Gene expression databases

ArrayExpressQ96JZ2.
BgeeQ96JZ2.
CleanExHS_HSH2D.
GenevestigatorQ96JZ2.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96JZ2.
GenomeRNAi84941.
NextBio75406.
PROQ96JZ2.
SOURCESearch...

Entry information

Entry nameHSH2D_HUMAN
AccessionPrimary (citable) accession number: Q96JZ2
Secondary accession number(s): B5ME72, Q6ZNG7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2006
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 101 of the entry and version 1 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 chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM