HSH2D_HUMAN
ID HSH2D_HUMAN Reviewed; 352 AA.
AC Q96JZ2; B5ME72; Q6ZNG7;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Hematopoietic SH2 domain-containing protein;
DE Short=Hematopoietic SH2 protein;
DE AltName: Full=Adaptor in lymphocytes of unknown function X;
GN Name=HSH2D; Synonyms=ALX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION
RP WITH FES AND TNK2, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=11700021; DOI=10.1006/bbrc.2001.5890;
RA Oda T., Muramatsu M.-A., Isogai T., Masuho Y., Asano S., Yamashita T.;
RT "HSH2: a novel SH2 domain-containing adapter protein involved in tyrosine
RT kinase signaling in hematopoietic cells.";
RL Biochem. Biophys. Res. Commun. 288:1078-1086(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RC TISSUE=Spleen;
RX PubMed=12960172; DOI=10.1074/jbc.m306283200;
RA Greene T.A., Powell P., Nzerem C., Shapiro M.J., Shapiro V.S.;
RT "Cloning and characterization of ALX, an adaptor downstream of CD28.";
RL J. Biol. Chem. 278:45128-45134(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, and Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=B-cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP MUTAGENESIS OF 10-PRO--PRO-13; PRO-116; TYR-135; 192-PRO--PRO-195; TYR-341
RP AND 346-PRO--PRO-349, FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=15284240; DOI=10.1074/jbc.m404198200;
RA Shapiro M.J., Powell P., Ndubuizu A., Nzerem C., Shapiro V.S.;
RT "The ALX Src homology 2 domain is both necessary and sufficient to inhibit
RT T cell receptor/CD28-mediated up-regulation of RE/AP.";
RL J. Biol. Chem. 279:40647-40652(2004).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=16169852; DOI=10.1074/jbc.m507441200;
RA Shapiro M.J., Chen Y.-Y., Shapiro V.S.;
RT "The carboxyl-terminal segment of the adaptor protein ALX directs its
RT nuclear export during T cell activation.";
RL J. Biol. Chem. 280:38242-38246(2005).
RN [9]
RP STRUCTURE BY NMR OF 24-129.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH2 domain of human HSH2D protein.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: May be a modulator of the apoptotic response through its
CC ability to affect mitochondrial stability (By similarity). Adapter
CC protein involved in tyrosine kinase and CD28 signaling. Seems to affect
CC CD28-mediated activation of the RE/AP element of the interleukin-2
CC promoter. {ECO:0000250, ECO:0000269|PubMed:11700021,
CC ECO:0000269|PubMed:12960172, ECO:0000269|PubMed:15284240}.
CC -!- SUBUNIT: Interacts with FES and TNK2. {ECO:0000269|PubMed:11700021}.
CC -!- INTERACTION:
CC Q96JZ2; P10721: KIT; NbExp=5; IntAct=EBI-3919324, EBI-1379503;
CC Q96JZ2; Q99816: TSG101; NbExp=4; IntAct=EBI-3919324, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96JZ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JZ2-2; Sequence=VSP_018052;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in spleen and hematopoietic
CC cells such as peripheral blood leukocytes and weakly expressed in
CC prostate, thymus, heart, small intestine and placenta.
CC {ECO:0000269|PubMed:11700021, ECO:0000269|PubMed:12960172}.
CC -!- PTM: May be phosphorylated by FES and ACK1.
CC {ECO:0000269|PubMed:11700021, ECO:0000269|PubMed:15284240}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY319652; AAQ81285.1; -; mRNA.
DR EMBL; AK027792; BAB55372.1; -; mRNA.
DR EMBL; AK131222; BAD18408.1; -; mRNA.
DR EMBL; AC008894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84529.1; -; Genomic_DNA.
DR EMBL; BC025237; AAH25237.1; -; mRNA.
DR CCDS; CCDS74304.1; -. [Q96JZ2-1]
DR PIR; JC7781; JC7781.
DR RefSeq; NP_001278203.1; NM_001291274.1.
DR RefSeq; NP_116244.1; NM_032855.3. [Q96JZ2-1]
DR PDB; 2CS0; NMR; -; A=24-129.
DR PDBsum; 2CS0; -.
DR AlphaFoldDB; Q96JZ2; -.
DR SMR; Q96JZ2; -.
DR BioGRID; 124375; 24.
DR IntAct; Q96JZ2; 17.
DR STRING; 9606.ENSP00000482604; -.
DR GlyGen; Q96JZ2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96JZ2; -.
DR PhosphoSitePlus; Q96JZ2; -.
DR BioMuta; HSH2D; -.
DR DMDM; 74732160; -.
DR EPD; Q96JZ2; -.
DR jPOST; Q96JZ2; -.
DR MassIVE; Q96JZ2; -.
DR MaxQB; Q96JZ2; -.
DR PaxDb; Q96JZ2; -.
DR PeptideAtlas; Q96JZ2; -.
DR PRIDE; Q96JZ2; -.
DR ProteomicsDB; 77021; -. [Q96JZ2-1]
DR ProteomicsDB; 77022; -. [Q96JZ2-2]
DR Antibodypedia; 27308; 165 antibodies from 25 providers.
DR DNASU; 84941; -.
DR Ensembl; ENST00000613986.4; ENSP00000483354.1; ENSG00000196684.12. [Q96JZ2-1]
DR Ensembl; ENST00000616645.4; ENSP00000482604.1; ENSG00000196684.12. [Q96JZ2-1]
DR GeneID; 84941; -.
DR KEGG; hsa:84941; -.
DR MANE-Select; ENST00000613986.4; ENSP00000483354.1; NM_001382417.1; NP_001369346.1.
DR UCSC; uc032hot.2; human. [Q96JZ2-1]
DR CTD; 84941; -.
DR DisGeNET; 84941; -.
DR GeneCards; HSH2D; -.
DR HGNC; HGNC:24920; HSH2D.
DR HPA; ENSG00000196684; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 608349; gene.
DR neXtProt; NX_Q96JZ2; -.
DR OpenTargets; ENSG00000196684; -.
DR PharmGKB; PA134927763; -.
DR VEuPathDB; HostDB:ENSG00000196684; -.
DR eggNOG; ENOG502RZYN; Eukaryota.
DR GeneTree; ENSGT00940000161678; -.
DR HOGENOM; CLU_067582_0_0_1; -.
DR InParanoid; Q96JZ2; -.
DR OMA; KAQSCCR; -.
DR OrthoDB; 1404128at2759; -.
DR PhylomeDB; Q96JZ2; -.
DR TreeFam; TF336893; -.
DR PathwayCommons; Q96JZ2; -.
DR SignaLink; Q96JZ2; -.
DR BioGRID-ORCS; 84941; 14 hits in 290 CRISPR screens.
DR ChiTaRS; HSH2D; human.
DR EvolutionaryTrace; Q96JZ2; -.
DR GenomeRNAi; 84941; -.
DR Pharos; Q96JZ2; Tbio.
DR PRO; PR:Q96JZ2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96JZ2; protein.
DR Bgee; ENSG00000196684; Expressed in granulocyte and 101 other tissues.
DR ExpressionAtlas; Q96JZ2; baseline and differential.
DR Genevisible; Q96JZ2; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035047; HSH2D.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR PANTHER; PTHR14388:SF3; PTHR14388:SF3; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..352
FT /note="Hematopoietic SH2 domain-containing protein"
FT /id="PRO_0000233129"
FT DOMAIN 34..125
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 157..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..259
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..72
FT /note="MTEAGKLPLPLPPRLDWFVHTQMGQLAQDGVPEWFHGAISREDAENLLESQP
FT LGSFLIRVSHSHVGYTLSYK -> MRGSRMSQPPQCLRR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018052"
FT MUTAGEN 10..13
FT /note="PLPP->ALPA: No change in the ability to inhibit
FT RE/AP up-regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT MUTAGEN 59
FT /note="R->K: Loss of the ability to inhibit RE/AP up-
FT regulation in response to TCR/CD28 stimulation."
FT MUTAGEN 116
FT /note="P->A: No change in the ability to inhibit RE/AP up-
FT regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT MUTAGEN 135
FT /note="Y->F: No change in the ability to inhibit RE/AP up-
FT regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT MUTAGEN 192..195
FT /note="PKSP->AKSA: No change in the ability to inhibit
FT RE/AP up-regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT MUTAGEN 341
FT /note="Y->F: No change in the ability to inhibit RE/AP up-
FT regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT MUTAGEN 346..349
FT /note="PFAP->AFAA: No change in the ability to inhibit
FT RE/AP up-regulation in response to TCR/CD28 stimulation."
FT /evidence="ECO:0000269|PubMed:15284240"
FT CONFLICT 180
FT /note="R -> G (in Ref. 3; BAD18408)"
FT /evidence="ECO:0000305"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2CS0"
FT HELIX 41..49
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 56..60
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:2CS0"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:2CS0"
FT HELIX 102..109
FT /evidence="ECO:0007829|PDB:2CS0"
SQ SEQUENCE 352 AA; 39002 MW; CB6B7EAE424A08C3 CRC64;
MTEAGKLPLP LPPRLDWFVH TQMGQLAQDG VPEWFHGAIS REDAENLLES QPLGSFLIRV
SHSHVGYTLS YKAQSSCCHF MVKLLDDGTF MIPGEKVAHT SLDALVTFHQ QKPIEPRREL
LTQPCRQKDP ANVDYEDLFL YSNAVAEEAA CPVSAPEEAS PKPVLCHQSK ERKPSAEMNR
ITTKEATSSC PPKSPLGETR QKLWRSLKML PERGQRVRQQ LKSHLATVNL SSLLDVRRST
VISGPGTGKG SQDHSGDPTS GDRGYTDPCV ATSLKSPSQP QAPKDRKVPT RKAERSVSCI
EVTPGDRSWH QMVVRALSSQ ESKPEHQGLA EPENDQLPEE YQQPPPFAPG YC
