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Q96JZ2

- HSH2D_HUMAN

UniProt

Q96JZ2 - HSH2D_HUMAN

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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

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 - Biological processi

  1. negative regulation of B cell apoptotic process Source: Ensembl
  2. negative regulation of mitochondrial depolarization Source: Ensembl
  3. positive regulation of signal transduction Source: Ensembl
  4. T cell activation Source: Ensembl
Complete GO annotation...

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. cytosol Source: Ensembl
  2. mitochondrion Source: Ensembl
  3. nucleus Source: UniProtKB-KW
Complete GO annotation...

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. 1 Publication
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. 1 Publication
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. 1 Publication

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

BgeeiQ96JZ2.
CleanExiHS_HSH2D.
ExpressionAtlasiQ96JZ2. baseline and differential.
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 – 303Combined sources
Beta strandi33 – 353Combined sources
Helixi41 – 499Combined sources
Beta strandi56 – 605Combined sources
Beta strandi62 – 7110Combined sources
Beta strandi74 – 763Combined sources
Beta strandi78 – 847Combined sources
Beta strandi99 – 1013Combined sources
Helixi102 – 1098Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00570000079047.
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

        10         20         30         40         50
MTEAGKLPLP LPPRLDWFVH TQMGQLAQDG VPEWFHGAIS REDAENLLES
60 70 80 90 100
QPLGSFLIRV SHSHVGYTLS YKAQSSCCHF MVKLLDDGTF MIPGEKVAHT
110 120 130 140 150
SLDALVTFHQ QKPIEPRREL LTQPCRQKDP ANVDYEDLFL YSNAVAEEAA
160 170 180 190 200
CPVSAPEEAS PKPVLCHQSK ERKPSAEMNR ITTKEATSSC PPKSPLGETR
210 220 230 240 250
QKLWRSLKML PERGQRVRQQ LKSHLATVNL SSLLDVRRST VISGPGTGKG
260 270 280 290 300
SQDHSGDPTS GDRGYTDPCV ATSLKSPSQP QAPKDRKVPT RKAERSVSCI
310 320 330 340 350
EVTPGDRSWH QMVVRALSSQ ESKPEHQGLA EPENDQLPEE YQQPPPFAPG

YC
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:
EMBLi
GenBanki
DDBJi
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.
CCDSiCCDS74304.1. [Q96JZ2-1]
PIRiJC7781.
RefSeqiNP_001278203.1. NM_001291274.1. [Q96JZ2-2]
NP_116244.1. NM_032855.3. [Q96JZ2-1]
UniGeneiHs.631617.

Genome annotation databases

EnsembliENST00000613986; ENSP00000483354; ENSG00000196684. [Q96JZ2-1]
ENST00000616645; ENSP00000482604; 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:
EMBLi
GenBanki
DDBJi
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 .
CCDSi CCDS74304.1. [Q96JZ2-1 ]
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:
PDBei
RCSB PDBi
PDBji
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 ENST00000613986 ; ENSP00000483354 ; ENSG00000196684 . [Q96JZ2-1 ]
ENST00000616645 ; ENSP00000482604 ; 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.
GeneTreei ENSGT00570000079047.
HOGENOMi HOG000112961.
HOVERGENi HBG081611.
InParanoidi Q96JZ2.
OMAi KLWRNLK.
OrthoDBi EOG751NG5.
PhylomeDBi Q96JZ2.
TreeFami TF336893.

Enzyme and pathway databases

SignaLinki Q96JZ2.

Miscellaneous databases

ChiTaRSi HSH2D. human.
EvolutionaryTracei Q96JZ2.
GenomeRNAii 84941.
NextBioi 75406.
PROi Q96JZ2.
SOURCEi Search...

Gene expression databases

Bgeei Q96JZ2.
CleanExi HS_HSH2D.
ExpressionAtlasi Q96JZ2. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 104 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