Q96JZ2 (HSH2D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 352

352

Hematopoietic SH2 domain-containing protein

PRO_0000233129

Regions

Domain

34 – 125

92

SH2

Natural variations

Alternative sequence

1 – 72

72

MTEAG…TLSYK → MRGSRMSQPPQCLRR in isoform 2.

VSP_018052

Experimental info

Mutagenesis

10 – 13

4

PLPP → ALPA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Mutagenesis

59

1

R → K: Loss of the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.

Mutagenesis

116

1

P → A: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Mutagenesis

135

1

Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Mutagenesis

192 – 195

4

PKSP → AKSA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Mutagenesis

341

1

Y → F: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Mutagenesis

346 – 349

4

PFAP → AFAA: No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation. Ref.7

Sequence conflict

180

1

R → G in BAD18408. Ref.3

Secondary structure

1

.

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352

Helix Strand Turn

Details...

Beta strand

28 – 30

3

Beta strand

33 – 35

3

Helix

41 – 49

9

Beta strand

56 – 60

5

Beta strand

62 – 71

10

Beta strand

74 – 76

3

Beta strand

78 – 84

7

Beta strand

99 – 101

3

Helix

102 – 109

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: CB6B7EAE424A08C3	FASTA	352	39,002
	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
	Isoform 2 [UniParc]. Checksum: 75269E0DC3046849	FASTA	295	32,704
	10 20 30 40 50 60 MRGSRMSQPP QCLRRAQSSC CHFMVKLLDD GTFMIPGEKV AHTSLDALVT FHQQKPIEPR 70 80 90 100 110 120 RELLTQPCRQ KDPANVDYED LFLYSNAVAE EAACPVSAPE EASPKPVLCH QSKERKPSAE 130 140 150 160 170 180 MNRITTKEAT SSCPPKSPLG ETRQKLWRSL KMLPERGQRV RQQLKSHLAT VNLSSLLDVR 190 200 210 220 230 240 RSTVISGPGT GKGSQDHSGD PTSGDRGYTD PCVATSLKSP SQPQAPKDRK VPTRKAERSV 250 260 270 280 290 SCIEVTPGDR SWHQMVVRAL SSQESKPEHQ GLAEPENDQL PEEYQQPPPF APGYC

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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.

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.

IPI

IPI00657885.
IPI00748347.

PIR

JC7781.

RefSeq

NP_116244.1. NM_032855.2.

UniGene

Hs.631617.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CS0	NMR	-	A	24-129	[»]

ProteinModelPortal

Q96JZ2.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96JZ2. 1 interaction.

STRING

9606.ENSP00000253680.

PTM databases

PhosphoSite

Q96JZ2.

Polymorphism databases

DMDM

74732160.

Proteomic databases

PaxDb

Q96JZ2.

PRIDE

Q96JZ2.

Protocols and materials databases

DNASU

84941.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253680; ENSP00000253680; ENSG00000196684.

GeneID

84941.

KEGG

hsa:84941.

UCSC

uc002ndp.4. human.
uc002ndr.3. human.

Organism-specific databases

CTD

84941.

GeneCards

GC19P016244.

HGNC

HGNC:24920. HSH2D.

HPA

HPA036616.

MIM

608349. gene.

neXtProt

NX_Q96JZ2.

PharmGKB

PA134927763.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG70356.

HOGENOM

HOG000112961.

HOVERGEN

HBG081611.

InParanoid

Q96JZ2.

OMA

DYEDLFL.

OrthoDB

EOG46MBJR.

Gene expression databases

ArrayExpress

Q96JZ2.

Bgee

Q96JZ2.

CleanEx

HS_HSH2D.

Genevestigator

Q96JZ2.

GermOnline

ENSG00000196684. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96JZ2.

GenomeRNAi

84941.

NextBio

75406.

SOURCE

Search...

Entry information

Entry name

HSH2D_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.