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Q96JZ2

- HSH2D_HUMAN

UniProt

Q96JZ2 - HSH2D_HUMAN

Protein

Hematopoietic SH2 domain-containing protein

Gene

HSH2D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    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.By similarity3 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct

    Enzyme and pathway databases

    SignaLinkiQ96JZ2.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hematopoietic SH2 domain-containing protein
    Short name:
    Hematopoietic SH2 protein
    Alternative name(s):
    Adaptor in lymphocytes of unknown function X
    Gene namesi
    Name:HSH2D
    Synonyms:ALX
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:24920. HSH2D.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi10 – 134PLPP → ALPA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
    Mutagenesisi59 – 591R → K: Loss of the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
    Mutagenesisi116 – 1161P → A: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. 1 Publication
    Mutagenesisi135 – 1351Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. 1 Publication
    Mutagenesisi192 – 1954PKSP → AKSA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
    Mutagenesisi341 – 3411Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. 1 Publication
    Mutagenesisi346 – 3494PFAP → AFAA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.

    Organism-specific databases

    PharmGKBiPA134927763.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 352352Hematopoietic SH2 domain-containing proteinPRO_0000233129Add
    BLAST

    Post-translational modificationi

    May be phosphorylated by FES and ACK1.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ96JZ2.
    PaxDbiQ96JZ2.
    PRIDEiQ96JZ2.

    PTM databases

    PhosphoSiteiQ96JZ2.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiQ96JZ2.
    BgeeiQ96JZ2.
    CleanExiHS_HSH2D.
    GenevestigatoriQ96JZ2.

    Organism-specific databases

    HPAiHPA036616.

    Interactioni

    Subunit structurei

    Interacts with FES and TNK2.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KITP107215EBI-3919324,EBI-1379503

    Protein-protein interaction databases

    BioGridi124375. 3 interactions.
    IntActiQ96JZ2. 5 interactions.
    STRINGi9606.ENSP00000253680.

    Structurei

    Secondary structure

    1
    352
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi28 – 303
    Beta strandi33 – 353
    Helixi41 – 499
    Beta strandi56 – 605
    Beta strandi62 – 7110
    Beta strandi74 – 763
    Beta strandi78 – 847
    Beta strandi99 – 1013
    Helixi102 – 1098

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CS0NMR-A24-129[»]
    ProteinModelPortaliQ96JZ2.
    SMRiQ96JZ2. Positions 13-164.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96JZ2.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini34 – 12592SH2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG70356.
    HOGENOMiHOG000112961.
    HOVERGENiHBG081611.
    InParanoidiQ96JZ2.
    OMAiKLWRNLK.
    OrthoDBiEOG751NG5.
    PhylomeDBiQ96JZ2.
    TreeFamiTF336893.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    [Graphical view]
    PfamiPF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96JZ2-1) [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

    MTEAGKLPLP LPPRLDWFVH TQMGQLAQDG VPEWFHGAIS REDAENLLES    50
    QPLGSFLIRV SHSHVGYTLS YKAQSSCCHF MVKLLDDGTF MIPGEKVAHT 100
    SLDALVTFHQ QKPIEPRREL LTQPCRQKDP ANVDYEDLFL YSNAVAEEAA 150
    CPVSAPEEAS PKPVLCHQSK ERKPSAEMNR ITTKEATSSC PPKSPLGETR 200
    QKLWRSLKML PERGQRVRQQ LKSHLATVNL SSLLDVRRST VISGPGTGKG 250
    SQDHSGDPTS GDRGYTDPCV ATSLKSPSQP QAPKDRKVPT RKAERSVSCI 300
    EVTPGDRSWH QMVVRALSSQ ESKPEHQGLA EPENDQLPEE YQQPPPFAPG 350
    YC 352
    Length:352
    Mass (Da):39,002
    Last modified:December 1, 2001 - v1
    Checksum:iCB6B7EAE424A08C3
    GO
    Isoform 2 (identifier: Q96JZ2-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-72: MTEAGKLPLP...SHVGYTLSYK → MRGSRMSQPPQCLRR

    Note: No experimental confirmation available.

    Show »
    Length:295
    Mass (Da):32,704
    Checksum:i75269E0DC3046849
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti180 – 1801R → G in BAD18408. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7272MTEAG…TLSYK → MRGSRMSQPPQCLRR in isoform 2. 1 PublicationVSP_018052Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    PIRiJC7781.
    RefSeqiNP_001278203.1. NM_001291274.1. [Q96JZ2-2]
    NP_116244.1. NM_032855.3. [Q96JZ2-1]
    UniGeneiHs.631617.

    Genome annotation databases

    EnsembliENST00000253680; ENSP00000253680; ENSG00000196684. [Q96JZ2-1]
    GeneIDi84941.
    KEGGihsa:84941.
    UCSCiuc002ndp.4. human. [Q96JZ2-1]
    uc002ndr.3. human. [Q96JZ2-2]

    Polymorphism databases

    DMDMi74732160.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    PIRi JC7781.
    RefSeqi NP_001278203.1. NM_001291274.1. [Q96JZ2-2 ]
    NP_116244.1. NM_032855.3. [Q96JZ2-1 ]
    UniGenei Hs.631617.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2CS0 NMR - A 24-129 [» ]
    ProteinModelPortali Q96JZ2.
    SMRi Q96JZ2. Positions 13-164.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124375. 3 interactions.
    IntActi Q96JZ2. 5 interactions.
    STRINGi 9606.ENSP00000253680.

    PTM databases

    PhosphoSitei Q96JZ2.

    Polymorphism databases

    DMDMi 74732160.

    Proteomic databases

    MaxQBi Q96JZ2.
    PaxDbi Q96JZ2.
    PRIDEi Q96JZ2.

    Protocols and materials databases

    DNASUi 84941.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000253680 ; ENSP00000253680 ; ENSG00000196684 . [Q96JZ2-1 ]
    GeneIDi 84941.
    KEGGi hsa:84941.
    UCSCi uc002ndp.4. human. [Q96JZ2-1 ]
    uc002ndr.3. human. [Q96JZ2-2 ]

    Organism-specific databases

    CTDi 84941.
    GeneCardsi GC19P016244.
    HGNCi HGNC:24920. HSH2D.
    HPAi HPA036616.
    MIMi 608349. gene.
    neXtProti NX_Q96JZ2.
    PharmGKBi PA134927763.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG70356.
    HOGENOMi HOG000112961.
    HOVERGENi HBG081611.
    InParanoidi Q96JZ2.
    OMAi KLWRNLK.
    OrthoDBi EOG751NG5.
    PhylomeDBi Q96JZ2.
    TreeFami TF336893.

    Enzyme and pathway databases

    SignaLinki Q96JZ2.

    Miscellaneous databases

    EvolutionaryTracei Q96JZ2.
    GenomeRNAii 84941.
    NextBioi 75406.
    PROi Q96JZ2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96JZ2.
    Bgeei Q96JZ2.
    CleanExi HS_HSH2D.
    Genevestigatori Q96JZ2.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    [Graphical view ]
    Pfami PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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. 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.

    Entry informationi

    Entry nameiHSH2D_HUMAN
    AccessioniPrimary (citable) accession number: Q96JZ2
    Secondary accession number(s): B5ME72, Q6ZNG7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 2, 2006
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 102 of the entry and version 1 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 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3